2020 WSoE Presenters
Professor of Pharmacology & Psychiatry
Director, Center for Epigenetic Research in Child Health and Brain Development
University of Maryland
Preconception delivery: Somatic signals impacting neurodevelopment and stress circuitry
Parental lifetime exposures to perturbations such as stress, infection, malnutrition, and advanced age have been linked with an increased risk for offspring disease, including a strong association with neurodevelopmental disorders. Our studies have focused on identifying the causal biological mechanisms whereby information in the preconception environment can be transmitted at fertilization and impact embryo development. In our models of male and female preconception stress we have been able to identify molecular mechanisms critical for parental transmission of stress signals. In males, we demonstrate a causal role for somatic-to-germline transmission of stress information capable of altering fetal neurodevelopment via extracellular vesicles (EVs) in a preclinical model. In these studies, the transmission of paternal stress and changes in epigenetic marks only occur following a stress recovery period suggesting a cellular allostatic shift in chromatin reprogramming. We further established the causal involvement of EEC EVs utilizing intracytoplasmic sperm injection of caput sperm incubated with EVs secreted following stress treatment recovery. Translationally, we have examined similar stress programming changes in human sperm miRNA content. utilizing within and between human subject comparisons of sperm samples and neuropsychiatric perceived stress reports collected repeatedly over six months. In our female preconception stress model, we have found similar evidence for germ cell programming of offspring stress circuitry and body weight dysregulation. Together, these studies demonstrate in both mice and humans a clear involvement of stress in the environment to alter germ cell programming and a novel role for reproductive tract EVs to harness changes in the parental milieu and integrate into germ cell signals.
Tracy L. Bale, Ph.D. is a Professor of Pharmacology and Psychiatry, and Director of the Center for Epigenetic Research in Child Health and Brain Development in the School of Medicine. Dr. Bale completed her Ph.D. at the University of Washington and her postdoctoral work at the Salk Institute with Dr. Wylie Vale. She was previously a Professor of Neuroscience at the University of Pennsylvania for 15 years. Dr. Bale was recruited to the University of Maryland School of Medicine as a STRAP recruit and the Director of the Center for Epigenetic Research in Child Health and Brain Development. Dr. Bale’s research focuses on understanding the role of stress dysregulation in neurodevelopmental and neuropsychiatric diseases, and the sex differences that underlie disease vulnerability. Her groundbreaking work has uncovered the molecular mechanisms by which the environment influences parental germ cell signals and placental trophoblast development, altering fetal brain development and maturation. She has been the recipient of numerous awards for her research including the Richard E. Weitzman Memorial award from the Endocrine Society, the Medtronic Award from the Society for Women’s Health Research, the Daniel H. Efron award from the American College of Neuropsychopharmacology, the NIH Award from the International Federation of Placenta Associations, and the Joseph Erlanger Distinguished Lecturer Award from the American Physiological Society.
- Driving the Next Generation: Paternal Lifetime Experiences Transmitted via Extracellular Vesicles and Their Small RNA Cargo
- Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact ofParental Stress Experience
- Parental Advisory: Maternal and Paternal Stress Can Impact Offspring Neurodevelopment
- Placental H3K27me3 Establishes Female Resilience to Prenatal Insults
- Transgenerational Epigenetic Programming via Sperm MicroRNA Recapitulates Effects of Paternal Stress
Poitras Professor of Neuroscience
McGovern Institute for Brain Research
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Director of Model Systems and Neurobiology
Stanley Center for Psychiatric Research
Broad Institute of MIT and Harvard
Dissecting Synaptic and Circuitry Mechanisms of Psychiatric Disorders
Recent genetic studies have identified a large number of candidate genes for autism spectrum disorder (ASD), many of which encode synaptic proteins, suggesting that synaptic dysfunction might be a key pathology in ASD. In addition, recently, genetic studies have revealed a significant overlap of risk genes for ASD and schizophrenia. However, it is not clear how different mutations of the same gene could contribute to the manifestation of different diseases. One such example is the Shank3 gene. The Shank3 gene encodes a postsynaptic scaffolding protein critical for the development and function of glutamatergic excitatory synapses. Disruption of the Shank3 gene is thought to be the cause of the core neurodevelopmental and neurobehavioral deficits in Phelan-McDermid Syndrome, an autism spectrum disorder. Using various Shank3 mutant mice and monkeys as model systems, I will discuss (1) recent findings on synaptic and circuit mechanisms underlying autistic-like behaviors in Shank3 mutant mice; (2) the reversibility of synaptic, circuit and behavioral abnormalities in adult mutant mice; and (3) molecular and synaptic mechanisms that may explain how different alleles of the same gene lead to distinct synaptic and behavioral phenotypes in mice (4) the potentials of using monkey models to develop biomarkers and therapeutics. Together, these findings may inform exploration of neurobiological mechanisms of ASD in human patients.
Dr. Feng is the Poitras Chair Professor of Neuroscience in the McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. He is also an Institute Member of the Broad Institute of MIT and Harvard and the Director of Model Systems and Neurobiology at the Stanley Center for Psychiatric Research at Broad Institute. Dr. Feng’s research is devoted to understanding the mechanisms regulating the development and function of synapses in the brain and how synaptic dysfunction may contribute to psychiatric disorders. Using genetically engineered animal models, Dr. Feng’s laboratory combines cutting-edge technologies and multidisciplinary approaches to unravel the neurobiological mechanisms of neurodevelopmental and psychiatric disorders.
Dr. Feng studied medicine at Zhejiang University School of Medicine in Hangzhou, China. He did his PhD training with Linda Hall at the State University of New York at Buffalo and postdoctoral training with Joshua Sanes at Washington University in St. Louis. Prior to joining the faculty at MIT, he was a faculty member in the Department of Neurobiology, Duke University School of Medicine. Dr. Feng has won numerous awards for his scientific achievement including Beckman Young Investigator Award, McKnight Neuroscience of Brain Disorders Award, Gill Young Investigator Award, Brain Research Foundation Science Innovation Award, Hartwell Individual Biomedical Research Award, and election to American Academy of Arts and Sciences.
- Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects
- Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
- Atypical behaviour and connectivity in SHANK3-mutant macaques
- Adult restoration of Shank3 expression rescues selective autistic-like phenotypes
- Thalamic reticular impairment underlies attention deficit in Ptchd1Y/− mice
Director of the National Institute of Mental Health (NIMH)
Model Organism Approaches to Anxiety and Emotion
Model organisms play a crucial role in modern neuroscience. Exploring the function of molecules, cells, circuits, and systems and how they relate to behavior often requires the use of methods to examine the intact brain that can only be performed in animals. Yet, the translation of results gained from animals into treatments for humans has been challenging. This is especially true for studies of mood and anxiety. I will approach the issue of animal models in mood and anxiety from both experimental and policy perspectives. On the experimental side, I will discuss work from my laboratory focused on dissecting the role of neural dynamics in the hippocampus and prefrontal cortex in the regulation of avoidance behaviors in mice. On the policy side, I will present the NIMH’s approach to neurobehavioral models of relevance to psychiatric illness, pointing out the promises and pitfalls of approaches such as those that I have used in my own laboratory. Taken together, these two perspectives will argue for an hypothesis-based approach to the design and evaluation of animal model experiments in mental health research.
Dr. Gordon received his MD/PhD degree at the University of California, San Francisco and completed his Psychiatry residency and research fellowship at Columbia University. He joined the Columbia faculty in 2004 as an Assistant Professor in the Department of Psychiatry where he conducted research, taught residents, and maintained a general psychiatry practice. In September of 2016, he became the Director of the National Institute of Mental Health.
Dr. Gordon’s research focuses on the analysis of neural activity in mice carrying mutations of relevance to psychiatric disease. His lab studies genetic models of these diseases from an integrative neuroscience perspective, focused on understanding how a given disease mutation leads to a behavioral phenotype across multiple levels of analysis. To this end, he employs a range of systems neuroscience techniques, including in vivo anesthetized and awake behaving recordings and optogenetics, which is the use of light to control neural activity. His work has direct relevance to schizophrenia, anxiety disorders, and depression.
Dr. Gordon’s work has been recognized by several prestigious awards, including the The Brain and Behavior Research Foundation – NARSAD Young Investigator Award, the Rising Star Award from the International Mental Health Research Organization, the A.E. Bennett Research Award from the Society of Biological Psychiatry, and the Daniel H. Efron Research Award from the American College of Neuropsychopharmacology.
- Hippocampal-Prefrontal Theta TransmissionRegulates Avoidance Behavior
- Direct Ventral Hippocampal-Prefrontal Input IsRequired for Anxiety-Related Neural Activity andBehavior
- Single Units in the Medial Prefrontal Cortex withAnxiety-Related Firing Patterns Are PreferentiallyInfluenced by Ventral Hippocampal Activity
- Testing the glutamate hypothesis of schizophrenia
John R. Andrews Distinguished Professor
Vice Chair for Faculty Development
Department of Pharmacology
University of North Carolina-Chapel Hill
Probing Modulation in Extended Amygdala Circuits
Drug and alcohol abuse are highly comorbid with anxiety and depression. In keeping with this, a large body of work from multiple laboratories points to the critical role of aversive brain systems in driving behavioral pathologies associated with addiction. The broad focus of my laboratory is to identify how discrete circuits in the brain can drive aversive behavior, and understand mechanistically how alcohol and drugs of abuse can dysregulate these circuits. Our goal is to identify novel circuit based approaches to treat addiction. Here I will discuss work from my lab that highlights the role of discrete circuits in the brain, centered on the extended amygdala, in driving both aversive and rewarding behavior. Specifically, I will discuss the dynamic role of a subpopulation of neurons that express the neuropeptide corticotrophin releasing factor (CRF) in the extended amygdala. In addition, I will highlight recent efforts from my group to determine what signal from these neurons actually contributes to changes in behavior.
Dr. Thomas Kash is an Associate Professor of Pharmacology and the John Andrews Distinguished Professor of Alcohol Studies at the University of North Carolina at Chapel Hill. He earned his BS in Chemistry at the State University of New York College of Environmental Science and Forestry in 1999. Following this, Dr. Kash worked briefly at the medical department at Brookhaven National Labs under the guidance of Dr. Andrew Gifford before joining Dr. Neil Harrison’s lab at Cornell University Graduate College of Biomedical Science in New York City. While a student in Dr. Harrison’s lab Dr. Kash worked on understanding the structure and function of ligand-gated ion channels, in particular GABA-A receptors. In 2004, Dr. Kash moved to Dr. Danny Winder’s lab at Vanderbilt University in Nashville, TN and began working on understanding how alcohol and peptides can modulate function in the extended amygdala. In 2009, Dr. Kash started his lab at the Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill where he has continued his efforts to understand how modulation of neuronal circuits can alter behavior. Research in the Kash lab has focused on understanding how stress and alcohol abuse can alter neuronal function in brain regions that regulate emotional behavior. This is performed using a multidisciplinary approach, ranging from behavioral analysis to detailed mechanistic signaling analysis. The major drive has been to understand how modulation of neuronal circuits can ameliorate pathological behavior associated with neuropsychiatric conditions.
- Acute engagement of Gq-mediated signaling… induces anxiety-like behavior
- Serotonin Engages an Anxiety and Fear Promoting Circuit in the extended amygdala
- NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking
- Dynorphin Controls the Gain of an Amygdalar AnxietyCircuit
- Alcohol Drinking Alters Stress Coping via Extended Amygdala Kappa Opioid Receptor Signaling in Male Mice
Distinguished Professor of Psychiatry and Neuroscience,
Thomas Detre Professor of Academic Psychiatry,
Chair, Department of Psychiatry
University of Pittsburgh
A Neural Circuitry Substrate for Cognitive Dysfunction in Schizophrenia
Depression and suicide are common comorbid features in people with schizophrenia. These features, as well as psychosis, typically emerge after a protracted period of impaired cognitive control, the ability to adjust thoughts or behaviors in order to achieve goals; these impairments are now considered to be a core feature of schizophrenia and to be the best predictor of long-term functional outcome. Cognitive control depends on the coordinated activity of a distributed neural network composed of multiple brain regions, including the dorsolateral prefrontal cortex (DLPFC). Subjects with schizophrenia exhibit altered activation of the DLPFC, and reduced power of frontal lobe gamma band (~40 Hz) oscillations, when performing tasks that require cognitive control. Gamma oscillations require robust activity in the reciprocal connections between the parvalbumin-containing basket cell class of inhibitory GABA neurons and neighboring excitatory pyramidal neurons. Thus, alterations in either the excitatory or inhibitory synapses in this circuit could contribute to impaired gamma oscillations and cognition in schizophrenia. Current findings converge on the hypothesis that the primary disturbances are in pyramidal neurons with the changes in parvalbumin neurons representing compensatory responses to maintain excitatory-inhibitory balance in DLPFC networks. In concert, the findings provide both a circuity-based explanation for gamma oscillations impairments and cognitive disturbances in schizophrenia and a possible mechanistic substrate for the emergence of psychosis and emotion regulation.
Dr. Lewis is an internationally recognized expert on schizophrenia. His research focuses on the neural circuitry of the prefrontal cortex and related brain regions and the alterations of this circuitry in schizophrenia. He received his medical degree from the Ohio State University, completed residencies in both internal medicine and psychiatry at the University of Iowa, and received his research training at the Research Institute of the Scripps Clinic. In 1987, Dr. Lewis came to the University of Pittsburgh to join the faculty of the Departments of Psychiatry and Behavioral Neuroscience and establish the Primate Neuroscience Lab. Over the past 30 years, he’s grown the program into the current Translational Neuroscience Program, which now includes 18 faculty members with their own research programs.
Dr. Lewis is the Thomas Detre Professor of Academic Psychiatry and Professor of Neuroscience at the University of Pittsburgh School of Medicine. Since 2009, he has served as chairman of the Department of Psychiatry, and Director of Research and Medical Director for Western Psychiatric Institute and Clinic of UPMC. In 2016, the University of Pittsburgh appointed Dr. Lewis as Distinguished Professor in recognition of his eminence and outstanding contributions in the fields of Psychiatry and Neuroscience.
In addition to his administrative responsibilities, Dr. Lewis directs a National Institute of Mental Health (NIMH) Conte Center for Translational Mental Health Research focused on understanding the mechanisms that link the pathology, pathophysiology and clinical features of schizophrenia. He serves as Deputy Editor of the American Journal of Psychiatry and Associate Editor for Neurobiology of Disease.
In 2007, Dr. Lewis was elected to membership in the Institute of Medicine of the National Academy of Sciences (recently renamed as the National Academy of Medicine) for his contributions to the advancement of schizophrenia research and his efforts to bring the importance of this major public health issue to the forefront. In addition, he is the recipient of numerous awards recognizing his extensive contributions to the field including the Lieber Prize from the National Alliance for Research on Schizophrenia and Depression and the American Psychiatric Association Award for Research in Psychiatry.
- Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder
- Pathological basis for deficient excitatory drive to cortical parvalbumin interneurons in schizophrenia
- Altered expression of ARP2:3 complex signaling pathway genes in prefrontal layer 3 pyramidal cells in schizophrenia
- Altered gradients of glutamate and GABA transcripts in the cortical visuospatial working memory network in schizophrenia
- Distinct properties of layer 3 pyramidal neurons from prefrontal and parietal areas of the monkey neocortex
Vilas Professor of Psychology and Psychiatry
Director, Center for Healthy Minds
University of Wisconsin - Madison
Richard J. Davidson received his Ph.D. from Harvard University in Psychology and has been at Wisconsin since 1984. He has published more than 400 articles, numerous chapters and reviews and edited 14 books. He is the author (with Sharon Begley) of “The Emotional Life of Your Brain” published by Penguin in 2012. He is co-author with Daniel Goleman of “Altered Traits: Science Reveals How Meditation Changes Your Mind, Brain, and Body”, published by Penguin Books in 2017.
He is the recipient of numerous awards for his research including a National Institute of Mental Health Research Scientist Award, a MERIT Award from NIMH, an Established Investigator Award from the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD), a Distinguished Investigator Award from NARSAD, the William James Fellow Award from the American Psychological Society, and the Hilldale Award from the University of Wisconsin-Madison. He was the year 2000 recipient of the most distinguished award for science given by the American Psychological Association –the Distinguished Scientific Contribution Award. He was the Founding Co-Editor of the new American Psychological Association journal EMOTION and is Past-President of the Society for Research in Psychopathology and of the Society for Psychophysiological Research.
In 2003 he was elected to the American Academy of Arts and Sciences and in 2004 elected to the Wisconsin Academy of Sciences, Arts and Letters. Named one of the 100 most influential people in the world by Time Magazine in 2006. In 2006 awarded the first Mani Bhaumik Award by UCLA for advancing the understanding of the brain and conscious mind in healing. Madison Magazine named him Person of the Year in 2007. In 2008, he founded the Center for Healthy Minds, a research center dedicated to the study of positive qualities, such as kindness and compassion. In 2011 given the Paul D. MacLean Award for Outstanding Neuroscience Research in Psychosomatic Medicine. Serves on the Scientific Advisory Board at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig from 2011-2020 and was Chair of the Psychology section of the American Association for the Advancement of Science from 2011-2013. In 2013 received the NYU College of Arts and Science Alumni Achievement Award. He is a current member of the World Economic Forum’s Global Agenda Council on Mental Health. From 1992-2017, he was a member of the Mind and Life Institute’s Board of Directors. In 2017 elected to the National Academy of Medicine, the premier authority dedicated to the health and medical sciences. In 2018, appointed to the Governing Board of UNESCO’s Mahatma Gandhi Institute of Education for Peace and Sustainable Development (MGIEP).
His research is broadly focused on the neural bases of emotion and emotional style and methods to promote human flourishing including meditation and related contemplative practices. His studies have included persons of all ages from birth though old age and have also included individuals with disorders of emotion such as mood and anxiety disorders and autism, as well as expert meditation practitioners with tens of thousands of hours of experience. His research uses a wide range of methods including different varieties of MRI, positron emission tomography, electroencephalography and modern genetic and epigenetic methods.
Chair, Department of Psychiatry
Director, HealthEmotions Research Institute
University of Wisconsin - Madison
Ned H. Kalin, MD, is Hedberg Professor and Chairman of the Department of Psychiatry at the University of Wisconsin School of Medicine and Public Health. He is the Editor in Chief of the American Journal of Psychiatry, the premier scientific journal of the American Psychiatric Association. Dr. Kalin is the Director of the HealthEmotions Research Institute and the Lane Neuroimaging Laboratory, a Professor in the Department of Psychology at the University of Wisconsin, and an affiliate scientist at the Wisconsin Regional Primate Center and the Harlow Primate Laboratory. He serves as the principal investigator for several ongoing NIH funded research projects and has published over 200 peer-reviewed journal articles related to the adaptive and maladaptive expression of emotion and anxiety. His research focuses on uncovering basic mechanisms that relate stress to the development of psychopathology and to understanding the mechanisms that cause some children to be vulnerable for the development of anxiety and depression. In addition to his research activities, he treats patients who suffer from anxiety and depression who are refractory to standard treatment.
Dr. Kalin earned his medical degree from Jefferson Medical School in Philadelphia, Pennsylvania, did his residency in the Department of Psychiatry at the University of Wisconsin, and a fellowship in Neuropsychopharmacology at the National Institute of Mental Health. Dr. Kalin is board certified by the American Board of Psychiatry and Neurology. He is a fellow of the American College of Neuropsychopharmacology and the American College of Psychiatry. He has been recognized for numerous awards including the 1985 A.E. Bennett Award for basic science research in biological psychiatry, the 2005 Edward A. Strecker Award, the 2007 American College of Psychiatrists Award for research in mood disorders, the 2007 Gerald Klerman Senior Investigator Award, and the 2015 Anna-Monika Prize of the European College of Neuropsychopharmacology. In 2013 he was inducted as a Fellow in the American Association for the Advancement of Science, and in 2015 he was elected as a member of the National Academy of Medicine. In 2017, Dr. Kalin was inducted as a Distinguished Life Fellow of the American Psychiatric Association, and was appointed to the Editorial Board, Journal of Psychiatric Research. He has served as President of the International Society of Psychoneuroendocrinology, and as a member of the National Advisory Mental Health Council. He is Co-Editor for the international journal, Psychoneuroendocrinology. He lectures regularly at national and international meetings.