Paul Forscher, PhD
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About
Titles
Professor of Molecular, Cellular, and Developmental Biology
Biography
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.
Education & Training
- Postdoctoral Fellow
- Yale HHMI (1988)
- PhD
- UNC Chapel Hill, Neurobiology (1985)
Research
Overview
- 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
Links & Media
Media
Traction Force Microspcopy
Traction forces measured in a neuronal growth cone moving on a substrate with a calibrated elastic modulus. Middle panel shows the stress vector field and net stress (large green arrow) the growth cone is exerting on the underlying substrate. Right image is a map of the work being done by the growth cone as it moves forward.Actin filament flow map
Vector map of actin filament kinematics obtained from single molecule tracking experiment.Cytoskeletal protein domains
Actin filaments (red), mictrotubules (blue) and intrapodia (yellow) in a neuronal growth cone.Neuronal growth cone ultra-strucutre
Ultrastructure of the growth cone neck. Microtbules labeled with colloidal gold (green), actin filaments (rec), clathrin coated pits (blue)Optical trapping
A laser trap (or tweezers) is being used to assess traction forces applied to a glass bead coated with an Ig super-family cell adhesion molecule.