Michael Frohman

 
Michael Frohman

 

Distinguished Professor and Chair of Pharmacological Sciences
Medical Scientist Training Program Director

Ph.D., M.D. University of Pennsylvania

Phone: (631) 632-1476
michael.frohman@stonybrook.edu

Pharmacology Faculty Profile Page

 

 

Research

Our laboratory examines lipid signals that alter cell morphology, regulate mitochondrial fusion, and trigger subcellular trafficking of membrane vesicles during regulated exocytosis and endocytosis. Disease-related topics include neurodegenerative disease (Charcot-Marie Tooth syndrome), diabetes, cancer, and impaired phagocytic immune responses to pathogens.

The specific topic constitutes study of signaling pathways mediated by members of the superfamiles of enzymes known as Phospholipase D (PLD) and PI4P Kinase. Classic PLD is activated by a wide variety of agonists that signal through G-protein coupled or tyrosine kinase receptors. PLD has varied cellular roles including facilitating membrane vesicle trafficking and fusion of the vesicles into the plasma membrane during regulated exocytosis, and reorganizing the actin cytoskeleton. We are currently investigating roles for PLD and PI4P lipid kinase in actin cytoskeleton reorganization, myoblast differentiation and fusion, Glut-4 glucose transporter translocation, phagocytosis, and regulated exocytosis (insulin and histamine release). In addition, we are exploring a novel member of the PLD superfamily that localizes to mitochondria and regulates fusion, and the mechanisms through which diminished rates of fusion cause neurodegenerative disease.

  • Publications
  • Laboratory Personnel
  •  
    • Zhao, C., Du, G., Frohman, M.A., and Bar-Sagi, D. (2007) PLD2-generated PA couples EGFR stimulation to Ras activation by Sos. Nature Cell Biology, 9:707-712.
    • Zeniou-Meyer et al. (2007) PLD1 production of phosphatidic acid at the plasma membrane promotes exocytosis of large dense-core granule at a late stage. J. Biol. Chem., 282:21746-57.
    • Huang, P. and Frohman, M.A. (2007) The potential for PLD as a new therapeutic target. Expert Opinion on Therapeutic Target 11:707-16.
    • Kobayashi-Nakano et al. (2007) Role of AP-2 complex activation of phosphatidylinositol 4-phosphate 5-kinase γ661 in synaptic vesicle endocytosis. EMBO J. 26:1105-16.
    • Choi, S.-Y., Huang, P., Jenkins, G.M., Chan, D.C., Schiller, J., and Frohman, M.A. (2006) A common signaling lipid requirement for Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis. Nature Cell Biology, 8:1255-62.
    • Scotto-Lavino, E., Du, G., and Frohman, M.A. Amplification of 5’ end cDNA with ‘New RACE’. (2006) Nature Protocols, 1:3056-61.
    • Vicogne, J., Vollenweider, D., Smith, J., Huang, P., Frohman, M. and Pessin, J. (2006) Asymmetric phospholipid distribution drives in vitro reconstituted SNARE-dependent membrane fusion. Proc Natl Acad Sci U.S.A., 103:14761-6.
    • Cai, D., Netzer, W.J., Zhong,, M., Lin, Y., Du, G., Frohman, M.A., Foster, D.A., Sisodia, S.S., Gorelick, F.S., Xu, H.. and Greengard, P. (2006) Presenilin-1 (PS1) utilizes Phospholipase D1as a negative regulator of b-amyloid formation. Proc Natl Acad Sci U.S.A. 103:1941-6.
    • Huang, P., Jiang, Z., Wong, Y.C., Chung, S.K., Frohman, M.A., and Chung, S.S.M. (2006) Overexpression of PLD2 in the lens increases Na, K-ATPase activity and causes cataract development. Invest. Ophthalmol. Visual Sci. 83:939-48.
    • Sasaki et al. (2005) The phosphatidylinositol 4-phosphate 5-kinase PIPKIa is a negative regulator of anaphylaxis and FcgRI signaling. J. Exp. Med., 201:859-70.
    • LaLonde, M.M., Janssens, H., Rosenbaum, E., Choi, S.-Y., Gergen, J.P.,  Colley, N.J., Stark, W.S., and Frohman, M.A. (2005) Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D–generated signaling lipid. J. Cell Biol. 169:471-9.
    • Watanabe, H., Yokozeki, T., Yamazaki, M., Miyazaki, H., Sasaki, T., Maehama, T., Itoh, K., Frohman, M.A., and Kanaho, Y. (2004) Essential role for PLD2 activation downstream of ERK MAP kinase in NGF-stimulated neurite outgrowth from PC12 cells. J. Biol. Chem., 279:37870-7.
  • Dr. Phyllis Tsang, Postdoctoral Fellow
  • Dr. Xiaoxue Peng, Postdoctoral Fellow
  • Wenjuan Su, Graduate Student
  • Akua Bonsra, Graduate Student
  • Liz Scotto-Lavino, Graduate Student
  • Mary Osisami, Graduate Student
  • Winnie Huang, Graduate Student
  •  Yeku Oladapo, Graduate Student (MSTP)
  • Krishna Sharma, undergraduate (HHMI, AGEP)
  • Alex Chamessian, undergraduate (HHMI)
  • Alyssa Genna, undergraduate
  • Yelena Altshuller, Senior Research Support Specialist
  • Jon Wood, Administrative Assistant