Stephen M. Beverley

Washington University in St. Louis


Primary Section: 61, Animal, Nutritional, and Applied Microbial Sciences
Secondary Section: 44, Microbial Biology
Membership Type:
Member (elected 2013)

Biosketch

Stephen M. Beverley is the Marvin A. Brennecke Professor and Head of Molecular Microbiology at Washington University in St. Louis. His group focuses on molecular parasitology and is recognized for work introducing and/or originating molecular genetics tools and approaches from microbial pathogenesis into the study of the trypanosomatid protozoan Leishmania, a widespread tropical disease. Beverley was born in California in 1951, graduated in Biology from the California Institute of Technology working with Lee Hood, and received his PhD in Biochemistry with Alan Wilson, studying the evolution of Hawaiian Drosophila from the University of California Berkeley in 1973. Postdoctoral work at Stanford University with Robert Schimke led unexpectedly to the emerging field of molecular parasitology and interests in drug resistance and gene amplification. In 1983, he joined the faculty of Harvard Medical School and ultimately was appointed the Hsien Wu and Daisy Yen Wu Professor of Biological Chemistry & Molecular Pharmacology. In 1997 he relocated to the School of Medicine of Washington University as Professor and Chairman of Molecular Microbiology. In St. Louis he cofounded Symbiontics Inc., whose accomplishments included new methods for biological delivery of therapeutic lysosomal storage disease proteins via engineered "safe" parasites or directly. He is a Burroughs-Welcome Scholar in Molecular Parasitology and a fellow of the American Academy of Microbiology and the American Association of Science.

Research Interests

Beverley's laboratory has focused on the introduction of modern concepts of microbial pathogenesis and molecular genetics into the study of protozoan parasites of humans, primarily the trypanosomatid Leishmania.  Studies of drug resistance, extra-chromosomal gene amplification and transcription led to the development of the first transfection system enabling both forward and reverse genetics, and have been widely adopted in the field.  Beverley's lab has put them to use in dissecting the role of major parasite surface glycoconjugates in parasite survival in both mammalian and insect hosts, immune recognition and evasion, identification of novel pathways of folate and pteridine metabolic amenable to chemotherapeutic attack, and the use of genetically modified parasites as safe live vaccine lines. Modified parasites also provide therapeutic opportunities for use as live nanoplatforms for delivery of therapeutic proteins, an approach pursued by a company Beverley co-founded. Leishmania genetic methods continue to evolve, including the use of imported mariner transposons, conditional gene expression, RNA interference, and genetic crossing (which occurs only in the sand fly vector). Beverley spearheaded an NIHGRI/AID project for trypanosomatid genome sequencing which has led to comprehensive coverage of the genomes of diverse Leishmania species manifesting widely varying severity in humans, and key outgroups relevant to the origins of vertebrate parasitism. Studies of RNA interference have led to the question of why most species of Leishmania have lost this vital pathway in evolution, and the potential role of transposable elements and RNA viruses. Remarkably, the dsRNA virus LRV1 dramatically increases the severity of leishmaniasis, perhaps providing a driving force for RNAi loss, but also providing new opportunities for understanding parasite virulence and the role of 'endosymbiontic' viruses in biology and as potential targets for therapeutic interventions.

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