Vytas A. Bankaitis, PhD
Distinguished Professor, E.L. Wehner-Welch Foundation Chair in Chemistry
Education and Post-Graduate Training
Edinboro University, Edinboro, PA; BS; 1978; Biology
Clemson University, Clemson, SC; MS; 1980 Microbiology
University of North Carolina, Chapel Hill, NC, PhD 1984; Microbiology
California Institute of Technology, Pasadena, CA Postdoctoral; 1986; Cell Biology
Positions and Honors
1978-1980 Graduate Student, Department of Microbiology, Clemson University, Clemson, South Carolina. Advisor: Dr. Ellis L. Kline.
1980-1984 Predoctoral Fellow of the Humphrey Foundation, Department of Microbiology and Immunology, The University of North Carolina School of Medicine. Advisor: Dr. Philip J. Bassford, Jr.
1984-1986 Postdoctoral Fellow of the Helen Hay Whitney Foundation, Division of Biology, The California Institute of Technology, Pasadena, CA.
1986-1992 Assistant Professor, Department of Microbiology, University of Illinois, Urbana, IL. Head: Dr. Charles G. Miller.
1992-2001 Associate Professor then Professor, Department of Cell Biology,University
of Alabama at Birmingham, Birmingham, AL. Head: Dr. Richard B. Marchase.
2001-2011 Professor and Chair, Department of Cell & Developmental Biology, The University of North Carolina School of Medicine, Chapel Hill, NC.
2012-Present E.L. Wehner-Welch Foundation Chair in Chemistry, Department of Molecular & Cellular Medicine, Texas A&M University Health Science Center, College Station, TX.
Recipient of an NCAA Postgraduate Fellowship - A national award presented to 6 outstanding student-athletes, 1978.
Recipient of the President’s Award for the outstanding student research presentation; regional meeting for the Southeastern and South Carolina branches of the American Society for Microbiology, November 1979.
Recipient of a Predoctoral Fellowship of the Humphrey Foundation - awarded to outstanding incoming graduate students at the University of North Carolina, August 1980.
Recipient of a Postdoctoral Fellowship of the Helen Hay Whitney Foundation, January 1984.
Designated an Arnold Beckman Scholar, University of Illinois, 1986.
Member, Cell Biology Advisory Panel, National Science Foundation, 1988-1992.
Member CDF-2 IRG, NIH, 2001-2004.
Chairman CDF-2 and MMBP Initial Review Group, NIH, 2004-2006.
Member, Faculty of 1000, Membrane Trafficking and Sorting Section
Member, Editorial Advisory Board, EMBO Reports, 2012-present.
Vice-Chair -- Gordon Research Conferences -- Signal Transduction Within the Nucleus, 2009.
Chair -- Gordon Research Conferences -- Signal Transduction Within the Nucleus 2011
Member, Program Planning Committee, American Society for Biochemistry and Molecular Biology Annual Meeting, 2011.
Director, Lipid Research Division, American Society for Biochemistry and Molecular Biology, 2013
Lipid-mediated Signal Transduction
My laboratory is interested in the regulatory interfaces between novel lipid-mediated signal transduction pathways and important cellular functions. The focus of our work is the phosphatidylinositol/ phosphatidylcholine transfer proteins (PITPs), a ubiquitous but enigmatic class of proteins. Ongoing projects in the laboratory derive from a multidisciplinary approach that encompasses biochemical characterization of novel members of the metazoan PITP family, and the application of genetic, molecular and biophysical approaches to detailed structural and functional analyses of PITPs. The laboratory breaks down into two groups: a group that studies the mechanism of function of fungal and plant PITPs, and a group that generates knockout mice and analyzes the function of specific PITP isoforms in the mammal. Our collective evidence indicates that PITPs coordinate key interfaces of lipid-driven metabolic reactions and intracellular signaling pathways in both yeast and mammals. Inappropriate regulation of these interfaces compromises membrane trafficking events, growth factor receptor function, cell growth control, and regulation of key developmental pathways. Because defects in any one of these pathways define recognized mechanisms cancer-potentiating mechanisms, PITPs represent essentially unstudied regulators whose dysfunction is likely to influence the activities of cellular processes required for cellular homeostasis. Of additional interest is our recent finding that one of our PITP-deficient mouse lines potentially provides a unique model for chylomicron retention disease, hypoglycemia and brain inflammatory disease. Relevant approaches that the laboratory employs include: molecular biology, protein and lipid biochemistry, confocal and electron microscopy, mouse gene knockout technology, and classical and molecular genetics. The lab is also developing new approaches for rapidly and confidently identifying the first small molecule inhibitors directed against target PITPs of interest and other key enzymes of lipid metabolism.
Key discoveries made by the lab include
- The first demonstration that lipids are integral components of the strategy by which the core membrane trafficking machinery is regulated.
- The first identification of an in vivo function for a phospholipid-transfer protein via the determination that one of the yeast sec gene products (i.e. Sec14) is a PITP.
- The ‘bypass Sec14’ studies that are widely credited as representing seminal advances in the membrane trafficking field on the basis of providing the first experimental evidence that lipid metabolism is intimately connected to membrane trafficking reactions. Previous to that work, an active role for lipids was ignored in discussions of how transport vesicles bud, dock and fuse.
- Solution of an apo-Sec14 crystal structure that provided the first description of a novel structural fold termed the Sec14-domain or, alternatively, the CRAL-TRIO domain.
- The first demonstration that Kes1, one of the enigmatic oxysterol binding proteins, regulates TGN membrane trafficking with the Pik1 PtdIns 4-OH kinase a likely target for control.
- The first isolation of headgroup-specific Class 1 PITP PL-binding mutants and the first analysis of what role individual PL-binding activities play in Class 1 PITP function.
- The first creation of a mammalian model for PITP nullizygosity and the demonstration that PtdIns binding is an essential functional property of a metazoan PITP.
- Structural, biochemical and genetic studies that demonstrate PITPs both potentiate and determine outcomes of PtdIns kinase action, a particularly interesting and novel mode of signaling control.
- Identification and in vivo and in vitro validation of small molecule inhibitors specifically directed against the yeast Sec14. This effort involved assembly of a unique screening platform for indentifying SMIs directed against any PITP of the investigator’s choice.
- Discovery that a specific ORP (Kes1) participates in a novel signaling pathway by integrating endosomal lipid metabolism with TOR signaling and nitrogen sensing.
- Ghosh, R., de Kampos, M.K.F., Hur, S., Huang, J., Orlowski, A., Yang, Y., Tripathy, A., Nile, A.H., Lee, H.-C., Schäfer, H., Dynowski, M., Rog, T., Lete, M.G., Ahyayauch, H., Alonso, A., Vattulainen, I. Igumenova, T.I., Schaaf, G., and Bankaitis, V.A. 2015. Sec14-nodulin proteins pattern phosphoinositide landmarks for developmental control of membrane morphogenesis. Molecular Biology of the Cell (In Press).
- Bankaitis, V.A. 2014. Peer review: rigor? Or rigor mortis? EMBO Reports 15: 818-819. PMID: 25006184 http://www.ncbi.nlm.nih.gov/pubmed/26006184
- Lee, A.Y., St Onge RP, Proctor MJ, Wallace IM, Nile AH, Spagnuolo PA, Jitkova Y, Gronda M, Wu Y, Kim MK, Cheung-Ong K, Torres NP, Spear ED, Han MK, Schlecht U, Suresh S, Duby G, Heisler LE, Surendra A, Fung E, Urbanus ML, Gebbia M, Lissina E, Miranda M, Chiang JH, Aparicio AM, Zeghouf M, Davis RW, Cherfils J, Boutry M, Kaiser CA, Cummins CL, Trimble WS, Brown GW, Schimmer AD, Bankaitis VA, Nislow C, Bader GD, Giaever G. 2014. Mapping the cellular response to small molecules using chemogenomic fitness signatures. Science 344: 208-211. PMID: 24723613 http://www.ncbi.nlm.nih.gov/pubmed/24723613
- Ren, J., Lin, C.P.-C., Pathak, M., Temple, B.R.S., Nile, A.H., Mousley, C.J., Duncan, M.C., Eckert, D., Leiker, T.J., Ivanova, P.T., Milne, D.S., Murphy, R.S., Brown, H.A., Verdaasdonk, J., Bloom, K.S., Ortlund, E.A., Neiman, A.M., and Bankaitis, V.A. 2014. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis. Molecular Biology of the Cell 25: 712-727. PMID: 24403601 http://www.ncbi.nlm.nih.gov/pubmed/24403601
- Nile,A.H., Tripathi, A., Yuan, P., Mousley, C.J., Suresh, S., Wallace, I.M., Shah, S.D., Teiotico-Pohlhaus, D., Temple, B., Nislow, C., Giaever, G., Tropsha, A., Davis, R.W., St. Onge, R.P., and Bankaitis, V.A. 2014. PITPs as targets for selectively interfering with phosphoinositide signaling in cells. Nature Chemical Biology 10: 76-84. PMID: 24292071 http://www.ncbi.nlm.nih.gov/pubmed/24292071
- Mousley, C., Yuan, P., Gaur, N.A., Trettin, K.D., Nile, A.H., Deminoff, S., Dewar, B.J.,Wolpert, M., Macdonald, J.M., Herman, P.K., Hinnebusch, A.G., and Bankaitis, V.A. 2012. A sterol binding protein integrates endosomal lipid metabolism with TOR signaling and nitrogen sensing. Cell 148: 702-715. PMID: 22341443 http://www.ncbi.nlm.nih.gov/pubmed/22341443
- Bankaitis, V.A., Garcia-Mata, R. and Mousley, C.J. 2012. Golgi membrane dynamics and lipid metabolism. Current Biology 22: R414-R424. PMID: 22625862 http://www.ncbi.nlm.nih.gov/pubmed/22625862
- Bankaitis, V.A., and Grabon, A. 2011. Phosphatidylinositol synthase and diacylglycerol platforms bust a move. Developmental Cell 21: 810-812. PMID: 22075144 http://www.ncbi.nlm.nih.gov/pubmed/22075144
- Bankaitis, V.A., Mousley, C.J., and Schaaf, G. 2010. Sec14-superfamily proteins and the crosstalk between lipid signaling and membrane trafficking. Trends in Biochemical Sciences 35: 150-160. PMID: 19926291 http://www.ncbi.nlm.nih.gov/pubmed/19926291
- Schaaf, G., Ortlund, E.A., Tyeryar, K.R., Mousley, C.J., Ile, K.E., Woolls, M.J., Garrett, T.A., Raetz, C.R.H., Redinbo, M.R., and Bankaitis, V.A. 2008. The functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the Sec14-superfamily. Molecular Cell 29: 191-206. PMID: 18243114 http://www.ncbi.nlm.nih.gov/pubmed/18243114
- Liu, Y., Boukhelifa, M., Tribble, E., Morin-Kensicki, E., Uetrecht, A., Bear, J.E., and Bankaitis, V.A. 2008. The Sac1 phosphoinositide phosphatase regulates Golgi membrane morphology and mitotic spindle organization in mammals. Mol. Biol. Cell 19: 3080-3096. PMID: 18480408 http://www.ncbi.nlm.nih.gov/pubmed/18480408
- Alb, J.G. Jr., Phillips, S.E., Wilfley, L.R., Philpot, B.D., and Bankaitis, V.A. 2007. The pathologies associated with functional titration of phosphatidylinositol transfer protein a activity in mice. J. Lipid Res. 48: 1857-1872. PMID: 17525475 http://www.ncbi.nlm.nih.gov/pubmed/17525475
- Ryan, M.M., Temple, B.R.S., Phillips, S.E., and Bankaitis, V.A. 2007. Conformational dynamics of the major yeast phosphatidylinositol transfer protein Sec14p: Insights into the mechanisms of phospholipid exchange and diseases of Sec14p-like protein deficiencies. Mol. Biol. Cell 18: 1928-1942. PMID: 17344474 http://www.ncbi.nlm.nih.gov/pubmed/17344474
- Slessareva, J.E., Routt. S.M., Temple, B., Bankaitis, V.A., and Dohlman, H.G. 2006. G protein activation of a PtdIns 3-kinase at the endosome. Cell 126: 191-203. PMID: 16839886 http://www.ncbi.nlm.nih.gov/pubmed/16839886
- Vincent, P., Chua, M., Nogue, F., Fairbrother, A., Mekheel, H., Xu, Y., Allen, N., Bibikova, T.N., Gilroy, S., and Bankaitis, V.A. 2005. A Sec14p-nodulin domain phosphatidylinositol transfer protein polarizes membrane growth of Arabidopsis root hairs. Journal of Cell Biology 168: 801-812. PMID: 15728190 http://www.ncbi.nlm.nih.gov/pubmed/15728190
- Li, X., Rivas, M.P., Fang, M., Marchena, J., Mehrotra, B., Chaudhary, A., Feng, L., Prestwich, G.D., and Bankaitis, V.A. 2002. Analysis of oxysterol binding protein homolog Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex. Journal of Cell Biology 157: 63-77. PMID: 11916983 http://www.ncbi.nlm.nih.gov/pubmed/11916983
- Phillips, S., Sha, B., Topalof, L., Xie, Z., Alb, J., Clenchin, V., Swigart, P., Cockcroft, S., Luo, M., Martin, T. and Bankaitis, V. 1999. Yeast Sec14p deficient in phosphatidylinositol transfer activity is functional in vivo. Molecular Cell 4: 187-197. PMID: 10488334 http://www.ncbi.nlm.nih.gov/pubmed10488334
- Sha, B., Phillips, S.E., Bankaitis, V.A.* and Luo, M.* 1998. Crystal structure of the Saccharomyces cerevisiae phosphatidylinositol transfer protein Sec14p. Nature 391: 506-510. PMID: 9461221 * -- Denotes co-corresponding authorship. http://www.ncbi.nlm.nih.gov/pubmed/9461221
- Kearns, B.G., McGee T.P., Mayinger, P., Gedvilaite, A., Phillips, S.E., Kagiwada, S., and Bankaitis, V.A. 1997. Essential role for diacylglycerol in protein transport from the yeast Golgi complex. Nature 387: 101-105. PMID: 9139830 http://www.ncbi.nlm.nih.gov/pubmed/9139830
- Cleves, A. E., T. P. McGee, E. A. Whitters, K. Champion, J. R. Aitken, W. Dowhan, M. Goebl, and V. A. Bankaitis. 1991. Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein. Cell 64: 789-800. PMID: 1997207 http://www.ncbi.nlm.nih.gov/pubmed/1997207
- Bankaitis, V. A., J. F. Aitken, A. E. Cleves, and W. Dowhan. 1990. An essential role for a phospholipid transfer protein in yeast Golgi function. Nature 347: 561-562. PMID: 2215682 http://www.ncbi.nlm.nih.gov/pubmed/2215682