Doron C. Greenbaum, Ph.D.
Assistant Professor of Pharmacology
Department: Pharmacology
Graduate Group Affiliations
Contact information
Department of Pharmacology
304G Lynch Labs
433 South University Avenue
Philadelphia, PA 19104-6019
304G Lynch Labs
433 South University Avenue
Philadelphia, PA 19104-6019
Office: (215) 746-2992
Fax: (215) 746-6697
Lab: (215) 746-2349
Fax: (215) 746-6697
Lab: (215) 746-2349
Email:
dorong@upenn.edu
dorong@upenn.edu
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.
Permanent linkB.A. (Biology and Chemistry, Magna cum laude)
Williams College, Williamstown, MA, 1994.
Ph.D. (Chemistry and Chemical Biology)
University of California, San Francisco, 2002.
Description of Research Expertise
Research InterestsDr. 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
Millholland, MG., Mishra, S., Dupont, CD., Love, MS., Patel, B., Shilling, D., Kazanietz, MG., Foskett, JK., Hunter, CA., Sinnis, P., and Greenbaum DC.: A Host GPCR Signaling Network Required for the Cytolysis of Infected Cells Facilitates Release of Apicomplexan Parasites Cell Host and Microbe 13(1): 15-28, Jan 2013 Notes: Highlighted in Voice of America. "Researchers Discover the Biological Mechanism of Malaria Infection", Jessica Berman, January 17, 2013. http://www.voanews.com/content/malariar-research/1586222.html.Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, DeGrado WF, Sinnis P, Scott RW, and Greenbaum DC: Platelet Factor 4 Activity Against Plasmodium falciparum and its Translation to Nonpeptidic Mimics as a New Class of Antimalarials. Cell Host and Microbe 12(6): 815-23, Dec 2012 Notes: Highlighted in "Host response: PF4 - platelets' poison." Nature Reviews Microbiology. 2013 Feb;11(2):72-3. Also highlighted in the F1000Prime.
Harbut, MB., Patel, BA., Yeung, BKS., McNamara, CW., Bright, AT., Ballard, J., Supekc,F., Golde, TE., Winzeler, EA.,Diagana, TT., Greenbaum, DC.: Targeting the ERAD Pathway via Inhibition of Signal Peptide Peptidase for Antiparasitic Therapeutic Design. Proceedings of the National Academy of Sciences of the United States of America 109(52): 21486, Dec 2012 Notes: Highlighted in "Infectious disease: A broad protozoan drug target?" Nature Reviews Drug Discovery.2013 Feb 1;12(2):102.
Jo H, Meinhardt N, Wu Y, Kulkarni S, Hu X, Low KE, Davies PL, Degrado WF, Greenbaum DC.: Development of α-Helical Calpain Probes by Mimicking a Natural Protein-Protein Interaction. Journal of the American Chemical Society 134(42): 17704-13, Oct 2012 Notes: Highlighted in FierceBiotechResearch, "Enzyme inhibitor could be key to treating malaria". Jan 2, 2013
Önder Özlem, Humphrey Parris T, McOmber Brian, Korobova Farida, Francella Nicholas, Greenbaum Doron C, Brisson Dustin: OspC is potent plasminogen receptor on surface of Borrelia burgdorferi. The Journal of Biological Chemistry 287(20): 16860-8, May 2012.
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.
