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Dr. Pieter C. Dorrestein

Bioanalytical Mass Spectrometry and Proteomics

Pieter C. Dorrestein

Pieter C. Dorrestein, Ph.D.

Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences

Email
pdorrestein@ucsd.edu

Phone
(858) 534-6607

Website
Dorrestein Lab


Research Summary: Mass Spectrometry and Proteomics of Therapeutic Leads and Their Targets.

The Dorrestein laboratory aims to develop new mass spectrometry approaches to detect and characterize therapeutic leads as well as their biosynthesis. The research in my lab falls into 4 areas: (1) The functional characterization of novel post-translational modifications involved in the biosynthesis of therapeutics or therapeutic targets. (2) Develop new methods to characterize metabolic exchange factors from microbial systems involved in cell-to-cell communication. All cells communicate with other cells. Currently, there are no tools to systematically study the molecular output of a small population of cells. My lab is developing mass spectrometry based approaches to study the universal phenomenon of cell-to-cell communication to discover new biological modulators. (3) Therapeutic target identification, including off-targets. Target identification is very important to the therapeutic discovery pipeline. This is done in collaboration with other scientists at UCSD, UCSC, SALK, SIO and elsewhere. (4) Monitoring the global response of therapeutics by monitoring the signaling proteome. While a therapeutic may have one or a few targets, the entire proteome of a cell or tissue will be affected. The phosphoproteome provides insight into the effect therapeutics have on cells or tissues and is monitored upon therapeutic stimulation providing insights into key regulatory pathways.

Academic Achievements

Education: B.A. in Chemistry (1999) Northern Arizona University; Ph.D. in Chemical Biology (2004) Cornell University; NRSA fellowship in Bioanalytical Chemistry (2006) University of Illinois.

Awards and Honors: ACACC award by Lilly in Analytical Chemistry (2008); V-foundation Scholar (2008); Featured in the journal Scientist as a “Scientist to Watch” (2008); Beckman Young Investigator (2008); Pharmaceutical Research and Manufacturers of America Research Award (2008).

Leadership Experience: Established the “Mass Spectrometry in Medicine and Biology group” at UCSD.

Teaching

  • Cell Biology and Biochemistry (CBB).
  • Proteomics and mass spectrometry for biologists (CMM264/SPPS268).
  • Chemistry of Enzyme Catalyzed reactions (Chem 116).

Key Contributions to Pharmaceutical Sciences

  • Development of tools to investigate the biosynthesis of polyketide or NRPS derived therapeutic agents (e.g. lovastatin and enediynes)
  • Development of tools to discover biological modulators via imaging mass spectrometry (e.g. anti-infectives, immune modulators and anti-cancer agents)
  • The structural characterization of therapeutic leads and in a system wide fashion, including target identification

Selected Recent Publications (from >50 peer-reviewed articles)

Lee et al. (2008). Discovery of a widely distributed toxin biosynthetic gene cluster. Proc. Natl. Acad. Sci. 105:5879-84.

Zhang et al. (2008). A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. Proc. Natl. Acad. Sci. 5:1460-1465.

Yang et al. (2009). Translating metabolic exchange with imaging mass spectrometry. Nature Chemical Biology. 5:885-887.

Hughes et al. (2009). Marinopyrrole A Target Elucidation by Acyl Dye Transfer. Journal of the American Chemical Society. 131:12094-12096.

Ng et al. (2009). Dereplication and de novo sequencing of nonribosomal peptides. Nature Methods. 6:596-599.

Potential Collaborative Programs with the Pharmaceutical Industry

  • Proteomics, mass spectrometry related to therapeutic discovery, target identification and system wide investigation.
  • 2009 Consultant to a biotechnology company for the detection strategies of secreted metabolites.