Faculty / Research

The Frohman Laboratory

MICHAEL A. FROHMAN, MD,PHD

Professor and Chair
 

Director, Medical Scientist Training Program

Postdoctoral fellowship, University of California at SanFrancisco

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

B.S. with Distinction, High Honors in Chemistry and in Cellular & Molecular Biology, University of Michigan

Lipid Signaling: Roles in mitochondrial biology, spermatogenesis, diabetes, immune function, the CNS, platelet activation, and cancer; - Imaging Pancreatic β-cells using metabolomics and MRI.

 

The Frohman Laboratory

Research InterestsSelected Publications CMM
Molecular Cloning FacilityCurrent Lab MembersFormer Lab Members

 


 

Research Interests:

Regulation of exocytosis, cell shape, and mitochondrial fusion by lipid signaling pathways

 

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.


Lab Members

TitleNameDegreeProjectPhone#
Principal InvestigatorMichael Frohman

 
MD, PhD, U. Penn.Making lab members feel happy about working hard 
 Sr. Research Support Specialist

Yelena Altshuller

 

MS, College of Chemistry & Pharmacology, 

St. Petersburg, Russia

 

Lab manager and Supervisor, Molecular Cloning Facility

 

2-1477

 Administrative Assistant

Jon Wood

 

BA, SUNY at Stony Brook

 Administration 631-632-1634

Postdoctoral Fellow

Phyllis Tsang PhD, Univ.of Hong Kong MRI imaging of pancreatic beta-cells  
Postdoctoral Fellow Xiao Xue (Sherry) Peng Ph.D., Shanghai U.  Structural biology of MitoPLD  
Postdoctoral Fellow  Qin (Grace) ChenShanghai Institute of Materia Medica Functional roles for PLD
Postdoctoral FellowQun GaoPh.D., New York Medical College Imaging Mitochondrial fusion

Graduate Student

Mary Osisami

 

 BS, SUNY Stony Brook Functional analysis of PLD superfamily proteins 

 

Postdoctoral Fellow

 

Wenjuan Su

 

 Ph.D., Stony Brook University Phosphoinositides and phagocytosis; PLD inhibitor 
Graduate Student

Huiyan Huang

BS, Fudan Univ., 

Shanghai, P. R. of China 

 Mitochondrial fusion 
Graduate Student

Oladapo Yeku

BS, Medgar Evers College Mitochondrial fusion and disease 
Graduate Student

Wahida Ali


B.S. SUNY Binghamton PLD roles in phagocytosis 

Graduate Student-mentor:

Dr. Guangwei Du

Akua Bonsra-Roach

 B.S. Stony Brook University PIP Kinases and PA 

 


 

Former Lab Members:

Past Title Name Current Position
TechnicianRitu Goyanka Graduate Student, NYU
 Wei AoTechnician, SUNY Stony Brook
Post-Docs
Olga E. Redina
Assoc.. Prof., U. Novosibirsk, Russia
 Juan A. CrosbyPost-doc., UMDNJ, Newark, NJ

Hilde JanssensFlyMine Administrator, England
 Guangwei Du
Assistant Professor, University of Texas at Houston
 Gary Jenkins
 
 Xiao Yu   
 
 Ping Huang
Instructor, Harvard University
Grad. Students
William C. Colley
Post-doc., St. Judes Hospital, Memphis, TN
 Tsung-Chang Sung
Post-doc., The Salk Institute
 Yue Zhang
Post-doc., SUNY Stony Brook
 Suyong Yun
Clinical pharmacology and discovery medicine investigator
 Si Wu
Graduate Student, Computer Science, SUNY Stony Brook
 Danxia Ke
Memorial Sloan-Kettering Cancer Center, New York, NY
 Nianzhou Xiao
Medical Residency
 Margie LaLonde
Resident, Fast-track program in Psychiatry, Columbia University
 Seok-Yong Choi
Assistant Professor Chonam University, South Korea
 Elizabeth Scotto-LavinoPost-doc, BNL

 


Selected Publications:


Huang, H., Gao, Q. Peng, X.X., Choi, S.-Y., Sarma, K., Ren, H., Morris, A.J., and Frohman, M.A. (2011) piRNA-associated germline nuage formation and spermatogenesis require MitoPLD pro-fusogenic mitochondrial-surface lipid signaling. Developmental Cell, 20:376-387.

Huang, P., Yeku, O., Zong, H., Tsang, P., Su, W., Xu, X., Teng, S., Osisami, M., Kanaho, Y., Pessin, J.E., and Frohman, M.A. (2011) PI4P5-Kinase a deficiency alters dynamics of glucose-stimulated insulin release and protects against type 2 diabetes and obesity in mice. Diabetes,60:454-63.

Elvers et al., (2010) Impaired integrin aIIbb3 activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Science Signaling, 3:1-10.

Tsukahara et al. (2010) The novel second messenger Cyclic PA Negatively Regulates the Nuclear Hormone Receptor PPARγ. Molecular Cell, 39:421-32.

Dall’Armi, C., Hurtado-Lorenzo, A., Voronov, S.V., Yeku, O., Frohman, M.A., and Di Paolo, G. (2010) The Phospholipase D1 Pathway Modulates Macroautophagy. Nature Communications, 1:142-152.

Scotto-Lavino, E., Garcia-Diaz, M., Du, G., and Frohman, M.A. (2010) The basis for the isoform-specific interaction of Myosin Phosphatase subunits PP1c b and MYPT1. J. Biol. Chem., 285:6419-24.

Huang, H., Choi, S.-Y., and Frohman, M.A. (2010) A Quantitative Assay for Mitochondrial Fusion using Renilla Luciferase Complementation. Mitochondrion, 10:559-66.

Nishikimi et al. (2009) Sequential Regulation of DOCK2 Dynamics by Two Phospholipids during Neutrophil Chemotaxis. Science, 324:384-7.

Du, G. and Frohman, M.A. (2009) A lipid-signaled myosin phosphatase surge disperses cortical contractile force early in cell spreading. Mol. Biol. Cell, 1:200-8.

Su, W., Yeku, O., Olepu, S., Genna, A., Park, J.-S., Ren, H., Du, G., Gelb, M.H., Morris, A.J., and Frohman, M.A. (2009) FIPI, a PLD pharmacological inhibitor that alters cell spreading and inhibits chemotaxis. Mol. Pharm. 75:437-46.

Yang, J.-S. et al. (2008) COPI vesicle fission: a role for phosphatidic acid and insight into Golgi maintenance. Nature Cell Biol., 10:1146-53.

Scotto-Lavino,E, Du,G, and Frohman,MA (2007) 5’ End cDNA Amplification using Classic RACE. Nature Protocols, 1:2555-2562.

Zhao, C., Du, G., Skowronek, K., Frohman, M.A., and Bar-Sagi, D. (2007) Phospholipase D2-generated PA couples EGFR stimulation to Ras activation by Sos. Nature Cell Biol, 9:707-12.

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 Biol., 8:1255-62.

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.

Sasaki, J. et al. (2005) The phosphatidylinositol 4-phosphate 5-kinase PIPKIa is a negative regulator of anaphylaxis and FceRI signaling. J. Exp. Med., 201:859-70.

Huang, P., Altshuller, Y.M., Hou, J.C., Pessin, J.E., and Frohman, M.A. (2005) Insulin-stimulated plasma membrane fusion of the Glut4 glucose transporter is regulated by PLD1. Mol. Biol. Cell, 16:2614–23.

Du, G., Huang, P., Liang, B.T. and. Frohman, M.A. (2004) PLD2 localizes to the plasma membrane and regulates AgntII receptor endocytosis. Mol. Biol. Cell, 15:1024-30.

Du, G, Altshuller, YM, Vitale, N, Huang, P, Morris, AJ, Bader, MF, and Frohman, MA (2003) Regulation of PLD subcellular cycling through coordination of multiple membrane association motifs. J. Cell Biol 62:305-15.

Vitale, N., Caumont, A.S., Chasserot-Golaz, S., Wu, S., Zhang, Y., Morris, A.M., Frohman, M.A. and Bader, M.F (2001) PLD1: a key factor for the exocytotic machinery in neuroendocrine cells. EMBO J., 20:2424-34.

Zhang, Y, Altshuller, Y.A., Hammond, S.A., Hayes, F., Morris, A.J., and Frohman, M.A. (1999) Loss of Receptor Regulation by a PLD1 mutant unresponsive to Protein Kinase C.  EMBO J., 18:6339-6348.

Honda et al. (1999) Phosphatidylinositol 4-phosphate 5-kinasea is a Downstream Effector of the Small G Protein ARF6 in Membrane Ruffle Formation. Cell, 99:521–32.

Colley, W.C., Sung, T.-C., Roll, R., Jenco, J., Hammond, S.M., Altshuller, Y.M., Bar-Sagi, D., Morris, A.J., and Frohman, M.A. (1997) Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization. Curr. Biol. 7:191-201.

Sung et al. (1997) Mutagenesis of Phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity. EMBO J. 16:4519-4530.

Chong et al. (1995) REST:  A Mammalian Silencer Protein that Restricts Sodium Channel Gene Expression to Neurons. Cell 80:949-957.

Hammond, S.M., Altshuller, Y.M., Sung, T.-C., Rudge, S.A., Rose, K., Engebrecht, J., Morris, A.J, and Frohman, M.A. (1995) Human ARF-activated phosphatidylcholine-specific Phospholipase D Defines a New and Highly Conserved Gene Family. J. Biol. Chem. 270: 29640-43.

Frohman, M.A., Dush, M.K., and Martin, G.R. (1988). Rapid production of full-length cDNAs from rare transcripts by amplification using a single gene-specific oligonucleotide primer. PNAS 85:8998-9002.