Forscher, Paul - Yale University - Biological & Biomedical Sciences

个人简介

I did my PhD thesis work in the Neuroscience Graduate Program at UNC Chapel Hill from 1979-1985. In Dr. Gerry Oxford’s lab I received training in classical excitable membrane biophysics and used the then emergent technology of “patch clamping” to investigate the mechanism of voltage dependent Calcium channel modulation by biogenic amines in dorsal root ganglion (sensory) neurons. In 1985, I joined Dr. Stephen Smith’s lab in the Section of Molecular Neurobiology and HHMI at YaleUniversity for post doctoral work. I maintained a keen interest in Calcium as a signaling molecule and was hoping to gain some experience in Calcium imaging to compliment my electrophysiological studies; however, by a quirk of scientific fate I began investigating neuronal growth cone motility using high resolution video enhanced DIC microscopy. This unexpected turn of events led me directly into the study of cell motility –a descriptive field of research at the time, especially when compared to the quantitative realm of ion channel biophysics which I was accustomed to. Working in cell motility necessitated learning about cytoskeletal protein dynamics and function, and I embarked on the road to becoming a cell biologist. In 1989 I started my lab in the Department of Biology (now the Department of Molecular, Cellular, and Developmental Biology) at Yale University. Our research initially focused on characterizing the cytoskeletal protein dynamics and molecular motor activity underlying growth cone motility. Over the years I have maintained an interest in understanding how classical signal transduction pathways (Ca, PKC, PKA, etc.) modulate cytoskeletal machinery to affect axon growth and guidance. To investigate mechanisms of growth cone guidance, we developed an in vitro turning assay using silica bead substrates coated with attractive cell adhesion molecules. These bioassays were first used to identify signal transduction pathways involved in substrate dependent growth cone turning and to characterize the role traction forces play in axon advance. A role for src family tyrosine kinases as mechano-transduction sensors emerged from this work. Recently we have been developing biophysical methods for measuring traction forces that growth cones exert on the underlying substrate while co-assessing cytoskeletal dynamics with fluorescently tagged proteins. These studies yield quantitative data amenable to mathematical modeling of the fundamental processes underlying neuronal growth and regenerative processes. PhD UNC Chapel Hill, Neurobiology (1985) Postdoctoral Fellow Yale HHMI

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Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating Zhang et al, Cell. 2016 Mar 16. pii: S0092-8674(16)30111-8. doi: 10.1016/j.cell.2016.02.009 Dynamic peripheral traction forces balance stable neurite tension in regenerating Aplysia bag cell neurons Hyland C, Mertz AF, Forscher P, Dufresne E. Sci Rep. 2014 May 14;4:4961. doi: 10.1038/srep04961 Regeneration of Aplysia bag cell neurons is synergistically enhanced by substrate-bound hemolymph proteins and laminin Mejean CO, Schaefer AW, Buck KB, Kress H, Shundrovsky A, Merrill JW, Dufresne ER, Forscher P. PLoS One. 2013 Sep 6;8(9):e73389. doi: 10.1371/journal.pone.0073389. eCollection 2013 Elastic coupling of nascent apCAM adhesions to flowing actin networks Mejean, C.O., A.W. Schaefer, K.B. Buck, H. Kress, A. Shundrovsky, J.W. Merrill, E.R. Dufresne, and P. Forscher. 2013. Elastic coupling of nascent apCAM adhesions to flowing actin networks. PloS one. 8:e73389. Protein kinase C activation decreases peripheral actin network density and increases central nonmuscle myosin II contractility in neuronal growth cones Yang, Q., X.F. Zhang, D. Van Goor, A.P. Dunn, C. Hyland, N. Medeiros, and P. Forscher. 2013. Protein kinase C activation decreases peripheral actin network density and increases central nonmuscle myosin II contractility in neuronal growth cones. Molecular biology of the cell. 24:3097-3114. Arp2/3 complex-dependent actin networks constrain myosin II function in driving retrograde actin flow Yang, Q., X.F. Zhang, T.D. Pollard, and P. Forscher. 2012. Arp2/3 complex-dependent actin networks constrain myosin II function in driving retrograde actin flow. The Journal of cell biology. 197:939-956. Membrane tension, myosin force, and actin turnover maintain actin treadmill in the nerve growth cone Craig, E.M., D. Van Goor, P. Forscher, and A. Mogilner. 2012. Membrane tension, myosin force, and actin turnover maintain actin treadmill in the nerve growth cone. Biophysical journal. 102:1503-1513. Calcineurin-dependent cofilin activation and increased retrograde actin flow drive 5-HT-dependent neurite outgrowth in Aplysia bag cell neurons Zhang, X.F., C. Hyland, D. Van Goor, and P. Forscher. 2012. Calcineurin-dependent cofilin activation and increased retrograde actin flow drive 5-HT-dependent neurite outgrowth in Aplysia bag cell neurons. Molecular biology of the cell. 23:4833-4848. Coordination of actin filament and microtubule dynamics during neurite outgrowth Coordination of actin filament and microtubule dynamics during neurite outgrowth. Schaefer AW, Schoonderwoert VT, Ji L, Mederios N, Danuser G, Forscher P. Dev Cell. 2008 Jul;15(1):146-62. Myosin II activity facilitates microtubule bundling in the neuronal growth cone neck Myosin II activity facilitates microtubule bundling in the neuronal growth cone neck. Burnette DT, Ji L, Schaefer AW, Medeiros NA, Danuser G, Forscher P. Dev Cell. 2008 Jul;15(1):163-9. Filopodial actin bundles are not necessary for microtubule advance into the peripheral domain of Aplysia neuronal growth cones Filopodial actin bundles are not necessary for microtubule advance into the peripheral domain of Aplysia neuronal growth cones. Burnette DT, Schaefer AW, Ji L, Danuser G, Forscher P. Nat Cell Biol. 2007 Dec;9(12):1360-9. Myosin II functions in actin-bundle turnover in neuronal growth cones Myosin II functions in actin-bundle turnover in neuronal growth cones. Medeiros NA, Burnette DT, Forscher P. Nat Cell Biol. 2006 Mar;8(3):215-26.