Contact Information

Department of Pharmacology

Uniformed Services University of the Health Sciences
Department of Pharmacology
4301 Jones Bridge Road
Bethesda, Maryland 20814-4799
Phone: (301) 295-3223
FAX: (301) 295-3220

Pubmed listing

Jeffrey M. Harmon, Professor and Chair, Department of Pharmacology

Jeffrey M. Harmon, Ph.D.

Professor and Chair

  • B.S. The Cooper Union for the Advancement of Science and Art
  • Ph.D. University of Rochester School of Medicine and Dentistry

Regulation of Sphingolipid Biosynthesis

Sphingolipids are involved in maintaining the structural integrity of cell membranes, serve as intra and intercellular signaling molecules and are highly enriched in lipid rafts implicated in protein trafficking. The rate limiting step in sphingolipid biosynthesis is catalyzed by the heteromeric protein serine palmitoyltransferase (SPT) found in the endoplasmic reticulum (ER), and mutations in the gene encoding the subunit common to both catalytic isoforms are responsible for the late-onset neurologic disorder Hereditary Sensory Neuropathy Type I (HSAN1), a disease selectively affecting peripheral sensory neurons. We study the organization and regulation of this ubiquitously expressed enzyme, as well as downstream components of the sphingolipid biosynthetic pathway. Our current focus is elucidation of the roles, intracellular localization and membrane topology of the two known SPT isoforms, and identification of mammalian orthologues (SPTLCx) of the yeast protein Tsc3p that modulates the activity of yeast SPT. We employ a combination of classical protein purification, proteomics, and molecular biology to address these questions, as well as the use of novel covalent subunit chimera.

Regulation of Sphingolipid Biosynthesis