BIOGRAPHICAL SKETCH NAME POSITION TITLE Jessica Jillian Walsh Assistant Professor eRA COMMONS USER NAME WALSH86 EDUCATION/TRAINING DEGREE (if INSTITUTION AND LOCATION MM/YY FIELD OF STUDY applicab le) Columbia College of Columbia University B.A. 08/2004-05/2008 Neuroscience & Behavior Icahn School of Medicine at Mount Sinai Medical M.S. 08/2008-05/2010 Biomedical Sciences Center Icahn School of Medicine at Mount Sinai Medical Ph.D 08/2010-08/2013 Neuroscience Center Stanford University 10/2013-06/2021 Neuroscience A. Personal Statement My long-term research goals are to elucidate the brain circuits and molecular mechanisms underlying motivated social behavior. One of the major focuses will be to understand how genetic mutations, as well as experience, lead to circuit adaptations that govern impaired behavior seen in mouse models of autism spectrum disorders (ASD). Utilizing a systems levels approach, I aim to: 1) model these disorders with well described genetic markers, 2) define causal relationships between activity within discrete anatomical structures in the brain that are critical to the physiology of the symptom under investigation (e.g. sociability), 3) perform deep characterization of the physiological profiles of these circuits and using that information, target specific receptors or molecules that may not have been considered for the treatment of specific ASD symptoms. My prior training and my current research environment in the laboratory of Dr. Robert Malenka have ideally equipped me to pursue these topics and make me particularly well-suited for achieving these goals. I have had the distinct privilege to be mentored by many amazing neuroscientists. I began my career volunteering in Dr. Gerald Fischbach’s laboratory when I was a high school student. More than simply learning many techniques, I began to understand how to develop hypotheses and ask scientific questions. I worked in Dr. Fischbach’s laboratory throughout college. I began my master’s degree at the Icahn School of Medicine at Mount Sinai, investigating changes in neuronal morphology in select brain regions implicated in Alzheimer’s disease through the use of a knockout mouse model. Following this, I pursued my dissertation in Dr. Ming-Hu Han’s laboratory investigating the circuitry underlying a mouse model of major depressive disorder. During my postdoctoral fellow, I built on my previous training in optogenetics and behavior by using a novel genetic knockout mouse model and basic electrophysiology techniques. These have allowed me to precisely identify a circuit and molecular mechanism important in social deficits seen in a mouse model with a 16p11.2 deletion. My research has resulted in numerous publications investigating social and reward-related behaviors. My training thus far has led to expertise in this subfield of neuroscience, and in numerous techniques that will aid me in my career. Further, throughout my pre- and post-doctoral studies, I have mentored several technicians, undergraduate and graduate students, many who have continued to pursue either basic science research or medical paths, thus preparing me to train and mentor the eventual members of my own lab. • I am uniquely suited to investigate these mechanisms because of my integrated training in circuit manipulation using viral and genetic tools, pharmacology and behavioral neuroscience. Overall, my research aims to fill a critical gap in our knowledge of circuit mechanisms in specific behaviors both in normative mice and the perturbed state in various mouse models of ASD. Thus, this work has enormous translational potential. I am confident this research will lead to the development of pharmocotherapies for all members of vulnerable populations and a deeper understanding of the molecular, cellular and circuit level mechanisms within the brain that are altered in various behavioral deficits seen in ASD. B. Positions and Honors BEGINNING ENDING ACTIVITY FIELD INSTITUTION/COMPANY SUPERVISOR DATE DATE Research Coordinator 05/08 08/08 Pharmacology Columbia University Dr. Gerald Fischbach Master’s Degree 08/08 05/10 Neuroscience Mount Sinai School of Medicine Dr. Patrick Hof Research Coordinator 05/10 08/10 Neuroscience Mount Sinai School of Medicine Dr. Patrick Hof Pre-doctoral Fellow 08/10 10/13 Neuroscience Mount Sinai School of Medicine Dr. Ming-Hu Han Postdoctoral Fellow 10/13 06/21 Neuroscience Stanford University Dr. Robert Malenka Assistant Professor 07/21 present Pharmacology University of North Carolina, Chapel Hill Academic and Professional Honors Sammy Kuo Award in Neuroscience (Stanford University) 2018 Best publication of the year authored by a Stanford postdoctoral fellow 11th Annual Autism Spectrum Disorders Update 2018 Scholarship, Stanford University FENS/IBRO-PERC Travel Grant 2016 Copenhagen, Denmark Ruth L. Kirschstein National Research Award (F32) 2014 National Institute of Mental Health A.P. Giannini Foundation Postdoctoral Research Fellowship 2014 Declined, San Francisco, California Society for Neuroscience 2013 Organizer, Chair and Speaker of a Nanosymposium, San Diego, California Hausfeld Award in Neuroscience (Mount Sinai School of Medicine) 2012 Endowment award for the most outstanding senior graduate student Society for Neuroscience 2012 Organizer, Chair and Speaker of a Nanosymposium, New Orleans, Louisiana Ruth L. Kirschstein National Research Award (F31) 2012 National Institute of Mental Health Mount Sinai School of Medicine Neuroscience Retreat 2012 Speaker Travel Award, Society for Neuroscience Conference 2012 New Orleans, Louisiana Travel Award, Society for Neuroscience Conference 2011 Washington, D.C. SfN Travel Fellowship to IBRO World Congress 2011 Florence, Italy First Place Poster Award at Mount Sinai Neuroscience Retreat 2011 Travel Award, International Conference on Alzheimer’s Disease 2010 ISTAART, Honolulu, Hawaii Second Place Poster Award at Mount Sinai Neuroscience Retreat 2009 The New York Academy of Science 2007 PHS 398/2590 (Rev. 06/09) Page 2 Biographical Sketch Format Page 4th Annual President’s Reception, Presenter C. Contribution to Science A complete list of my publications: https://www.ncbi.nlm.nih.gov/myncbi/jessica.walsh.1/bibliography/public/ Molecular mechanisms and circuit function of Dorsal Raphe (DR) serotonin (5-HT) neurons in social behavior: My recent work showed that deficits in 5-HT signaling resulted in social deficits in the 16p11.2 mouse model of autism spectrum disorder (ASD). This work not only precisely identified the role of 5-HT release in the nucleus accumbens (NAc) in normal social behavior, but also showed that rapid activation of a specific serotonin receptor, known as 5-HT1b, in the NAc alleviates the social deficits caused by a 16p11.2 deletion. This research has demonstrated that sufficient levels of 5-HT release can have rapid effects on sociability and has opened potential novel therapeutic interventions for ASD. These initial findings were followed up by examining the effects of a 5-HT releaser (MDMA) on baseline sociability and uncovered that a specific dose of MDMA enhances sociability in a manner that is dependent upon the 5-HT1b receptor. a. Walsh JJ, Christoffel DJ, Ben-Dor GA, Selimbeyoglu A, Taylor M, Hung LW, Deisseroth K, Malenka RC. (2018) 5-HT release in nucleus accumbens rescues social deficits in mouse autism model. Nature. 560. 589-594. b. Heifets BD, Salgodo JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Walsh JJ, Steinberg EE, Sze JY, Malenka RC. (2019) Distinct neural mechanisms for prosocial and rewarding properties of MDMA. Science Translational Medicine. 522. eaaw6435. Molecular mechanisms and circuit function of midbrain dopamine (DA) neurons in social defeat stress: I was one of the first to report on the contribution of DA neurons of the ventral tegmental area (VTA) that selectively project to the nucleus accumbens and prefrontal cortex to regulation of stress response. Specifically, I utilized the social defeat stress mouse model in combination with optogenetics to explore the neural circuit mechanisms underling susceptibility and resilience to this stress. These initial findings were followed up by examining the ionic mechanisms underlying the differential physiological properties of VTA DA neurons in these two phenotypes and identified the KCNQ channel as a critical mediator of the development of resilience to social defeat stress. Finally, I published a review on the role of the neurons in the VTA and their projections in a number of mood-related dysfunctions, including depression. a. Chaudhury D*, Walsh JJ*, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC, Pomeranz L, Christoffel DJ, Nectow AR, Ekstrand M, Domingos A, Mazei-Robison M, Mouzon E, Lobo MK, Neve RL, Russo SJ, Deisseroth K, Nestler EJ, and Han MH. (2013) “Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons” Nature. 493. 532-536. *Co-first authors b. Friedman AK, Walsh JJ, Juarez B, Chaudhury C, Ku SM, Wang J, Li X, Dietz DM, Vialou VF, Neve RL, Yue Z, Deisseroth K, Han MH. (2014) Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science. 344. 313-319. c. Friedman AK, Juarez B, Ku SM, Zhang H, Walsh JJ, Chaudhury C, Hawkins A, Zhang S, Calizo R, Dietz D, Murrough J, Ribadeneira M, Wong E, Neve R, Han MH. (2016) KCNQ channel openers reverse depressive symptoms via an active resilience mechanism. Nature Communication. 7. 11671-11678. d. Walsh JJ*, Han MH. (2014) The heterogeneity of ventral tegmental area neurons: projection functions