Doron C. Greenbaum, Ph.D.

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Assistant Professor of Pharmacology
Department: Pharmacology

Contact information
Department of Pharmacology
304G Lynch Labs
433 South University Avenue
Philadelphia, PA 19104-6019
Office: (215) 746-2992
Fax: (215) 746-6697
Lab: (215) 746-2349
Education:
B.A. (Biology and Chemistry, Magna cum laude)
Williams College, Williamstown, MA, 1994.
Ph.D. (Chemistry and Chemical Biology)
University of California, San Francisco, 2002.
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Description of Research Expertise

Research Interests

Dr. Greenbaum's laboratory is developing and exploiting new technologies at the interface between biology and chemistry to study protease function. The lab uses a variety of techniques including the synthesis of small molecule inhibitors, quantitative proteomics, recombinant protein expression and molecular genetics in order to better understand proteolytic systems. Although these tools are useful to study any biological system, the laboratory is concentrating on understanding host and malaria parasite proteases.

Dr. Greenbaum has developed universal chemical-based proteomics tools to functionally analyze the role of proteases in a variety of biological systems. He also adapted these chemical tools to allow screening of small molecule libraries for specific inhibitors and drug design. His lab will continue to develop new chemical proteomic tools and small molecule libraries to facilitate protease drug target discovery, characterization and therapeutic design with a particular interest in malaria.

The chemical probes that Dr. Greenbaum is developing led to the recent discovery that parasites such as plasmodium and toxoplasma hijack host calpains in order to facilitate their escape (Chandramonanadas et al, Science 324:794-7; 2009). This surprising finding suggests the concept of targeting host pathways for chemotherapy, a strategy that might limit the emergence of drug-resistance.

Selected Publications

Kalińska Magdalena, Kantyka Tomasz, Greenbaum Doron C, Larsen Katrine S, Władyka Benedykt, Jabaiah Abeer, Bogyo Matthew, Daugherty Patrick S, Wysocka Magdalena, Jaros Marcelina, Lesner Adam, Rolka Krzysztof, Schaschke Norbert, Stennicke Henning, Dubin Adam, Potempa Jan, Dubin Grzegorz: Substrate specificity of Staphylococcus aureus cysteine proteases - Staphopains A, B and C. Biochimie 94(2): 318-27, Feb 2012.

Millholland Melanie G, Chandramohanadas Rajesh, Pizzarro Angel, Wehr Angela, Shi Hui, Darling Claire, Lim Chwee Teck, Greenbaum Doron C: The malaria parasite progressively dismantles the host erythrocyte cytoskeleton for efficient egress. Molecular & cellular proteomics : MCP 10(12): M111.010678, Dec 2011.

Doyle Patricia S, Zhou Yuan M, Hsieh Ivy, Greenbaum Doron C, McKerrow James H, Engel Juan C: The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS pathogens 7(9): e1002139, Sep 2011.

Harbut Michael B, Velmourougane Geetha, Dalal Seema, Reiss Gilana, Whisstock James C, Onder Ozlem, Brisson Dustin, McGowan Sheena, Klemba Michael, Greenbaum Doron C: Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases. Proceedings of the National Academy of Sciences of the United States of America 108(34): E526-34, Aug 2011.

Velmourougane Geetha, Harbut Michael B, Dalal Seema, McGowan Sheena, Oellig Christine A, Meinhardt Nataline, Whisstock James C, Klemba Michael, Greenbaum Doron C: Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase. Journal of medicinal chemistry 54(6): 1655-66, Mar 2011.

Lucumi Edinson, Darling Claire, Jo Hyunil, Napper Andrew D, Chandramohanadas Rajesh, Fisher Nicholas, Shone Alison E, Jing Huiyan, Ward Stephen A, Biagini Giancarlo A, DeGrado William F, Diamond Scott L, Greenbaum Doron C: Discovery of potent small-molecule inhibitors of multidrug-resistant Plasmodium falciparum using a novel miniaturized high-throughput luciferase-based assay. Antimicrobial agents and chemotherapy 54(9): 3597-604, Sep 2010.

Shah Parag P, Wang Tianhua, Kaletsky Rachel L, Myers Michael C, Purvis Jeremy E, Jing Huiyan, Huryn Donna M, Greenbaum Doron C, Smith Amos B, Bates Paul, Diamond Scott L: A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells. Molecular pharmacology 78(2): 319-24, Aug 2010.

Chandramohanadas Rajesh, Davis Paul H, Beiting Daniel P, Harbut Michael B, Darling Claire, Velmourougane Geetha, Lee Ming Yeh, Greer Peter A, Roos David S, Greenbaum Doron C: Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. Science 324(5928): 794-7, May 2009.

Harbut Michael B, Velmourougane Geetha, Reiss Gilana, Chandramohanadas Rajesh, Greenbaum Doron C: Development of bestatin-based activity-based probes for metallo-aminopeptidases. Bioorganic & medicinal chemistry letters 18(22): 5932-6, Nov 2008.

Mallari Jeremy P, Shelat Anang A, Obrien Terri, Caffrey Conor R, Kosinski Aaron, Connelly Michele, Harbut Michael, Greenbaum Doron, McKerrow James H, Guy R Kiplin: Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. Journal of medicinal chemistry 51(3): 545-52, Feb 2008.

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Last updated: 05/18/2012
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