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DEPARTMENT OF IMMUNOLOGY & MICROBIOLOGY, A Leader in Immunology, Microbiology and Microbial Pathogenesis Research and Training

Immunology and Microbiology
 

Kathryn V. Holmes, Ph.D.

Professor Emerita of Immunology & Microbiology



12800 E. 19th Ave., RC-1 N 9127
Mail Stop 8333, Aurora, CO 80045

Phone: (303) 724-4231
E-mail: kathryn.holmes@ucdenver.edu

Kathryn V. Holmes, Ph.D., earned her doctoral degree from Rockefeller University in New York, NY, in 1968. She completed 2 years of postdoctoral research training at Harvard University in 1968-70.

Dr. Holmes served on the faculty of the Georgetown University Schools of Medicine and Dentistry, the University of Texas Southwestern Medical School, and the Uniformed Services University before she joined the faculty of the University of Colorado School of Medicine Department of Microbiology in 1995.

Major interests: Characterization of coronavirus receptors and analysis of the role of receptor specificity in coronavirus pathogenesis and evolution. We are interested in molecular mechanisms that determine how coronaviruses jump from one host to another to cause emerging diseases of humans and animals.

Enveloped viruses infect cells that express specific virus receptors by fusion of the viral envelope with host cell membranes. Membrane fusion is mediated by spike glycoproteins on the viral envelope. Coronavirus entry is mediated by a single large spike glycoprotein, S, that undergoes conformational changes when bound to its specific cellular receptor at 37°C. Our lab has analyzed the spike glycoproteins of murine coronavirus MHV, human coronavirus HCoV-229E and SARS coronavirus SARS-CoV. We have identified receptors for MHV (murine CEACAM1a), HCoV-229E (human and feline aminopeptidase N), and feline coronaviruses (feline aminopeptidase N). We recently discovered that a C-type lectin called L-SIGN or CD209L is an alternative receptor for SARS-CoV and also for HCoV-229E. We are studying receptors for coronaviruses of other species. We are exploring the structure and functions of the S glycoproteins and their interactions with their receptors to elucidate the molecular mechanisms of coronavirus entry. We are identifying inhibitors of coronavirus entry for use as candidate anti-viral drugs.

We are studying animal models that have genetically manipulated coronavirus receptors to examine the role of virus receptors in viral pathogenesis. We have shown that knocking out the CEACAM1a gene that encodes the MHV receptor from inbred mice made them resistant to MHV infection and disease. We made transgenic mice that express human APN, the receptor for HCoV-229E, and showed that although cells from these animals are susceptible to infection, the mice are resistant. We are developing small animal models for human diseases.

Dr. Holmes has received many awards and honors throughout her career, including being president of the American Society for Virology in 1993-94 and an AAAS fellow in 1997. She has served on editorial boards, NIH grant study sections, and numerous chairmanships throughout her career.