Dr. Huber obtained her Ph.D. in Neurobiology from the University of Texas Health Science Center at Houston where she worked in the laboratory of Dr. Paul Kelly studying the role of protein kinases in long-term potentiation of synaptic transmission. Dr. Huber completed a postdoc with Dr. Mark Bear at Howard Hughes Medical Institute and Brown University. In Dr. Bear&rsquos lab she discovered a novel form long-term synaptic depression, termed LTD, which relies on rapid synthesis of new proteins locally at synapses. She went on to show that this form of synaptic plasticity is specifically altered in the mouse model of Fragile X Syndrome, a form of human mental retardation and autism. New therapeutic strategies for treatment of Fragile X Syndrome and autism have been developed based on her research findings and are currently being tested. She joined the faculty at University of Texas Southwestern Medical School in 2001 where she received an Endowed Scholars Award for Biomedical Research.
Research Interests: One major focus of the Huber lab is to understand the cellular and molecular mechanisms which mediate synaptic plasticity. A major mechanism by which synaptic plasticity occurs is through the localized and synaptic synthesis of new proteins. Much of our work is focused on studying a form of synaptic weakening or depression which relies on very rapid, protein synthesis at synapses. Long-term synaptic depression or LTD is induced by activation of Gq coupled receptors, such as the metabotropic glutamate receptors (mGluRs). By studying the mechanisms mGluR-dependent LTD, we can address major research questions such as: How does synaptic activity regulate rapid protein synthesis at synapses? What are the proteins which are synthesized and how do they affect synapse function? What role does synaptic or dendritic protein synthesis play in the nervous system and how do alterations or dysfunction of the dendritic protein synthesis machinery contribute to neurological disease?
Altered synapse structure and dysfunction is thought to be the origin of many neurological diseases. Motivated by our basic research findings, we discovered altered synaptic plasticity and function in the mouse model of mental retardation and autism, Fragile X Syndrome. Therefore, another aim of the lab is to identify and understand how alterations in synaptic function and connectivity lead to mental retardation and autism. Specifically, we find that LTD is enhanced and abnormally regulated in a mouse model of human mental retardation, Fragile X Syndrome. Fragile X Syndrome is caused by loss of function mutations in an RNA binding protein called Fragile X Mental Retardation Protein (FMRP) which is an RNA binding protein and regulates protein synthesis at synapses. A third goal of our lab is to determine how RNA binding proteins, such as FMRP, regulate dendritic protein synthesis and, in turn, synapse function. To address these research questions we use a multi-disciplinary approach including electrophysiology, imaging, and biochemical methods in the hippocampus and neocortex, major brain structures implicated in human cognition. Work is our laboratory is supported by grants from the NIH-NINDS, the FRAXA Research and Autism Speaks Foundations.
