Professor of Chemistry and Pharmaceutical Chemistry
Principal Investigator/Program Director
|Ph.D.||Chemistry, Physics||1962||Massachusetts Institue of Technology, Cambridge, MA|
|B.Sc.||Chemistry||1959||University of Rhode Island, Kingston, RI|
|2006-present:||Co-editor, Molecular and Cellular Proteomics.|
|2006-present:||Member, UCSF Comprehensive Cancer Center.|
|2002-2004:||Physiological Chemistry Study Section, CSR, NIH.|
|1999-2006:||Deputy Editor, Molecular and Cellular Proteomics.|
|1996-2003:||Professor of Biochemistry, University College, London, UK.|
|1993-1994:||Visiting Professor, Ludwig Institute for Cancer Research, London, UK.|
|1990-present:||Elected Fellow, American Association for the Advancement of Science, Rockville, MD.|
|1981-present:||Professor of Chemistry & Pharmaceutical Chemistry, U.C. San Francisco, San Francisco, CA.|
|1980-present:||Member, The Liver Center, School of Medicine, U.C. San Francisco, San Francisco, CA.|
|1978-present:||Director, Biomedical Mass Spectrometry Resource, School of Pharmacy, U.C. San Francisco, San Francisco, CA.|
|1978-1981:||Adjunct Professor of Chemistry & Pharmaceutical Chemistry, U.C. San Francisco, San Francisco, CA.|
|1973-1984:||Director, Biomedical Mass Spectrometry Resource, Space Sciences Lab, U.C. Berkeley, Berkeley, CA.|
|1972-1984:||Research Chemist, Space Sciences Lab, U.C. Berkeley, Berkeley, CA.|
|1970-1972:||Guggenheim Fellow, Karolinska Institute, Stockholm, Sweden.|
|1968-1972:||Assoc. Research Chemist, Space Sciences Lab, U.C. Berkeley, Berkeley, CA.|
|1963-1968:||Asst. Professor of Chemistry, Dept. of Chemistry & Space Sciences Lab, U.C. Berkeley, Berkeley, CA.|
My research interests focus on the development of state of the art methodologies in mass spectrometry for use in advancing our global knowledge of human biology, specifically the dynamic, epigenetic modulation and regulation of the proteome. This occurs in the context of deciphering molecular alterations and defects that underlie disease and cancer.
Some specific projects include research on the mammalian and human proteomes including large macromolecular assemblages that are dynamic, functional entities in cells. These include the signal processing protein machine, a pseudo-organelle called the postsynaptic density, and RNA/protein complexes such as the spliceosome. In addition, we study the nature and role of posttranslational modulation in cell biology including protein complexes in signaling networks such as ras, p53, and chromatin biology including DNA damage sensing.
Many covalent modifications are under active investigation including phosphorylation, sulfation, O-GlcNAcylation, methylation, acetylation, ubiquitinylation, lipidation, and controlled proteolysis. For some classes of proteins, posttranslational occupancies occur in multiple "combinatorial" motifs and function in a concerted, synergistic manner, e.g., the "histone code" in chromatin biology. We are interested in defining these isoform occupancies and the discovery of the effector proteins that "read" this epigenetic code. Finally we employ residue specific chemical cross-linking to provide distance constraints use in homology modeling of protein complexes.
With collaborators, we have exciting new results from proteomic characterization of retrograde signaling following axon injury in Aplysia. These studies provide the first linkage between retrograde axonal and nuclear transport mechanisms in neurons that has implications for therapeutics by a novel route for drug delivery to the CNS. In other collaborations there are examples where discoveries may lead to new routes to human therapy. One is based on identification of Shoc2-PP1c holoenzyme that provides an attractive therapeutic target for inhibition of the MAPK pathway in cancer. Another is the discovery of a selective inhibitor of human carbonyl reductase. The latter could be employed therapeutically and inhibit formation of the cardiotoxic metabolite of deoxyrubicin.