Yale Combined Program in the Biological and Biomedical Sciences (BBS): Biochemistry, Biophysics and Structural Biology: Cell Cycle and Signal Transduction; Membrane Biology and Motion; Neurobiology
Have you ever wondered how your brain got wired? How a single neuron finds a unique signaling partner among over 10 billion other neurons? During
development neurons not only face this daunting task but often migrate extremely long distances (>50,000 cell diameter equivalents) to accomplish it.
My lab focuses on this problem and the specialized guidance device called the growth cone that provides the motility and signal transduction capabilities
needed for axon guidance. Current lab projects include: 1) Molecular motor and cytoskeletal protein dynamics underlying growth cone motility. 2) Cell surface receptors involved in target recognition. 3) Investigation of signal transduction pathways involved in controlling the cytoskeletal protein effectors involved. We address the relevant cell biological processes using a "molecular physiology"
approach. This typically entails generation of molecular probes to investigate dynamics of the process and/or protein-protein interactions in living neurons. We use a variety of high resolution imaging and biophysical approaches such as: multimode fluorescent speckle microscopy, laser trapping, photobleaching, and "caged" probe photoactivation.
Extensive Research Description
- Actin filament turnover dynamics in neuronal growth
- Rho GTPase and Ca signaling crosstalk in regulation of motility
- Mechano-transduction in axon growth and neuronal differentiation
- 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
- 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.
- 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.
- 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.
- 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.
- 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. 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. 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. 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. Medeiros NA, Burnette DT, Forscher P. Nat Cell Biol. 2006 Mar;8(3):215-26.