MSTP Post Fall 2013 - University of Wisconsin School of Medicine
Transcription
MSTP Post Fall 2013 - University of Wisconsin School of Medicine
Fall 2013 THE MSTP POST THE MSTP POST MSTP Symposium 2014: The Who What When and Where Details You’ve Been Waiting For The annual MSTP symposium has been scheduled for Thursday, April 24th, 2014 and will be held in the Wisconsin Institutes for Discovery Town Center and H.F. DeLuca Forum. Our keynote speaker this year will be Dr. Mike Yaffe (pictured to the left). Dr. Yaffe will be visiting from Massachusetts Institute of Technology, where he currently serves as the David H. Koch Professor of Biology and Biological Engineering. He is also affiliated with the Beth Israel Deaconess Medical Center of Harvard Medical School where he practices as an attending surgeon and has helped to found multiple pharmaceutical companies. Dr. Yaffe recieved his MD-PhD training at Case Western Reserve University. His lab currently investigates signaling pathways that control cell cycle progression and DNA damage responses in cancer and cancer therapy as well as the cross-talk between inflammation, cytokine signaling, and cancer. In addition to Dr. Yaffe’s address, the event will also showcase research from current MSTP students in the form of posters and talks throughout the day. For all those current MSTP students with awesome research to share, there will be a call for student presenters in Spring of 2014. In the past, other disinguished guests in attendence at MSTP Symposium have included UW MSTP alumni, physician scientists currently affiliated with UW-Madison, and former UW MSTP director Deane Mosher. So mark your calendars because you won’t want to miss it! University of Wisconsin - Madison In This Issue A look at the M1 class and our new program directors Page 2; Page 4 Scientific Review: Spotlight on Jeff Jensen Page 3 New MSTP Publications Pages 5-7 Scenes from the MSTP Retreat 2013 Page 8 Cook’s Corner: Food Edition Page 9 A Day in the Life: Spotlight on Laura Felley Page 10 On Wisconsin! 1 Fall 2013 THE MSTP POST Wow, those are some really really ridiculously good looking people! A quick look at our 2013 M1 MSTP class. From left to right: Richard Merkhofer Jack Hunt Erin DeCloux Mazdak Bradberry Yang Hu Amelia Haj Peter Carlson Jorge Rodriguez-Gil Nick Vogt Laura Swanson Check out Page 4 for some quick facts about our new administrators and our M1 class! We didn’t just gain a new M1 class this fall, we also welcomed two new associate directors to the program. Here’s a quick look at these new members of the UW MSTP community. Caitlin Pepperell MD Scott Reeder MD, PhD Caitlin Pepperell recieved her MD from Queen’s University in Kingston, ON. She then continued her medical training with an internal medicine residency and fellowship in infectious Scott Reeder recieved his MD-PhD from Johns Hopkins University in Baltimore, MD and continued his training with a radiology residency and fellowship in abdominal and cardiovascu- disease at the University of Toronto and an additional fellowship in infectious disease at Stanford University. Dr. Pepperell’s research focuses on bacterial pathogenesis with an emphasis on granulomatous diseases, human-pathogen interactions, and the ecology and evolution of human pathogens. lar imaging at Stanford University. In addition to acting as an MSTP associate director, he now serves as the UW Chief of MRI and the Director of the UW Liver Imaging Research Program. Dr. Reeder’s current research focuses on the development of new MRI methods and contrast agents for quantitative measures used to assess healthy and diseased livers. Fun fact: Both of our new MSTP associate directors come to us from Canada, eh? University of Wisconsin - Madison 2 THE MSTP POST Fall 2013 Scientific Review: Jeff Jensen’s recent publication “MAP3K8 kinase regu- lates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages” by Laura Felley Multiple myeloma has been a thorn in the side of oncologists for decades. The production of neoplastic plasma cells essentially chokes the bone marrow, preventing the formation of normal blood cells and causing anemia. Overproduction of light chains by the malignant cells can damage the kidneys, resulting in renal failure. Patients may complain of chronic bone pain, due to lesions and fractures precipitated by overactive osteoclasts stimulated tumor cell RANKL expression. However, the truly disheartening feature of this disease is the lack of good treatment options: while many oncologists use combinations of chemotherapy, radiotherapy, and immunomodulators, the disease remains incurable. Average survival for an untreated patient is three to four years. Aggressive, intensive therapy only boosts the mean survival time to five to seven years. With this bleak prognosis in mind, Jeff’s goal is to identify new targets for therapy by studying the immunologic milieu associated with the cancer. Jensen’s lab noticed a strange feature of the macrophages associated with myeloma tumors. Typically, a macrophage is thought of as either M1 or M2. A macrophage with an “M1” profile represents what we classically think of as a macrophage: these cells are very anti-microbial, readily engulfing pathogens or infected cells. M1 macrophages have a high IL-12 to IL-10 secretion ratio, which is typically regarded as inflammatory. An “M2” macrophage is referred to as “alternatively activated”, and can be viewed as the anti-inflammatory counterpart to the M1 cell. M2 macrophages are involved in healing and inflammation resolution, and secrete comparably high levels of IL-10. Tumor associated macrophages are gen- University of Wisconsin - Madison erally thought of as having an M2 profile. Jensen’s lab previously showed that macrophages located in myeloma tumors acquire an inflammatory phenotype, and transcribe genes associated with an M1 profile. However, the lab has also found that these myeloma macrophages/monocytes are not limited to M1-associated genes, and freely transcribe genes associated with an M2 profile. This led the group to hypothesize that myeloma promotes “significant plasticity” in terms of inflammatory profile. But how might this plasticity be achieved? A potential mechanism was identified in MAP3K8. The beautifully named mitogenactivated protein kinase kinase kinase 8 appears to have a key role in regulating the innate immune response, as well as growth signals capable of activating ERK. (ERK, which stands for “extracellular-signal-related kinase”, is a component of an extensive signaling pathway involved in mitosis and meiosis). Jensen and his lab hypothesized that MAP3K8 regulates macrophagemyeloma tumor cell interactions within the e bone marrow; and it is through these intertions that macrophages achieve their promyeloma inflammatory phenotype. To test this hypothesis, bone marrow aspirates were collected from patients with multiple myeloma. Macrophages were isolated and lysed. An antibody against phosphorylated (and thus activated) MAP3K8 was added to the lysates. Of all samples collected, MAP3K8 was universally phosphorylated, regardless of disease stage or treatment received. Furthermore, phosphorylated ERK was seen in myeloma patient smaples, but not in control samples—this finding reflects the fact that MAP3K8-dependent ERK activity promotes the synthesis of pro-myeloma inflammatory mediators. Likewise, ADAM17, a protease needed to cleave and process Continued on Page 4 3 Fall 2013 THE MSTP POST The MSTP Post polled the incoming M1 class and the MSTP Administrators with random questions. Here ‘s what we learned*. More M1’s prefer cake to pie. (The great cake-pie divide was split evenly among our administrators.) Unnecessary Pie Chart About M1 Pie Preferences Prefer Pie Prefer Cake The M1 class is rather well-travelled! Total Countries Visited This is not the appropriate way to graph the worldliness of our M1 class 20 15 10 5 0 0 2 4 6 8 10 M1 Responder The high school versions of our administrators were more mathematically inclined than the high school versions of our M1s. Why is this format even an option? 0.8 0.6 0.4 0.2 0 Admininstrators M1s Proportion reporting a better score on SAT math than SAT verbal One administrator reports their age as 100! *Facts and figures based on responses from 9 M1’s and 4 MSTP Administrators University of Wisconsin - Madison Continued from Page 3 the pro-inflammatory TNFα, is a known target of ERK. As one might expect, analysis of the lysates revealed constitutive ADAM-17 phosphroylation at a site regulated by MAP3K8 signaling. Interestingly, MAP3K8 activation seems to be very important to multiple myeloma; expression levels of activated MAP3K8 are much higher as compared to other tumor cells. To investigate whether MAP3K8 is capable of transmitting inflammatory signals in myeloma cells themselves, the lab used a line of human myeloma tumors. It is known that myeloma cells respond to the inflammatory TNFα signal by activating ERK, but the lab found that this effect could be reduced by the addition of a MAP3K8 inhibitor. Inhibiting MAP3K8 also reduces phosphorylation of another kinase (MEK kinase); this reduction in kinase activation is associated with a deficit in growth. Reasoning that MAP3K8 appears to be tightly linked to myeloma growth, myeloma cells were imaged for MAP3K8 activation as well as cell cycle markers. Cells that contained activated MAP3K8 tended to show ploidy (an increased number of chromosome sets). Interestingly, MAP3K8 was not only necessary for expansion—it also appeared to be critical for survival. Myeloma cells showed higher levels of apoptosis when blocked with a MAP3K8 inhibitor, even when incubated with supportive cellular stroma. It is clear that MAP3K8 appears essential to multiple myeloma cells in numerous contexts. --Its expression in tumor-associated macrophages promotes an inflammatory environment and growth signals that are beneficial to myeloma survival, while its expression in the cancerous cells promotes proliferation and survival. MAP3K8 thus appears to be a fantastic therapeutic target. Amazingly, loss of MAP3K8 is compatible with normal blood cell growth and development, so a treatment that inhibited the kinase would likely be welltolerated. Jeff’s lab is currently testing its therapeutic potential in mouse models of myeloma, with promising responses. Go Jeff, and great paper! 4 Fall 2013 THE MSTP POST New Pubs! Wow, the UW MSTP certainly seems to have had a prolific year. Here are all the publications our students have contributed to since the last newsletter, including those from our class of 2013 grads. Good job, everyone! Jabe Best: Markandeya YS, Feng L, Best JM, Lea ML, Buss CR, Kamp TJ, Balijepalli RC. Loss of Caveolin-3 Results in Qt(C) Prolongation and Causes Delayed Cardiac Repolarization in a CardiacSpecific Conditional CAV-3 Knockout Mouse Model. Biophysical Journal. 2013 Jan 29;104(2):209A-209A Boczek NJ, Best JM, Tester DJ, Giudicessi JR, Middha S, Evans JM, Kamp TJ, Ackerman MJ. Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome. Circ Cardiovasc Genet. 2013 Jun;6(3):279-89. PMID: 23677916 Patrick Brown: Brown PT, Handorf AM, Jeon WB, Li WJ. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration. Curr Pharm Des. 2013 Feb 11;19(19):3429-45. PMID: 23432679 Eric Bultman: Brodsky EK, Bultman EM, Johnson KM, Horng DE, Schelman WR, Block WF, Reeder SB. High-spatial and hightemporal resolution dynamic contrastenhanced perfusion imaging of the liver r with time-resolved three-dimensiona l radial MRI. Magn Reson Med. 2013 Ma r 20. [Epub ahead of print] PMID : 235198 Tim Chang: Chang TS, Lemanske Jr RF, Guilbert TW, Gern JE, Coen MH, Evans MD, Gangnon RE, Page CD, Jackson DJ. Evaluation of the modified asthma predictive index in high risk preschool children. Journal of Allergy and Clinical Immunology: In Practice. 2013 Mar; 1(2):152-156. Peter Chen: Colson BA, Patel JR, Chen PP, Bekyarova T, Abdalla MI, Tong CW, Fitzsimons DP, Irving TC, Moss RL. Myosin binding protein-C phosphorylation is the principal mediator of protein kinase A effects on thick filament structure in myocardium. J Mol Cell Cardiol. 2012 Nov;53(5):609-16. PMID: 22850286 Jason Chiang: Chiang J, Hynes K, Brace CL. Flowdependent vascular heat transfer during microwave thermal ablation. Conf Proc IEEE Eng Med Biol Soc. 012;2012:5582-5. PMID: 2336719 Chiang J, Hynes KA, Bedoya M, Brace CL. A dual-slot microwave antenna for more spherical ablation zones: ex vivo and in vivo validation. Radiology. 2013 Aug;268(2):382-9. PMID:23579048 Chiang J, Wang P, Brace CL. Computational modelling of microwave tumour ablations. Int J Hyperthermia. 2013 Jun;29(4):308-17. PMID: 23738698 Omar Demerdash: Zhu X, Ericksen SS, Demerdash ON, Mitchell JC. Data driven models for protein interaction and design. Proteins. 2013 Aug 28. [Epub ahead of print] PMID: 24038640. Mike Devinney: Devinney MJ, Huxtable AG, Nichols NL, Mitchell GS. Hypoxia-induced phrenic long-term facilitation: emergent properties. Ann N Y Acad Sci. 2013 Apr;1279(1):143-53. PMID: 23531012 Mike Devinney & Daryl Fields: Devinney MJ, Fields DP and Mitchell GS. Spinal PKC-θ activity is required for phrenic long-term facilitation after acute intermittent hypoxia. Faseb Journal. 2013 Apr;27. John Floberg: Struck AF, Hall LT, Kusmirek JE, Gallagher CL, Floberg JM, Jaskowiak CJ, Perlman SB. (18)F-DOPA PET with and without MRI fusion, a receiver operator characteristics comparison. Am J Nucl Med Mol Imaging. 2012 Oct 30;2(4):47582. PMID: 23145363 Floberg JM, Struck AF, Peters BK, Jaskowiak CJ, Perlman SB, Hall LT. Impact of expectation-maximization reconstruction iterations on the diagnosis of temporal lobe epilepsy with PET. Am J Nucl Med Mol Imaging. 2012;2(3):335-43. Floberg JM, Holden JE. Nonlinear spatio-temporal filtering of dynamic PET data using a four-dimensional Gaussian filter and expectationmaximization deconvolution. Phys Med Biol. 2013 Feb 21;58(4):1151-68. PMID: 2337069 Brendan Floyd: Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ. Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation. J Biol Chem. 2013 Sep 6;288(36):26209-19. PMID: 23864654 University of Wisconsin - Madison Travelle Franklin-Ford: Franklin-Ford T, Shah N, Leiferman E, Chamberlain CS, Raval A, Vanderby R, Murphy WL. Tracking injectable microspheres in dynamic tissues with encapsulated superparamagnetic iron oxide nanoparticles. Macromol Biosci. 2012 Dec;12(12):1615-21. PMID: 23124987 Keith Hanson: Zhan L, Hanson KA, Kim SH, Tare A, Tibbetts RS. Identification of Genetic Modifiers of TDP-43 Neurotoxicity in Drosophila. PLoS One. 2013;8(2):e57214. PMID: 23468938 Shawn Jackson: Jackson SS, Coughlin EE, Coon JJ, Miyamoto S. Identifying posttranslational modifications of NEMO by tandem mass spectrometry after high affinity purification. Protein Expr Purif. 2013 Sep 6. [Epub ahead of print] PMID: 2401278 Jeffrey Jensen: Hebron E, Hope C, Kim J, Jensen JL, Flanagan C, Bhatia N, Maroulakou I, Mitsiades C, Miyamoto S, Callander N, Hematti P, Asimakopoulos F. MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myelomaassociated monocytes/macrophages. Br J Haematol. 2013 Mar;160(6):779-84. PMID: 2325262 Asimakopoulos F, Kim J, Denu RA, Hope C, Jensen JL, Ollar SJ, Hebron E, Flanagan C, Callander N, Hematti P. Macrophages in multiple myeloma: emerging concepts and therapeutic implications. Leuk Lymphoma. 2013 Apr 11. [Epub ahead of print] PMID: 23432691 *Co-authored by Ryan Denu Bornali Kundu: Kundu B, Sutterer DW, Emrich SM, Postle BR. Strengthened effective connectivity underlies transfer of working memory training to tests of short-term memory and attention. J Neurosci. 2013 May 15;33(20):8705-15. PMID: 23678114 Voss J, Meier TB, Freidel R, Kundu B, Nair VA, Holdsworth R, Kuo JS, Prabhakaran V. The role of secondary motor and language cortices in morbidity and mortality: a retrospective functional MRI study of surgical planning for patients with intracranial tumors. Neurosurg Focus. 2013 Apr;34(4):E7. PMID: 23544413 Continued on Page 6 5 Fall 2013 THE MSTP POST Continued from Page 5 Kundu B, Penwarden A, Wood JM, Gallagher TA, Andreoli MJ, Voss J, Meier T, Nair VA, Kuo JS, Field AS, Moritz C, Meyerand ME, Prabhakaran V. Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors. Neurosurg Focus. 2013 Apr;34(4):E6. PMID: 23544412 Eric Landsness: Plante DT, Landsness EC, Peterson MJ, Goldstein MR, Riedner BA, Wanger T, Guokas JJ, Tononi G, Benca RM. Sex-related differences in sleep slow wave activity in major depressive disorder: a high-density EEG investigation. BMC Psychiatry. 2012 Sep 18;12:146. PMID: 22989072 Plante DT, Goldstein MR, Landsness EC, Peterson MJ, Riedner BA, Ferrarelli F, Wanger T, Guokas JJ, Tononi G, Benca RM. Topographic and sex-related differences in sleep spindles in major depressive disorder: a high-density EEG investigation. J Affect Disord. 2013 Mar 20;146(1):120-5. PMID: 22974470 Plante DT, Goldstein MR, Landsness EC, Riedner BA, Guokas JJ, Wanger T, Tononi G, Benca RM. Altered overnight modulation of spontaneous waking EEG reflects altered sleep homeostasis in major depressive disorder: A high-density EEG investigation. J Affect Disord. 2013 Sep 25;150(3):1167-73. PMID: 23810359 Josh LaRocque: LaRocque JJ, Lewis-Peacock JA, Drysdale AT, Oberauer K, Postle BR. Decoding attended information in short-term memory: an EEG study. J Cogn Neurosci. 2013 Jan;25(1):127-42. PMID: 23198894 Emrich SM, Riggall AC, Larocque JJ, Postle BR. Distributed patterns of activity in sensory cortex reflect the precision of multiple items maintained in visual short-term memory. J Neurosci. 2013 Apr 10;33(15):6516-23. PMID: 23575849 Siclari F, Larocque JJ, Postle BR, Tononi G. Assessing sleep consciousness within subjects using a serial awakening paradigm. Front Psychol. 2013 Aug 20;4:542. PMID: 23970876 Jeremy Lavine: Krautkramer KA, Linnemann AK, Fontaine DA, Whillock AL, Harris TW, Schleis GJ, Truchan NA, Marty-Santos L, Lavine JA, Cleaver O, Kimple ME, Davis DB. Tcf19 is a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. Am J Physiol Endocrinol Metab. 2013 Sep;305(5):E600-10. PMID: 23860123 *Co-authored by Kim Krautkramer Rachel Lenhart: Thelen DG, Lenz AL, Francis C, Lenhart RL, Hernández A. Empirical assessment of dynamic hamstring function during human walking. J Biomech. 2013 Apr 26;46(7):1255-61. PMID: 23540723 Francis CA, Lenz AL, Lenhart RL, Thelen DG. The modulation of forward propulsion, vertical support, and center of pressure by the plantarflexors during human walking. Gait Posture. 2013 Jun 17. pii: S0966-6362(13)00239-7. [epub ahead of print] PMID: 23787149 Lenhart RL, Thelen DG, Wille CM, Chumanov ES, Heiderscheit BC. Increasing Running Step Rate Reduces Patellofemoral Joint Forces. Med Sci Sports Exerc. 2013 Aug 2. [Epub ahead of print] PMID: 23917470 Mike Levine: Levine MN, Hoang TT, Raines RT. Fluorogenic probe for constitutive cellular endocytosis. Chem Biol. 2013 Apr 18;20(4):614-8. PMID: 23601650 David Manthei: Denlinger LC, Manthei DM, Seibold MA, Ahn K, Bleecker E, Boushey HA, Calhoun WJ, Castro M, Chinchili VM, Fahy JV, Hawkins GA, Icitovic N, Israel E, Jarjour NN, King T, Kraft M, Lazarus SC, Lehman E, Martin RJ, Meyers DA, Peters SP, Sheerar D, Shi L, Sutherland ER, Szefler SJ, Wechsler ME, Sorkness CA, Lemanske RF Jr; the NHLBI Asthma Clinical Research Network Investigators. P2X 7 –Regulated Protection from Exacerbations and Loss of Control is Independent of Asthma Maintenance Therapy. Am J Respir Crit Care Med. 2013 Jan 1;187(1):28-33. PMID: 23144325 Anna Mirer: Hagen EW, Mirer AG, Palta M, Peppard PE. The sleep-time cost of parenting: sleep duration and sleepiness among employed parents in the wisconsin sleep cohort study. Am J Epidemiol. 2013 Mar 1;177(5):394-401. PMID: 23378502 Clint Morgan: Morgan CT, Noble D, Kimble J. Mitosismeiosis and sperm-oocyte fate decisions are separable regulatory events. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3411-6. PMID: 2340150 Julian Motzkin: Pujara M, Motzkin JC, Newman JP, Kiehl KA, Koenigs M. Neural correlates of reward and loss sensitivity in psychopathy. Soc Cogn Affect Neurosci. 2013 May 9. [Epub ahead of print] PMID: 23552079 University of Wisconsin - Madison Farsh Moussavi-Harami: Moussavi-Harami SF, Annis DS, Ma W, Berry SM, Coughlin EE, Strotman LN, Maurer LM, Westphall MS, Coon JJ, Mosher DF, Beebe DJ. Characterization of Molecules Binding to the 70K N-Terminal Region of Fibronectin by IFAST Purification Coupled with Mass Spectrometry. J Proteome Res. 2013 Jul 5;12(7):3393-404. PMID: 23750785 *Co-authored by MSTP 2012 graduate Lisa Maurer Philip Mudd: Mudd PA, Martins MA, Ericsen AJ, Tully DC, Power KA, Bean AT, Piaskowski SM, Duan L, Seese A, Gladden AD, Weisgrau KL, Furlott JR, Kim YI, Veloso de Santana MG, Rakasz E, Iii SC, Wilson NA, Bonaldo MC, Galler R, Allison DB, Piatak Jr M, Haase AT, Lifson JD, Allen TM, Watkins DI. Vaccine-induced CD8(+) T cells control AIDS virus replication. Nature. 2012 Nov 1;491(7422):129-33. PMID: 23023123 Walsh AD, Bimber BN, Das A, Piaskowski SM, Rakasz EG, Bean AT, Mudd PA, Ericsen AJ, Wilson NA, Hughes AL, O'Connor DH, Maness NJ. Acute Phase CD8+ T Lymphocytes against Alternate Reading Frame Epitopes Select for Rapid Viral Escape during SIV Infection. PLoS One. 2013 May 6;8(5):e61383. PMID: 23671565 Mike Palte: Caes BR, Palte MJ, Raines RT. Organocatalytic conversion of cellulose into a platform chemical. Chemical Science. 2013 April; 4(1):196-199. Arick Park: Yang C, Park AC, Davis NA, Russell JD, Kim B, Brand DD, Lawrence MJ, Ge Y, Westphall MS, Coon JJ, Greenspan DS. Comprehensive Mass Spectrometric Mapping of the Hydroxylated Amino Acid residues of the α1(V) Collagen Chain. J Biol Chem. 2012 Nov 23;287(48):40598610. PMID: 23060441 Kelli Pointer: Pointer K, Kuo JS, Dempsey RJ. CLARITY-A Clearer View of the Brain. Neurosurgery. 2013 Aug;73(2):N16. PMID: 23867270 Rene Roy: Roy RM, Paes HC, Nanjappa SG, Sorkness R, Gasper D, Sterkel A, Wüthrich M, Klein BS. Complement component 3C3 and C3a receptor are required in chitin-dependent allergic sensitization to Aspergillus fumigatus but dispensable in chitininduced innate allergic inflammation. MBio. 2013 Apr 2;4(2). PMID: 2354991 Roy RM, Klein BS. Fungal glycan interactions with epithelial cells in allergic airway disease. Curr Opin Microbiol. 2013 Aug;16(4):404-8. PMID: 23602359 Continued on Page 7 6 Fall 2013 THE MSTP POST Continued from Page 6 Brandhorst TT, Roy R, Wüthrich M, Nanjappa S, Filutowicz H, Galles K, Tonelli M, McCaslin DR, Satyshur K, Klein B. Structure and function of a fungal adhesion that binds heparin and mimics thrombospondin-1 by blocking T cell activation and effector function. PLoS Pathog. 2013 Jul;9(7):e1003464. PMID: 23853587 Yash Somnay: Somnay Y, Simon K, Harrison AD, Kunnimalaiyaan S, Chen H, Kunnimalaiyaan M. Neuroendocrine phenotype alteration and growth suppression through apoptosis by MK-2206, an allosteric inhibitor of AKT, in carcinoid cell lines in vitro. Anticancer Drugs. 2013 Jan;24(1):66-72. PMID: 23147412 Somnay Y, Chen H, Kunnimalaiyaan M. Synergistic Effect of Pasireotide and Teriflunomide in Carcinoids in vitro. Neuroendocrinology. 2013;97(2):183-92. PMID: 22965070 Aadhavi Sridharan: Sridharan A, Xu G, Kastman E, Oh J, Ries M, Hermann B, LaRue A, Asthana S, Carlsson C, Gleason C, Sager M, Johnson S. Longitudinal changes in left anterior hippocampal activation in cognitively normal subjects with APOE 4 polymorphism. Alzheimer’s & Dementia. 2011 Jul;7(4):S225-S225. Sridharan A, Pehar M, Shahriar Salamat M, Pugh TD, Bendlin BB, Willette AA, Anderson RM, Kemnitz JW, Colman RJ, Weindruch RH, Puglielli L, Johnson SC. Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: a preliminary quantitative imaging study. Brain Res. 2013 May 1;1508:1-8. PMID: 23473840 Jon Stefely: Hebert AS, Merrill AE, Stefely JA, Bailey DJ, Wenger CD, Westphall MS, Pagliarini DJ, Coon JJ. Amine-reactive neutron-encoded labels for highlyplexed proteomic quantitation. Mol Cell Proteomics. 2013 Jul 23. [Epub ahead of print] PMID: 2388203 Jeremy Weiss: Weiss JC, Natarajan S, Peissig PL, McCarty C, Page D. Machine Learning for Personalized Medicine: Predicting Primary Myocardial Infarction from Electronic Health Records. AI Magazine. 2012 Dec;33(4):33-45. Weiss J, Natarajan S, Page D. Multiplicative Forests for Continuous-Time Processes. Neural Information Processing Systems (NIPS). 2012 Dec; 25;467475. Weiss JC, Natarajan S, Peissig P, McCarty C, Page CD. Statistical Relational Learning to Predict Primary Myocardial Infarction from Electronic Health Records. 2012 July. Proceedings of the Twenty-Fourth IAAI Conference. Weiss JC, Page CD. Forest-based point processes for event prediction from electronic health records. In Blockeel H, Kersting K, Nijssen S, Zelezny F (eds.), Machine Learning and Knowledge and Discovery in Databases. Berlin, Germany: Springer Berlin Heidelberg. 2013: 547-562). Andrew Wentland: Kramer JH, Arnoldi E, François CJ, Wentland AL, Nikolaou K, Wintersperger BJ, Grist TM. Dynamic and Static Magnetic Resonance Angiography of the Supra-aortic Vessels at 3.0 T: Intraindividual Comparison of Gadobutrol, Gadobenate Dimeglumine, and Gadoterate Meglumine at Equimolar Dose. Invest Radiol. 2013 Mar;48(3):121-8. PMID: 23211552. Richard Yang: Van De Voort TJ, Felder MA, Yang RK, Sondel PM, Rakhmilevich AL. Intratumoral delivery of low doses of anti-CD40 mAb combined with monophosphoryl lipid a induces local and systemic antitumor effects in immunocompetent and T cell-deficient mice. J Immunother. 2013 Jan;36(1):29-40. PMID: 23211623 Yang RK, Kalogriopoulos NA, Rakhmilevich AL, Ranheim EA, Seo S, Kim K,Alderson KL, Gan J, Reisfeld RA, Gillies SD, Hank JA, Sondel PM. Intratumoral treatment of smaller mouse neuroblastoma tumors with a recombinant protein consisting of IL-2 linked to the Hu14.18 antibody increases intratumoral CD8+ T and NK cells and improves survival. Cancer Immunol Immunother. 2013 Aug;62(8):1303-13. PMID: 23661160 Brittany Young: Gallagher TA, Nair VA, Regner MF, Young BM, Radtke A, Pankratz J, Holdsworth RL, Baniulis D, Kornder NK, Voss J, Austin BP, Moritz C, Meyerand ME, Prabhakaran V. Characterizing the relationship between functional MRI-derived measures and clinical outcomes in patients with vascular lesions. Neurosurg Focus. 2013 Apr;34(4):E8 . PMID: 23544414 Wentland AL, Wieben O, François CJ, Boncyk C, Munoz Del Rio A, Johnson KM, Grist TM, Frydrychowicz A. Aortic pulse wave velocity measurements with undersampled 4D flow-sensitive MRI: comparison with 2D and algorithm determination. J Magn Reson Imaging. 2012 Nov 2. PMID: 23124585 Wentland AL, Grist TM, Wieben O. Repeatability and Internal Consistency of Abdominal 2D and 4D Phase Contrast MR Flow Measurements. Acad Radiol. 2013 Jun; 20(6):699-704. PMID: 23510798 Nadia Sundlass: Sundlass NK, Eller CH, Cui Q, Raines RT. Contribution of Electrostatics to the Binding of Pancreatic-Type Ribonucleases to Membranes. Biochemistry. 2013 Aug 30. [Epub ahead of print] PMID: 23947917 Sarah Wernimont: Wiemer AJ, Wernimont SA, Cung TD, Bennin DA, Beggs HE, Huttenlocher A. The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ T cell activation. Biochem Pharmacol. 2013 Sep 15;86(6):770-81. PMID: 23928188 Heather Taff: Mitchell KF, Taff HT, Cuevas MA, Reinicke EL, Sanchez H, Andes DR. Role of Matrix β-1,3 Glucan in Antifungal Resistance of Non-albicans Candida Biofilms. Antimicrob Agents Chemother. 2013 Apr;57(4):1918-20. PMID: 23318790 Cecilia Westbrook & Brittany Young: Schalick WO, Westbrook C, Young B. Communication with Individuals with Intellectual Disabilities and Psychiatric Disabilities: A Summary of the Literature. University of Michigan, Michigan Retirement Research Center Working Papers. 2012 Aug;wp264. University of Wisconsin - Madison In case you missed the emails, Grumpy Cat Drew wants you to know that the UW MSTP has a blog. Check out wisconsinmstp.blogspot.com for more Drew and other related media from the UW MSTP! Updated daily. Send in blog submissions to [email protected] 7 Fall 2013 THE MSTP POST Photos! Snapshots from the 2013 UW MSTP Retreat Ray Zhang, Jason Chiang, and Andy Voter enjoying the last days of summer University of Wisconsin - Madison 8 Fall 2013 THE MSTP POST Cook’s Corner In this issue’s Cook’s Corner, students wanted to hear Paul’s take on food, food, and more food. In particular, we wanted to get the scoop on some of his most popular recipes. Would you share the recipe for your Ginger Salsa? See Side Panel Would you share the recipe for your "salmony dip"? Dip for salmon: Mayonaise and ground horseradish to taste...... that's it, really! Some of us have heard about The Church of Paul, also known as Brasserie V. When is the most likely time that you might be found at your church, and more importantly, what should someone order when dining there? The Church of Paul and All Mankind, otherwise known as the Brasserie V on Monroe Street, has many fine dishes. You may find me there at lunch or after work, but I have been so busy that I haven't worshiped for some time. If you need a tour or companion, let me know. The Moules and Frites (mussels and french fries) are a favorite..... however, I have burned out on them. If you are there at lunch, the sandwiches (the Ahi Tuna and Avacado BLT are two of my favorites) and soups are wonderful. Saint Bernardus Apt 12 is my beer of choice. Enjoy! And a short announcement from Paul Cook himself: I have officially moved! My new office is next to Chelsea's, 2375 HSLC. It is deep in the library, 2nd Floor. If you haven't been to Chelsea's office yet, here are the directions. Enter the library and turn left, walk to the end of the space and turn right. Straight ahead you will see a door with a sign that reads "Information Resources, Information Architecture, Rm 2370-2376." Go through that door (it is not a trap) and turn to your right. My office is straight ahead. I lovingly call it "Storeroom B." Come visit sometime! University of Wisconsin - Madison PAUL’S SALSA 1 lg. can diced tomatoes – well drained, then finely chopped and drained again 1 garlic clove – minced Equal amount of fresh ginger root – minced 4-5 scallions, with green portion – chopped Fresh cilantro – chopped Fresh basil – chopped (dried basil is OK, too) 1-2 jalapeno peppers, with seeds – chopped Salt and pepper - to taste Squeeze of lime juice (optional....if it needs a little zest) This is fairly easy. I am careful to drain the tomatoes as well as possible... I don’t want the salsa to be too watery. (The lime juice adds more liquid.) All ingredients are adjustable to your taste. The ginger root and garlic are essential, the fresh herbs are a real treat. Enjoy!! 9 Fall 2013 THE MSTP POST A day in the life... ...of a 2nd year clinical investigations PhD student Compiled by Cecilia Westbrook and Laura Felley Name: Laura Felley Year: G2 PhD Program: Clinical Investigations (ICTR) Lab and general focus: Gumperz Lab, NKT cell Research interests: I’m interested in determining how the application of NKT cells might be used to modulate immune responses to viral infections. A project you're working on: Right now, I’m looking at inflammasome activation in NKT-instructed monocytes. The inflammasome is a protein complex that activates caspase-1, which cleaves all sorts of stuff, including the pro-form of IL-1β, so we use the production of mature IL-1β as an indicator of inflammasome activation. 5:00 AM: Stagger out of bed to feed the cats. Plan on changing into gym clothes to go for an early morning run. But internet is calling me… 5:30 AM: Stare blankly at eyebrows in bathroom mirror. Blink at self. Look at gym clothes on the floor. 5:50 AM: Finally out the door! 7:00 AM: Stagger back inside. Be grateful that the weather has cooled, thus staunching the epic torrents of sweat. Wonder how some girls manage to look attractive while exercising. 7-8 AM: Shower, dress, and assemble ALL THE FOODS: three breakfasts (banana “pancake” for me, bagel for Doug*, severed nightcrawler for axolotols), 1 lunch (ritz crackers and peanut butter, apple), 1 dinner (Trader Joe’s Breakfast Burrito, for I am a rebel). 8-8:30 AM: I’m never sure what happens in this extra half hour that ensures I’m never out the door by 8, but it’s always there. 9:00 AM: Arrive in lab with Doug, who actually works 2 floors upstairs as the Forrest’s lab artist in residence. Draw blood for today’s experiment. 9-10 AM: As blood separates, work on a clinical trial protocol proposal for BMI 544 (despite the fact that I do no clinical research forever) and a piece in the MSTPost. 10-11:30 AM: Isolate PBMCs, harvest and count NKT cells, plan out experiment. Realize I left the Trader Joe’s Breakfast Burrito on the counter. Wonder how long I’d have to nuke the burrito to kill the bacteria. 11:30 AM: Lab meeting is supposed to start. 11:50 AM: Lab meeting actually starts. Newish post-doc is presenting data from his PhD. It looks better than mine. I am jealous. 12:45 PM: Sneak out of lab meeting early to go to Stat 641. 1-2:15 PM: Stat 641 is an actual statistics class with math and everything, so I am woefully unprepared. Thankfully, the professor is competent, kind and non-judgmental (useful when I show up to office hours). 2:30-4:15 PM: The free-for-all. Finish setting up first half of an experiment (I’m generating supernatants for a calcium flux assay that I will do tomorrow morning, which will require yet more blood), answer emails, finish paper, eat stale leftover mini donut from lab meeting, am unsatisfied with donut, buy peanut butter M&Ms and tea and eat those too. 4:40-6:10 PM: BMI 544. It is long. The students are all early- to mid-career doctors, so I feel young and stupid. 6:10-7:00 PM: Walk home 7:00-7:30PM: Futz around on internet, give up on Trader Joe’s burrito, eat leftover tomato soup and a grilled cheese instead. 7:30-9:00 PM: Study for virology exam on Friday, interspersed with more futzing around online. 9:00-10:00 PM: Watch QI with Doug on Youtube while half-heartedly pedaling on exercise bike. 10:15 PM: Goodnight *Doug is Laura’s husband. THE MSTP POST THE MSTP POST Editors: Brittany Young Sumit Kar Many thanks to Chelsea Hanewall for making the newsletter possible! N.B. The MSTPost is written, edited, and assembled by students of the UW MSTP. The views represented in the MSTPost do not necessarily represent those of the University of Wisconsin Madison, the UW School of Medicine and Public Health, or the Medical Scientist Training Program. University of Wisconsin - Madison 10