Professor and Chair
Department of Molecular Medicine
College of Veterinary Medicine
Ithaca, New York 14853
Office: (607) 253-3893
Lab: (607) 253-3653
Fax: (607) 253-3659
Our research addresses the mechanism and consequences of protein S-palmitoylation, a reversible posttranslational modification of proteins that regulates membrane association, protein trafficking, and protein stability. Discovered in 2002, the DHHC (Asp-His-His-Cys) protein S-acyltransferases are responsible for palmitoylation of proteins on the cytoplasmic leaflet of cell membranes. Our recent studies have revealed the catalytic mechanism of DHHC proteins and current work is focused on understanding how DHHC proteins are regulated by posttranslational modifications and oligomerization.
We also have a longstanding interest in lipidation of cell signaling proteins and we have recently identified an alternative CaaX processing pathway for Cdc42 and Ral GTPases. Work is ongoing to elucidate how the alternatively processed isoforms bypass conventional CaaX processing and how they are functionally distinct from the conventionally processed isoforms.
A third project is to determine the molecular mechanisms that underlie a syndromic form of X-linked intellectual disability caused by mutations in the ZDHHC9 gene. The objectives are to identify the substrates of DHHC9 by comparing the palmitoylomes of wild type and ZDHHC9 knockout mice and determine if ZDHHC9 knockout mice display altered behaviors in assays of cognitive, sensory, and motor functions.
- Ph.D. - 1987 Molecular and Cell Biology, School of Medicine, University of Texas at Dalla, TX
- Internship - 1977 Medical Technology Program,
St. Joseph Mercy Hospital, MI
- B.Sc. - 1976 Medical Technology (cum laude), Michigan State University
- 2009-present Professor and Chair, Department of Molecular Medicine, Cornell University
- 2006-2009 Professor, Department of Cell Biology and Physiology, Washington University in St. Louis
- 1999-2006 Associate Professor, Department of Cell Biology and Physiology, Washington University
- 1993-1999 Assistant Professor, Department of Cell Biology and Physiology, Washington University
- 1991-1993 Instructor, Department of Pharmacology, University of Texas, Southwestern Medical Center
- 1989-1991 Assistant Instructor, Department of Pharmacology, University of Texas, Southwestern Medical Center
- 1987-1989 Research Fellow, Department of Pharmacology, University of Texas, Southwestern Medical Center
Honors and Awards
- 2009 Fellow, American Association for the Advancement of Science (AAAS)
- 2001-2004 American Heart Association Established Investigator
Professional Society Memberships
- American Society for Cell Biology
- American Society for Biochemistry and Molecular Biology
- American Society for Pharmacology and Experimental Therapeutics
- 2013-present Editorial Board, Journal of Biological Chemistry
- 2006-2013 ASBMB Publications Committee
- 2004-2008 Biomedical Research Training Grant Study Section (NIH)
- 2000 Co-chair, FASEB Conference on Lipid Modifications of Proteins
- 1999-2000 Molecular Signaling Study Committee, American Heart Association
- 1997-2002 Editorial Board, Journal of Biological Chemistry
- Lai, J., and Linder, M.E. (2013) Oligomerization of DHHC protein S-acyltransferases. J. Biol. Chem. 288:22862-22870.
- Nishimura, A., and Linder, M.E. (2013) Identification of a novel prenyl and palmitoyl modification at the CaaX motif of Cdc42 that regulates RhoGDI binding. Mol. Cell. Biol. 33:1417-1429.
- Jennings, B.C., and Linder, M.E. (2012) DHHC protein S-acyltransferases use a similar ping-pong kinetic mechanism but display different acyl-CoA specificities. J. Biol. Chem. 287:7236-7245.
- Swarthout, J.T., Lobo, S., Farh, L., Croke, M., Greentree, W.K., Deschenes, R.J., and Linder, M.E. (2005) DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J. Biol. Chem. 280:31141-31148.
- Lobo, S., Greentree, W.K., Linder, M.E., and Deschenes, R.J. (2002) Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J. Biol. Chem. 277:41268-41273.
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