Wilma Friedman

Wilma Friedman

Email

wilmaf [at] newark.rutgers.edu

Phone

973-353-1160,973-353-1161

Office Location

501D Life Sciences Building

Cellular Neurobiology

Neurotrophic factors are proteins that are traditionally known to influence survival and function of neurons in the central and peripheral nervous systems. Recent studies, however, have shown that specific neurotrophic factors may cause neuronal death instead of survival, depending upon which receptors and signaling pathways are activated.  When these factors activate their receptor tyrosine kinase, the Trk receptors, they promote neuronal survival, axonal growth, and support many aspects of neuronal function.  However, when these factors activate the p75 neurotrophin receptor, they can elicit neuronal death, axonal retraction and degeneration.  We are examining mechanisms governing death- vs. survival-promoting actions of nerve growth factor and related neurotrophins during development and under conditions of brain injury.   Although the p75 neurotrophin receptor can evoke neuronal death in the context of brain injury, we find that in the developing brain, this receptor can regulate proliferation of neuronal progenitor cells.  Thus, we find that these factors have different functions depending on the cellular context. 

Work in my lab investigates specific cellular mechanisms of neurotrophin actions on CNS neurons and glia during development and after brain injury.  We use primary cultures of embryonic neurons  to investigate mechanisms by which specific trophic factors influence neuronal survival, differentiation or degeneration.  We also use in vivo models of brain injjury to determine how these factors regulate survival or degeneration under these conditions.  Our work is geared to understanding how these factors affect neuronal survival and function, development and degeneration, and how they may ultimately influence neuronal survival under inflammatory conditions associated with disease and injury  in the brain.

Education

B.A., Oberlin College, 1979.
Ph.D., The Rockefeller University, 1986.

Publications

Dasgupta, S., L. Montroull, M. Pandya, W. Wang, Z. Wu, and W.J. Friedman, Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via p75NTR, eNeuro in press

Zanin, J.P., M.A. Pandya, D. Espinoza, W.J. Friedman, and M.W. Shiflett, Excess cerebellar granule neurons induced by the absence of p75NTR during development elicit social behavior deficits in mice, Frontiers in Molecular Neuroscience, Volume 16, | https://doi.org/10.3389/fnmol.2023.1147597, 2023

Subhashini Joshi, Michelle J. Frondelli, Juan P. Zanin, Steven W. Levison and Wilma J. Friedman, Oligodendrocyte progenitor development from the postnatal rat subventricular zone is regulated by the p75 neurotrophin receptor, Glia, https://doi.org/10.1002/glia.24430, 2023

Zanin, J.P. and W.J. Friedman, p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation, eLife, https://doi.org/10.7554/eLife.79934, 2022

Montroull, L.E., D. Rothbard, H.D. Kanal, V. D'Mello, V. Dodson, C.M. Troy, J.P. Zanin, S.W. Levison, and W.J. Friedman, Proneurotrophins induce apoptotic neuronal death after controlled cortical impact injury in adult mice, ASN Neuro, 12: 1-13, https://doi.org/10.1177/1759091420930865, 2020

Zanin, J.P., L.E. Montroull, M. Volosin, and W.J. Friedman, p75NTR modulated TrkB trafficking and signalling in response to BDNF treatment in hippocampal neurons, Frontiers in Cellular Neuroscience, https://doi.org/10.3389/fncel.2019.00485, 2019

Zanin, J.P., J. Verpeut, Y. Li, M.W. Shiflett, S.-S. Wang, V. Santhakumar, and W.J. Friedman, The p75NTRinfluences cefebellar circuit development and adult behavio via regulation of cell cycle duration of granule cell progenitors,  J. Neurosci. 39 (46): 9119-9129, https://doi.org/10.1523/JNEUROSCI.0990-19.2019, 2019

Saadipour, K., A. Tiberi, S. Lomardo, L. Montroull, N. Manucat, J. LaFancois, M. Cammer, P. Mathews, H. Scharfman, F.-F. Liao, W. Friedman, X.-F. Zhou, G. Tesco, and M. Chao, REgulation of BACE1 expression after injury is linked to the p75 neurotrophin receptor, Mol. Cell Neurosci., 99, https://doi.org/10.1016/j.mcn.2019.103395, 2019

Cragnolini, A.B. G. Montenegro, W.J. Friedman, and D.H. Masco, Brain-region specific responses of astrocytes to an in vitro injury and neurotrophins, Mol. Cell. Neurosci, 88: 250-248, https://doi.org/10.1016/j.mcn.2018.02.007, 2018

Greenwood, S.G., L. Montroull, M. Volosin, H.E. Scharfman, K.K. Teng, M. Light, R. Torkin, F. Maxfield, B.L. Hempstead, and W.J. Friedman, A novel neuroprotective mechanism for lithium that prevents association of the p75NTR-sortilin receptor complex and attenuates proNGF-induced neuronal death in vitro and in vivo, eNeuro 5 (1) : https://doi.org/10.1523/ENEURO.0257-17, 2017

Zanin, J.P., E. Abercrombie, and W.J. Friedman, Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrohin receptor, eLife, 10.7554/eLife.16654, 2016

VonDran, M.W., J. LaFrancois, V.A. Padow, W.J. Friedman, H.E. Scharfman, T.A. Milner, and B.L. Hempstead, ProBDNF, but not proNGF, is upregulated following seizures in mice, ASN Neuro, 10.1177/1759091414552185, 2014

Friedman, W.J. A.P. Le, S. Choi, and M. Volosin, Seizures tip the balance of neurotrophin signaling toward neuronal death, in Handbook of Neurotoxicology "Physiology and pathophysiology of neurotrophins" (R.M. Kostrzewa, ed) Springer, pp. 1945-1953, 2014

Choi, S. and W.J. Friedman, Interleukin-1ß enhances neuroal vulnerability to proNGF-mediated apoptosis by increasing surface expression of p75NTR and sortilin, Neuroscience, 257: 11-19, 2014

Cragnolini, A.B., Volosin, M., Huang, Y.Y., and W.J. Friedman WJ.  Nerve growth factor induces cell cycle arrest of astrocytes.  Dev Neurobiol. 72(6):766-776, 2012.

Pichardo-Casas, I., Goff, L.A., Swerdel, M.R., Athie, A., Davila, J., Ramos-Brossier, M., Lapid-Volosin, M., Friedman, W.J., Hart, R.P., and L. Vaca.  Expression profiling of synaptic microRNAs from the adult rat brain identifies regional differences and seizure-induced dynamic modulation.  Brain Res. 1436:20-33, 2012.

Le, A.P., and W.J. Friedman.  Matrix metalloproteinase-7 regulates cleavage of pro-nerve growth factor and is neuroprotective following kainic acid-induced seizures.  J. Neurosci. 32(2):703-712, 2012.

Huang, Y.Y., Smith, D.E., Ibanez-Sandoval, O., Sims, J.E., and W.J. Friedman.  Neuron-specific effects of Interleukin-1 beta are mediated by a novel isoform of the IL-1 receptor accessory protein.  J. Neurosci. 31(49):18048-18059, 2011.

Song, W., Volosin, M., Cragnolini, A.B., Hempstead, B.L., and W.J. Friedman, ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons, J Neurosci. 30(46):15608-15615, 2010.

W.J. Friedman, Proneurotrophins, seizures, and neuronal apoptosis, Neuroscientist 16(3): 244-252, 2010.