Department Affiliation: Primary: Chemistry (Homewood); Secondary: Biology (Homewood)
Degree:Ph.D. Yale University
Rank: Professor
Telephone Number: 410-516-7444
Fax Number: 410-261-1233
E-mail address: ctownsend@jhu.edu
Homewood Address: 252 Remsen Building, Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218
Organic and bioorganic chemistry: biosynthesis of natural products and biomimetic synthesis; protein isolation, expression and mechanistic enzymology; structural, mutational and engineering of biosynthetic enzymes; study of the role and inhibition of fatty acid synthesis in human cancer, obesity and tuberculosis, and the design and synthesis of potential therapeutic agents
Research programs in Dr. Townsend's group are broadly in bioorganic chemistry with specific interests in natural product biosynthesis, the enzymology and molecular biology of secondary metabolism, and rational drug design. Particular emphasis has been placed on studies of biochemical reaction mechanism and organic synthesis, notably biomimetic synthesis; discovery of biosynthetic gene clusters and discerning their function; mechanistic and structural studies of their encoded proteins and their engineering for synthetic purposes; the applications of molecular biology and microbiology in bioorganic chemistry, inhibitor design and synthesis based on understanding of enzyme mechanisms and protein structures. Major efforts are currently underway with: (1) the aflatoxins, a family of environmental carcinogens of wide distribution and their fundamental engines of synthesis, the iterative Type I polyketide synthases, (2) the beta-lactam antibiotics represented classically by penicillin and cephalosporin, but more recently by the nocardicins and their precursor polypeptide synthetases, the potent beta-lactamase inhibitor clavulanic acid, and the clinically-important carbapenems, and (3) in collaboration with microbiologists, pathologists, oncologists and neurobiologists in the School of Medicine, to investigate a family of inhibitors discovered in my laboratory effective against Mycobacterium tuberculosis, the causative agent of TB, and (4) to prepare inhibitors of fatty acid synthase as potential drugs against human cancers and obesity.
Representative Publications:
- Loftus, T. M.; Jaworsky D. E.; Frehywot, G. L.; Townsend, C. A.; Ronnett, G. V.; Lane, M. D.; Kuhajda, F. J. Reduced Body Weight in Mice Treated with Fatty Acid Synthase Inhibitors, Science 2000, 288, 2379-2381. Pub Med Reference
- Jones, P. B.; Parrish, N. M.; Houston, T. A.; Stapon, A. S.; Bansal, N. P.; Dick, J. D.; Townsend, C. A. A New Class of Anti-Tuberculosis Agents, J. Med Chem 2000, 43, 3304-3314. Pub Med Reference
- Udwary, D. W., Merski, M., and Townsend, C. A. A method for prediction of linker regions within large multifunctional proteins, and its application to a type I polyketide synthase, J. Mol. Biol. 323:585-598 2002. Pub Med Reference
Li. R.; Stapon, A.; Blanchfield, J.T.; Townsend, C. A. Three Unusual Reactions Mediate Carbapenem and Carbapenam Biosynthesis, J. Amer. Chem. Soc. 2000,122, 9296-9297.
- Miller, M. T., Bachmann, B. O., Townsend, C. A., and Rosenzweig, A. C. The catalytic cycle of b-lactam synthetase observed by x-ray crystallographic snapshots, Proc. Nat'l. Acad. Sci., 99:14752-14757 2002. Pub Med Reference
- Zhou, W.; Simpson, P. J.; McFadden, J. M.; Townsend, C. A. Medghalchi, S. M.; Vadlamudi, A.; Pinn, M. L.; Ronnett, G. V.; Kuhajda, F. P. Fatty Acid Synthase Inhibition Triggers Apotosis During S Phase in Human Cells, Cancer Res. 2003, 63, 7330-7337. Pub Med Reference
- Gunsior, M.; Breazeale, S. D.; Lind, A. J.; Ravel, J., Janc, J. W.; Townsend, C. A. The Biosynthetic Gene Cluster for a Monocyclic b-Lactam Antibiotic, Nocardicin A, Chem. & Biol. 2004, 11, 927-938. Pub Med Reference
- McFadden, J. M.; Medghalchi, S. M.; Thupari, J. N.; Pinn, M, L.; Vadlamudi, A.; Miller, K. I.; Kuhajda, F. P.; Townsend, C. A. Application of a Flexible Synthesis of (5R)-Thiolactomycin to Develop New Inhibitors of Type I Fatty Acid Synthase, J. Med. Chem. 2005, 48, 946-961. Pub Med Reference
- Crawford, J. M.; Dancy, B. C. R.; Hill, E. A.; Udwary, D. W.; Towsend, C. A. Identification of a Starter-Unit Acyl-Carrier Protein Transacylase Domain in an Iterative Type I Polyketide Synthase. Proc. Nat’l. Acad. Sci. 2006, 103, 16728-16733. Pub Med Reference
- Arnett, S. O.; Gerratana, B.; Townsend, C. A. Rate-Limiting Steps and Role of Active Site Lys443 in the Mechanism of Carbapenem Synthase, Biochemistry 2007, 46, 9337-9345. [selected as a 2007 Hot Article] Pub Med Reference
- Merski, M.; Townsend, C. A. Observation of an Acryloyl–Thiamin Diphosphate Adduct in the First Step of Clavulanic Acid Biosynthesis, J. Amer. Chem. Soc. 2007, 129, 15750-15751. Pub Med Reference
- Aja, S.; Landree, L. E.; Kleman, A.; Medghalchi, S. M.; Vadlamudi, A.; McFadden, J. M.; Aplasca, A.; Hyun, J.; Plummer, E.; Daniels, K.; Kemm, M.; Townsend, C. A.; Thupari, J. N.; Kuhajda, F. P.; Moran, T. H.; Ronnett, G. V. Pharmacological Stimulation of Carnitinepalmitoyl Transferase-I Decreases Food Intake and Body Weight, Amer. J. Physiol-Regulatory Integrative & Comp. Physiol. 2008, 294, R352-R361. Pub Med Reference
- Crawford, J. M.; Thomas, P. M.; Scheerer, J. R.; Vagstad, A. L.; Kelleher, N. L.; Townsend, C. A. Deconstruction of Iterative Multidomainal Polyketide Synthase Function, Science 2008, 320. 243-246. Pub Med Reference “Perspectives” article: Science 2008, 320, 186-187. “Research Highlight” article: Nat. Rev. Microbiol. 2008, 6, 414-415.
Other graduate program in which Dr. Towsend participates:
Anti-Cancer Drug Development Program
Chemistry-Biology Interface Program (CBI)
