Full Program Book - The New York Academy of Sciences

Transcription

9th Annual
Network
Research
Symposium
June 15 – 17, 2015
Presented by Rutgers University-Robert Wood Johnson
Medical School and Ernest Mario School of Pharmacy,
New York Medical College, the National Institutes of
Health, and the New York Academy of Sciences
TABLE OF CONTENTS
Welcome...........................................................................................1
CounterACT Research Network.......................................................2
Scientific Organizing Committee.......................................................4
Stay Connected................................................................................4
Presenting Partners..........................................................................5
Quad Charts......................................................................................5
Acknowledgement of Support...........................................................6
Agenda..............................................................................................7
Layout of Conference Center...........................................................12
Breakout Room Assignments...........................................................13
Faculty Disclosures..........................................................................14
CounterACT Efficacy Research Facility (CERF)..............................18
CounterACT Neurotherapeutics Screening Program (CNS)............20
CounterACT Preclinical Development Facility (CPDF).....................24
ASPR/BARDA and Medical Countermeasures.................................27
Poster Session Information...............................................................28
Additional Information.......................................................................34
Notes................................................................................................35
WELCOME
We are living in a world of chemical threats which arise due to conflict, terrorism, industrial
accidents and natural disasters. Of utmost priority is to define potential chemical threats,
monitor and assess the risk of exposures to human populations, and develop specific and
efficacious countermeasures. Thus, the 9th Annual NIH CounterACT Network Research
Symposium, with its focus on the identification and advancement of drugs to counter high
priority chemical threats, is quite timely. The meeting takes on special meaning this year, being
held at the New York Academy of Sciences in New York City, across from the World Trade
Center site and the World Trade Center Memorial. Bringing together investigators with diverse
backgrounds from across the country, the symposium will provide a comprehensive overview of
the latest research on the development of countermeasures against chemical threats. Key
discoveries will be highlighted in plenary and specialty sessions, clinical presentations, and in
two exciting poster sessions. We would like to thank each of you for participating in the
meeting, and to give special thanks to our sponsors for offering invaluable support to the
conference. We hope that you will enjoy the conference, the interaction with colleagues, the
dramatic vistas from the New York Academy of Sciences and the surrounding memorials to the
World Trade Center.
Jeffrey D. Laskin, PhD
Professor & Chief, Division of Toxicology
Director of the Rutgers University CounterACT Research Center of
Excellence
Rutgers University-Robert Wood Johnson Medical School
First, we would like to thank the Rutgers University CounterACT Research Center of Excellence
and the New York Academy of Sciences for hosting the 2015 annual meeting. Recent events
have truly emphasized the need for better medical countermeasures for agents such as sarin
and chlorine. Nearly a decade of research excellence within the NIH CounterACT Network has
led to exciting breakthroughs in our understanding of how chemical threats exert their toxicity,
new targets for therapeutic development, and several new promising candidates that are now
poised for advanced development and approval for use in humans. We at NIH look forward to
hearing about the hard work you have been doing over the past year, and we hope you use this
meeting to explore opportunities to collaborate. Thank you on behalf of all the CounterACT staff
from the participating NIH Institutes.
David A. Jett, PhD
Director, NIH CounterACT
National Institutes of Health, NINDS
Page 1
CounterACT
Research Network
The increased risk of a terrorist attack in the United States involving chemical agents has created new
challenges for many departments and agencies across the federal government. Within the Department
of Health and Human Services (DHHS), the NIH is taking a leadership role in pursuing the development
of new and improved medical countermeasures designed to prevent, diagnose, and treat the conditions
caused by potential and existing chemical agents of terrorism. In addition, many of the same chemicals
posing a threat as terrorist agents may also be released from transportation and storage facilities by
industrial accidents or during a natural disaster. The NIH has developed a comprehensive CounterACT
Research Network that includes Research Centers of Excellence, individual research projects, SBIRs,
contracts and other programs. The CounterACT network conducts basic, translational, and clinical
research aimed at the discovery and/or identification of better therapeutic and diagnostic medical
countermeasures against chemical threat agents, and facilitates their movement through the regulatory
process. The overarching goal of this research program is to enhance our medical response capabilities
during an emergency. This program is a trans-NIH effort, involving participation from the National Eye
Institute, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and
Human Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institute of Environmental Health Sciences, National Library of Medicine, and the National Institute of
Neurological Disorders and Stroke.
Higher Priority Chemical Threats
• Anti-cholinesterase and GABA-inhibiting agents that cause seizures and
neuropathology such as sarin, parathion, aldicarb, and tetramine (TETS)
• Metabolic/Cellular poisons and agents that target the blood such as hydrogen sulfide, sodium
fluoroacetate, arsenic trioxide, and strychnine
• Agents that target the respiratory tract such as ammonia and phosgene
• Vesicating agents that cause blisters and other skin pathologies such as Lewisite
Scope of Research
• Mechanistic research to identify targets for therapeutic/diagnostic development
• Development of in vitro and animal models for efficacy screening of therapeutics and
diagnostic tools
• Efficacy screening of therapeutics/diagnostics using new and validated in vitro and
animal models that are appropriate
• Advanced efficacy studies with appropriate animal models including non-human primates
using current Good Laboratory Practices (cGLP)
• Clinical studies, including trials, when appropriate
• Special consideration will be given to research relevant to people who are particularly vulnerable,
including the young, the elderly, and individuals with pre-existing medical conditions.
Page 2
Scientific Contacts for
Questions Concerning
the CounterACT Program
David A. Jett, Ph.D. (NINDS)
Program Director - CounterACT
Telephone: (301) 496-6035
Email: [email protected]
Ernest T. Takafuji, M.D., M.P.H. (NIAID)
Director - Office of Biodefense Research
Telephone: (301) 435-2860
Dave Yeung, Ph.D. (NINDS)
Project Manager - CounterACT
Telephone: (301) 443-7534
Gennady E. Platoff Jr., Ph.D. (NIAID)
CBRN Scientific Advisor Office of Biodefense Research
Telephone: (301) 451-4418 (direct)
Sarah Norring, Ph.D. (NINDS)
Program Specialist - CounterACT
Telephone: (301) 443-8189
Houmam Araj, Ph.D. (NEI)
Program Director - Lens and Cataract
Telephone: (301) 451-2020
Pertti (Bert) J. Hakkinen, Ph.D. (NLM)
Acting Head - Office of Clinical Toxicology,
and Senior Toxicologist, and Toxicology and
Environmental Health Science Advisor (to the
Director) Specialized Information Services
Telephone: (301) 827-4222
Andrea Harabin, Ph.D. (NHLBI)
Program Director - Critical Care/Acute Lung
Injury
Telephone: (301) 435-0222
Elizabeth A. Maull, Ph.D. (NIEHS NTP)
Program Administrator –
National Toxicology Program
Telephone: (919) 316-4668
Srikanth S. Nadadur, Ph.D. (NIEHS)
Health Scientist Administrator –
Cardiovascular Health
Telephone: (919) 541-5327
David Siegel, M.D. (NICHD)
Program Director – Biodefense Research
Channels, Synapses, and Circuits
Telephone: (301) 594-8670
Randall Stewart, Ph.D. (NINDS)
Program Director –
Channels, Synapses, and Circuits
Telephone: (301) 496-1917
Hung Tseng, Ph.D. (NIAMS)
Health Scientist Administrator –
Div. of Skin and Rheumatic Diseases
Telephone: (301) 594-5032
CounterACT Program Website
http://www.ninds.nih.gov/counterACT
Page 3
SCIENTIFIC ORGANIZING COMMITTEE
Jeffrey D. Laskin, PhD, Rutgers University Robert Wood Johnson Medical School
Debra L. Laskin, PhD, Rutgers University Ernest Mario School of Pharmacy
Diane E. Heck, PhD, New York Medical College
Donald Gerecke, PhD, Rutgers University Ernest Mario School of Pharmacy
Marion Gordon, PhD, Rutgers University Ernest Mario School of Pharmacy
Patrick J. Sinko, PhD, Rutgers University Ernest Mario School of Pharmacy
Ned Heindel, PhD, Lehigh University
Laurie B. Joseph, PhD, Rutgers University Ernest Mario School of Pharmacy
Local Organizing Committee
Paul J. Lioy, PhD, Rutgers University Robert Wood Johnson Medical School
Brooke Grindlinger, PhD, The New York Academy of Sciences
Siobhán Addie, PhD, The New York Academy of Sciences
STAY CONNECTED
Wireless Internet Access
Username: nyasguest
Password: nyasguest7WTC
Join the Twitter Conversation
@NYASEvents
LinkedIn
Search for:
‘The New York Academy of Sciences’
PRESENTING PARTNERS
QUAD CHARTS
Visit http://www.nyas.org/QuadCharts2015 to access an electronic file of the Quad Charts
from this symposium. The password to access the file is: counteractnyas.
ACKNOWLEDGEMENT OF SUPPORT
GRANT SUPPORT
Funding for this Symposium was made possible, in part, by a grant from the National
Institutes of Health (U54 AR055073). The views expressed in this symposium do not
necessarily reflect the official policies of the Department of Health and Human Services
or endorsement by the U.S. Government.
BRONZE SPONSOR
Battelle
ACADEMY FRIENDS
CH Technologies USA, Inc.
Emergent BioSolutions
emka TECHNOLOGIES & SCIREQ
Genemarkers
MRIGlobal
Novus Biologicals – a Bio-Techne Brand
RUCDR Infinite Biologics
Rutgers School of Public Health
Rutgers, The State University of New Jersey, Ernest Mario School of Pharmacy
Rutgers, The State University of New Jersey, School of Biomedical Sciences
Rutgers, The State University of New Jersey, Biomedical and Health Sciences, Office of
the Chancellor
Society of Toxicology
SRI International
Target Health, Inc.
The Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers, The
State University of New Jersey
Thermo Fisher Scientific
SYMPOSIUM AGENDA
DAY 1
Monday, June 15, 2015
7:30 AM
Registration and Continental Breakfast
8:00 AM
Welcome and Opening Remarks
Siobhan Addie, PhD, The New York Academy of Sciences
Jeffrey D. Laskin, PhD, Rutgers University
David A. Jett, PhD, National Institute of Neurological Disorders and Stroke (NINDS)
8:15 AM
Keynote Address
History of Chemical Warfare
Joseph Gal, PhD, University of Colorado School of Medicine
8:55 AM
From the Bench to the Bedside: BARDA’s Role in the Development of Medical Countermeasures for Chemical Threats
Judith Laney, PhD, BARDA
9:15 AM
Break into Concurrent Sessions
9:30 AM
SESSION 1A: PULMONARY AGENTS
Chairperson: Srikanth Nadadur, PhD, National
Institutes of Environmental Health (NIEHS)
9:30 AM
10:00 AM
10:30 AM
SESSION 1B: NEUROLOGICAL
AGENTS
Chairperson: David A. Jett, PhD, National Institute
of Neurological Disorders and Stroke (NINDS)
Multifunctional Therapeutics for Treatment of
Acute Chlorine Inhalational Injury
Phorate Oxon: Reactivation Kinetics and Acute
Oral Toxicity in the Sprague Dawley Rat
Garry Southan, PhD, Radikal Therapeutics, Inc.
Tom Snider, Battelle and Robert Moyer, PhD,
Battelle
Intracellular Targeting HSP70 for Pulmonary
Cytoprotection after Toxin Inhalation
Accelerated AChE Reactivator Design by
Mechanistic Neutron Scattering Studies
Missag Parseghian, PhD, Rubicon Biotechnology,
Inc.
Zoran Radic, PhD, University of California, San
Diego; Don Blumenthal, PhD, University of Utah;
Xiaolin Cheng, PhD, Oak Ridge National
Laboratory; Andrey Kovalevsky, PhD, Oak Ridge
National Laboratory
TIE2 Activation for the Treatment of Chemical
Induced Acute Lung Injury
Improved Standard of Care Reactivators and
Facilitative Transport into the Central Nervous
System
Christopher D. Kontos, MD, Duke University
SESSION 1C: VESICATING AGENTS
Chairperson: Hung Tseng, PhD, National Institute
of Arthritis and Musculoskeletal and Skin Diseases
and Houmam Araj, PhD, National Eye Institute
Rutgers University CounterACT Research Center
of Excellence
(U54 Center Report)
Jeffrey D. Laskin, PhD, Rutgers University
Brian McCranor, PhD, US Army Medical Research
Institute of Chemical Defense; Jayendra B.
Bhonsle, PhD, Astha Drug Discovery & Research;
John Koh, PhD, University of Delaware
11:00 AM
Extracellular RNA as Therapeutic Target After
Toxic Chemical Inhalation
Brain-Penetrating Acetylcholinesterase
Reactivators for Several Organophosphates
Amelioration of Vesicant-Induced Skin Injury by
High Dose 25-Hydroxyvitamin D
Aftab Ahmad, PhD, University of Alabama,
Birmingham
Janice Chambers, PhD, Mississippi State
University
Kurt Lu, MD, Case Western University
11:30 AM
Central Role of Heme Oxygenase in Reversing
Bromine Morbidity and Mortality
Sadis Matalon, PhD, University of Alabama,
Birmingham
12:00 PM
Reactivation of Aged Acetylcholinesterase:
Design and Development of Novel Therapeutics
against Exposure to OP Chemical Nerve Agents
Christopher Hadad, PhD, Ohio State University
Lunch
Poster Session 1 Set-up
1:30 PM
1:30 PM
Development of Therapeutics for ChlorineInduced Airway and Lung Injury
M. Dee Gunn, MD, Duke University
AGENTS
Chairperson: Pertti Hakkinen, PhD, National
Library of Medicine (NLM)
Oxime Therapy Doses That Provide 50% Survival
Against Subcutaneous and Topical
Organophosphate Challenges at 2X LD50
Christy Wilhelm, Battelle and Michael Babin, PhD,
Battelle
2:00 PM
2:30 PM
Nitrite Dependent Protection Against Cl2 Gas
Toxicity – Role of Chlorinated Lipids
BChE Reactivators for Nerve Agent and Pesticide
OP Detoxification in Human Tissue
Rakesh Patel, PhD, University of Alabama
Birmingham
Zoran Radic, PhD, University of California, San
Diego and Palmer Taylor, PhD, University of
California, San Diego
Functional Genomics of Chemical-Induced Acute
Lung Injury
Induced Therapeutic Overexpression of
Acetylcholinesterase in vivo
George Leikauf, PhD, University of Pittsburgh
Richard Rotundo, PhD, University of Miami Miller
School of Medicine
3:00 PM
Coffee Break/Networking
3:30 PM
Novel Therapies for Chlorine-Induced Lung Injury
Gary Hoyle, PhD, University of Louisville
Pharmacotherapy to CounterACT ParathionInduced NMJ Dysfunction
Steven Bird, MD, University of Massachusetts
4:00 PM
4:30 PM
Countermeasures for Chlorine-Induced Airway
Fibrosis
Efficacy and Safety of an Aerosolized
Recombinant Butyrylcholinesterase Pretreatment
Gary Hoyle, PhD, University of Louisville
Yvonne Rosenberg, PhD, PlantVax, Inc
Targeting Injury Pathways to Counteract
Pulmonary Agent and Vesicant Toxicity
Developing Drugs to Mitigate Parathion
Intoxication
Sven-Eric Jordt, PhD, Duke University
Jason R. Richardson, PhD, DABT, and Jeffrey D.
Laskin, PhD, Rutgers University
5:00 PM
Poster Session 1 and Networking Reception
7:00 PM
Day 1 Adjourns (Poster Session 1 poster removal)
Effective Therapies for Ocular Injuries by
Vesicating Agents
Rajesh Agarwal, PhD, University of Colorado
DAY 2
7:30AM
Tuesday, June 16, 2015
Continental Breakfast
Poster Session 2 Set-up
8:00 AM
Keynote Address: Preparedness and Response to Chemical Threats: The Role of Exposure Science
Paul J. Lioy, PhD, Rutgers University Robert Wood Johnson Medical School
8:25 AM
Keynote Address: Poisoning Through the Ages
Michael A. Gallo, PhD, Rutgers University Robert Wood Johnson Medical School
8:50 AM
The Challenge of Medical Countermeasure Development
Claire Croutch, PhD, MRIGlobal
9:00 AM
Successful Medical Countermeasure Development…It Takes a Village
Jill Harvilchuck, PhD, Battelle
9:15 AM
Break into Concurrent Sessions
9:30 AM
9:30 AM
10:00 AM
11:30 AM
Chairperson: Elizabeth Maull, PhD, National
Institutes of Environmental Health Sciences (NIEHS)
SESSION 3C: CELLULAR AGENTS
Chairperson: Gennady Platoff, PhD, National
Institute of Allergy and Infectious Diseases (NIAID)
Thioredoxin Mimicry: Novel Treatment of
Toxicant-Mediated Inhalational Lung Injury
Screening Therapies to Counteract
Developmental Chlorpyrifos Intoxication
Intralipid: A Novel Frontline Countermeasure for
Brodifacoum Poisoning
Garry Southan, MD, Radikal Therapeutics, Inc.
Jared Goldstone, PhD, Woods Hole
Oceanographic Institute
Douglas Feinstein, PhD, University of Illinois
Mitochondrial Bioenergetic Dysfunction and
Chlorine Toxicity
Developing and Evaluating Countermeasures
Against Tetramethylenedisulfotetramine
Sadis Matalon, PhD, University of Alabama,
Birmingham
Michael Shakarjian, PhD, New York Medical
College
A Discovery and Development Pipeline for
Cyanide Countermeasures
Novel Anticonvulsant and Neuroprotective
Therapies for TETS and OP Intoxication
(U54 Center Report)
Chemicals Affecting the Respiratory Tract –
Pulmonary Toxicants (Interagency Report)
(U54 Center Report)
Calum MacRae, MD, PhD, Brigham and Women’s
Hospital
Speaker Forthcoming
Pamela Lein, PhD, University of California at Davis
10:30 AM
11:00 AM
AGENTS
US Army Medical Research Institute of Chemical
Defense
Development of a Field-Deployable Device to
Rapidly Measure Blood Cyanide Levels
Hans Boehringer, PhD, Diagnostic Consulting
Network
12:00 PM
1:30 PM
1:30 PM
Lunch and Poster Session 2
SESSION 4A: CELLULAR AGENTS
SESSION 4B: NEUROLOGICAL AGENTS
Chairperson: Gennady Platoff, PhD, National Institute of Allergy and Infectious
Diseases (NIAID)
Chairperson: Randall Stewart, PhD, National Institute of Neurological
Disorders and Stroke (NINDS)
Cyanide Decorporation by Co(III) Schiff-Base Macrocycles
Linda Pearce, PhD, University of Pittsburgh
2:00 PM
Pre-Clinical and Clinical Studies of Cobinamide, A New Cyanide
Detoxifying Agent
Gerry Boss, MD, University of California, San Diego
2:30 PM
Countermeasures Against Chemical Threats: Countermeasures Against
Cyanide
Chemicals Affecting the Nervous System – Anticonvulsants and
Neuroprotectants (Interagency Report)
Speaker Forthcoming
US Army Medical Research Institute of Chemical Defense
Steven Patterson, PhD, University of Minnesota
3:00 PM
Coffee and Refreshment Break
3:30 PM
Nitrites as Antidotes for Hydrogen Sulfide Poisoning
James Peterson, PhD, University of Pittsburgh
Efficacy of GluR5 Antagonists Against Soman-Induced Seizures and
Neuropathology
Maria Braga, DDS, PhD, Uniformed Services University of the Health Sciences
4:00 PM
Efficacy of Cobinamide for Treatment of Hydrogen Sulfide-Induced
Neurotoxicity
Neurosteroid Treatment for OP Intoxication
Doodipala S. Reddy, PhD, Texas A&M University
Wilson Rumbeiha, DVM, PhD, DABVT, DABT VDL, Iowa State University
4:30 PM
Open Discussion
5:00 PM
Optional Visit to the National September 11 Memorial & Museum
6:30 PM
Day 2 Adjourns (Poster Session 2, poster removal), dinner on your own
Open Discussion
DAY 3
7:30AM
Wednesday, June 17, 2015
Continental Breakfast
Concurrent Sessions
8:00 AM
8:00 AM
8:30 AM
SESSION 5A: VESICATING AGENTS
SESSION 5B: NEUROLOGICAL AGENTS
SESSION 5C: CELLULAR AGENTS
Chairperson: Dave Yeung, PhD, National Institute of
Neurological Disorders and Stroke (NINDS)
Chairperson: Gennady Platoff, PhD, National
Institute of Allergy and Infectious Diseases (NIAID)
Novel Treatments of Acrolein-Induced
Cardiotoxicity
CounterACT Neurotherapeutics Screening (CNS)
Program (Interagency Report)
Methylene Blue, A Novel Treatment of H2S
Poisoning-Induced Brain Injury
Daniel Conklin, PhD, University of Louisville
John McDonough, PhD, US Army Medical Research
Institute of Chemical Defense, Edward Dudek, PhD,
University of Utah, Hilary S. McCarren, PhD, US Army
Medical Research Institute of Chemical Defense
Philippe Haouzi, MD, Pennsylvania State
University, Hershey Medical Center
Novel Therapeutics for Vesicant and Toxic
Inhaled Chemicals
Parathion Exposure: Mechanisms of Toxicity and
Treatment
(U54 Center Report)
Robert DeLorenzo, MD, PhD, Virginia Commonwealth
University
Cyanide Diagnostics and Efficacy Testing of
Next Generation Cyanide Antidotes (Interagency
Report)
9:00 AM
Carl White, MD, University of Colorado, Denver
Prostanoid Modulators That Reduce Brain Injury
After Seizures
Raymond Dingledine, PhD, Emory University
9:30 AM
Speaker Forthcoming
Defense
Evaluation of Neuroprotective Effects of AEOL
10150 Against Organophosphate Toxicity
Manisha Patel, PhD, University of Colorado, Denver
10:00 AM
Chemicals Affecting Skin, Eyes, and Mucous
Membrane – Toxic Vesicants and Industrial
Chemicals (Interagency Report)
Definitive Studies for Use of Galantamine as a PreTreatment Countermeasure Against Nerve Agent
Poisoning
Cyanide and the Human Brain
Desire Tshala-Katumbay, MD, PhD, Oregon
Health & Science University
William Basinger, Jr., Countervail Corporation
10:30 AM
Speaker Forthcoming
Defense
Rational Polytherapy in the Treatment of Cholinergic
Seizures
Claude Wasterlain, MD, UCLA, VA Greater Los
Angeles Healthcare System
11:00 AM
Open Discussion
11:30 AM
CounterACT Preclinical Development Facility (CPDF)
Carol Green, PhD, DABT, SRI International
12:00 PM
1:00 PM
Lunch
Presentation by SRI International
“An Overview of the Preclinical Development Process: From Idea to IND and Beyond”
3:00 PM
Conference Adjourns
Open Discussion
LAYOUT OF CONFERENCE CENTER
Legend:
1 – Main Auditorium
3 – Lobby
2 – Conference Room
4 – Board Room
Page 12
BREAKOUT ROOM ASSIGNMENTS
MONDAY, JUNE 15
9:30 AM - 12:00 PM
1A: Pulmonary Agents
Board Room
1B: Neurological Agents
Main Auditorium
1C: Vesicating Agents
Conference Room
1:30 PM - 5:00 PM
Board Room
Main Auditorium
TUESDAY, JUNE 16
9:30 AM - 12:00 PM
Board Room
Main Auditorium
3C: Cellular Agents
Conference Room
1:30 PM - 5:00 PM
4A: Cellular Agents
Board Room
Main Auditorium
WEDNESDAY, JUNE 17
8:30 AM - 11:30 AM
5A: Vesicating Agents
Board Room
Main Auditorium
5C: Cellular Agents
Conference Room
Note: All joint sessions will be presented in the Main Auditorium.
Page 13
FACULTY DISCLOSURES
All faculty participating in this activity are required to disclose to the audience any significant financial interest
and/or other relationship with the manufacturer(s) of any commercial product(s) and/or provider(s) of
commercial services discussed in his/her presentation and/or the commercial contributor(s) of this activity.
An * after the speaker’s name indicates that the speaker intends to discuss unlabeled uses of a commercial
product, or an investigational use of a product not yet approved for this purpose.
N/A – information not available at the time of printing.
Rajesh Agarwal, PhD
None
Maria Braga, PhD
None
Aftab Ahmad, PhD
None
Janice Chambers, PhD
None
Houmam Araj, PhD
None
Xiaolin Cheng, PhD
None
Michael Babin, PhD
None
Daniel Conklin, PhD
None
William Basinger, Jr.
Employee
CounterVail Corporation
Robert DeLorenzo, MD, PhD
N/A
Jayendra Bhonsle, PhD, PMP
None
Steven Bird, MD
None
Don Blumenthal, PhD
None
Hans Boehringer, PhD
Employee
DCN Diagnostics
Gerry Boss, MD
N/A
Raymond Dingledine, PhD
None
Edward Dudek, PhD
N/A
Douglas Feinstein, PhD*
Consultant
Lipid Rescue, LLC
Joseph Gal, PhD
None
Michael Gallo, PhD, DABT
None
Page 14
FACULTY DISCLOSURES
Jared Goldstone, PhD
N/A
Carol Green, PhD, DABT
Employee
SRI International
Sven-Eric Jordt, PhD
Research Support
GlaxoSmithKline
Hydra Biosciences
Consultant
Hydra Biosciences
M. Dee Gunn, MD*
None
John Koh, PhD
N/A
Christopher Hadad, PhD
None
Perti Hakkinen, PhD
None
Christopher Kontos, MD
Speakers Bureau
Aerpio Therapeutics, Inc.
Research Support
Aerpio Therapeutics, Inc.
Michael Babin, PhD
N/A
Andrey Kovalevsky, PhD
None
Phillippe Haouzi, MD
N/A
Judith Laney, PhD
None
Jill Harvilchuck, PhD
Employee
Battelle
Jeffrey D. Laskin, PhD
N/A
Gary Hoyle, PhD
None
David A. Jett, PhD
N/A
George Leikauf, PhD
N/A
Pamela Lein, PhD
None
Peter Lentini
Employee
Microdermis
Page 15
FACULTY DISCLOSURES
Paul J. Lioy, PhD
None
Rakesh Patel, PhD
N/A
Kurt Lu, MD
N/A
Manisha Patel, PhD
None
Calum MacRae, MD, PhD
N/A
Steven Patterson, PhD
N/A
Sadis Matalon, PhD
N/A
Linda Pearce, PhD
N/A
Elizabeth Maull, PhD
N/A
James Peterson, MD
N/A
Hilary McCarren, PhD
None
Gennady Platoff, PhD
N/A
Bryan McCranor, PhD
None
Zoran Radic, PhD
None
John McDonough, PhD
None
Doodipala Reddy, PhD
None
Robert Moyer, PhD
None
Jason Richardson, PhD, DABT
None
Srikanth Nadadur, PhD
N/A
Yvonne Rosenberg, PhD
Employee
PlantVax, Inc.
Missag Parseghian, PhD
Employee
Rubicon Biotechnology
Richard Rotundo, PhD
None
Page 16
FACULTY DISCLOSURES
Wilson Rumbeiha, DVM, PhD
None
Hung Tseng, PhD
N/A
Michael Shakarjian, PhD
None
Desire Tshala-Katumbay, MD, PhD
N/A
Tom Snider
None
Claude Wasterlein, MD
None
Garry Southan, PhD
Employee
Radikal Therapeutics
Carl White, MD*
Other Financial Support
Genentech
Randall Stewart, PhD
None
Christy Wilhelm
Employee
Battelle
Palmer Taylor, PhD*
None
David Yeung, PhD
None
Page 17
CounterACT Efficacy Research Facility (CERF)
The CounterACT program includes a state-of-the-art facility to accelerate the research and development of
medical countermeasures for chemical threats. This facility is a NIH supported laboratory equipped to
conduct translational research (including full Good Laboratory Practices (GLP) capability) on the efficacy of
compounds against the lethal and non-lethal effects of chemical threat agents using new and established
animal models.
A purpose of the CERF program is to assist applicants to obtain important proof-of-concept efficacy data, i.e.,
pilot studies, in support of a research application to the CounterACT peer-reviewed grant program. The
proposed studies must not overlap with, but may be done in concert with studies done within other
CounterACT efficacy and preclinical programs (e.g., CounterACT Preclinical Development Facility). See
www.ninds.nih.gov/counteract for more details. If approved by NIH, studies are performed at no cost to the
investigator. Participants will retain custody of and have primary rights to the data developed under these
awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the
participants any proprietary rights, including intellectual property rights, or any materials needed by the
applicant to perform the project. Participants are free to establish a separate Material Tech-Transfer/Lab
service agreement with the CERF and/or the NIH.
* The CERF does not replace the need to formally establish (and budget for) collaboration with laboratories,
such as the Department of Defense U.S. Army Medical Research Institute of Chemical Defense
(USAMRICD) and others, that are certified to work with restricted as well as unrestricted chemical agents
within those research applications submitted in response to CounterACT FOAs available at
http://www.ninds.nih.gov/research/counterterrorism/FundingOpportunities.htm.
Procedures for Submitting Compounds to the CounterACT Efficacy Research Facility (CERF)
General Procedure:
1. NIH will accept Product Development Pre-Proposals (PDP) from individual PIs. PIs may consult with
NIH to determine eligibility and general efficacy needs.
2. Cover Letter
a. Project Director/Principal Investigator (PD/PI) name
b. Title of requested research effort
c. Name, title of the authorized organizational representative (AOR)
d. Phone, email, and address information for both the PD/PI and the institutional official.
The cover letter must be signed by the AOR and PD/PI.
3. The PDP will be 3-5 pages. If they do not contain the following sections, they will be returned without
further review:
a. Introduction – Describe how these studies will advance the development of the candidate
therapeutic. How will these studies serve as a go/no go point for further drug development?
b. Justification – Describe any efficacy and preclinical (i.e., PK, safety, chemistry, etc.) studies and
results that have already been completed on the specifically proposed product.
c. Research Needs summarizing, in general, which research track is proposed in this pre-proposal, what
type of work you are requesting, and specifics for the studies (i.e., required animal model, route of
agent exposure, administration route of therapeutic, endpoints, etc.).
REV 06/2015
Page 18
4. The NIH will begin accepting PDPs immediately, commencing December 1, 2010. There are no receipt
deadlines.
5. PDPs will be reviewed by the CounterACT Program Steering Committee (CPSC) within 3-4 weeks of
receipt.
6. Review criteria include eligibility (e.g., previous efficacy data of the specifically proposed product),
impact on the overall drug development process, programmatic priorities, and availability of NIH
resources.
7. If the PDP is approved, the investigator and CERF study directors will prepare a full CERF Study
Proposal (CSP) and budget for final review and approval by the NIH before the studies begin, no later
than one month after initial approval of the PDP.
8. A final Technical Report (TR), including task background, objectives, assumptions, specific data
collected, analyses conducted, conclusions and recommendations, will be delivered to the investigator by
the NIH at the conclusion of the study.
Study Criteria:
Track 1: Pilot Studies
1. These limited studies will facilitate characterization and optimization of leads early in the
development process.
2. Efficacy of the specifically proposed product must be demonstrated in at least one acceptable in
vitro and/or in vivo (preferable) model prior to submission of the PDP.
3. Efficacy of the specifically proposed product may be shown against the actual threat agent OR an
acceptable surrogate agent within the same chemical class.
Track 2: Definitive Studies
1. These studies will satisfy some of the requirements for FDA approval and submission of a New
Drug Application (NDA), including definitive GLP Animal Rule studies with non-human
primates and other animal models.
2. Substantial efficacy of the specifically proposed product must already be shown against the actual
chemical threat agent(s) that warrants definitive animal studies.
3. It is recommended that the FDA be consulted in pre-IND meetings prior to submitting a PDP.
Utilization of this facility will require an FDA Special Protocol Assessment (SPA) of the
proposed studies.
Applicants are strongly encouraged to contact CounterACT program staff for further information (e.g.,
eligibility, research interest).
Submit Pre-Proposals by email to:
David Yeung, Ph.D.
NIH CounterACT Program
[email protected]
REV 06/2015
Page 19
CounterACT Neurotherapeutics Screening (CNS) Program
Executive Summary
The CounterACT program includes established animal screening models to identify and accelerate
the research and development of novel medical countermeasures (MCM) for organophosphorus
(OP) chemical threats that target the central nervous system. These models are available through the
U.S. Army Medical Research Institute (USAMRICD; http://chemdef.apgea.army.mil) via a NIHsupported laboratory equipped to conduct translational research on the efficacy of compounds
against the lethal and non-lethal effects of OP chemical threat agents in vivo. If accepted for the CNS
program, studies are performed at no cost to the investigator/supplier.
The purpose of the CNS program is to provide applicants with important proof-of-concept efficacy
data in support of a research application to the CounterACT (or others) peer-reviewed grant
program. The CNS program does not replace the need to establish direct collaborations with
laboratories that are certified to work with restricted chemical agents within those applications
submitted in response to the research solicitations at
http://www.ninds.nih.gov/research/counterterrorism/FundingOpportunities.htm.
The proposed studies must not overlap, but may be conducted in concert with, studies performed
within other CounterACT efficacy, preclinical, grant programs (see www.ninds.nih.gov/counteract
for details). Participants will retain custody of and have primary rights to the data developed, subject
to Government rights of access consistent with current U.S. Government (USG) policies.
Before, during, and subsequent to entry into the program, the USG is not required to obtain for the
participants any proprietary rights, including intellectual property rights, or any materials needed by
the applicant to perform the project. Participants are advised to establish a separate Material TechTransfer or Lab service agreement between themselves and the NIH-supported laboratories before
commencing any studies.
Program Description and Goal
OP-induced seizures result from overstimulation of susceptible brain circuits by abnormally high
levels of the excitatory neurotransmitter acetylcholine, which rapidly builds up after inhibition of the
enzyme acetylcholinesterase by nerve agent1. These seizures rapidly progress to a condition known
as status epilepticus (SE), a medical emergency that responds to only a subset of known
anticonvulsant drugs. Moreover, the longer these seizures persist the more difficult they are to stop
pharmacologically2, and in the case of chemical warfare nerve agents (NAs), as little as 20 min of
continuous seizure activity is sufficient to produce neuropathology, the severity and extent of
neuropathology is then proportional to the duration of the seizures3,4.
1
2
3
4
McDonough JH.Neurosci. Biobehav. Rev. 1997; 21(5):559-579.
Shih TM, et al. Toxicol. Appl. Pharmacol. 2003; 188(2):69-80.
Lallement G, et al. Neuroreport 1994; 5(17):2265-2268.
McDonough JH, et al. Neurotoxicology 1995; 16(1):123-132.
REV 06/2015
Page 20
The current MCM approach to treat OP-induced seizures includes the administration of atropine,
pralidoxime chloride (2-PAM Cl), and an anticonvulsant (diazepam/midazolam). Though efficacious
to an extent, overall improvement in both mortality and morbidity outcomes is still highly desired.
Through CounterACT, the goal of the CNS program is to identify novel neurotherapeutics that may
be administered with the approved treatments, in a civilian first-responder setting, to more
effectively suppress SE activity and/or mitigate neuropathology after OP exposure.
Screening Models
The CNS program employs the following in vivo screening models:
1) OP Diisopropylfluorophosphate-(DFP) induced electrographic SE model in male, SpragueDawley rats (125-175 g) surgically prepared with surface cortical electrodes one week before
actual exposure to record brain electroencephalographic (EEG) activity.
a. Implanted animals will be pre-treated with pyridostigmine (PB, 0.026 mg/kg, i.m.) at
30 min before injection of DFP (6.0 mg/kg, s.c.), followed by co-administration of
atropine methyl nitrate (AMN, 2.0 mg/kg, i.m.) and 2-PAM (25 mg/kg, i.m.) within 1
min later. The test neurotherapeutic compound +/- midazolam (1.78 mg/kg, i.m.)
will be administered at 60 min after the occurrence of the first electrographic seizure,
based on the appearance of repetitive spikes and sharp waves in the EEG.
b. The model utilizes 24-hr EEG recordings with objective, semi-automated, and
quantitative methods of data analysis5,6 to determine the efficacy of different
investigational compounds at suppressing DFP-induced electrographic SE.
c. Additional studies will quantify neuronal death under these conditions to assess
neuroprotection via Fluoro-Jade B staining in at least four perfused brain areas that
are highly susceptible to DFP-induced brain damage.
2) NA Soman-(GD) induced electrographic SE model in male, Sprague-Dawley rats (250-300 g
at time of surgery) also surgically prepared with surface cortical electrodes to record brain
EEG activity.
a. Animals are pretreated with the oxime HI-6 (125 mg/kg, i.p.); 30 min later the
animals are challenged with 1.6xLD50 GD (180 ug/kg, s.c.), at a dose that elicits EEG
seizure activity in 100% of the animals. The animals will receive AMN (2.0 mg/kg,
i.m.) within 1 min after GD challenge.
b. At 20 min following the onset of electrographic seizure activity, animals will receive
standard medical countermeasures for NA intoxication via intramuscular injection
(0.45 mg/kg atropine sulfate, 25.0 mg/kg 2-PAM-Cl, 1.78 mg/kg midazolam) along
with a dose of the test neurotherapeutic compound previously identified from the
DFP model. EEG is also continuously recorded and 24 hr later at the end of the
recording period, the animals are perfused, the brain stained with Fluoro-Jade B
and/or hematoxlyn and eosin (H&E), then evaluated to rate the degree of pathology
by examining up to five brain areas highly susceptible to NA-induced damage7,8.
5
6
7
8
Lehmkuhle MJ, et al. J Neurophysiol 2009; 101:1660-70.
Pouliot W, et al. Neuroscience 2013; 231:145-56.
REV 06/2015
Page 21
3) NA GD-induced electrographic SE model in male, Hartley guinea pigs (250-300 g at time of
surgery) also surgically prepared with surface cortical electrodes to record brain EEG
activity.
a. Animals are pretreated with PB (0.024 mg/kg, i.m.) to produce 20-40% inhibition in
red blood cell cholinesterase 30 min after administration. Thirty min later the
animals are challenged with 2.0xLD50 GD (56 ug/kg, s.c.), a dose that elicits seizures
in
100% of the animals. One min after GD challenge, the animals receive atropine
sulfate (2.0 mg/kg; i.m.). Beyond these differences in eliciting the seizures, all other
aspects of the testing will be performed in the same manner as the rat model.
*GD-induced seizures in guinea pigs respond to lower doses of anticonvulsant drugs and at longer treatment
delays than similar seizures in rats. The substantially higher cost of guinea pigs precludes them from being
used as the primary animal screening model, but they can confirm and extend positive findings from the rat
studies. Only drugs that produce a potent (low doses required) and/or rapid anticonvulsant response or robust
neuroprotection against the NA-induced brain pathology in the rat GD model will be candidates for testing in
the guinea pig model.
Screening Approach
Step 1
Entry Criteria
1. Previous efficacy studies
2. TD50, MTD, or LD50
3. Purity & Solubility Info
Step 2
Initial EEG screen
Escalating/de-escalating
dosing regimen in OP DFP Model
(4 vehicle + 16 drug animals)
Up to 4 doses = 4 animals per dose
Test drug + Midazolam
Neuroprotection
Arm
Go
Go: If observed to be
additive or synergistic with
Anti-seizure Arm
Step 3/4
Initial histopathology screen
(FJB) in OP DFP Model
Analyze 2 animals per dose
4 brain regions
4 sections per region
NA GD
Model
No Go
midazolam at terminating
seizure / convulsion
Step 3
Confirmation of antiseizure activity
with EEG screening in OP DFP Model
(2 vehicle + 6 drug animals)
Single dose based on Step 2 data
Test drug alone
Step 4/5
Additional histopathological
analyses in OP DFP Model
Analyze 2 more animals per dose
4 additional sections per region
for a total of 8 sections
Go
No Go
Better than Midazolam alone?
No Go
Go
No Further Testing
No Further Testing
NA GD
Model
REV 06/2015
Page 22
The test neurotherapeutic compound may be coded throughout the study, so that experiments are
performed under blind procedures.
A final Study Report (SR), including task background, methodology, assumptions, specific data
collected, analyses conducted, conclusions and recommendations, will be delivered to the
investigator / supplier at the conclusion of the study.
Eligibility Criteria
The CNS program is available to all investigators inside and outside of the CounterACT network
with promising medical countermeasure(s) that would be responsive to CounterACT FOAs. A
minimum requirement for the test neurotherapeutic supplier is to provide documentation regarding
compound toxicity, solubility, purity, and previous in vivo efficacy studies related to this effort.
Supplier must be able to provide sufficient quantity of the compound with purity ≥ 95% by NMR or
HPLC analysis for evaluation in up to 60 animals based on the highest ED50 value of the previous
efficacy studies.
Solubility information would facilitate determination of the best vehicle and route of administration
(IM or IP). Toxicity data, such as the median toxic dose 50 (TD50), maximum tolerated dose
(MTD), or median lethal dose 50 (LD50), and previous efficacy studies would assist in identifying
the range of doses to be considered for evaluation and aid in prioritizing the compounds to be tested.
These information are required before testing of analogs and congeners as well.
For additional information or to enroll in the CNS program, please contact (preferably by email):
Sarah Norring, Ph.D.
Program Specialist, CounterACT Program
NIH/NINDS
Tel: 301.443.8189
[email protected]
REV 06/2015
Page 23
The CounterACT program includes a Preclinical Development Facility. This facility is a resource
for CounterACT investigators that enable them to conduct preclinical studies that would be needed
for drug discovery and development and ultimate FDA approval. If approved by NIH, the studies
are performed at no cost. Although the facility is primarily for CounterACT investigators,
investigators outside the CounterACT network who have a promising medical countermeasure that
would be responsive to one of CounterACT current FOAs, and meet other eligibility criteria outlined
below, may submit to NIH for consideration.
The types of studies available at this facility include:
 Chemistry and Manufacturing Services
 Developing and performing analytical methods to characterize therapeutic agents
 Current GMP (cGMP)-compliant stability studies
 Synthesis, resynthesis, purchase, or acquisition of reagent grade or clinical grade compounds
 Develop cGMP-compliant manufacturing processes and procedures
 Manufacture of pharmaceutical materials in compliance with cGMP regulations in amounts
sufficient for preclinical evaluation
 Formulation and manufacture of drug using cGMP to demonstrate cGMP capability in
support of an IND application
 Formulation appropriate for in vivo studies
Preclinical Safety, Toxicology, and Pharmacodynamics/Pharmacokinetics (PD/PK) Services
 Determination of maximum tolerated dose and no observed effect levels (NOEL)
 Acute and subchronic toxicity; single and repeated dose toxicity studies
 Determination of relevant pharmacokinetic/toxicokinetic parameters
 Bioavailability studies; biotransformation assays conducted in vitro
 Absorption, distribution, metabolism, and excretion studies
 Various toxicity studies (e.g. genotoxicity, carcinogenicity, reproductive, cytotoxicity,
immunotoxicity)
 Behavioral pharmacology
 Cell permeability
Intellectual Property Rights will be consistent with standard NIH guidelines. Applicants are free to
establish a separate Material Tech-Transfer/Lab Service Agreement directly with the CPDF, if
desired.
REV 06/2015
Page 24
Procedures for Submitting Compounds to the CPDF
Goal: Conduct Pharmaceutical studies on selected candidate therapeutics
General Procedure:
1. NIH will accept Product Development Pre-Proposals from the individual CounterACT PIs.
PIs may consult with NIH to determine eligibility and general product development needs.
2. Cover Letter
a. Project Director/Principal Investigator (PD/PI) name
b. Titles of requested research effort and parent CounterACT-funded project
c. Name and Title of the authorized organizational representative (AOR)
d. Phone, email, and address information for both the PD/PI and the institutional official.
e. Names and contact info of key collaborators, partnerships, etc.
The cover letter must be signed by the AOR and PD/PI.
3. The Product Development Pre-Proposal should be 3-5-Pages. If they do not contain the
following sections they will be returned without further review:
a. Introduction – background information on the compound and what type of work you
are requesting, i.e., Track #1 or Track #2 below. Also indicate how these studies
would impact the overall parent project, e.g., will you use these studies to chemically
optimize promising compounds (hits)? Will these studies serve as a go/no go
decision point for the project?
b. Justification describing how your compound meets the eligibility criteria for one of
the two Tracks below, including a brief description of efficacy data and any
preclinical (safety, chemistry) studies that have already been completed.
c. Research Needs summarizing, in general, what preclinical work needs to be done,
e.g. full FDA-enabling safety studies, or pilot PK study to see if it reaches the brain,
or shelf-life study, etc.
4. The NIH will begin accepting Pre-Proposals immediately, commencing July 1, 2007. There
are no receipt deadlines.
5. Pre-proposals will be reviewed by the NIH for the CPDF, within 30 days of receipt.
6. Review criteria include, but not limited to, satisfying the eligibility criteria (efficacy data),
impact on your overall project, programmatic priorities, regulatory input from the FDA,
availability of NIH resources to include funds, etc.
7. If your preproposal is approved, the CPDF, in consultation with you and the NIH, will
prepare a full Test Implementation Plan (TIP) for final review and approval by the NIH
before the studies begin; typically within 90 days of initial approval of your Pre-Proposal.
8. The NIH will make arrangements for accepting the compound to be tested from the source
(PI) and transfer to the CPDF for testing. Note: the compound may be synthesized by the
CPDF under the contract.
REV 06/2015
Page 25
Eligibility Criteria:
Track 1: Definitive Studies
1. These studies should enable submission of an IND. It is strongly recommended that the
FDA be consulted in pre-IND meeting(s) prior to submitting a Pre-Proposal for Track 1
efforts.
2. A lead compound must be identified and efficacy must be demonstrated in at least two
animal species, including one rodent and one non-rodent species (e.g. rabbit, dog or
NHP).
3. Efficacy must be shown against the actual threat agent(s) – not just with a surrogate agent
and in a manner that is consistent with the compound’s ultimate concept of use.
4. No budget limitation.
Track 2: Pilot Studies
1. These limited studies will facilitate characterization and optimization of hits early in the
development process. These studies may serve as a “go”/”no go” decision point for the
project.
2. Efficacy must be demonstrated in at least one animal species.
3. Efficacy may be shown against the actual threat agent OR an acceptable surrogate agent.
4. Must document a medicinal chemistry lead optimization capability if this is the goal of
the preliminary ADME Tox and/or Pharmaceutical studies.
5. Budget is limited to $50K direct costs. A new application will have to be submitted and
approved for continued support beyond the $50 K preliminary work.
Submission Instructions:
Submit Pre-Proposals by email to:
Sarah Norring, Ph.D.
CounterACT Program Specialist, NIH
[email protected]
REV 06/2015
Page 26
ASPR/ BARDA Supported Development of Medical Countermeasures for Chemical
Exposure
The Chemical threat landscape is uniquely large and diverse, and presents several challenges to
effective response. The Department of Homeland Security (DHS) Chemical Terrorism Risk Assessment
lists more than 125 chemicals of concern, including both traditional and emerging chemical weapon
agents as well as many widely available toxic industrial chemicals. DHS has issued a material threat
determination covering nerve agents and cyanide chemical threats. There are also Material Threat
Assessments for several other chemical agents. Development of a robust portfolio of post-exposure
antidotes and non-pharmaceutical interventions for chemical exposure supports the Public Health
Emergency Medical Countermeasures Enterprise (PHECME) and the Biomedical Advanced Research
and Development Authority (BARDA) strategic goals of developing medical countermeasures (MCMs)
against threats identified by the Department of Homeland Security. The advanced development of these
MCMs in order to make them available to protect the American people is the goal of the BARDA Chemical
MCM program.
BARDA provides an integrated, systematic approach supporting development and acquisition of the
necessary drugs and diagnostic tools for chemical emergencies. The BARDA Chemical MCM Program’s
goal is to support development of effective chemical threat countermeasures, including nonpharmaceutical interventions such as decontamination, as well as novel and repurposed therapeutics for
treatment of exposure. Current BARDA Chemical MCM initiatives include the development of new and
repurposed drugs to treat the effects of nerve agents, vesicants, and cyanide: animal models for chemical
exposure; and enhancement of the emergency MCMs forward-deployed in the CHEMPACK program of
the Strategic National Stockpile. A vital goal is to develop MCMs that can be easily used in a mass
casualty situation and that are safe and effective for adults, children, and the elderly.
As we move into the future, BARDA remains focused on the development and regulatory approval of vital
MCMS making them available to protect the civilian exposure from Chemical threats. Through improved
response, improved standards of care, and improved therapeutic interventions we can achieve our
ultimate mission of improving the health outcomes for all victims of chemical exposure.
Judith Wolfe Laney, Ph.D.
Chief, Chemical Medical
Countermeasures
Division of CBRN Countermeasures
HHS/ASPR/BARDA/CBRN
Office: 202-205-8043
[email protected]
Tom C.-C. Hu, Ph.D. MBA
DABMP
Project Officer
HHS/ASPR/BARDA/CBRN
Office: 202-260-2092
[email protected]
Efrain E. Garcia, Ph.D.
Project Officer, Division of CRBN
Countermeasures
HHS/ASPR/BARDA/CBRN
Office: 202- 205-3817
[email protected]
www.medicalcountermeasures.gov
Page 27
POSTER SESSION INFORMATION
POSTER SESSION 1: MONDAY, JUNE 15 (5:00PM – 7:00PM)
Session
Poster No.
1
N.1
Synthesis and storage stability of diisopropylfluorophosphate (DFP)
Bobby N. Brewer, Donald W. Zehnder II, Derik R. Heiss, GE Platoff Jr, DT Yeung
1
N.2
Phorate oxon: Acute oral toxicity in the Sprague-Dawley rat and acetylcholinesterase
reactivation kinetics
TH Snider, RA Moyer, CM Wilhelm, MC Babin, GE Platoff Jr, DT Yeung
1
N.3
Towards design of accelerated OP-hAChE reactivators by analysis of conformational changes
in hAChE upon reversible and covalent ligand binding in solution and in crystal
Donald. K. Blumenthal, Andrey Kovalevsky, Xiaolin Cheng, Palmer Taylor and Zoran Radic
1
N.4
Improved standard of care reactivators and facilitative transport into the
central nervous system
Bryan J. McCranor, Jayendra Bhonsle, John T. Koh, Raghupathi Neelarapu, Wei Bao,
Yuchen Zhang, and Gregory Garcia
1
N.5
Novel brain-penetrating oxime reactivators increase survival of rats to surrogates of sarin and
VX and paraoxon
Janice Chambers, Edward Meek and Howard Chambers
1
N.6
Reactivation of aged acetylcholinesterase: Design and development of novel therapeutics
against exposure to organophosphorus chemical nerve agents
Q Zhuang, A Awad, R McKenney, T Blanton, R Dicken, A Franjesevic, C Callam, C McElroy,
O Dogan-Ekici, R Yoder, CM Hadad
1
N.7
Oxime therapy doses that provide 50% survival against subcutaneous and topical
organophosphate challenges at 2xLD50
CM Wilhelm, TH Snider, MC Babin, GE Platoff Jr, DT Yeung
1
N.8
Refinement and pharmacokinetic studies of BChE and AChE reactivators for nerve agent and
pesticide OP detoxification in human tissue
Palmer Taylor, Zrinka Kovarik, Rakesh K. Sit, Jeremiah Momper, Yvonne Rosenberg, Valery
V. Fokin and Zoran Radic
1
N.9
Induced therapeutic overexpression of acetylcholinesterase in vivo
Susana G. Rossi and Richard L. Rotundo
1
N.10
Pharmacotherapy to counterACT parathion-induced NMJ dysfunction
Naofumi Bunya, Hanif Benoit, Romolo Gaspari, Teji Khurana, Emanuelle Loro, Steve Bird
N.11
Efficacy and safety of an aerosolized recombinant butyrylcholinesterase pretreatment against
inhaled OP toxicity
Yvonne Rosenberg, S. Moises Hernandez, Xiaoming Jiang, Lingjun Mao, Sami Cardak,
Beth Laube, Robert Adams
1
N.12
Redox cycling by vitamin K3 (menadione) inhibits parathion metabolism and protects against
parathion intoxication in rats
Yi-Hua Jan, Jason R Richardson, Angela B Baker, Vladimir Mishin, Diane E Heck, Debra L
Laskin, Jeffrey D. Laskin
1
N.13
Structural screening in zebrafish cytochrome P450s
Jared Goldstone, Joanna Wilson, Philippe Urban, John Stegeman
1
N.14
A novel in vitro model for studying tetramethylenedisulfotetramine-induced neurotoxicity
Linnea R. Vose, Marcela Laukova, Jana Veliskova, Libor Velisek, Patric K. Stanton, Michael
P. Shakarjian
Page 28
1
Neurological Agents
N.15
Diazepam and midazolam effectively terminate tetramethylenedisulfotetramine-induced status
epilepticus and enhance survival in mice.
Dorota Zolkowska, Donald A. Bruun, Casey A. Boosalis, Bruce D. Hammock, Pamela J. Lein and
Michael A. Rogawski
1
N.16
Comparative efficacy of diazepam versus midazolam in mitigating persistent neuropathology in a
rat model of acute OP intoxication
Brad Hobson, Douglas Rowland, Kiran Dhakal, Abdul Wahab, Donald Bruun, Jill Silverman,
Michael Rogawski, Daniel Tancredi, Simon Cherry, Joel Garbow and Pamela Lein
1
N.17
Rapid analyses of TETS and DFP neurotoxicity: Achieving predictive screens for novel
antiseizure and neuroprotective interventions
Atefeh Mousavi Nik, George Kenneth Todd, Susan Hulsizer, and Isaac N. Pessah
1
N.18
Potent inhibitor of the soluble epoxide hydrolase synergizes the efficacy of diazepam while
reducing its adverse effects through independent mechanisms
Bora Inceoglu, Sung Hee Hwang, Kin Sing Stephen Lee, Jun Yang, Bogdan Barnych, Natalia
Vasylieva, Sean Kodani, Vikrant Singh, Stephen Vito, Donald Bruun, Susan Hulsizer, Isaac
Pessah, Pamela Lein, Heike Wulff and Bruce Hammock
1
N.19
Modulation of synaptic and extrasynaptic GABAA receptors by diazepam and allopregnanolone
Hai M. Nguyen, Brandon M. Brown, Brandon Pressly, Heike Wulff
1
N.20
Targeted statistical support for UC Davis CounterACT Research
Yingjia Chen, Danielle Harvey, Danh Nguyen, Susan Hulsizer, Isaac Pessah and Daniel
Tancredi
1
N.21
The development of a neuroprotective treatment for nerve agent poisoning using central A1
adenosine receptor agonists
Thaddeus Thomas and Tsung-Ming Shih
1
N.22
Zebrafish: An in vivo high throughput model for evaluating the efficacy of oximes to reactivate
organophosphate-inhibited acetylcholinesterase
TM Shih, T Dao, J Koenig, RK Kim, and RK Kan
1
N.23
Evaluation of anticonvulsants to treat nerve agent- and pesticide-induced seizures and prevent
brain damage in pediatric rats
Stephanie M Miller-Smith, Erika A Scholl, Sergiu Costinas, Emylee McFarland, Wafae Driwech,
Emily Dunn, Ashley Hubbard, Cecelia Jackson, John H. McDonough, F. Edward Dudek
1
N.24
The efficacy of medical countermeasures to attenuate the neuropathological
and behavioral consequences of soman exposure in the aging rat model
MC Moffett, TM Turner, MF Stone, LA Lumley
1
N.25
Evaluation of cannabinoids as adjunct to standard therapy for soman-induced toxicity in rats
F Rossetti, L Wright, S Sanjakdar, C Jennings, M Stone, C Schultz, M Pham, M Moffett, M
Schultz, L Lumley
1
N.26
Percutaneous VX in rats: efficacy of medical countermeasures and decontamination at onset of
toxic signs
L Lumley, L Wright, F Rossetti, C Schultz, M Schultz, M Stone, E Clarkson
1
N.27
Evaluation of hippocampal circuit function and synapse strengths following
soman-induced seizures in acute slices”
Katie Hoffman, Phil Beske, Katelynn Schulz, Jim Apland and Patrick McNutt
1
Page 29
1
N.28
The efficacy of LY293558, a GluR5 Kainate receptor antagonist, against soman-induced seizures
and neuropathology in female rats
Taiza H. Figueiredo, James P. Apland, Vassiliki Aroniadou-Anderjaska, Volodymyr I. Pidoplichko,
and Maria F.M. Braga
1
N.29
Efficacy of neurosteroid therapy against soman-induced seizures and brain injury
DS Reddy, R Kuruba, X Wu
1
N.30
A new delayed-treatment rodent organophosphate-exposure model to identify novel
neurotherapeutic adjuncts
F. Edward Dudek, Steven Bealer, Bonnie Roach and Wendy Pouliot
1
N.31
Rat and guinea pig models of nerve agent intoxication to evaluate delayed treatment with novel
anticonvulsants
Hilary S. McCarren, Sergiu Costinas, Emily Dunn, Wafae Driwech, Ashley Hubbard, Cecelia
Jackson, Ryan Krempel, Emylee McFarland, Craig Oppel, John H. McDonough
1
N.32
Parathion exposure: Mechanisms of toxicity and treatment- neuroprotection
R. J. DeLorenzo, L. Deshpande, R. Blair, L. Phillips and B. Huang
1
N.33
Circulating Ccr2+ monocytes display delayed brain infiltration after status epilepticus and
contribute to the innate neuroimmune response
Nicholas H. Varvel, Jonas J. Neher, Richard J. Miller, Richard M. Ransohoff, Mathias Jucker and
Raymond Dingledine
1
N.34
Evaluation of oxidative stress and therapeutic window of AEOL10150 in the rat organophosphate
models
Li-Ping Liang, Pallavi Bhuyan, Jie Huang, Brian J. Day, and Manisha Patel
1
N.35
Definitive studies for use of galantamine as a pre-treatment countermeasure against nerve agent
poisoning.
EX Albuquerque, EFR Pereira, Y Aracava, JD Pescrille, DA Carter, GW Basinger
1
N.36
Rational therapy in the treatment of cholinergic seizures
C Wasterlain, R Baldwin, K Norman, J Niquet, L Suchomelova, F Rossetti, L Lumley
Session
Poster No.
1
P.1
Multifunctional therapeutics for treatment of acute chlorine inhalation injury
Garry Southan, Andrew Salzman, Perenlei Enkhbaater
1
P.2
In vivo and in vitro correlation of targeted Hsp70 activity for pulmonary cytoprotection
Missag H. Parseghian, Stephen T. Hobson, Claire Croutch, Rick Tuttle, Richard Richieri,
Thomas R. Carpenter, Glenn T. Reynolds, Richard H. Weisbart, Robert Nishimura
1
P.3
VE-PTP inhibition for the prevention of phosgene-induced acute lung injury
TJ McCord, M Padgett, JL Reinardy, J Janusz, WM Foster, KG Peters, CD Kontos
1
P.4
Extracellular RNA in 2-chloroethyl ethyl sulfide (CEES)-induced lung injury
Maroof Husain, Iram Zafar, Sarah C. Christiaans, Jean-Francois Pittet, Shama Ahmad and Aftab
Ahmad
1
P.5
Heme attenuation ameliorates irritant gas inhalation induced acute lung injury
Sadis Matalon
1
P.6
A small molecule NOS2 inhibitor prevents acute lung injury after chlorine exposure
Timothy McCord, Michael Gentile, Michael Foster, Michael Dee Gunn
Pulmonary Agents
Page 30
POSTER SESSION 2: TUESDAY, JUNE 16 (12:00 PM – 1:30 PM)
2
P.7
Nitrite dependent protection against Cl2 gas toxicity: Role for chlorinated lipids
Jaideep Honavar, Joo-Yeun Oh, David Ford, Sadis Matalon, Rakesh P Patel
2
P.8
Functional genomics of chemical-induced acute lung injury
GD Leikauf, K Bein, RL Birru, BB Chen, TM Martin, JP Fabisiak
2
P.9
Novel therapies for chlorine-induced lung injury
Gary W. Hoyle, Sadiatu Musah, Connie F. Schlueter, David M. Humphrey, Jr., Gregory Rawson,
Joe A. Nino, Kenneth H. Carson, and Andrew M. Roberts
2
P.10
Countermeasures for chlorine-induced airway fibrosis
Gary W. Hoyle, Sadiatu Musah, David M. Humphrey, Jr., Connie F. Schlueter, and Andrew M.
Roberts
2
P.11
Accelerating inflammation resolution to counteract chemical injury
S. Achanta, S. Balakrishna, N.R. Chintagari, A. I. Caceres, Z. Yu, S. Doran, S. Matalon and S. E.
Jordt
2
P.12
Pharmacokinetics and efficacy of a TRPV4 inhibitor in a porcine model of chlorine-induced
pulmonary injury
S. Achanta, M. Gentile, A. I. Caceres, M. M. Kaelberer, D. J. Behm, T. Roethke, I. Cheifetz, M. D.
Gunn and S. E. Jordt
2
P.13
Thioredoxin mimicry: novel treatment of toxicant-mediated inhalational lung injury
Garry Southan, Andrew Salzman, Waylon Weber and Jake McDonald
2
P.14
Upregulation of autophagy decreases chlorine gas induced mitochondrial injury and lung
inflammation
Sadis Matalon
2
P.15
Halogen inhalation-induced myocardial depression and failure
Shama Ahmad and Sadis Matalon
2
P.16
Assessment of treatment strategies following inhalational ammonia exposure in male rats
Michael W. Perkins, Benjamin Wong, Ashley Rodriguez, Justin Tressler, Reese Baker, Jennifer
Devorak, and Alfred M. Sciuto
2
P.17
Genomic assessment of phosgene-induced lung injury and evaluation of potential therapeutics
Wesley W. Holmes, Danielle C. Paradiso, Cristin C. Rothwell, Heidi M. Hoard-Fruchey, Alfred M.
Sciuto, Dana R. Anderson
2
P.18
Acute physiological, biochemical, and genomic responses in rats exposed to the toxic gas
phosphine
H. Hoard-Fruchey, J. Tressler, J. Simons, C. Rothwell, M. Martens, B. Wong, J. Andres, R.
Deckert, C. Hofmann, T. Hamilton, J. Devorak, A. Rodriguez, T. Gutierrez, M. Wegner, and A.
Sciuto
2
P.19
Novel treatments of acrolein-induced cardiotoxicity
Daniel J. Conklin
Session
Poster No.
2
V.1
Vesicant Agents
Activation of the epidermal growth factor receptor (EGFR) by nitrogen mustard and potential
therapies to attenuate corneal injury.
AS DeSantis, A Miller, RA Hahn, P Zhou, N Heindel, YC Chang, DR Gerecke, KK Svoboda and
MK Gordon
Page 31
2
V.2
Alterations in expression of connexins in hairless mouse skin following exposure to nitrogen
mustard YC Chang, HY Chang, RA Hahn, EE Lee, RP Casillas, JD Laskin, PJ Sinko, DE Heck,
MK Gordon and DR Gerecke
2
V.3
Regulation of macrophage activity by histone deacetylases during nitrogen mustard-induced lung
injury A Venosa, J Gow, I Berman, R Malaviya, A Gow, JD Laskin and DL Laskin
2
V.4
Attenuation of nitrogen mustard-induced skin inflammation with 25-hydroxyvitamin-D3
Lopa Das, Rebecca Boxer, and Kurt Lu
2
V.5
Reversal of nitrogen mustard-induced corneal injury by dexamethasone or doxycycline treatment
Dinesh G Goswami, Neera Tewari-Singh, Rama Kant, Dileep Kumar, Chapla Agarwal, David A
Ammar, J Mark Petrash, Rajesh Agarwal
2
V.6
Comparative effects of silibinin and AEOL 10150 in reversing skin toxicity from topical nitrogen
mustard exposure
Anil K. Jain, Dileep Kumar, Neera Tewari-Singh, Rama Kant, Dinesh G. Goswami, Chapla
Agarwal, David J Orlicky, Carl W. White, Brian J Day, and Rajesh Agarwal
2
V.7
Pulmonary vascular thrombosis in rats exposed to high dose sulfur mustard
C. Osborne, L.A. Veress, N Serkova, P. Houin, T. Hendry-Hofer, J. Rioux, R. Garlick, J.E.
Loader, R. Smith, W. Holmes, D. Paradiso, D. Anderson, and C.W. White
2
V.8
AEOL 10150 improves morbidity and mortality after sulfur mustard inhalation
C.S. McElroy, E. Min; J. Huang, J.E. Loader, T.B. Hendry-Hofer, R.B. Garlick, J.S. Rioux, L.A.
Veress, R. Smith, C. Osborne, D.R. Anderson, W.W. Holmes, D. Paradiso, C.W. White, B.J. Day
2
V.9
Changes in the expression of Urokinase (uPA) and its receptor (uPAR) on airway monocytes in
response to CEES inhalation
Raymond C. Rancourt, Livia A. Veress, Russell W. Smith, and Carl W. White
2
V.10
tPA decreases long term mortality in rats with bronchiolitis obliterans (BO) and pulmonary fibrosis
(PF) during chronic recovery from sulfur mustard vapor inhalation
Livia A. Veress, Rhonda Garlick, Jacqueline Rioux, Christopher Osborne, Russell Smith, Joan
Loader, Carol Burns, and Carl W. White
2
V.11
Vesicant and toxic industrial chemical ocular injury: High-throughput screening approaches to
identify therapeutic targets and understand mechanisms of injury
John G. Lehman, Robert D. Causey, Cristina V. Lagrasta, and Albert L. Ruff
2
V.12
Evaluation of endotheliotrophic modulators to mitigate acute and persistent corneal symptoms
resulting from ocular exposure to sulfur mustard vapor
Patrick McNutt, Kaylie Tuznik, Timm Varney, Marian Nelson, Elliot Glotfelty, Angela Adkins,
Megan Lyman, Justin Grynovicki and Tracey Hamilton
Session
Poster No.
2
2
2
Cellular Agents
C.1
Brodifacoum poisoning: development of adult and in utero rat models, and lipid intervention
regimens
Douglas Feinstein, Israel Rubinstein, Richard van Breeman, Belinda Akpa, Sergey Brodsky,
Guy Weinberg
C.2
A Discovery and development pipeline for cyanide countermeasures: Project 1 - High throughput
in vivo discovery of cyanide antidotes
Patrick Sips, Anjali K. Nath, You Wang, Yan Liu, Amy Kelly, Brittney Mikell, Matthew Brenner,
Sari Mahon, Gerry R. Boss, Robert E. Gerszten, Randall T. Peterson, Calum A. MacRae
C.3
A Discovery and development pipeline for cyanide countermeasures: Project 2 - Optimization of
novel cyanide countermeasures.
Anjali K. Nath, You Wang, Yan Liu, Patrick Sips, Matthew Brenner, Sari Mahon, Gerry R. Boss,
Robert E. Gerszten, Calum A. MacRae, Randall T. Peterson
Page 32
2
C.4
A Discovery and development pipeline for cyanide countermeasures: Project 3 – Validating
promising drug candidates in mammalian models of cyanide poisoning
Matthew Brenner, Tanya Burney, Jangwoen Lee, Sari Mahon, David Mukai, Adriano Chan,
Gerry R. Boss
2
C.5
Development of a field-deployable device to rapidly measure blood cyanide levels
Winnie Tong, Roy Chung, Keith Kopitzke, Brendan O’Farrell, and Hans Boehringer
2
C.6
Cobalt Schiff-base macrocycles as antidotes to acute cyanide poisoning
Andrea A. Cronican, Elisenda Lopez Manzano, Kristin L. Frawley, Jim Peterson and Linda L.
Pearce
2
C.7
Pre-clinical and clinical studies of cobinamide, a new cyanide detoxifying agent
Adriano Chan, Jingjing Jiang, Matthew Brenner, Tanya Burney, Jangwoen Lee, Sari Mahon,
David Mukai, Carol Green, Mingtao Liu, Helen Parish, Jennie Wang, Vikhyat Bebarta, Susan
Boudreau, Patricia Dixon, Matthew Brittain, Michael Babin, and Gerry R. Boss
2
C.8
Preclinical development of the cyanide antidote Sulfanegen
Bryant Moeller, Avian Chang Alexandre Monteil, Simranjit Sra, Harpreet Singh, David Beebe,
Kristal Jackson, Herbert Nagasawa, Kumar Belani and Steven Patterson
2
C.9
Antagonism of acute sulfide poisoning by nitrite anion
Kristin L Frawley, Andrea A. Cronican, Humza Ahmed, Linda L Pearce, Jim Peterson
2
C.10
Qualifying a mouse model of hydrogen-sulfide induced neurotoxicity
Poojya Anantharam, Elizabeth Whitley, Paula Imerman, Arthi Kanthasamy, Gerry Boss, and
Wilson Rumbeiha
2
C.11
H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinum chromophores
Takashi Sonobe, Annick Haouzi, Matthew Rannals, Timothy K. Cooper and Philippe Haouzi
2
C.12
Establishing a realistic model of ingested chemical agents in rats
Nathaniel C. Rice, Jeffrey L. Langston, Todd M. Myer
2
C.13
Preclinical development of novel cyanide medical countermeasures
JD Downey, DM Hildenberger, MO Rhoomes, AR Allen, I Petrikovics,
BA Logue, M Brenner, SB Mahon, GR Boss, and GA Rockwood
2
C.14
Comprehensive gene expression profile analysis in mouse tissues after
cyanide exposure
AR Allen, JD Downey, MO Rhoomes, DM Hildenberger, HM Hoard-Fruchey, and GA Rockwood
Session
Poster No.
Others
2
O.1
CounterACT Preclinical Development Facility
CE Green and HJ Parish
2
O.2
ASPR/BARDA-supported development of medical countermeasures for chemical exposure
Tom Hu, Efrain Garcia and Judith Laney
2
O.3
Multidisciplinary approaches developed in Italy to stimulate wound healing; advances in stem cell
technology
R Businaro, M Corsi, T Di Raimo, S Marasco, B Salvati and R Capoano
Page 33
ADDITIONAL INFORMATION
Interested in Submitting a Conference Proposal?
The Academy invites conference proposals in a variety of fields: biomedical sciences,
chemistry, physical sciences, engineering, technology, and others. The Academy will
give priority to conferences in cutting-edge, problem-oriented, multidisciplinary
subject areas, as well as on issues faced by the public and private sectors at the
interface of science, technology, and society. Proposals are accepted throughout the
year; there is no specific deadline. To submit a conference proposal or for more
information on organizing a conference with the Academy, please contact Dr. Brooke
Grindlinger at [email protected].
Special Needs
The New York Academy of Sciences complies with the public accommodation
requirements of the Americans with Disabilities Act and the rules and regulations
thereof. Please let us know if you require any assistance during the meeting,
including child/family care resources available to conference attendees.
Recording
The New York Academy of Sciences requests that you do not take photographs or
make audio or video recordings of the conference presentations, or present
unpublished data on any open-access websites, unless specific permission is
obtained from the speaker.
Page 34
NOTES
Page 35
NOTES
Page 36
NOTES
Page 37
DEPOSIT YOUR
POSTERS
A N D S L I D E P R E S E N TAT I O N S
...to broadcast to a
wider audience
The New York Academy of Sciences is
an F1000 Posters partner. See the latest
presentations from recent Academy
symposia at http://f1000.com/posters/nyas,
and deposit your own posters/slides at
http://f1000.com/posters/depositor
The open repository for posters/slides in
Biology & Medicine from
Page 38
Inspiring Centuries of
Scientific Progress
The Academy fosters vital communities and spurs scientific advances by working with
investigators, researchers, policymakers, industry leaders and funders to exchange ideas
and forge partnerships across a wide range of scientific disciplines.
The Academy hosts more than 100+ conferences, symposia
and discussion groups annually.
JUN
4
2015
JUN 8
TO
AUG 10
2015
JUN
8
2015
HIV 2015: Using Phylogenetics to
Enhance the HIV Response
www.nyas.org/HIV2015
Scientists Teaching Science
(Online Summer Course)
www.nyas.org/
ScientistsTeaching2015
2015 Ross Prize in Molecular
Medicine: Harnessing Cell
Signaling Pathways to Treat
Cancer
www.nyas.org/RossPrize2015
JUN
11
2015
JUN
19
2015
Learning from Cancer to Advance
Neurodegeneration Drug
Discovery and Development
www.nyas.org/NDDiseaseCancer
Microbes in the City:
Mapping the Urban Genome
www.nyas.org/UrbanGenome2015
For a full list of Academy
programing, visit us at
www.nyas.org
STAY CONNECTED WITH THE ACADEMY
Become a part of our social networking communities to receive relevant new information
and connect with others in your ﬁeld.
facebook.com/NewYorkAcademyofSciences
@NYASEvents
The New York Academy of Sciences

Full Program Book - The New York Academy of Sciences

Transcription

Similar documents

Distortion Social

You Can Help - Goombay Bash

international conference places on the edge creating a sense of

Interconnected World

The International PhD program in Biomedicine and

NZASI Newsletter JULY 2016 - Australasian Society for Immunology

Consulting with television writers to encourage cancer and