Matthew Dalva, PhD

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				Matthew B. Dalva, Ph.D. Assistant Professor, Dept of Neuroscience School of Medicine 1114 BRB II/III Tel: (215) 746-2752 Fax: (215) 573-7601 Email: dalva@mail.med.upenn.edu Lab Web Site: mail.med.upenn.edu/~dalvalab Click here for selected publications since Dr. Dalva's arrival at Penn RESEARCH INTERESTS My laboratory studies the mechanisms that directs neurons to form synaptic connections early in development, the functional significance of appropriately formed synaptic contacts, and the dynamics of the intracellular signaling that mediate these events. RESEARCH TECHNIQUES Molecular and cell biology; biochemistry; physiology; single + multi-photon microscopy; brain slice and neuronal cell culture; proteomics and genomics. RESEARCH SUMMARY Central nervous system (CNS) synapses - specialized sites of cell-cell contact that mediate transmission of information between neurons - represent a major site of regulation within neural networks. As a result, increased understanding of synapse formation and refinement will provide fundamental insights into how the nervous system acts to store information and modulate behavior. Moreover, work within this field has important implications in the study of addiction as well as a variety of human developmental and neurodegenerative disorders. Over the last decade, significant progress has been made in identifying both the extracellular factors and membrane-associated receptors and ligands that regulate synaptic development. Such transmembrane proteins include EphB/ephrinB, synCAM, SALM2, NGL-2, neurexin/neuroligin and cadherins . Despite these advances, the molecular mechanisms that underlie synapse formation as well as how these diverse factors act to coordinate synapse formation in the developing animal remain to be determined. We have focused our efforts on understanding the role of the EphB family of receptor tyrosine kinases and their ephrinB ligands. Importantly, removal of all EphB proteins from cortex results in a loss of 40% of excitatory synaptic contacts in vivo . Thus, identification of the mechanisms by which Eph signaling promotes synaptic development will provide important insights into the processes controlling synapse formation and refinement. To develop a detailed picture of the events underlying synapse development, we take an integrated approach relying on electrophysiology, biochemistry, molecular and cell biology, intrinsic signal imaging, and 2-photon microscopy. By having all of these tools in one laboratory, we can effectively examine the cellular and molecular mechanisms that guide synaptogenesis. Currently, there are three major ongoing projects in my laboratory, which together aim towards a comprehensive understanding of cortical synapse development. First we are examining how one set of candidate molecules, EphB/ephrinBs, acts to coordinate the formation of pre- and postsynaptic specializations. Second we are exploring how the presence of certain types of synaptic contacts is relevant to the development of functional circuits. Finally we seek to visualize the dynamic signaling events at single cell and sub-cellular levels in living tissues and organisms as neurons begin to form synapses.