Faculty


George A. Garcia

Professor and Chair, Medicinal Chemistry
Director, Interdepartmental Program in Medicinal Chemistry

Ph.D., University of California, San Francisco
Postdoctoral Fellow, Cambridge University, England

Research Focus: Antibiotic drug discovery for tuberculosis and acute diarrheal disease

Phone: 734.764.2202
E-mail: gagarcia@umich.edu

A long-standing research interest of the Garcia lab has been the biosynthesis and physiological roles of modified bases in RNA. More recently we have shifted our focus to antibiotic discovery in two areas. Tuberculosis is a global human health problem of staggering proportions, causing nearly 1.4 million deaths in 2011. Current TB drugs require up to nine months of treatment and poor compliance promotes the emergence of drug-resistant strains. We are using a structure-based approach to discover improved RNAP inhibitors in collaboration with the Showalter lab here at U-M and the Murakami lab at Penn State. Shigella flexneri is a human enteropathogen that infects ca. 165 million people and claims more than 1 million lives per year worldwide. Targeting Shigella virulence pathways is attractive because such drugs would be expected to exhibit less emergence of drug resistance and have no effect on normal colonic microbiota. We have successfully conducted high-throughput screens of ~142,000 compounds and ~20,000 natural product extracts against VirF, which initiates expression of the key Shigella virulence genes. We are characterizing the hits, which block VirF activity in collaboration with the Maurelli lab at USUHS in Maryland and the Sherman lab here at U-M.

Garcia Research Group

 

Awards

2005
Student Appreciation Award, University of Michigan College of Pharmacy
1988-1990
National Institutes of Health Postdoctoral Research Fellowship
1987
American Foundation for Pharmaceutical Education
1987
"Johnson & Johnson Pharmaceutical Chemistry Fellow"
1985-1987
American Foundation for Pharmaceutical Education "H. A. B. Dunning Memorial Fellow,"
1983-1986
University of California Regent's Fellowship
1984-1985
University of California, San Francisco Graduate Division, Minority Mentorship

 

Representative Publications

  1. Emanuele, A.A. and Garcia, G.A., “Mechanism of Action and Initial, In vitro SAR of an Inhibitor of the Shigella flexneri Virulence Regulator VirF”, PLOS One (2015), 10 (9), e0137410, PMCID: PMC4564171.

  2. Emanuele, A.A., Praskievicz, N.A., Chen, Y.-C., Maurelli, A.T., and Garcia, G.A., “Potential Novel Antibiotics from HTS Targeting the Virulence-regulating Transcription Factor, VirF, from  Shigella flexneri”, Journal of Antibiotics (2014), 67, 379-386, PMCID: 4050983.  Note that this paper was featured on the journals webpage for this issue and was noted as #1 of the top 10 articles downloaded in the 15 days since the issue was published.

  3. *Molodtsov, V., Nawarathne, I.N., Scharf, N.T., Kirchhoff, P.D., Showalter, H.D.H., Garcia, G.A., and Murakami, K.S., “X-ray crystal structures of the Escherichia coli RNA polymerase in complex with benzoxazinorifamycins”, Journal of Medicinal Chemistry (2013), 56 (11), 4758-4763, PMCID: 3745299  *Note that this paper was highlighted on the cover of this issue.

  4. Gill, S.K., Hao, X., Kirchhoff, P.D., Wan, B., Zhang, N., Peng, K.-W., Franzblau, S.G., Garcia, G.A., and Showalter, H.D.H., “Structure-based Design of Novel Benzoxazinorifamycins with Potent Binding Affinity to Wild-type and Rifampin-resistant Mutant Mycobacterium Tuberculosis  RNA Polymerases”, Journal of Medicinal Chemistry (2012), 55 (8), 3814–3826, PMID: 22452568

  5. Gill, Sumandeep K. and Garcia, G.A., “Rifamycin inhibition of WT and Rif-resistant Mycobacterium tuberculosis and Escherichia coli RNA polymerases in vitro”, Tuberculosis (2011), 91 (5), 361-369, PMID: 21704562

 

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