Estrogen Receptor Signaling in the Brain: A Trip Down Memory Lane

Speakers

Organizer

Feng Liu, PhD

Pfizer

Feng Liu conducted her PhD thesis work at Fox Chase Cancer Center and received PhD in Biochemistry from Temple University in 1997. Then she continued her studies as a post-doctoral researcher in Dr. Paul Greengard's laboratory at the Rockefeller University. In Greengard's lab, Feng conducted research determining the impact of glutamate and dopamine in regulating synaptic activity through protein kinases. A highly productive effort resulted in novel inroads into synapse function, and publications of peer-reviewed articles. In 2002, Feng joined Neuroscience department at Wyeth Discovery Research in Princeton. She led the effort of identifying and validating a number of targets as well as extensive basic biology in Schizophrenia/Bipolar disorder areas. She also led a discovery breakthrough for ERβ biology that provided rationale and validation for pursing this target for multiple CNS therapeutics. Utilizing pharmacological, biochemical and behavioural techniques, she led a team of scientists to demonstrate for the first time that the effects of estrogens on hippocampal synaptic plasticity and memory in rodents are mediated through ERβ. Selective ERß agonists increase key synaptic proteins and induce morphological changes in hippocampal neurons in vivo, enhance LTP and improve performance in hippocampus-dependent memory tasks. This data set suggests that targeting ERß may have therapeutic potential without the feminizing effects of estrogens. Feng continues to lead the drug discovery effort at Pfizer of finding ERß selective agonist for treating CNS disorders, such as Alzheimer's disease and Schizophrenia. Dr. Liu holds two US patents and had published over 25 articles in journals such as Nature Neuroscience, PNAS, J. Biological Chemistry, Current Biology and JPET.

Speakers

Enikö Kramár, PhD

University of California, Irvine

Enikö A. Kramár graduated with a PhD in Neuroscience from Washington State University in 2000 and then continued her studies as a post-doctoral researcher in Dr. Gary Lynch’s laboratory at the UC Irvine (UCI). Supported by a NIH post-doctorate fellowship, Kramár made a series of discoveries showing that adhesion receptors belonging to the integrin family play a critical role in the consolidation (as opposed to induction and initial expression) of long-term potentiation (LTP). Using a method she helped invent, Kramár then found that integrins exert their consolidation effects by promoting the stabilization of actin networks that form shortly after LTP induction. Following promotion to an Assistant Researcher position in 2003, Kramár expanded her research program to include the question of whether integrins interact with releasable 'synaptic modifiers' to regulate the cytoskeletal changes underlying consolidation. This collaborative work ultimately resulted in the first clear descriptions of how Brain-Derived Neurotrophic Factor (BDNF) and adenosine modulate LTP consolidation. Before leaving to accept a position in industry in 2006, Dr. Kramár had published over 25 articles in journals such as PNAS, J. Biological Chemistry, and J. Neurosci. She returned to academia in 2007 as an Associate Project Scientist (UCI) to initiate a new research program testing if the plasticity and memory losses associated with low levels of estrogen can be explained within her model of LTP consolidation. These experiments led to the proposal that estrogen is itself a synaptic modifier acting positively on the same actin signaling pathways suppressed by adenosine. They have also pointed to a novel therapeutic strategy for offsetting the plasticity deficits that accompany conditions (e.g., menopause) in which estrogen levels are chronically depressed.

Bruce McEwen, PhD

Rockefeller University

Bruce S. McEwen, PhD, is the Alfred E. Mirsky Professor and Head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The Rockefeller University. He is a member of the US National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences and a Fellow of the New York Academy of Sciences. He served as Dean of Graduate Studies from 1991-3 and as President of the Society for Neuroscience in 1997-98. As a neuroscientist and neuroendocrinologist, McEwen studies environmentally-regulated, variable gene expression in brain mediated by circulating steroid hormones and endogenous neurotransmitters in relation to brain sexual differentiation and the actions of sex, stress and thyroid hormones on the adult brain. His laboratory discovered adrenal steroid receptors in the hippocampus in 1968. His laboratory combines molecular, anatomical, pharmacological, physiological and behavioral methodologies and relates their findings to human clinical information. His current research focuses on stress effects on amygdala and prefrontal cortex as well as hippocampus, and his laboratory also investigates sex hormone effects and sex differences in these brain regions. In addition, he served on the MacArthur Foundation Research Network on Socioeconomic Status and Health, in which he helped to reformulate concepts and measurements related to stress and stress hormones in the context of human societies. This led to the concept of “allostatic load” that describes the wear and tear on the body and brain from chronic stress and related life style behaviors that lead to dysregulation of physiological stress pathways that are normally protective. He is also a member of the National Council on the Developing Child which focuses on healthy brain development as a key to physical and mental health. He is the co-author of book with science writer Elizabeth Lasley for a lay audience called “The End of Stress as We Know It” published in 2002 by the Joseph Henry Press and the Dana Press and another book with science writer Harold M. Schmeck, Jr. called “The Hostage Brain” published in 1994 by The Rockefeller University Press.

John H. Morrison

Mount Sinai School of Medicine

Dr. John H. Morrison is Dean of Basic Sciences and the Graduate School of Biological Sciences, Professor of Neuroscience, and the Willard T.C. Johnson Professor of Geriatrics and Adult Development in Neurobiology of Aging at the Mount Sinai School of Medicine. Prior to becoming Dean, Dr. Morrison served as Chair of the Department of Neuroscience.

Dr. Morrison earned his doctorate from Johns Hopkins University in 1979 and completed postdoctoral studies at the Salk Institute for Biological Studies. He then served as a faculty member at The Salk Institute and The Scripps Research Institute. In 1989, he joined the faculty at Mount Sinai.

Dr. Morrison’s research incorporates basic neurobiological research on neuronal specialization and the biochemical coding of brain circuits with human neuropathology in order to illuminate the cellular events that lead to Alzheimer’s disease. His research also focuses on the neurobiological events that accompany normal aging, as well as the differences between these events and those that accompany Alzheimer’s disease. Within this context, Dr. Morrison is interested in the effects of estrogen on the cerebral cortex, the interface between endocrine and neural aging, and the effects of stress on cortical neurons. Since 1985 the National Institutes of Health has funded Dr. Morrison’s research without interruption. He currently directs a large program on estrogen and the aging brain funded by the National Institute on Aging (NIA), as well as one on the neurobiological basis of cognitive aging that has been designated as an NIA MERIT Award. In addition Dr. Morrison is a project leader in the NIMH-funded Conte Center for the Neuroscience of Fear and Anxiety.

Dr. Morrison has published more than 250 scholarly works on the molecular, cellular, and neuroanatomic organization of the cerebral cortex, the cellular pathology of neurodegenerative disorders, and the neurobiology of aging. He is ranked among the most highly cited investigators in neuroscience (i.e. ISIHighlyCited/Neuroscience), and has served on multiple editorial boards.

Dr. Morrison is the recipient of numerous research awards and is a Fellow in both the New York Academy of Sciences (NYAS) and the American Association for the Advancement of Science (AAAS). He has served on advisory boards and review committees of several leading scientific organizations, including the National Institute of Aging, National Institute of Mental Health, The Howard Hughes Medical Institute, Society for Neuroscience, American Federation for Aging Research, and Amyotrophic Lateral Sclerosis Association.