DEPARTMENT OF PATHOLOGY

Michael J. Kelner, M.D.

Michael J. Kelner, M.D.

  • Professor
  • Director of Clinical Chemistry Laboratory
  • Acting Director of the Clinical Toxicology Laboratory
  • M.D. - University of Minnesota, 1981
  • Residency Training: UCSD Medical Center
  • Board Certifications: Clinical and Chemical Pathology

Research Interests

A novel anti-cancer compound synthesized by scientists at the University of California, San Diego more than a decade ago from toxins of the poisonous jack-o-lantern mushroom, has been granted "fast track" status by the U.S. Food and Drug Administration (FDA) after demonstrating promise against one of the most deadly cancers. "Fast track" designation, an important accelerated phase in the nation's drug review and approval process, signifies that the FDA can expedite the review and development of the drug candidate irofulven, which in clinical studies has demonstrated shrinkage of solid tumors of the pancreas and other cancers. Pancreatic cancer claims an estimated 29,000 lives each year in the United States and about 170,000 lives worldwide. It is one of the most deadly malignancies and has few effective treatment options.

Irofulven is currently being developed by MGI PHARMA, Inc., an emerging oncology-focused pharmaceutical company based in Minneapolis. Phase III clinical trials involving the drug have been underway since early this year at sites in the U.S. and Europe. In 1993, MGI PHARMA acquired the rights from the University of California to all illudin-S analogs devised by McMorris and Kelner, including irofulven, which was first synthesized by McMorris. Irofulven's unique mechanism of action as an anti-tumor agent is due to its ability to be rapidly absorbed by tumor cells. Once inside the cells, the compound binds to DNA and protein targets. This binding interferes with DNA replication and cell division of tumor cells, leading to tumor-specific apoptotic cell death, or "cell suicide." During this process, tumor cells tend to automatically shut themselves down when they sense their function is compromised.

Representative Publications

  1. T.C. McMorris, S. Moon, and M.J. Kelner. Reaction of Irofulven with Zinc and Acid. J Nat Products. 66:310-312, 2003.
  2. L. Ekstrom, L. Lyrenasa, P-J. Jakobsson, R. Morgenstern, and M.J. Kelner. Basal expression of the human MAPEG members microsomal gutathione transferase 1 and prostaglandin E synthase genes is mediated by Sp1 and Sp3. Biochimica Biophys Acta. 1627: 79-84, 2003.
  3. T.C. McMorris, Q. Cong, and M.J. Kelner. Structure-activity relationship studies of Illudins: Analogues possessing a spiro-cyclobutane ring. J. Org. Chem. 68:9648-53, 2003.
  4. T.C. McMorris, M.D. Staake, and M.J. Kelner. Synthesis and biological activity of enantiomers of antitumor Irofulven. J. Org. Chem. 69:619-623, 2004.
  5. M.J. Kelner, R.D. Bagnell, and R. Morgenstern. Structural organization of the murine microsomal glutathione S-transferase gene (MGST1) from the 129/SvJ strain, identification of the promoter region and a comprehensive oldsmith MA. Haploinsufficiency identifies STAT5 as a modifier of IL-7-induced lymphomas. Oncogene. 2005; 24:5252-5257.
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Biography

Dr. Kelner received his MD from the University of Minnesota in 1981. He completed a rotating internship at UCSF and matriculated into the Straight Laboratory Medicine (Clinical Pathology) residency at UCSD in 1982. He served as Chief Resident in Clinical Pathology from 1984-85, and was awarded the David Jay Epstein Memorial Award for Research Excellence by a Pathology Resident in 1985. He was also honored with Young Investigator Awards from the Academy of Clinical Laboratory Physicians and Scientists for three consecutive years. He was board certified in 1985 in both Clinical and Chemical Pathology.

Dr. Kelner joined the faculty of UCSD as an Assistant Professor of Pathology in Residence in 1985, and was appointed to Assistant Professor of Pathology in 1988. He was then promoted to Associate Professor in 1991 and to Professor of Pathology in 1997. Dr. Kelner is a highly productive publisher and contributor in research and teaching. As Director of the General Chemistry Laboratory at UCSD Medical Center, Associate Director of Toxicology, and participant on the Medical Directors Committee for the UCSD Medical Center, Dr. Kelner maintains a high level of University service.

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