Reaching the Biological Cure - Diabetes Research Institute

Transcription

annual report 2013 >
ONE
GOAL:
A
CURE
To restore natural insulin production and
normalize blood sugar levels without
imposing other risks.
Highlights of the Year
2
Financial Summary
30
Message from the Director
4
Making Progress Possible
32
Research Review
6
The Heritage Society
36
The Diabetes Education and
Nutrition Service at the DRI
Boards of Directors
38
24
DRI Foundation Staff
40
Faculty and Staff
25
DRIF Chairman's Message
28
Highlights
of the
Year
At the Diabetes Research Institute, scientists are urgently pursuing
the most promising research findings that show true potential to benefit
people living with diabetes. Nothing exemplifies that commitment more
than moving exciting discoveries out of the laboratory and into clinical
trials, which help move cutting-edge therapies ahead.
This past year DRI scientists, together with their global collaborators,
took several steps to advance cell replacement initiatives, pioneering
a host of new possibilities for those with T1D.
The FDA Phase III “registration” trial of islet transplantation
by the NIH Clinical Islet Transplantation Consortium (CIT)
was just completed. DRI Director Dr. Camillo Ricordi presented
the results of this unprecedented multicenter clinical trial at
the International Cell Therapy Society (ICTS) congress in Paris,
France, on April 25, 2014. While islet transplantation is already
approved at other DRI Federation locations, including Canada,
England and Switzerland, the DRI is confident that this
trial will lead to approval and eventual reimbursement
of islet transplantation for the most severe forms of type 1
diabetes in the United States, as well. This could represent
the first time that a biologically active cell product is
approved in the U.S. by the FDA. The BLA (biologic license
application) is currently in preparation, together with
extensive manufacturing and clinical FDA reports by the NIH
CIT Consortium Team. The comprehensive islet cell product
manufacturing master batch record has been published
and is available worldwide for “open access” download at
http://www.cellr4.org/article/891.
Advancing Research to Patients
In this multicenter trial, as in most current trials of islet
transplantation, the islets are transplanted into the
liver of patients with the most severe forms of type 1 diabetes.
However, this transplant site is not ideal for taking the next
step on the path to a biological cure by moving away from
generalized treatment with anti-rejection drugs, toward
local immunomodulation and immunoprotection of the
transplanted insulin-producing cells. In this direction,
DRI scientists have been investigating other sites within
the body that can serve as a better home for islet cells while
eventually allowing for successful biologic replacement of
insulin-producing cells without systemic immunosuppression
of the recipients. In addition, this novel site to house
the DRI BioHub mini organ would provide the insulinproducing cells with the spacing, support, oxygen and
nutrients they need to survive and thrive long term, while
allowing for strategies for prevention of recurrence of
autoimmunity and/or immune rejection without the need
for chronic administration of anti-rejection drugs.
One area of focus is the omentum, an apron-like lining
inside the abdomen. DRI scientists have been testing the
omentum as a possible location for a DRI BioHub. Encouraging
preliminary data has shown that islets in the omentum can
3 [2013 annual report]
engraft and improve blood glucose control. This exciting
research is now moving into clinical trials.
The Food and Drug Administration (FDA) has approved the
DRI’s submission to initiate a pilot clinical study to test islets
transplanted into one of the platforms considered for a DRI
BioHub – a “biodegradable scaffold.” The pilot trial, which is
expected to be underway in 2014, will compare the omentum
to the liver as an optimal home for islets.
The DRI also plans to test other BioHub platforms, including
a “silicone scaffold.” Researchers are in late-stage discussions
with the FDA and awaiting approval for that pilot clinical
trial, which will also utilize the omentum as a transplant site.
The DRI is also planning for clinical trials in the two additional
key strategic areas: tolerance induction and cell supply. In
the area of tolerance induction, the DRI is looking toward
a pilot trial using tolerance-inducing cells to re-educate the
immune system and restore self-tolerance to eliminate
autoimmunity. This strategy, when successful, will also allow
for transplantation of insulin-producing cells without antirejection drugs. Alternatively, it will allow for regeneration of
insulin-producing cells from patients’ own tissues, such as
the native pancreas or skin cells obtained from a minimallyinvasive biopsy.
In the area of cell supply, the DRI was selected as one of the
sites for future clinical trials involving transplantation of
stem cell-derived insulin-producing cells.
We look forward to sharing exciting progress as
the DRI’s research continues to advance.
Message
from the
Director
Among these is the completion of an important Phase III
clinical trial, sponsored by the Clinical Islet Transplantation
Consortium (CIT), a multi-year, multi-center undertaking
supported by two NIH institutes – the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) and the
National Institute of Allergy and Infectious Diseases (NIAID).
The next steps will require centers in the United States to
band together and successfully complete a biological license
application so that islet transplantation can be offered on
a more widespread basis in our country. This cell replacement
therapy is already available to patients in other countries,
such as Switzerland and Canada, where it is an approved and
reimbursable procedure through one’s health insurance.
I am proud to share this report, highlighting the ongoing work at the Diabetes
Research Institute and our efforts both here and abroad. This next year will be
a pivotal one for cure-focused research, with several efforts coming to fruition
across many areas and with significant impact in the field as a whole and for
patients with T1D.
Also, the DRI is planning to test another BioHub platform
in the coming year. We are in discussions with the FDA and
are awaiting approval for that pilot trial to begin testing a
“silicone scaffold” implanted in the omentum.
This regulatory hurdle, while not insurmountable, is important
to the public’s understanding for the need of a worldwide
collaboration – a strategy that the DRI continues to employ
in structuring its long term research plans. The complexity of
the U.S. regulatory system and the time/cost it takes to bring
cellular therapies to the bedside can often move ahead much
faster and more efficiently in other countries.
Please join the Diabetes Research Institute and its
Foundation and be part of the team that will shape the
future, making it one free of diabetes in our lifetime.
At the DRI, we capitalize on the opportunity to more swiftly
translate promising findings to patients through our network
of global collaborators and international partners. You’ll read
about some of the exciting results of these initiatives in the
pages to follow.
Warmest regards,
Other clinical trials are in our research pipeline and will be
conducted with our collaborators. The DRI has been selected
as a testing site for several pending patient studies.
Today, the DRI is gearing up for critically important clinical
trials that will take place in 2014. Among these, is the
BioHub Initiative.
About a year ago, the DRI announced the BioHub Initiative,
a multidisciplinary effort to design, develop and test a
bioengineered “mini organ” that mimics the environment
of one’s own pancreas. This groundbreaking platform
would house insulin-producing cells (islets) capable of
sensing blood sugar and releasing insulin as needed, in
real time, and represents a major step forward in cell
replacement strategies.
As opposed to infusing islets into the liver, a BioHub allows
researchers to select a dedicated location for the mini-organ.
This provides the ability to monitor the site and cells,
incorporate other cell types that would facilitate engraftment,
slow or prevent rejection, and allow for its retrieval if needed.
[diabetes research institute foundation] 4
DRI scientists have been investigating an optimal site within
the human body that can host a BioHub, a location that would
allow us to move toward a delivery system that will avoid the
need for long-term use of anti-rejection drugs. To that end,
a new site within the abdomen will be tested this year in a
Phase I/II pilot trial, as part of the BioHub Initiative, pending
final regulatory approvals. This first trial will test the use of
a “biodegradable scaffold” to ensure the targeted site of
implant is a suitable place for long-term islet survival.
5
[2013 annual report]
Camillo Ricordi, M.D.
Stacy Joy Goodman Professor of Surgery
Distinguished Professor of Medicine
Professor of Biomedical Engineering,
Microbiology & Immunology
Director, Diabetes Research Institute
and Cell Transplant Center
University of Miami
Research
Review
[
Cases of diabetes have been documented for several thousand years, though
the term wasn’t coined until the first century. For almost 2,000 years since
then, the only treatment option for patients was starvation until the discovery
of insulin in 1922.
Insulin has indeed saved the lives of millions of people with this disease. Over the last
century, advancements in new treatments, aided by the remarkable developments in
computer technology, have helped patients better manage daily blood glucose (sugar)
control. While it is a life-saving breakthrough, insulin is not a cure and insulin treatment
still cannot fully prevent the chronic complications associated with diabetes. Additionally,
intensive insulin treatment has led to an increased risk of severe hypoglycemia
(dangerously low blood sugar levels).
[diabetes
[diabetes
research
research
institute
institute
foundation]
foundation]6
6
Despite patients’ best attempts, diabetes
management remains a challenging,
daily balancing act that requires constant
vigilance and attention. In other words,
there are no breaks because technology
cannot ideally mimic the exquisite,
biological function of a healthy pancreas.
Why?
Pancreatic islet cells, which make up only one to two
percent of the organ, have a built-in glucose sensor,
produce their own insulin, secrete the precise amount
needed in a perfectly-timed release, and produce counterregulatory hormones, such as glucagon, keeping blood
sugar levels in a normal range for an entire lifetime – until
these cells are destroyed by the immune system in those
with type 1 diabetes.
For decades, scientists across the globe have investigated
methods to give back to patients the ability to make
their own insulin. This has been the intense focus of the
Diabetes Research Institute and Foundation, where the
goal is to restore natural insulin production and normalize
blood sugar levels without imposing other risks.
7
Years of research advancements in cell replacement
therapies have yielded promising results. The DRI and its
collaborators worldwide already have demonstrated that
natural insulin production can be restored through islet
transplantation. Patients involved in clinical trials have
achieved insulin-independence after receiving infusions
of these cells; some study patients are living without
the need for insulin injections for more than a decade.
Those receiving islet transplants not only have had
normalized blood sugar levels, they have also been
freed from frightening hypoglycemic episodes and
have experienced a much higher quality of life.
Yet for all the benefits of islet transplantation, this
therapy has been limited to only the most severe
cases of diabetes due to several remaining challenges.
Through decades of experience in clinical islet
transplantation, DRI researchers are armed with
critical insights for overcoming these hurdles and
Reaching the Biological Cure.
Reaching the Biological Cure
The DRI BioHub – A Unique Solution
The Institute’s approach to restore natural insulin
production is to develop a DRI BioHub, an integrated mini
organ that mimics the native pancreas, containing the
critical insulin-producing cells that naturally control blood
sugar levels. But the BioHub goes beyond traditional islet
transplantation and is uniquely different from the various
approaches underway at other research centers.
The BioHub attempts to replicate the cells’ ideal
environment, where healthy islets thrive prior to their
destruction by the immune system. Inside the pancreas,
the insulin-producing cells have sufficient oxygen,
adequate space and all the nutrients needed to perform
their demanding job of normalizing blood sugar levels.
With a BioHub, scientists can manipulate and enhance
the transplant site, add vital components, like oxygengenerating materials, “helper” cells or other agents to
promote the cells’ long term function. Additionally, a
BioHub platform can be used to house not just islets, but
any insulin-producing cell type that scientists may create.
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9
THE DRI’S TEAMS OF RESEARCHERS ARE COMBINING THEIR
MULTIDISCIPLINARY EXPERTISE TO ADDRESS THREE MAJOR
CHALLENGES THAT THE BIOHUB PLATFORM OVERCOMES:
AREA 1: The Site – developing an optimal environment within the body to
house and protect insulin-producing cells.
AREA 2: Sustainability – retraining the immune system to prevent the
rejection of donor tissue and reversing the autoimmune attack which caused
the onset of diabetes.
AREA 3: Supply – identifying, developing and/or regenerating a limitless
supply of cells to sense blood glucose levels and produce insulin.
Over the last year, DRI scientists have made significant progress in each of these areas
toward the development of the DRI BioHub.
AREA 1
Preliminary data has been very encouraging in
demonstrating that islets in the omentum can
fully engraft and improve blood glucose control
in experimental and pre-clinical models.
While pursuing FDA approval, the DRI is speaking with its
DRI Federation collaborators outside of the United States
to assess the ability to begin initial clinical testing in their
centers so that the pilot studies are not delayed.
DRI scientists are focused on two approaches using the
omentum as an alternative transplant site. In the past
year, significant progress has been made with each as
the work moves toward pilot clinical trials.
BIODEGRADABLE SCAFFOLD
In addition to using silicone scaffolds, DRI researchers are
developing and testing a biodegradable scaffold to serve
as a BioHub platform.
SILICONE SCAFFOLD
The DRI’s tissue engineering team, led by Dr. Cherie Stabler,
has created a sponge-like scaffold to serve as a physical
platform for housing the transplanted islet cells. These
scaffolds are comprised of only 10 percent silicone. The rest
is open space, creating tiny pores that can house thousands
of insulin-producing cells of many shapes and sizes.
While the islet-loaded scaffold has shown safety and the
ability to achieve insulin independence in pre-clinical study
models, DRI researchers have been confronted with several
regulatory hurdles. When the IND (Investigational New
Drug/Device) application was submitted, the FDA classified
the silicone scaffold platform as a combination of both
a new “Biological” and new “Device” application, and
required further pre-clinical studies before approving
pilot clinical trials.
THE SITE
This approach uses the patient’s own plasma, the liquid
part of the blood that does not contain any cells, together
with thrombin, a commonly-used, clinical-grade enzyme.
When combined, they create a gel-like substance that
sticks to the omentum and holds the islets in place.
Researchers will then fold over part of the omentum to
create a protective pouch around the biodegradable
scaffold mixture.
Over time, the body will absorb the gel, leaving the islets
intact, while new blood vessels are formed to support their
survival and function.
The biodegradable scaffold will allow researchers to add
vital components to optimize islet acceptance and promote
their long-term survival and function, such as oxygen
promoters, helper cells, local drug delivery and cells
encapsulated with protective coatings.
In traditional islet cell transplantation, the donor cells are infused into the patient’s liver.
The liver has been the site of choice due to its many advantages: it is easily accessible;
cells can be implanted without invasive surgery; and it’s rich in blood vessels, which can
supply the cells with oxygen and nutrients.
While this approach has shown that islet replacement
can work, there are concerns that only a portion of
the islets may survive post-transplant. That’s because
when islets are infused into the liver, the site becomes
inflamed, the cells tend to clump together due to the
lack of appropriate spacing, and blood flow and oxygen
are reduced. Also, the cells are continuously exposed
to harmful medications and other toxins that are
processed in the liver.
[
For years, scientists have been
transplanting islet cells into the liver,
but that site may not be an ideal
home for the cells. The focus is now
on the omentum, an apron-like lining
inside the abdomen.
To overcome this challenge, the DRI is exploring alternative
implant sites and is now focused on the omentum, the
inside lining of the abdomen. The omentum plays an
important role in protecting the internal organs from
infections, bleeding, trauma and inflammation. Implanting
islets into the omentum is appealing because the site is
rich with blood vessels throughout its large surface area.
Also, it can be easily accessed surgically.
[
11
Dr. Cherie Stabler, director of tissue engineering, and her team developed
a silicone scaffold, one of the platforms being tested for a DRI BioHub.
AREA 2
SUSTAINABILITY
The body’s immune system serves as a protector from harmful bacteria and viruses in
the environment. This is why people rarely become ill with infections despite the fact
that they probably encounter infectious agents every day. Like built-in “radar,” the
immune system continually scans the body, discriminating what is “self” and what is
“foreign” and needs to be eliminated.
Yet the immune system is
not perfect, and despite
many mechanisms of control
and regulation, mistakes
can occur. Such mistakes
can result in autoimmune
diseases; like “friendly fire,”
the immune system
mistakenly destroys its own
tissues or cells. This is the
case with type 1 diabetes
(T1D) in which the insulinproducing cells within the pancreas are mistakenly
targeted and destroyed.
The DRI already has shown that natural insulin production
can be restored by transplanting insulin-producing islet
cells into patients with type 1 diabetes. Many transplant
recipients have been able to stop taking insulin injections;
some for more than 10 years.
But challenges remain, among them keeping the
transplanted islets healthy and functioning. That’s
because the recipient’s immune system sees the cells
as “foreign” and wants to destroy them.
To prevent the body from rejecting the cells, patients
must take powerful anti-rejection drugs. They’re called
immunosuppressants because they suppress the
immune system.
But these powerful drugs, which the recipient must take
long-term, suppress a patient’s entire immune system,
leaving him or her exposed to illnesses. The drugs also
can cause serious side effects and can even damage the
transplanted cells.
That’s why islet transplantation has been limited to only
the most severe cases, including people who are unaware
when their blood sugar levels drop dangerously low (a
condition called hypoglycemic unawareness).
The DRI is committed to making this therapy available
to all who can benefit. DRI scientists are focusing a
great deal of attention, and resources, on protecting
islets and establishing immune tolerance by educating
the immune system so it “tolerates” the transplanted
insulin-producing cells without the need for long-term
immunosuppressants.
With the DRI BioHub, the Institute is pursuing several
promising strategies to sustain the long-term health
and function of the insulin-producing cells by preventing
their destruction by the immune system.
USING BONE MARROW-DERIVED CELLS
TO ACHIEVE TOLERANCE
Scientists have shown that transplanting bone marrow
from a donor to a recipient can help re-educate the
recipient’s immune system. If a peaceful co-existence of
the two immune systems can be maintained, then the
recipient will recognize any transplanted organs, tissues or
cells from the same bone marrow donor as “self” and no
chronic immunosuppression will be needed. The mixture
of these two immune systems is known as chimerism.
DRI Director Dr. Camillo Ricordi and the University of
Louisville’s Dr. Suzanne Ildstad were among the first to
show that establishing stable chimerism resulted in
tolerance to transplanted pancreatic insulin-producing
islet cells – preventing immune destruction.
inflammation that is characteristic of autoimmunity.
The DRI’s goal is to determine what causes this imbalance
and dysregulation in the innate immune system and to
restore the natural balance between those NK cells that
initiate an immune response, and those that prevent it.
Utilizing a new process with a specialized population of
bone marrow cells, Dr. Ildstad and her team performed
bone marrow transplants using the new protocol in kidney
transplant patients. Over 20 patients have been treated
with this novel protocol that was successful in establishing
high levels of chimerism, allowing patients to discontinue
the use of anti-rejection drugs, now for over five years.
NK cells are especially important because they’re involved
so early in immune response. By focusing on NK cells,
researchers are trying to stop the autoimmune process
“upstream.” They believe that upstream imbalances in
the NK cell population, particularly in the regulatory
subpopulation, likely lead to the "downstream" destruction
of “self” tissue in autoimmunity. Additionally, they feel that
by fixing the “upstream” problems, the downstream effect
might be the correction of the dysregulated late immune
response and inflammation of autoimmunity.
The DRI is collaborating with Dr. Ildstad and her
colleagues to adapt this approach for the reversal of
type 1 diabetes. The new processing technology, developed
by Dr. Ildstad, has shown great potential to eliminate the
need for anti-rejection drugs in organ transplant recipients.
RESTORING IMMUNE SYSTEM BALANCE
When the immune system works properly, it performs a
delicate balancing act. On one side: cells that are poised to
attack. On the other: cells that prevent an attack. When all
goes according to plan, the first group will attack “foreign”
invaders such as viruses. But the second group will prevent
the first from attacking “self” – a person’s own organs
and tissues.
Additional studies will focus on identifying NK cells during
disease progression, how to utilize these cells as a cellular
therapy in the context of islet transplantation and their role
in cell replacement therapies.
In autoimmune diseases such as type 1 diabetes, the
immune system loses that balance and cells are able
to harm the body. DRI researchers are focused on
restoring that balance and are currently pursuing
two strategies.
NATURAL KILLER CELLS – THE FIRST LINE OF DEFENSE
In the past, scientists were reluctant to use this approach.
That’s because they had to give recipients harsh preconditioning treatments prior to the bone marrow
transplant. For example, in cases of blood disease, the
patient undergoes radiation to destroy the diseased cells
and to make space for the new, healthy bone marrow cells.
Researchers could not justify this risky pre-conditioning
regimen in patients with type 1 diabetes who are
otherwise healthy.
When something foreign enters the body, “innate
immunity” is the first line of defense. The immune system
initiates a cascade of events that ultimately eliminates
the invader. The first responders are called “Natural Killer”
or “NK” cells. As the name suggests, they are the attackers
of the innate immune system. As in downstream immune
responders, the NK cells have both an “attacking” arm and
a “regulatory” arm to keep the immune response from
getting out of control.
But now, improved technology and advances in the
laboratory have led to innovative clinical trials using
bone marrow aimed at establishing immune tolerance
to transplanted organs.
Research shows that in people with autoimmune diseases,
such as type 1 diabetes, NK cells are dysfunctional and are
fewer in number, causing dysregulated immune responses
and the shift to the late immune responses and unchecked
Drs. Luca Inverardi, Allison Bayer and Chris Fraker are
investigating the role of regulatory NK cells in the onset
of autoimmunity, using type 1 diabetes as the model
system. Current studies at the DRI are providing important
signaling data involved in increasing the numbers of
functional regulatory NK cells.
13
[
Drs. Chris Fraker and Allison Bayer are investigating the
role of a special population of immune cells that play a
key role in autoimmunity.
BOOSTING THE NUMBER OF REGULATORY T CELLS
The effector (attacker) cells involved in the downstream
immune response, mentioned above, identify what is
“foreign” and then destroy the invaders.
But in autoimmune diseases, effector cells target a
patient’s own tissues and cells. In type 1 diabetes,
they attack the insulin-producing cells in the pancreas.
Another group of immune cells is supposed to control
effector cells and prevent autoimmunity.
These protective cells are known as Regulatory T cells, or
T-regs. In many autoimmune diseases, T-regs appear to be
impaired. If researchers are able to boost their numbers
and improve their function, then they may help them
control effector cells and avoid autoimmunity.
Over the past several years, DRI researchers have been
studying the role of IL-2 (interleukin 2), a natural substance
and a growth factor released by certain types of immune
cells. IL-2 plays a critical role in the function of both
effector cells and T-regs. High dose IL-2 has been used in
cancer patients as a way to stimulate the effector cells
to eliminate the cancer. The DRI’s Dr. Thomas Malek’s
landmark studies in experimental mice showed that
IL-2 also plays a key role in maintaining proper T-reg
function – preventing autoimmunity.
This past year, Drs. Alberto Pugliese and Malek showed
that human T-regs are highly sensitive to IL-2 and respond
to much lower doses compared to effector and memory
immune cells, which need much higher levels of IL-2 to
initiate a response.
Other researchers also showed that low-dose IL-2
improved T-reg function and was able to reverse
autoimmune diabetes in experimental models. These
important findings point to the use of IL-2 itself, at
low dose, as a potential therapy for the control of
autoimmunity. By using low doses of IL-2, researchers
hope to selectively boost the levels and function of
T-regs without activating effector cells.
In doing so, enhanced T-reg function should control
autoimmunity with a therapy that stimulates the natural
regulatory properties of the immune system, as opposed
to the conventional anti-rejection drug therapy and their
associated harsh side effects.
Low dose IL-2 recently has been tested in clinical trials
of two immune-mediated diseases, showing safety and
improved T-reg function, as well as improvements of
clinical symptoms.
that caused type 1 diabetes in the first place doesn’t
attack the new cells.
Dr. George Burke, a University of Miami transplant
surgeon, and Dr. Pugliese have identified pancreas
transplant recipients, who, over time, had a recurrence
of autoimmunity. The insulin-producing cells in the
transplanted pancreas are targeted for destruction which,
again, results in type 1 diabetes. The researchers plan to
test low dose IL-2 in these patients to see if this approach
can stop the process and save the cells.
LEARNING FROM CANCER
Drs. Pugliese and Malek have been working with
Dr. David Klatzmann at the Université Pierre et
Marie Curie in Paris. He recently completed a pilot
clinical trial in patients with type 1 diabetes. The study
tested safety and compared various low doses of IL-2 to
begin to determine the optimal dose and the potential
effects on diabetes and T-reg function.
Scientists have been studying how some tumors have
evolved in such a manner that they can escape from the
immune system so that they’re not eliminated. That’s why
tumors are able to grow and spread. The DRI is studying
how tumors actually block the immune system from
targeting and destroying them – and trying to turn that
into a positive for type 1 diabetes.
The researchers are encouraged by the preliminary results
and enthusiastic about the potential of low dose IL-2
therapy to stimulate regulation and restore the immune
system’s balance in type 1 diabetes. The use of a natural
substance should be much safer than conventional
anti-rejection drug therapy and their associated
harsh side effects.
Can something be learned from cancer – and protect islet
cells from attack, too? Malignant tumors can produce
certain molecules, “chemokines,” that help them escape
destruction. These molecules help suppress the immune
system by recruiting a population of immune cells called
myeloid-derived suppressor cells (MDSCs) to the tumor.
The MDSCs block the immune system’s attack on the
tumor cells.
Success will enable researchers to intervene and prevent
diabetes in individuals at the time of diagnosis, while
they still have some functioning insulin-producing cells,
and pre-empt the onset of diabetes in those who are
known to be at high risk for developing the disease. This
therapy may also be applicable to patients undergoing
an islet transplant (or any other insulin-producing cell
replacement therapies under development), as a
means of ensuring that the autoimmune disease
[
In an effort to restore immune system balance,
Drs. Alberto Pugliese (left) and Thomas Malek
have shown that the use of low doses of IL-2 is
effective in increasing the number of Regulatory
T cells, which play a critical role in autoimmune
diseases, like T1D.
Researchers want to use this same protective mechanism
to stop an immune response to the body’s own insulinproducing islet cells (autoimmunity) or to newly
transplanted islets. The ultimate goal is to establish
permanent acceptance of the insulin-producing cells
without the need for anti-rejection drugs. Currently
available agents have been used to trigger the production
[
15
Dr. Alice Tomei and her team are
investigating ways that tumors evade
attack by the immune system and
applying those findings to protect
insulin-producing cells.
of MDSCs. DRI scientists believe that similar results may
be achieved by giving the recipient a short course of these
chemokines at the time of islet transplantation.
In experimental models, Dr. Luca Inverardi, DRI’s deputy
director, and his immunology team, have achieved
encouraging results suggesting that giving chemokines
to recipients at the time of an islet transplant prolongs the
survival of the tissue. During the past year, the researchers
have also gained a greater understanding of why MDSCs
have the ability to suppress the immune system’s
recognition and reaction to unwanted cells.
They have been studying MDSCs taken from the umbilical
cord blood of healthy babies and learned that MDSCs are
capable of producing Regulatory T Cells (T-regs), which
are critical in maintaining the immune system’s balance.
They have also observed that the increase in T-reg cells
was dependent on the production of a key molecule (IDO).
IDO activates the process that leads to immune tolerance
during pregnancy, which is why pregnant women are
able to accept a fetus instead of rejecting it, even
though the unborn child’s immune system is different
than the mother’s.
The researchers have found MDSCs offer other potential
benefits. As they began in-depth studies of the cells’
characteristics, they discovered that these cells express
unique markers that also classify them as fibrocytes.
Fibrocytes play a key role in promoting wound healing.
The team believes that this novel discovery will have a
positive impact on the use of these MDSC/fibrocytes for
both their powerful immunosuppressive properties as
well as their ability to repair injured tissue.
The DRI's Biomedical and Immune Engineering team is
exploring another approach to protect transplanted
pancreatic islets without the need for any anti-rejection
therapy. The focus: the molecule CCL21.
[
Dr. Antonello Pileggi and his
team are investigating methods
to reduce harmful inflammation
that threatens the survival of
transplanted islet cells in the critical,
early phase post-transplant
[
pic 12
Dr. Alice Tomei, the DRI’s co-director of bioengineering,
has shown that tumors release the molecule CCL21,
which plays a central role in protecting them from
immune attack. More recently, Dr. Tomei has applied those
findings to cell transplantation in experimental models.
She and her team engineered cells to express CCL21 within
the transplanted tissue. They also engineered proteins
to deliver CCL21 within a local transplant environment,
such as a DRI BioHub. By delivering the molecule locally,
many recipients accepted the cells – without systemic
anti-rejection drugs.
inflammation and are harmful to islet cells. When
someone gets a splinter in their finger, the immune
system senses something foreign, and potentially
dangerous, and reacts immediately.
Also, in preliminary studies, the team showed that the
production of CCL21 in islets creates a lymph node-like
environment, removing unwanted cells that can promote
an autoimmune response. Ongoing studies are looking
at the mechanism by which these structures prevent
the development of autoimmune diabetes in
experimental models.
Controlling inflammation is a major research priority
and the focus of numerous studies aimed at protecting
transplanted islets, as well as the onset or recurrence of
autoimmune diabetes. DRI researchers are currently
pursuing two different approaches.
Preliminary evidence points to the involvement of certain
stromal cells within these structures. Stromal cells are
the connective tissue cells of any organ. The interaction
between stromal cells and tumor cells is known to play
a major role in cancer growth and progression.
Based on the initial findings, the team will conduct
additional studies to further characterize these cells and
the role they can play in preventing the development of
autoimmunity, as well as the recurrence of autoimmunity
after islet transplantation.
CONTROLLING INFLAMMATION
As part of the multi-pronged approach to protect
insulin-producing cells from immune attack, researchers
are also aiming to quell the danger signals that cause
A series of highly-regulated, complex responses kick into
gear – and the skin around the finger becomes inflamed.
This process also occurs when transplanting islet cells. The
immune system reacts to the biological “insult,” triggering
inflammation that can damage the transplanted cells
and prompt further immune attacks.
The DRI’s Dr. Antonello Pileggi and his team are working
with a molecule that appears to be a critical player
in activating inflammation: extracellular adenosine
tri-phosphate (eATP). ATP serves as a source of energy
within each cell. In pancreatic beta cells, the release of
low amounts of ATP is part of a sophisticated check-andbalance mechanism that regulates optimal cell function.
But when cells are stressed – by a biological insult or
other unfavorable conditions (such as a transplant and
autoimmunity development) – they release large amounts
of ATP into the local environment (that is eATP). The
team is assessing whether the release of high levels
of ATP stimulates an immune response that, in turn,
contributes to the destruction of the cells themselves.
Initial studies in experimental models of islet, heart and
lung transplantation demonstrated that, by blocking the
function of eATP, they were able to reduce the activation
of pro-inflammatory immune cells and, in turn, prolong
the survival of transplanted tissues.
Dr. Peter Buchwald is testing agents
that prevent inflammation, as well
as low-dose anti-rejection drugs
that may be used locally within a
DRI BioHub to prevent an immune
attack on the transplanted cells.
The studies also revealed a remarkable synergy when
combined with immune-modulating agents. The
findings were the result of an international collaborative
initiative with Professor Fabio Grassi at the Institute
for Research in Biomedicine, Bellinzona, Switzerland,
and Dr. Paolo Fiorina at Children’s Hospitals, Harvard
University in Cambridge, MA.
Their research led to the publication of three seminal
manuscripts that appeared in the peer-reviewed, scientific
journals, Diabetes (islet transplantation), Circulation (heart
transplantation), and American Journal of Respiratory Cell
and Molecular Biology (lung transplantation), respectively,
as well as a recent review manuscript describing the
working hypothesis published in the American Journal of
Transplantation. The data has been presented at recent
professional scientific meetings.
Having demonstrated the beneficial effects of the systemic
modulation of eATP signaling in transplantation models,
the current efforts are concentrating on the role of eATP
on islet immunogenicity and in the development of T1D.
Dr. Pileggi’s group is further pursuing this important
research to better understand the role and mechanisms
associated with the eATP pathway in islet immunity
(innate immunity, rejection and autoimmunity), as well as
identifying other potential targets involved in this process.
The ultimate goal is to characterize the presence of specific
signaling molecules and test methods to modulate the
immune response and restore immune regulation in T1D,
and protect islet transplants in the local microenvironment.
This approach could result in synergy with cell-based
immunotherapies aimed at protecting islet cells at
the time of autoimmune diabetes onset as well as
in a DRI BioHub.
17
In another approach, researchers are looking at a part of the
immune system – the TGF-ß molecule – that is supposed to
control inflammation. However, scientists have learned that
in certain diseases, a protein, Smad7, interferes with the
TGF-ß pathway. The result: Smad7 promotes immune cell
signaling and immune responses.
The DRI is testing agents that block Smad7. This would
allow TGF-ß to function properly and help regulate
inflammation. Scientists already have identified a
therapeutic agent that targets Smad7 and are using this
agent in clinical trials to treat inflammatory bowel disease
(IBD), with encouraging early results.
In addition to preventing the inflammatory and immune
response associated with islet transplantation, there
is also the intriguing possibility of preventing or even
reversing diabetes in new-onset patients. At the DRI,
Dr. Peter Buchwald, director of drug discovery, and his
colleagues have conducted preliminary studies showing
that, by inhibiting/blocking Smad7 at the time of diabetes
onset, diabetes went into remission. More than half of the
treated models experienced normal blood glucose levels
and adequate insulin secretion – even long-term after
discontinuation of the treatment.
These results are particularly encouraging, raising the
possibility of reducing inflammation and controlling the
immune attack to the ongoing destruction of the insulinproducing cells in new-onset patients. This could also
be beneficial to islet transplant recipients.
Ongoing studies are aimed at assessing the timing
and dosing requirements needed for efficacy as well
as assessing the mechanism of action. The researchers
are also conducting larger-scale experiments needed to
evaluate the potential of translating these encouraging
results into novel type 1 diabetes clinical trials.
[
Dr. Norma Kenyon and her team
conducted pre-clinical studies testing
the co-transplantation of islets and
mesenchymal stem cells (MSCs)
within a DRI BioHub platform.
This encapsulation methodology provides significant
control over the properties of the layers, resulting in
a coating that is 500-fold smaller than conventional
microcapsules. The team’s recently published study in
the journal Advanced Healthcare Materials is the first
to show that layer-by-layer nanoscale coating can
prevent rejection of transplanted islets in rodents,
resulting in long-term function. This is a major step
forward in nanoscale encapsulation research. These
layered coatings also provide a platform for attaching
immunomodulatory agents to the surface of the cells
that can help fight off an immune attack.
Dr. Alice Tomei and her team are developing another
encapsulation strategy, the conformal coating process,
that “shrink wraps” each islet cell with the coating
material as it passes through a special microfluidic
system. As with a person’s own skin, which has small
pores that provide protection and allow oxygen to enter,
cell coatings must be designed in much the same way.
The pores need to screen out destructive immune system
cells but allow oxygen, glucose (blood sugar) and insulin
to easily pass through.
The DRI is also investigating the use of certain types
of cells in the body that can hamper inflammation,
promote tissue repair and enhance blood vessel growth.
Mesenchymal stem cells, or MSCs, can become a variety of
cell types, including bone, cartilage and fat. They also have
several properties that can help improve the success of
islet transplantation.
DRI immunologists, along with colleagues on the tissue
engineering team, have shown that by co-transplanting
insulin-producing cells with MSCs, they were able to
promote blood vessel growth and tissue repair. Dr. Norma
S. Kenyon, who heads the MSC research project, conducted
pre-clinical studies using this combination of cells within a
silicone scaffold, one of the platforms being tested for a
DRI BioHub.
This BioHub platform was placed within an omental
pouch, which was created by folding a piece of the apronlike tissue covering the abdomen. This approach has
resulted in enhanced acceptance and extended viability
of transplanted insulin-producing cells. With the support
of a multi-center NIH grant, Dr. Kenyon and her colleagues
are now conducting research to identify the specific
characteristics of the most effective MSC populations
for islet transplantation and their incorporation into
a DRI BioHub.
Once an effective MSC product is defined and
demonstrated to be optimal for intrahepatic (within
the liver) islet transplantation, the same cells will be
utilized in future tissue engineering experiments.
CELL ENCAPSULATION: PROTECTIVE BARRIERS
FOR ISLETS
What if islet cells could be physically shielded from attack
by immune system cells by encapsulating the cells in a
protective skin, or barrier?
For more than 40 years, the encapsulation of islet cells has
been researched as a potential therapy for type 1 diabetes.
However, there has been limited success in translating this
approach to patients due to a number of issues, including
the size of the capsules themselves, the materials used to
coat the cells and the inability to provide the encapsulated
islets with enough oxygen to keep them healthy and
functioning long term.
The DRI has been pursuing several strategies aimed at
overcoming these challenges and has made significant
progress over the last year. The bioengineering team
has invented and optimized several new technologies
to individually coat the islets in ultra-thin layers that
camouflage them from the recipient’s immune system.
By minimizing the space surrounding the islet cell, not
only can they enhance the oxygen and nutrient delivery
to the cells, but also have the ability to transplant the
cells within a DRI BioHub.
The DRI’s Dr. Cherie Stabler and her team have invented
a technology that generated nanoscale (less than
microscopically thin) coatings onto islets. This is achieved
by “dipping” the cells in polymers to create individual
layers. Nanoscale, or layer-by-layer, encapsulation is a
technique that has been used for decades in the
electronics, optics and sensor industries.
Over the last two years, the team has demonstrated
long-term immunoprotection of transplanted islets
encapsulated with conformal coatings in rodent models
of diabetes. In these studies, diabetes was reversed
in less than two weeks and the coatings were able
to protect transplanted islets from rejection while
maintaining normal blood sugar levels in the
experimental models. The islets continued to function
long term without the use of any anti-rejection drugs.
The team is currently reproducing these results in
a larger cohort of experimental models, in larger
pre-clinical models, and in clinically relevant sites.
DRI scientists are also tackling another major factor that
inhibits islet engraftment – the lack of adequate oxygen
in the immediate post-transplant period. After islets are
transplanted into a patient, it takes several weeks for new
blood vessels to form, which transport the critical oxygen
and nutrients these cells demand. Closing this oxygen
gap is a top priority for healthy islet function.
Several approaches are underway to address this issue.
First, the use of specific growth factors released in a
controlled manner, which have been successful in
speeding blood vessel development (as early as seven
days after transplant) and improving post-transplant
islet function and reducing islet loss. Alternatively, in a
unique approach to oxygen delivery, DRI researchers are
focusing on incorporating oxygen directly within each
capsule by mimicking a process that occurs in nature
every day – photosynthesis.
Plants convert sunlight and water into its components,
one of which is oxygen. Dr. Chris Fraker has developed a
19
>
An Eye on Immune Tolerance
DRI scientists have been working to determine
if the successful achievement of immune
tolerance through the anterior chamber of
the eye will allow for survival of transplanted
islets without immunosuppression. Following
their cover-featured publication in the peerreviewed journal Diabetologia, which reported
on the use of the anterior chamber of the eye as
a transplantation site in pre-clinical models to
treat type 1 diabetes, Drs. Per-Olof Berggren,
Midhat Abdulreda, Norma Kenyon, and Dora
Berman-Weinberg developed a collaboration
with researchers from Seoul National University
in Korea to further investigate this approach and
help establish it as a clinical transplantation site.
Studies have been ongoing concurrently in Seoul
and at the DRI in Miami. These studies explore
the feasibility of intraocular islet transplantation
in pre-clinical models of type 1 diabetes.
similar process in the lab using naturally-occurring metals
(minerals) that can, under the proper conditions, generate
oxygen spontaneously from water. A side benefit to this
approach is that these metals can also scavenge free
radicals and other damaging particles by converting those
into oxygen in addition to other harmless components.
He and his team are making microscopic particles
(nanoparticles) out of the metals and incorporating them
into the polymers used to encapsulate the cells, giving
them a type of built-in oxygen provider. The nanoparticles
can be used together with any type of biomaterials used
for the coatings, as well as being incorporated within a
BioHub platform, to increase oxygen levels and improve
transplant outcomes.
LOCAL DRUG DELIVERY
The development of a DRI BioHub provides the ability to
incorporate anti-inflammatory and anti-rejection drugs
within the bioengineered device. Local drug delivery is
commonly used in a variety of treatments requiring antiinflammatory steroid delivery and hormone therapy.
DRI researchers are testing similar approaches to those
in use for these conditions, such as thin rods and drugeluting polymers for the long-term, sustained release of
therapeutic agents as a means of protecting transplanted
islets within the local environment. This could allow for
the use of much smaller local doses and avoid or minimize
the systemic side effects of current therapies.
The DRI’s bioengineering team, in conjunction with
Dr. Peter Buchwald, head of DRI's drug discovery program,
is using a unique embedding and coating process to
deliver sustained-released drugs that are known to
minimize this initial immune inflammatory response.
This past year, the team tested several combinations of
drugs to determine the best results. The local delivery of
low-dose anti-inflammatory and/or anti-rejection drugs
at the transplant site offers the opportunity to minimize
or maybe even eliminate the current, systemic drugs
that pose so many unwanted side-effects.
TARGETING CELLS IN VIVO
Researchers continue to develop new and significantly
more precise methods to deliver desired molecules
and other agents to targeted cells within the body
or in a DRI BioHub. New advances in imaging and
nanotechnology are allowing scientists to test a
special class of molecules which are, essentially,
the chemical equivalent of antibodies.
Known as aptamers, these tiny strands are able to
hone in and bind to specific targets on the cell surface.
Aptamers are an attractive alternative to previous drug
delivery techniques due to their small size and relatively
low production cost. Aptamers also have the advantage
of being highly specific, meaning they can bind to
targeted cell markers without eliciting a foreign
tissue (immune) response.
Area 3
Supply
Currently, islets used for transplantation come from the pancreases of deceased
donors. With organ donation in the United States at critically low levels – about
1,700 pancreases were available last year – there is clearly not enough supply to
treat the millions of children and adults living with diabetes.
The DRI team, including Drs. Luca Inverardi, Paolo Serafini,
Alessia Zoso, and Giacomo Lanzoni, have selectively
screened for aptamers unique to islets and beta cells for
the rodent model. The team is now focused on adapting
the same methods to create an aptamer library specific to
human islets and beta cells.
The team is also using this novel technology to "tag"
living insulin-producing cells within the native pancreas
or in a DRI BioHub by attaching fluorescent markers to
the aptamers. After binding to the targeted islet/beta
cell, sophisticated scanners will be able to pick up the
fluorescently-labeled islets, providing valuable information
as to the quantity of living islets/beta cells and their
location. The team is also adapting this technology for its
use with clinical instruments, such as Magnetic Resonance
Imaging (MRI), that is routinely used in the clinic. This will
also allow for the delivery of anti-inflammatory and/or
anti-rejection agents directly to the desired cells instead
of shutting down the entire system with systemic
immunosuppression.
Since the discovery of aptamers in the early 1990s, great
efforts have been made to make them clinically relevant
for diseases like cancer, HIV, and macular degeneration. In
the last two decades, many aptamers have been clinically
developed and FDA approved. In 2004, aptamer-based
therapy was approved for the treatment of age-related
macular degeneration and several other aptamers are
currently being evaluated in clinical trials.
The DRI is pursuing several
strategies to develop a
reliable supply of insulinproducing cells. Identifying
the right stem cells – those
with the potential to
become islet cells – is a
key step for the design
of cell replacement,
regenerative and
reprogramming strategies.
At the DRI, researchers are using certain populations of
stem cells, as well as reprogramming other cells of the
body that have an entirely different function to becoming
insulin-producing cells.
THE BILIARY TREE: A NOVEL SOURCE OF
INSULIN-PRODUCING CELLS
An area that has sparked great interest is the discovery
of stem cells in the "biliary tree" – a network of drainage
ducts that connect the liver and pancreas to the intestine.
DRI scientists are interested in these cells because they
are pancreatic "precursor" cells – that is, they already have
started down the path to become pancreatic cells. This could
make it easier for scientists to produce a more efficient
maturation and a higher yield of islet cells.
The DRI’s Drs. Luca Inverardi, Giacomo Lanzoni and Juan
Dominguez-Bendala are collaborating with Dr. Lola Reid
from the University of North Carolina, a recognized expert
in liver development and regeneration, who discovered
these peculiar stem cells.
[
Drs. Alessia Zoso and Paolo Serafini are part of the
team that is testing a special class of molecules,
called aptamers, that bind to insulin-producing
beta cells. The aptamers enable researchers to
attach markers directly to the cells in order to
track and image the living cells in the body.
In the past year, they showed that stem cells within the
biliary tree can transform into both liver and pancreatic
cells, including insulin-producing islet cells. They obtained
the pancreatic precursor cells from the biliary tree. The
researchers then cultured these cells with a mixture of
growth factors and components found in the natural islet
environment. These molecular signals instruct the cells to
mature into islets. The process resulted in structures
that looked like islets and contained both insulin- and
glucagon-producing cells.
21
These islet structures released insulin and C-peptide (a
component of natural insulin production) in response to
glucose challenges. The researchers demonstrated that
transplanting these structures into diabetic mice
dramatically improved blood sugar control.
The group has identified an extended network of stem
cell pockets that branch out from the more naïve stem
cells in the biliary tree to more and more mature cells in
the pancreas and liver. These findings suggest that the
development of the pancreas does not come to an end in
adulthood and may continue as a life-long process that
can regenerate the stressed organ, islet cells included.
The investigators are scaling up these findings and testing
regenerative strategies based on biliary tree stem cells for
type 1 diabetes.
As a result of this collaboration between Miami and
Chapel Hill, several research papers have been published in
prestigious journals, and others are in press. A paper titled
“Biliary Tree Stem Cells, Precursors to Pancreatic Committed
Progenitors: Evidence for Possible Life-long Pancreatic
Organogenesis” appeared in the journal Stem Cells, along
with a review on “Clinical programs of stem cell therapies
for liver and pancreas.”
Ongoing studies are aimed at establishing proof of
concept that these cells can be used to reverse diabetes
in pre-clinical models. The team is also assessing
optimal implantation sites as well as strategies to aid
in “transforming” or differentiating these pancreatic
precursors by mimicking the critical components of their
native environment combined with newly discovered
islet-specific growth factors.
REPROGRAMMING THE NON-ISLET TISSUE OF THE
PANCREAS INTO INSULIN-PRODUCING CELLS
Rather than educating a stem cell from its earliest stages of
development – pushing it down the long path to become an
islet-type cell – transdifferentiation can potentially offer a
short cut. In this approach, scientists take a more mature
cell type and “reprogram” it, transforming it directly into an
insulin-producing cell.
To accomplish this, the DRI has been focusing on
the part of the pancreas that does not produce
insulin: the nonendocrine pancreatic tissue, or NEPT.
NEPT makes up almost 98 percent of the organ. It helps
process food by producing digestive enzymes. NEPT
typically is discarded after an islet isolation procedure.
Since the DRI is a leading islet isolation facility, it has
a plentiful supply of NEPT.
One of the interesting features of NEPT is its high
plasticity – its ability to turn into other cell types or
tissues. At the DRI, Drs. Juan-Dominguez-Bendala,
Ricardo Pastori and Luca Inverardi are developing and
testing new methods to reprogram human NEPT into
insulin-producing cells. The team is assessing whether
this tissue can be transformed and used as a source
for cell transplantation.
During the past year, the researchers discovered that,
once placed in culture, these cells tend to lose their
identity within days, progressively becoming a cell
type called “mesenchymal” that is virtually useless for
reprogramming purposes. This “degradation” process is
known as Epithelial to Mesenchymal Transition (EMT).
The team took the novel approach of adding a currently
available agent to the culture – and successfully
blocked EMT. This led to robust reprogramming and an
extraordinary yield of NEPT into insulin-secreting cells.
The ability to chemically block EMT allowed for the
generation of cells that secrete insulin in response to
glucose with total insulin levels comparable to those
of native islets. Importantly, preliminary experiments
showed that reprogramming is also possible using
frozen NEPTs. This could be important for clinical islet
transplantation because, down the line, it might allow
for a second infusion of insulin-producing cells from
the same donor.
The DRI is now focused on optimizing the culture
conditions to induce reprogramming into insulinproducing cells and subsequently transplanting these
cells in experimental models. They will also optimize
conditions for reprogramming of previously frozen
NEPTs. Additional research will focus on identifying
subsets of cells within the NEPT that may be more
prone to islet cell reprogramming.
When injected into diabetic mice, EpiCC, which were
developed from human skin cells, quickly restored normal
blood glucose levels. All mice were able to maintain these
levels for 133 days, at which time the EpiCC were removed.
Subsequently, a rapid increase of blood sugar was observed
along with an equally rapid loss of detectable human
insulin, which was previously present.
CONVERTING SKIN FIBROBLAST CELLS INTO
BETA CELLS
Preliminary results indicate that EpiCC may be converted
into insulin-expressing cells. The researchers will continue
to characterize the converted fibroblasts, following the
method developed in the Brevini lab, to evaluate insulin
production and other characteristics of pancreatic
endocrine cells.
When a stem cell is undifferentiated or uncommitted –
before it “decides” to become a certain kind of cell – its
DNA is “loose.” It’s able to develop into many cell types.
This ability is known as “pluripotency.” As a cell develops
and commits to a specific function, its DNA “hardens.”
But scientists are now able to “loosen” the DNA of an
adult, committed cell. And that cell can regain some
degree of pluripotency. This “loose” state does not last
long, but long enough for scientists to push the cell
down a new path to become a different kind of cell.
DRI collaborators at the University of Milan, Italy, led
by Dr. Tiziana Brevini, recently developed a method to
convert skin “fibroblast” cells into insulin-producing beta
cells. Fibroblasts are found throughout the human body.
These cells are known as pancreatic epigenetic converted
cells (EpiCC). They show many characteristics of mature
beta cells and also include other key endocrine cells
of healthy islets.
As reported in the May, 2013 Proceedings of the National
Academy of Science (PNAS), studies have demonstrated
that the EpiCC are able to secrete C-peptide in response
to glucose and maintain this ability for more than 100 days.
[
Drs. Juan Dominguez-Bendala
(standing, left), Luca Inverardi
and Ricardo Pastori (seated) are
developing and testing methods to
reprogram the nonendocrine tissue
of the pancreas to increase the
supply of insulin-producing cells.
The DRI is pursuing the potential of using EpiCC as an
alternative source because such cells could provide a near
limitless supply of insulin-producing cells in response
to changing levels of glucose. In addition, the converted
skin cells obtained from the patient would not be seen
as “foreign” and therefore would not be rejected, which
occurs with transplanted cells from another donor.
The research projects that comprise the DRI BioHub
receive critical philanthropic support from the Diabetes
Research Institute Foundation. Funding for the DRI
BioHub is also provided by other sources including
the ADA, JDRF, The Leona M. and Harry B. Helmsley
Charitable Trust, National Institutes of Health (NIH),
NIH Small Business Innovation Research, Ri.MED
Foundation, University of Miami, and additional
public and corporate partners.
TRIALNET UPDATE
[
Dr. Jay Skyler, DRI deputy director, serves
as study chairman for the NIH-sponsored
TrialNet, an international network
conducting clinical trials to prevent,
delay and reverse type 1 diabetes.
TrialNet has conducted several studies aimed at slowing
the immune system’s attack on insulin-producing cells
in people newly diagnosed with type 1 diabetes. Two
of the studies that TrialNet has conducted, and a third
organized by the Immune Tolerance Network with TrialNet
participation, have identified drugs with promise of benefit.
Currently, TrialNet is focused on altering the immune
system attack in order to delay or prevent type 1 diabetes
in relatives found to be at risk for the disease. Three
prevention studies are ongoing – using oral insulin, the
23
immune co-stimulation blocking drug abatacept, and a
monoclonal antibody targeting activation of the immune
system. In addition, TrialNet is poised to launch additional
studies in people newly diagnosed with type 1 diabetes.
The studies are conducted by the National Institutes of
Health’s international network of researchers, Type 1
Diabetes TrialNet Study Group, which is housed at the
DRI, under the direction of Dr. Jay Skyler, TrialNet national
chairman. To learn more about TrialNet, visit
www.DiabetesTrialNet.org.
THE DIABETES EDUCATION AND
NUTRITION SERVICE AT THE DRI
DIABETES RESEARCH INSTITUTE
FACULTY AND STAFF
The Diabetes Education and Nutrition Service
at the DRI’s Eleanor and Joseph Kosow Diabetes
Treatment Center continues to use collaboration,
innovation, integration and evaluation as
the driving forces behind its patient initiatives.
Faculty
The past year has represented one of transition – education team members leaving for new professional
opportunities and new education team members coming to the DRI to experience the incredible educational
offerings that comes from working with highly-skilled providers and researchers. New leadership is already in
place with the directorship being shared by two past DRI diabetes educators, Lisa E. Rafkin, MS, RD, LD, CDE, CCRC,
research assistant professor of medicine, and Della Matheson, RN, CDE, both of whom have worked for many
years at the DRI in the area of clinical research, and on the DRI diabetes management team under the guidance
of Dr. Jay Skyler some 20 years ago. They will be joined by several newly hired specialists, including dietitians
and certified diabetes educators, so that they will be able to meet the increasing demand for patient education
and medical nutrition therapy at the DRI.
The program remains certified as an American Diabetes Association’s Education Recognized Program, which
enables collection of revenues for education and nutrition services. Under Dr. Skyler’ s supervision, the new
team will continue to strive for excellence and continued improvement in overall patient services.
Dr. Camillo Ricordi
Dr. Jeffrey Hubbell
Stacy Joy Goodman Professor of Surgery
Division of Cell Transplantation
Distinguished Professor of Medicine
Director, Diabetes Research Institute and
Cell Transplant Center
Adjunct Professor of Surgery
Director, Integrative Biosciences Institute
Institute for Chemical Sciences and
Engineering at Ecole Polytechnique
Fédérale de Lausanne, Switzerland
Dr. Midhat H. Abdulreda
Dr. Luca Inverardi
Assistant Professor of Surgery
Research Professor of Medicine,
Microbiology and Immunology
Director, Immunobiology of Islet
Transplantation
Deputy Director for Translational Research
Dr. Rodolfo Alejandro
Professor of Medicine
Director, Clinical Cell Transplant Center
Associate Director of Clinical Research
Associate Director, Cell Transplant Center
Dr. Allison Bayer
Research Assistant Professor of
Looking back over the past 12 months:
• More and more patients are being referred to the
DRI’s unique education program, and these patients
come from the DRI Clinic, University departments,
including Pediatric Endocrinology, and a growing
number of community providers. The recent closure
of three large, community-based diabetes education
programs over the past two years has made the
services provided by the DRI even more crucial for
patients and their families.
• With over 8,000 visits captured, the DRI’s use of an
innovative data management system has enabled
optimization of existing services and targeted
improvements of internal processes and future
provision of services.
• The DRI team continues to be involved in professional
and community outreach initiatives, including but
not limited to:
– UM campus and community health services,
including expansion sites throughout South Florida
– Diabetes Research Institute Foundation – PEP
(Parents Empowering Parents) Squad and
‘Top Tips’ articles
– Seminole Media Productions
• The DRI Diabetes Education and Nutrition Service
also coordinated more than a dozen clinical
experience training programs during the past year,
up-skilling industry representatives on the medical
and education standards for diabetes care. Over 800
representatives attended, with outstanding program
satisfaction ratings across all programs offered.
With an eye toward the future, the DRI Diabetes
Education and Nutrition Service is updating its very
successful educational curriculum to continue the
current class schedule (e.g., Healthy Me, Diabetes
Made Simple, Pump Training and the highly acclaimed
Mastering Your Diabetes program), and is adding
several innovative components in the near future:
– Florida International University Dietetic Student
Internship Program
• A DRI online, interactive diabetes education program,
tailored for health care professionals involved in the
care of people living with diabetes.
– Local professional presentations by the
American Diabetes Association, Health Choice
Network, National Podiatry Association and the
University of Miam iGrand rounds
• A multi-disciplinary Transition Program, to assist
children and parents in transition from pediatric
to adult-based diabetes management and care
– Professional Association Positions (NCBDE, AADE,
GMADE)
• A Diabetes Prevention Recognition Program (based
on CDC and AADE program standards)
Dr. Per-Olof Berggren
Mary Lou Held Visiting Scientist
Adjunct Professor of Surgery
Head of Cell Biology and Signal Transduction
Professor and Head, Experimental
Endocrinology at the Karolinksa
Institute, Sweden
Dr. Dora Berman-Weinberg
Research Associate Professor of Surgery
Dr. Peter Buchwald
Associate Professor of Molecular and
Cellular Pharmacology
Director, Drug Discovery Program
Dr. Juan Dominguez-Bendala
Dr. Norma S. Kenyon
Martin Kleiman Professor of Surgery,
Medicine, Microbiology and Immunology,
and Biomedical Engineering
Director, Wallace H. Coulter Center For
Translational Research
Chief Innovation Officer, University of Miami
Dr. Jennifer Marks
Division of Endocrinology, Diabetes
and Metabolism
Dr. Armando Mendez
Research Associate Professor of Medicine
and Metabolism
Director, Advanced Technology Platforms
Dr. Daniel H. Mintz
Scientific Director Emeritus
Professor Emeritus of Medicine
Dr. Bresta Miranda-Palma
Director, Stem Cell Development for
Assistant Professor of Medicine
Interim Director, Eleanor and Joseph Kosow
Diabetes Treatment Center Division of
Endocrinology, Diabetes, and Metabolism
Dr. Chris Fraker
Dr. Ricardo Pastori
Research Assistant Professor of Surgery
Research Professor of Medicine,
Immunology and Microbiology
Director, Molecular Biology Laboratory
Dr. Maria del Pilar Solano
Assistant Professor of Medicine
Dr. Antonello Pileggi
Director, Pre-Clinical Cell Processing and
Translational Models
Dr. Alberto Pugliese
Research Professor of Medicine, Microbiology
and Immunology
Director, Immunogenetics Program
Dr. Jay Skyler
Professor of Medicine, Pediatrics
and Psychology
and Metabolism
Deputy Director for Clinical Research
and Academic Programs,
Diabetes Research Institute
Chairman, NIDDK Type 1 Diabetes
TrialNet Study Group
Dr. Cherie Stabler
Associate Professor of Biomedical
Engineering, Surgery
Director, Tissue Engineering Laboratory
Dr. Alice Tomei
DIABETES RESEARCH INSTITUTE
FACULTY AND STAFF
Administrative
Clinical Chemistry Lab
Drug Discovery Program (DPP)
Flow Cytometry Lab
Microbiology and Immune Tolerance Alexander Rabassa,
Dr. Mitra Zehtab,
Dr. Armando Mendez,
Dr. Peter Buchwald, Associate Professor
Dr. Oliver Umland, Assistant Scientist
Dr. Tom Malek, Professor of Microbiology
Chief Operating Officer and Deputy Director
Research Associate Professor of
Medicine, Director
Histology
Dr. Allison Bayer, Assistant Professor of
Mabel Luis, Executive Assistant
Dora Cardenal, Director, Accounting
Sabrina Boulazreg, Sr. Manager,
Business Operations
Angie Arzani, Sr. Manager, Finance
Juan Perez-Scholz, Manager,
Sponsored Programs
Ligia Delgado, Sr. Accounting Assistant
Grace Perez, Sr. Buyer
Marc Friedenthal, Buyer
Ilvis Torres, Administrative Assistant
Medical Development
Gary Kleiman,
Dr. Ronald B. Goldberg,
Dr. Marcos Levy-Bercowski,
Voluntary Assistant Professor of Surgery
Dr. Monia Cecati, Research Scholar
Esperanza Perez, Supervisor,
Eleanor and Joseph Kosow
Diabetes Treatment Center
Clinical Cell Transplant Program
(CCTP)
Professor of Medicine, Director
Dr. Joel Szust, Scientist
Dr. Alejandro Alvarez-Garcia,
Dr. Ricardo Pastori, Research Professor
of Medicine, Director
Professor of Surgery, Director
Research Laboratory Technician
Dr. Fanuel Messaggio, Post-Doctoral
Image Analysis Facility
Marta Garcia Contreras, Sr. Research
of Medicine
Dr. Bresta Miranda-Palma,
Assistant Professor of Clinical of Medicine,
Interim Director
Fast Track
Dr. Camillo Ricordi, Stacy Joy Goodman
Xiumin Xu, Director, DRI-China, Collaborative
Human Cell Transplant Programy
Associate
Dr. Marcia Boulina, Assistant Scientist
Associate 1
Dr. Maria del Pilar Solano,
Assistant Professor of Clinical of Medicine
Dr. Alice Tomei,
Dr. Bresta Miranda-Palma,
Assistant Professor of Medicine, Director
Vita Manzoli, Sr. Research Associate 1
Mejdi Najjar,
Burlett Masters,
Dr. Jay Sosenko, Professor of Medicine
Dr. Jay S. Skyler,
Research Support Specialist
Professor of Medicine, Pediatrics and
Psychology
Ada Konwai, Sr. Research Assistant
Dr. Lisa Rafkin-Mervis,
Chiara Villa, Non-Enrolled Fellow
Research Assistant Professor of Medicine
Bio-Informatics
Diabetes Prevention Program
(Type 2)
Roopesh Sadashiva-Reddy,
Professor of Medicine, Director
Juliet Ojito, Nurse Specialist, Research
Jeanette Gonzalez-Calles,
Research Associate
Maria Valbuena, Research Associate 1
Bertha Veciana, Medical Assistant
Wanda Ramirez, Secretary
Health Care Professionals
Lory Gonzalez, Nurse Educator
Gwen Enfield, Clinical Dietitian
Amy Kimberlain, Dietitian
Clinical Administration
Dina Bardales,
Immunobiology of Islet
Transplantation
Pre-Clinical Cell Processing and
Translational Models
Dr. Luca Inverardi, Research Professor of
Dr. Antonello Pileggi, Research Professor
Medicine, Director
Dr. Alessia Zoso, Scientist
Dr. Giacomo Lanzoni, Assistant Scientist
Dr. Sophie Borot, Research Scholar
Matteo Battarra, Research Scholar
Immunogenetics Program
Dr. Alberto Pugliese, Research Professor
of Medicine, Director
Dr. Francesco Vendrame, Scientist
Dr. Isaac Snowhite, Research Scholar
Gloria Allende, Sr. Research Associate
Supervisor, Patient Access
Arleen Barreiros, Project Coordinator
Starlette Canamero,
Sr. Administrative Assistant
of Surgery, Director
Dr. Ruth Damaris Molano, Scientist
and Core Director
Dr. Carmen Fotino, Assistant Scientist
Dr. Ulissi Ulisse, Research Scholar
Alejandro Tamayo-Garcia,
Research Associate 1
Yelena Gadea, Sr. Veterinary Technician
Adriana Lopez-Ospina, Research Assistant
Pre-Clinical Research
Dr. Norma Sue Kenyon, Martin Kleiman
Professor of Surgery, Director
Islet Physiology
Dr. Dora Berman-Weinberg,
Dr. Per-Olof Berggren, Adjunct Professor
Research Associate Professor
of Surgery, Director
Dr. Midhat Abdulreda,
Assistant Professor of Surgery
Dr. Joana Almaca, Research Scholar
Alexander Shishido, Research Associate 1
Dr. Dongmei Han, Scientist
Dr. Ana Hernandez, Associate Scientist
Waldo Diaz, Sr. Manager,
Research Laboratory
Melissa Willman,
Sr. Manager, Research Support
Veterinary Technician
Stem Cell Development for
Dr. Juan Dominguez-Bendala, Research
Associate Professor of Surgery, Director
Dr. Sara Garcia Serrano, Research Scholar
Silvia Alvarez, Manager, Research Laboratory
Tissue Engineering
Dr. Xiao Jing Wang, Associate Scientist
Dr. Greta Minonzio, Research Scholar
Dr. Muyesser Sayki, Research Scholar
Carmen Castillo,
Dr. Jennifer Marks, Professor of Medicine
Dr. Daniel H. Mintz, Professor Emeritus
James Geary, Sr. Veterinary Tech
Reiner Rodriguez-Lopez,
Dr. Dagmar Klein, Scientist
Clinical Research Center
Database Administrator
Director Laboratory Services
Molecular Biology
Associate Scientist
Research Assistant Professor 1
Dr. Allison Bayer, Assistant Professor
Human Cell Processing (cGMP) Facility Cecilia Cabello, Research Associate 3
Shane Mackey, Research Associate 1
Dr. Luca Inverardi, Research Professor of
Faculty
Dr. Eduardo Peixoto, Assistant Scientist
Ana Alvarez Gil, ARNP
Alina Cuervo, Sr. Medical Biller
Dr. Chris Fraker,
Kevin Johnson, Sr. Research Associate 3
Dr. Elina Linetsky, Director, Interim
Medical Technologists
Aimee Siegel-Harris,
and Immunology
Medicine, Facility Director
Rosa Hernandez, Research Associate 1
Elsa Cribeiro, Sr. Research Assistant
Zackary Barnes, Sr. Research Assistant
Dr. Rodolfo Alejandro,
Bioengineering
Dr. Sirlene Cechin, Assistant Scientist
Dr. Jinshui Chen, Post-Doctoral Associate
Omar Lopez-Ocejo, Research Associate 1
Yun Song, Student Research Assistant
Sr. Development Director, Major Gifts
Manager, Donor Relations
of Molecular and Cellular Pharmacology,
Director
Sr. Research Associate 3
Dr. Cherie Stabler, Associate Professor of
Biomedical Engineering, Director
Dr. Jeffrey Hubbell, Adjunct Professor
of Surgery
Dr. Kerim Gattas-Asfura, Associate Scientist
Joshua Gardner, Sr. Research Associate 1
Irayme Labrada-Miravet, Research Assistant
Maria Coronel, Student Research Assistant
Anthony Frei, Student Research Assistant
Jaime Giraldo, Student Research Assistant
Kaiyuan Jiang, Student Research Assistant
Mike Valdes, Student Research Assistant
Ethan Yang, Student Research Assistant
Diabetes TrialNet
Dr. Jay Skyler, National Chairman
Dr. Norma Sue Kenyon,
Associate Chair for Immunology
Dr. Jennifer Marks,
Principal Investigator –TrialNet Clinical Center
Dr. Alberto Pugliese,
Co-Investigator, Clinical Center
Dr. Gerit Holger-Schernthaner,
Voluntary Assistant Professor of Surgery
Dr. Lisa Rafkin-Mervis, Study Co-Chairman
Dr. Luz Arazo, Clinical Research Coordinator
Dr. Carlos Blaschke,
Clinical Research Coordinator
Della Matheson, Trial Coordinator
Natalia Sanders, Research Associate 1
Irene B. Santiago, Sr. Administrative Assistant
Elizabeth Machado, Administrative
Assistant
DRIF
Chairman's
Message
This past year, the unveiling of the DRI BioHub, coupled with
the Institute’s plans to initiate Phase I/II clinical trials in 2014,
has further cemented my belief that we are on our way to
ending diabetes once and for all.
Subsequent to the BioHub roll-out, the DRI Foundation
received a number of significant contributions from donors
who recognize the inherent promise of this ground-breaking
initiative – and, also, are acutely aware of the tremendous
investment in research that is needed to bring the BioHub to
fruition. While we have witnessed a successful year in terms of
our fundraising – one in which we were able to direct a greater
level of funding to our scientists – these gifts represent a mere
fraction of the resources necessary to get this job done.
The overwhelming need for research funding is palpable
and serves as the driving force behind all of our activities.
Having streamlined our operating expenses over the past
several years, we were in a strong position to move forward
and maximize the revenue we transferred to the DRI for
BioHub programs. In turn, that support helped to deliver
these research advancements.
We allocated the DRIF’s funding, which came from generous
people like you, to a number of projects within the major
scientific areas that comprise the DRI BioHub: the Site,
Sustainability, and Supply. As summarized in the Research
Review section of this report, our DRI scientists have
made progress in these areas across the board, and have
demonstrated encouraging results that are moving into
the next phases of testing.
Those who are involved with the Diabetes Research Institute Foundation, like my wife,
Kelly, and I, want nothing more than to find a cure for their loved ones, themselves, and
millions of others who have diabetes. Despite the many advances that have been made
in managing diabetes, none of us is content to just live with this disease. Certainly, people
with T1D have benefited from advances in management and treatment, but our focus is
on a cure so we can render all of that moot.
The DRI’s cure-driven mission exemplifies why an ever-growing circle of passionate and committed people have
chosen to invest their support – in both time and money – here.
More than a decade ago, when I first learned about the DRI, it marked the first time that I really felt there was a
strategy in place for Reaching the Biological Cure. In the years since, while we have seen wonderful progress toward
that goal, we continue to feel an urgent need to cross the finish line for our son, Will, and for every other family
affected by diabetes.
Undeniably, the most exciting news centers on the DRI’s
plan to begin pilot clinical trials in 2014. Demonstrating their
commitment to bringing the most promising findings from
the lab to patients with type 1 diabetes, DRI scientists will test
whether an alternative site in the body – the omentum – is a
more ideal home for transplanted islet cells than the liver.
In this trial, the islet cells will be implanted within a
“biodegradable scaffold,” one of the platforms originally
considered for a DRI BioHub. Plans are also underway to
utilize the omentum as a site for a second BioHub platform,
a “bioengineered scaffold,” once approval is obtained from
the regulatory bodies.
As you read in Dr. Ricordi’s message, the research process
is not without its hurdles, and unforeseen delays certainly
extend the timeline for moving our work forward. What
we cannot and should not accept, however, is for the lack of
adequate funding to be an additional impediment to progress.
As those of us who are affected by this devastating disease
well know, tomorrow is not soon enough to find a cure.
Thankfully, numerous individuals, families, businesses, and
foundations have played a huge role in bolstering our efforts
to further the research this past year. None of this work would
have been possible without the extraordinary contributions
from those who have made supporting cure-focused research
their top priority. Many of these donors are pictured on the
following pages. On behalf of the entire organization, I want
to extend our deepest gratitude to them and countless others
for their generosity and tireless efforts.
While this past year has been one of significant advances, it
was also a year of transition as we welcomed new leadership
at the Diabetes Research Institute Foundation with the
appointment of Joshua Rednik as president and CEO. Josh,
who brings with him almost two decades of experience in
fundraising organizations, will help guide the Foundation into
an exciting era for those living with this disease. I, together
with my board colleagues, have the highest confidence in
his ability to lead with distinction and integrity.
A new governance structure for the Northeast Region was
adopted and new co-chairs were appointed. The members
of the new Northeast Region Executive Committee and
Board are a strong contingent of new and veteran leaders,
each of whom has a personal stake in fulfilling our mission.
This group of individuals joins our National and Florida
Region leadership in ensuring the highest standards of
fiscal oversight, accountability, and donor stewardship.
As we head into the next year with excitement and
optimism, we hope we can count on your continued
support to make our progress possible. Thank you
again for your generosity and friendship.
Sincerely,
Harold G. Doran, Jr.
Chairman
Diabetes Research Institute Foundation
Statement of Activities for the Year ended June 30, 2013
Support and Revenue
Financial
Summary
Contributions
Reimbursement Contracts
Special Events, net of expenses
Investment Income
$7,144,705
184,950
4,332,230
1,006,302
Total Support and Revenue
12,668,187
Expenses and Fund Balances
Program Services
Research provided to the Diabetes
Research Institute
Community Education
7,031,358
804,661
Total Program Services
7,836,019
Support Services
Administration and General
Fundraising
1,610,401
1,765,139
Total Support Services
3,375,540
Change in Net Assets
1,456,628
Net Assets, Beginning of Year
24,850,703
Net Assets, End of Year
$26,307,331
Through the support of private
philanthropy, the Diabetes Research
Institute Foundation has funded
six chairs totaling almost $13 million.
The J. Enloe and Eugenia J. Dodson
Chair in Diabetes Research
Fundraising Percentage
Fundraising Expense as a
Percentage of Support and Revenue
Stacy Joy Goodman Chair in
Diabetes Research
Mary Lou Held Chair for Diabetes Research
14%
Martin Kleiman Endowed Investigatorship
Daniel H. Mintz Visiting Professorship
Ricordi Family Chair in Transplant
Immunobiology.
Diabetes Research Institute Statement of Activities
Support and Revenue
Research Funding is Critical
The Diabetes Research Institute Foundation provides the DRI with critical seed
funding to gather data that is often a prerequisite for larger grants. The mission
– to provide the Diabetes Research Institute with the funding necessary to cure
diabetes now – is a testament to the belief that tomorrow is not soon enough
to cure this disease. The DRIF's funding stream is at the heart of DRI’s ability to
innovate and make significant strides toward a cure. In addition to receiving
the DRIF's support, DRI scientists have been awarded competitive grants from
numerous funding entities for almost 40 consecutive years.
Diabetes Research Institute Foundation
National Institute of Health
JDRF Grants*
Kosow Center
University of Miami
Corporate Grants
American Diabetes Association/
American Heart Association Grants
State of Florida Education Grant
Total Support
$7,031,358
6,455,822
2,104,852
1,094,725
491,940
405,718
40%
36%
12%
6%
3%
2%
51,566
34,708
.5%
.5%
$17,670,689
100%
Expenditures
Research Grants
Research & Clinical Support
$15,862,809
1,129,433
Total Expenditures
$16,992,242
*includes support from The Leona M. and
Harry B. Helmsley Charitable Trust
“Your support means the
world to the millions of families
like mine who have been affected by
diabetes. Over the years, these funds
have helped the scientists get closer
to finding a cure.”
Making
Progress
Possible
– Renee Aronin (center)
“In total, the Dad's Day
program has raised over $40
million, which has enabled the
DRI to make exciting advances
toward finding a cure for this
disease that afflicts so many
Americans.”
– Sean McGarvey, president,
North America's Building
Trades Unions (right).
>
To Our Generous Donors and Volunteers...
The Diabetes Research Institute and Foundation wishes to gratefully
acknowledge all of our donors and volunteers who are enabling us
to make great strides toward a biological cure for diabetes.
Your generous contributions and tireless efforts make the DRI's progress possible.
Thank you to every individual, family, foundation and business, many of whom are pictured
on the following pages, that have given generously over the last year and throughout the
years. We would not have been able to come this far without you.
>
“Our children are our
inspiration, and we need
to find a cure for everyone
living with diabetes as quickly
as possible.” “Walgreens is honored to support the work
of the Diabetes Research Institute. We are very grateful
to our customers and associates who have been
exceptional in supporting the DRI Walk For Diabetes
& Family Fun Day, as well as supporting our in-store
fundraising program."
– Bonnie Inserra
(second from left)
>
– Roy Ripak, Walgreens market vice president (left)
pic 37
“My family and I, are
led by my parents, Rowland and
Sylvia Schaefer, became involved
with the DRI because we believe
the cure for diabetes is within reach
and that it will be found by these
scientists."
– Roberta Waller (second from left)
“We had the opportunity
to tour the Diabetes Research
Institute and we saw what they
do first hand...When we talk
about finding a cure, they are
the ones who are in the lab
every single day really making
it happen.”
– Ray Allen (second from left)
>
>
>
pic 51
The
Heritage
Society
“This will help me rest in
peace knowing that I’ve left
behind a legacy. I also hope
to set an example for my
daughter so that she is
charity-oriented when she
is my age.”
“I am thankful for the life
I have lived and truly believe
that each of us can make a
difference by giving back.”
– Shirley Harris
“Now is the time when
we can and must give back
and help people.”
– Norman Shapiro
“Of all the diabetes
organizations, I chose the
Diabetes Research Institute
because most of the funds
go toward what the gift is
intended for – a cure.”
– Mark Hariton
– Cindi Elias
The Heritage Society of the Diabetes Research Institute Foundation was created
to recognize individuals who have generously made provisions in their wills,
through life insurance, charitable remainder trusts and gift annuities, or other
deferred giving vehicles to ensure that critical funding for the Diabetes Research
Institute continues into the future.
Over the years, planned giving programs have enabled many donors to make
substantial gifts to the DRI in ways that have complemented their individual
financial objectives. Heritage Society members have chosen to create their own
personal legacies and perpetuate their philanthropic goals for all those affected
by diabetes.
“I knew that I wanted to support research for a cure...It’s really a miracle what they’re
doing at the Diabetes Research Institute…My advisor was looking out for my best interest
and assured me that this was the thing to do. I’m happy that I could establish this gift.”
- Frances Harrow
We are exceptionally grateful to all of our Heritage Society donors who
demonstrate the passion and vision to advance a cure beyond their lifetime.
NATIONAL BOARD
OF DIRECTORS
Chairman
Harold G. Doran, Jr.
President and CEO
Joshua W. Rednik
Immediate Past Chairman
Thomas D. Stern
Directors
Diane Beber
Marlene Berg
Ronald Maurice Darling, Jr.
John C. Doscas
Piero Gandini
Esther E. Goodman
Marc S. Goodman
Arthur Hertz
Glenn Kleiman
Eleanor Kosow
Sandra Levy
Sean McGarvey
Vice Chairmen
William J. Rand, M.D.
Charles Rizzo
Treasurer
William J. Fishlinger
Secretary
Bonnie Inserra
REGIONAL BOARDS
OF DIRECTORS
Shelia F. Natbony, D.O.
Allan L. Pashcow
Ramon Poo
Ricardo Salmon
David Sherr
Kenneth A. Shewer
Kathy Simkins
Sheldon L. Singer
Jill Viner
Bruce Waller
Sonja Zuckerman
Florida Region
Northeast Region
Chairman
William J. Rand, M.D.*
Co-chairs
Marc S. Goldfarb
Bruce A. Siegel
Directors
Sari Addicott
Bernard Beber, M.D.
Diane Beber*
Crystal Blaylock Sanchez
Sabrina R. Ferris
Bruce Fishbein
Joel S. Friedman
Rene W. Guim
Shirley Harris
Javier Holtz
Norman Kenyon, M.D.
Vito La Forgia
Sandra Levy*
Ramon Poo*
Cristina Poo
Deborah Rand
The organization of choice
for those who are serious,
passionate and committed
to curing diabetes.
*Also member of National Board
of Directors
39
Michelle Robinson
Rosa Schechter
James Sensale
Jacci Seskin
Don Strock
Richard P. Tonkinson
Stephen Wagman
Rita Weinstein
Sonja Zuckerman*
Executive Committee
William J. Fishlinger*
Marc S. Goodman*
Barbara Hatz
Bonnie Inserra*
Directors
Greg Besner
John Carrion
Diane Cohen
Delia DeRiggi-Whitton
Peter L. DiCapua
Kim Dickstein
Douglas R. Donaldson
Iris Feldman
Joan Fishlinger
Lindsey Inserra-Hughes
John Luebs
Louise Pashcow
Hon. C. Raymond Radigan
Marie Rizzo
Ricardo Salmon*
Samantha Shanken Baker
Meryl Lieberman
Allan L. Pashcow*
Charles Rizzo*
Thomas P. Silver
Bruce Waller*
Roberta Waller
Wendy Waller
DRI FOUNDATION
STAFF
Joshua W. Rednik
Laurie Cummings
President and Chief Executive Officer
Communications Assistant
Deborah L. Chodrow
Aurora Nunez
Chief Operating Officer
Administrative Assistant
Jeffrey Young
Oneida Osuna
Chief Financial Officer
Accounting Assistant
Tom Karlya
Mary Revie
Vice President
Administrative Assistant
Director of Special Events,
Jericho Office
Jill Shapiro Miller
Mylinda Auguste
Jill Salter
Vice President of Gift Planning
Data Entry Clerk
Development Manager
Lori Weintraub, APR
Marisol McKay
Melinda Megale
Northeast Region
Anthony E. Childs
Director
Amy Epstein
Vice President of Marketing
and Communications
Lauren Schreier
Director of Special Events,
Manhattan Office
Lily Scarlett
Date Entry Clerk
Special Events Coordinator
Eddy Garcia
Tricia Pellizzi
Courier
Director of Marketing and
Communications
Barbara Singer
Director of Special Projects
Florida Region
Sheryl Sulkin
Director of Special Events
Karen Paraboo
Administration and
Database Coordinator
Nicole Otto
Joelle Parra
Dena Kawecki
Communications and
Social Media Coordinator
Melissa Peña
Development Coordinator
Associate Director of Special Events
Special Events Manager
Sarah Mehan
National Office
Florida Region
200 South Park Road
Suite 100
Hollywood, FL 33021
Telephone 954.964.4040
Toll-free 1.800.321.3437
Fax 954.964.7036
Northeast Region
Jericho Office
410 Jericho Turnpike
Suite 201
Jericho, NY 11753
Fax 516.822.3570
Manhattan Office
381 Park Avenue South
Designed by Franz Franc Design Group
Suite 1118
New York, NY 10016
Fax 212.888.2219
DiabetesResearch.org
44

Reaching the Biological Cure - Diabetes Research Institute

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