ZNI Scientific Advisory Board
The following individuals, all world-renowned scientists who are experts in their respective fields, have agreed to assist the Zilkha Neurogenetic Institute achieve its mission of engaging in first-rate research by serving on the ZNI Scientific Advisory Board. The members visit and meet periodically to review and evaluate ZNI’s progress in blending the very best translational and clinical neuroscientists in an effort to solve the mystery of disease etiologies and produce new treatments. Their fresh ideas and unique viewpoints help ZNI be the best that we can be.
Michael E. Greenberg PhD
Director, Division of Neuroscience, Department of Neurology, Children’s Hospital Boston
Nathan Marsh Pusey Professor & Chair of Neurobiology, Harvard Medical School
The Greenberg laboratory has a long-standing interest in the mechanisms by which neurotrophic factors and neurotransmitters act through cell surface receptors to regulate transcriptional responses that are critical for nervous system development and function. Michael Greenberg began his research in this area with the observation that growth factors and neurotrophic factors trigger the induction of c-fos proto-oncogene transcription within minutes of receptor tyrosine kinase activation (Greenberg and Ziff, 1984). He and his group have for many years characterized in some detail the signaling pathways by which neurotrophic factors induce the transcription of c-fos and other immediate early genes, with an emphasis on the role that protein phosphorylation cascades play in this process. Their studies, together with those of other laboratories, have led to the identification of a network of signaling cascades that couple growth factor activation of cell surface receptors to transcriptional responses. Over the last decade, these studies have expanded to include investigation of the effects of extracellular factors and intracellular signaling pathways on the processes of axon guidance, cell fate determination, synaptic development, and neuronal survival within the developing and adult nervous system. Today, the lab studies many aspects of neuronal signaling and biology.
Richard I. Morimoto PhD
Director, Rice Institute for Biomedical Research
Bill & Gayle Cook Professor of Biology, Northwestern University
The current research in Richard Morimoto’s laboratory is to understand how eukaryotes sense and respond to physiologic and environmental stress by the activation of stress signaling pathways that integrate stress responses with cell growth and cell death. At the biochemical level, they are investigating how molecular chaperones recognize and capture folded intermediates and the processes by which proteins are refolded, degraded or undergo aggregation. Through the combination of molecular, cellular, and genetic approaches, they hope to understand how misfolded proteins and protein aggregates cause diseases such as Huntington's, Parkinson's, ALS, Scrapie/Prion, Cystic Fibrosis, and Alzheimers. Specifically, the Morimoto laboratory is interested in the fundamental events that underlie the appearance of misfolded proteins and their consequence to protein homeostasis, cellular function, and organismal adaptation and survival: transcriptional regulation of heat-shock response; the roles of molecular chaperones in protein folding and trafficking and as stress sensors in cell growth and death; molecular events associated with the expression of misfolded and aggregation-prone proteins in neurodegenerative diseases; C. elegans as a model system for analysis of stress response and diseases of protein misfolding; small molecular screening for the stress response.
Nicholas C. Spitzer PhD
Distinguished Professor & Vice Chair, Section of Neurobiology
University of California, San Diego
Specification of neurotransmitters and selection of transmitter receptors are processes that depend on patterned spontaneous embryonic calcium-dependent electrical activity. The Spitzer lab is investigating the triggers of this spontaneous activity to understand its origins. Nicholas Spitzer and his associates are studying activity-dependent regulation of expression of serotonin and dopamine in the embryonic brain, because these transmitters have broad impact on cognitive states and on behavior. They have begun analyzing the signaling mechanisms mediating activity-dependent transmitter specification, generating transgenic lines expressing fluorescent reporters of neurotransmitter synthesis to enable mutant screens. They are determining the extent to which there is environmental regulation of activity-dependent differentiation at early stages of development, revealing a partnership of electrical activity and genetic programs in the assembly of the nervous system. Their work is aimed at understanding the roles of electrical activity in assembly of the nervous system, by analyzing the effects of calcium transients on neuronal differentiation and determining the molecular mechanisms by which they exert these effects.
Stephen T. Warren PhD
William Patterson Timmie Professor & Chair of Human Genetics
Professor of Biochemistry & Pediatrics, Emory University School of Medicine
Research in the Warren lab is directed toward understanding the mechanisms of human diseases. A large component of the research program involves fragile X syndrome, a common cause of mental retardation and autism that is due to a trinucleotide repeat expansion in the FMR1 gene. The research is multifaceted and broad in approach. Dr. Warren’s group works with patients as well as with model systems (mouse, fly, and cell culture) to understand the pathophysiology of the disorder. For example, biochemical and neurobiological studies are directed at understanding the consequence of the loss of FMR1 expression on local protein synthesis (the normal function of the encoded protein) in neuronal dendrites. Drosophila and mouse studies are aimed at discovering and evaluating potential drugs that may abrogate the loss of FMR1 function. Large-scale resequencing of FMR1 in patients is being undertaken to uncover conventional mutations and examine genotype/phenotype correlations. High-throughput diagnostics have been developed for ongoing prevalence studies in 100,000 newborns. Other studies involve genome-wide analysis of copy number variation in humans as normal polymorphisms as well as pathological variants influencing schizophrenia or cognitive deficiencies.
For more information about the ZNI Scientific Advisory Board, please contact ZNI at zni@usc.edu