Neuroimmunology and Brain-body Integration

Dr. Arnsten is an international expert on the molecular regulation of higher cortical circuits, and a member of the National Academy of Medicine. She received her B.A. in Neuroscience from Brown University in 1976 (where she created the Neuroscience major), and her Ph.D. in Neuroscience from UCSD in 1981. She did post-doctoral research with Dr. Susan Iversen at Cambridge University in the UK, and with Dr. Patricia Goldman-Rakic at Yale. Dr. Arnsten's research examines the neural basis of higher cognition. Her work has revealed that the newly evolved cortical circuits that underlie higher cognition are uniquely regulated at the molecular level, conferring vulnerability in mental illness and age-related cognitive disorders such as Alzheimer's Disease. Arnsten's research has led to new treatments for cognitive disorders in humans, including the successful translation of guanfacine (IntunivTM) for the treatment of ADHD and related prefrontal cortical disorders.

Sreeganga S. Chandra received her Ph.D. in Chemistry from Purdue University. In her postdoctoral research, she pursued her interest in neuronal cell biology and neurodegeneration in the lab of Thomas C. Südhof at UT Southwestern Medical Center at Dallas. She is currently an Associate Professor in the Departments of Neurology and Neuroscience.

Rui Chang received his B.S. in Biological Sciences and Biotechnology from Tsinghua University, China in 2005. He then studied sensory transduction with Emily Liman and earned his Ph.D. in Neuroscience at the University of Southern California in 2011. He completed his postdoctoral training with Stephen Liberles at Harvard Medical School, where he investigated how body sensory cues are monitored by the brain through the vagus nerve, and how these internal signals regulate whole body physiology. He joined both the Department of Neuroscience and the Department of Cellular and Molecular Physiology at Yale University School of Medicine in January 2018.The Chang lab uses state-of-the-art molecular, genetic, and imaging approaches including single-cell gene expression profiling, virus-based anatomical mapping, in vivo imaging, optogenetics, and chemogenetics to reveal the physiological functions of diverse organ-to-brain circuits. The goal is to better understand the important body-brain interface, and to develop novel neuronal-based therapeutic strategies for disease intervention.

Dr. Cosgrove uses neuroreceptor imaging techniques such as PET to gain insights into the brains of people with substance use and other stress-related disorders. Trained as a clinical psychologist who worked with individuals managing alcohol and drug use disorders, Dr. Cosgrove transitioned to conducting research in order to inform the treatment of substance use disorders. Her laboratory develops and applies innovative brain imaging paradigms to track changes in critical neurochemicals over time, to identify treatment targets for psychiatric disorders, and to examine individual and sex and gender differences.

Emilia Favuzzi is an Assistant Professor in the Department of Neuroscience and Wu Tsai Institute at Yale University. She grew up in Italy and received a B.S. in Biology and a M.S. in Neurobiology from Sapienza University of Rome. She did her doctoral training at the Institute of Neuroscience in Alicante (Spain) and the Centre for Developmental Neurobiology at King’s College London. Her graduate research focused on the cellular and molecular mechanisms of inhibitory circuit development and plasticity in the cerebral cortex. In her postdoctoral work at Harvard Medical School and the Broad Institute, she focused on microglia-inhibitory synapse interactions during development and discovered that specialized microglia differentially engage with specific synapse types. Her past work opened a new avenue in understanding neuroimmune crosstalk by showing that neuroimmune interactions within the brain may be as specific as those between neurons. This novel conceptual framework is the foundation of the Favuzzi lab focused on the immune and glial mechanisms underlying brain wiring and function, with an emphasis on (1) interactions among neuronal and non-neuronal cells and (2) brain-body communication. Over the years, Emilia was awarded numerous prizes such as the Beddington Medal from the British Society for Developmental Biology, the Krieg Cortical Kudos Scholar Award from the Cajal Club, the Next Generation Leader by the Allen Institute, and the Gruber International Research Award.

Sourav Ghosh, Ph.D. obtained a M.Sc. in Zoology at the University of Calcutta, where he studied Drosophila and mosquito genetics. Next, he completed his graduate studies on cell cytoskeleton and protein trafficking under the direction of John V. Cox at the University of Tennessee, Memphis. Subsequently, Dr. Ghosh did his postdoctoral research on cell signaling at the Salk Institute for Biological Studies under the guidance of Tony Hunter. In 2007, Dr. Ghosh joined University of Arizona as an Assistant Professor, and in 2014 he moved to Yale University School of Medicine. Dr. Ghosh and Dr. Carla Rothlin co-direct a lab studying the regulation of inflammation (Rothin, Ghosh et al. Cell, 2007, Carrera Silva et al. Immunity, 2013, Bosurgi et al. Science, 2017). While inflammation is a cardinal feature for immune defense, the magnitude and period of the inflammatory response has to follow the ‘Goldilocks Principle’ wherein inflammation would be detrimental if its amplitude is too little or too much, or its period too short or too long. Drs. Rothlin and Ghosh investigates the principles and molecular mechanisms that negatively regulate inflammation and ensure that the amplitude and period of inflammation is ‘just right’. Defects in these molecular circuits can manifest as wide ranging clinical problems including chronic or pathological inflammation, autoimmunity and pathological wound healing, while harnessing these checkpoints can improve anti-cancer immunity.

Dr. Grutzendler obtained his MD from Universidad Javeriana in Bogota, Colombia, where he was born and raised. He completed a medical internship in Internal Medicine and a residency in Neurology at Washington University/Barnes-Jewish Hospital in St. Louis. Following that, he pursued a combined clinical and research fellowship in the Alzheimer Disease Research Center and the Department of Neurobiology at Washington University, with additional neurobiology research training at the Skirball Institute of New York University. Dr. Grutzendler's laboratory is dedicated to understanding the cellular and molecular mechanisms of normal brain function and neuropathology. They have a particular focus on elucidating mechanisms underlying neurodegeneration, such as those found in Alzheimer's disease. Additionally, they aim to advance the understanding of cell-cell interactions through the utilization of intravital optical imaging techniques, enabling them to study the brain in real-time and observe dynamic processes at the cellular and molecular levels. Moreover, their laboratory is interested in developing therapeutics for brain disorders. Leveraging their expertise in brain imaging, they work with chemists to develop novel small molecules to target specific brain cell types for drug delivery and as imaging probes. In addition to the research endeavors, Dr. Grutzendler is actively involved in clinical activities focused on dementia and Alzheimer's patients. He works closely with individuals affected by these neurodegenerative disorders, providing comprehensive care and support.

Ansel obtained his Ph.D. in Medical Physics from the University of Wisconsin, Madison in 2014. His research program features core areas of translational characterization of novel PET radiotracers, developing new imaging paradigms to improve quantification of brain neurobiology, and human neuroimaging research studying mechanisms underlying diverse psychiatric conditions. Research efforts are complemented by didactic activities lecturing at Yale and individual mentoring of trainees. Current projects include characterizing novel PET radiotracers of immune-related targets in the brain; developing novel imaging paradigms to study acute alcohol effects on neuroimmune and glutamate systems; assessment of dopamine release from smoked cannabis; method development for analyzing multimodal imaging data from fMRI-PET or PET-PET datasets; and implementing Independent Component Analysis (ICA) to identify different sources of PET radiotracer uptake.

Ellen J. Hoffman, M.D., Ph.D. was appointed as Assistant Professor in the Child Study Center in July 2015. Ellen is a child psychiatrist, psychiatric geneticist and neurobiologist, and a graduate of the Investigative Medicine PhD Program at Yale, who specializes in the functional analysis of genes in neurodevelopmental disorders. The Hoffman laboratory conducts translational research aimed at understanding the biological mechanisms underlying autism spectrum disorders and discovering new pharmacological treatments. Ellen's research focuses on investigating the function of genes that are strongly associated with autism to determine how disruption of these genes alters brain development and the neural circuits underlying simple behaviors. The long-term goal of her research is to use this gene-based approach to identify relevant biological pathways and novel pharmacological treatments that target these pathways. Ellen also works clinically as a child psychiatrist and as an attending supervising Yale child psychiatry fellows.

Tamas Horvath is Professor and Chair of the Department of Comparative Medicine and Professor of Neurobiology and Ob/Gyn at Yale University School of Medicine, New Haven, Connecticut. He is also the Director for the Yale Program on Integrative Cell Signaling and Neurobiology of Metabolism. He received a Doctor of Veterinary Medicine (D.V.M.) degree from the Faculty of Veterinary Sciences in Budapest, Hungary, and a Doctor of Philosophy (Ph.D.) degree from the University of Szeged in Hungary. His research has been focusing on neuronal circuitries that support physiological and pathological homeostatic conditions, including processes associated with reproduction, energy metabolism and neurodegeneration.

Dr. Kaffman is a physician-scientist who works as a psychiatrist at the Newington VA, where he treats a large number of veterans with PTSD. He also has a basic neuroscience lab at Yale, where he studies the impact of early life adversity (ELA) on neurodevelopment and complex behavior in mice. Dr. Kaffman is a Principal Investigator on several NIH-funded grants that integrate molecular/cellular, genomic, pharmacological, and behavioral approaches with imaging techniques such as resting state fMRI and high-resolution dMRI conducted in rodents. This translational approach allows for a direct comparison between findings in rodents and human studies. The objective of this translational research is to elucidate the impact of early adversity on the neurodevelopment of circuits that regulate psychiatrically relevant behaviors, and to utilize this knowledge in the development of novel diagnostic and treatment modalities.

Ken Loh is an Assistant Professor in the Department of Comparative Medicine in the Institute for Biomolecular Design and Discovery at Yale University’s West Campus. A native of Singapore, he received his B.S. in Chemistry from Harvey Mudd College in 2009 and earned his Ph.D in Chemistry with Alice Ting at MIT in 2016, developing chemical-enzymatic methodologies for tagging proteins in cells. Ken next received postdoctoral training with Jeffrey Friedman at Rockefeller University, studying the role of leptin in its regulation of sympathetic nerves in the fat organ, and joined the faculty at Yale in August of 2022. His lab is interested in studying brain-body interactions at a molecular length scale, using tools in chemical biology.

Dhasakumar Navaratnam MD, PhD is a neurotologist and neurologist who provides advanced comprehensive evaluation and treatment for patients with hearing and balance problems. He received his MD from the University of Colombo and his PhD from the University of Oxford. He completed his residency in neurology and post-doctoral training in hearing research at the University of Pennsylvania, Philadelphia, PA. Dr. Navaratnam is funded by the NIH and performs basic science research on aspects of hearing and balance, and regeneration in the auditory and vestibular systems.

Dr. Rachel Perry is an Associate Professor in Medicine/Endocrinology and Cellular & Molecular Physiology, with secondary appointments in Comparative Medicine and Neuroscience, at the Yale University School of Medicine. Rachel's background is in the use of hyperinsulinemic-euglycemic clamps and stable isotope infusions to assess insulin sensitivity, having earned her B.S. in Biomedical Engineering, Ph.D. (with Distinction) in Cellular & Molecular Physiology, and performed her postdoctoral training in Medicine/Endocrinology, all in the laboratory of Dr. Gerald Shulman. She opened her independent laboratory with K99/R00 funding in 2018. The Perry laboratory focuses on applying stable isotope tracer methods to understand obesity- and insulin-associated alterations in metabolic flux pathways. Dr. Perry and her colleagues have recently identified hyperinsulinemia-induced increases in tumor glucose uptake and oxidation as a critical driver of colon cancer in two mouse models of the disease, and mitochondrial uncoupling as a potential therapeutic strategy against the disease, and went on to show that responsiveness to insulin is a metabolic signature of obesity-associated tumor types in vitro. Current work in the Perry lab expands upon these themes to study the intersection between systemic metabolism and immunometabolism in cancer as well as in sepsis and exercise. We have recently been or are currently funded by the NIH (R37, R21), the Melanoma Research Alliance, and the Juvenile Diabetes Research Foundation. Current projects in the Perry lab include: 1. What is the molecular mechanism by which obesity and hyperinsulinemia promote tumor growth? How does insulin alter rates of glycolytic, oxidative, and anaplerotic metabolism? Can we invent better tracer methods than currently exist, allowing us to reliably measure rates of these pathways in vivo? 2. What is the impact of exercise, a classic insulin-sensitizing intervention, on obesity-associated tumor growth - and what is the mechanism? 3. Are alterations in tumor immunometabolism permissive for tumor progression? How does cancer therapy alter substrate preference in immune cells? Can we exploit systemic metabolic changes to enhance anti-cancer immunity? 4. How do tumor metabolism and immunometabolism differ - in rate and regulation - in metastases as compared to primary tumor? 5. What drives the changes in glucose metabolism commonly observed in inflammation that occurs following various stimuli? In addition, Dr. Perry places great value on mentorship and has completed multiple trainings to help her hone these skills. The Perry lab is honored to have trainees at the high school, undergraduate, and graduate level from around the world working with us both remotely and in person.

Chris Pittenger earned his MD and Ph.D. degrees from Columbia University, where his graduate work was done with Nobel Prize recipient Eric Kandel. He returned to Yale University, his undergraduate alma mater, for residency and research training in psychiatry in 2003. He joined the faculty as an Assistant Professor in 2007 and is now Elizabeth Mears and House Jameson Professor of Psychiatry, Professor of Psychology and in the Child Study Center, and Deputy Chair for Translational Research in the Department of Psychiatry .Chris has always been fascinated by the question of how the brain, a complex but ultimately a physical structure, creates thought, feeling, consciousness, and other aspects of the mind.  As a psychiatrist he is additionally focused on how these processes go wrong - how brain dysregulation leads to dysregulated cognition, emotion, and behavior and to mental suffering, and how advancing our understanding of these relationships can guide us to new strategies to alleviate that suffering.  Much of his work has focused on obsessive-compulsive disorder and Tourette syndrome and on the cortico-basal ganglia circuitry that is implicated in their pathophysiology.  More recently he has co-founded the Yale Program for Psychedelic Science, focused on understanding how molecules like psilocybin and LSD can teach us about brain and behavior and may lead to new treatments for a range of neuropsychiatric pathology.  He is also one of the founding Directors of the Yale Center for Brain and Mind Health, which seeks to bridge disciplines and levels of analysis to bring new therapeutics to individuals suffering from disorders of the mind and brain.Dr. Pittenger's research and clinical work have been acknowledged by a number of prestigious awards, including grant funding from the National Institute of Mental Health, the National Institute of Neurological Disease and Stroke, NARSAD, the Tourette Syndrome of America, the Doris Duke Charitable Trust, and other organizations.  He has won a number of awards, including from the National Institute of Mental Health, the Society for Neuroscience, the American College of Neuropsychopharmacology, the American Psychiatric Association, and the American College of Psychiatrists. He is a member of the Scientific Advisory Board of the International OCD Foundation and Chair of both their Grant Review Committee and their Annual Research Symposium Planning Committee.  He is a Fellow of the American College of Neuropsychopharmacology, the American Psychiatric Association, and the American Neurological Association.

Dr. Sansing completed her residency in Neurology in 2006 followed by a Vascular Neurology fellowship from 2006-2008, both at the Hospital of the University of Pennsylvania. Her clinical interests include acute ischemic stroke and intracerebral hemorrhage as well as other complex neurovascular diseases. Following clinical training, she completed a Master of Science in Translational Research at Penn studying immune mechanisms of injury after intracerebral hemorrhage. She then joined the faculty at the University of Connecticut and Hartford Hospital in 2010, where she was active in the Departments of Neurology, Neuroscience, Neurosurgery, and Immunology. Dr. Sansing came to Yale in the summer of 2014, where she continues her work in cerebrovascular diseases and neuro-inflammation through basic, translational, and clinical studies. She leads a NIH-funded laboratory identifying immunological treatment targets for stroke, intracerebral hemorrhage, vascular cognitive impairment and dementia. She has received numerous national and international awards for her research, including the Established Investigator Award from the American Heart Association, the Derek Denny-Brown Neurological Scholar Award from the American Neurological Association, the Michael S. Pessin Stroke Leadership Award from the American Academy of Neurology, and is an elected member of the Henry Kunkel Society and the American Society for Clinical Investigation.

Marc Schneeberger Pané received his B.S. in Pharmacy from Barcelona University, Catalonia in 2010. Next, he received his M.S. in Biomedicine from Barcelona University, Catalonia in 2011. He then studied how the powerhouse of the cell (mitochondria) is responsible for controlling whole body energy balance and metabolism in the canonical site for energy balance control (hypothalamus) with Marc Claret, PhD and earned his Ph.D. in Biomedicine at the Barcelona University, Catalonia in 2015. He then became a KAVLI postdoctoral fellow and a Pathway to Independence fellow in Prof. Jeffrey M.Friedman laboratory at The Rockefeller University. There he conducted whole mount activity maps in energy states to decipher the role of two novel subsets of neurons in the Dorsal Raphe Nucleus of the brainstem in energy balance control. He joined the Department of Cellular and Molecular Physiology at Yale University School of Medicine as an Assistant Professor in July 2022.The Schneeberger Pané laboratory employs state-of-the-art technologies in neuroscience combining unbiased whole mount imaging of circuits, activity and vasculature; molecular profiling single-cell gene expression technologies, neuoromodulation (optogenetics, and chemogenetics) to understand the fundamental principles in the brain governing homeostasis. The overarching goal of the laboratory is to advance in the understanding of how neuronal, immune and vascular networks coordinately control homeostasis, with a focus on energy homeostasis.