Assistant Project Scientist
Pep's primary research focus is the development and implementation of novel methods to discover new therapeutics against drug-resistant microbial pathogens. A secondary research focus is the application of systems biology methods to study mechanisms underlying infection and antibiotic resistance in the pathogens.
One of Pep's specific research projects involves the use of adaptive laboratory evolution of one microbe against another to overproduce known antibiotics. This method also has the potential to yield compounds with new molecular structures as well. He demonstrated that this method can lead to a series of mutant Streptomyces clavuligerus strains that produce inhibitors against methicillin-resistant Staphylococcus aureus (MRSA) where none existed initially. The work has now been published (Charusanti et al, PLoS One, 2012), and is the subject of two provisional patents (see below). Importantly, however, this technique is a general, systematic platform that in theory can be used against other pathogens, not just MRSA. Several possibilities include pathogenic fungi, potential biowarfare agents such as Y. pestis and F. tularensis, and many drug-resistant Gram-negative bacteria such as A. baumannii, K. pneumoniae, and P. aeruginosa. Moreover, this method can be applied to other fields besides medical microbiology since the principal requirement for implementation is simply the ability to culture the organisms of interest on the same growth medium. One possible example is the discovery of agents to control plant pathogens important to agriculture.
A second project involves the mathematical modeling of metabolism and transcriptional regulation in Enterobacteria, specifically K. pneumoniae, S. Typhimurium and Y. pestis, and the integration of the models with high-throughput -omics data sets. The former is part of a collaboration with the National Health Research Institutes in Taiwan, and the latter two are part of an NIAID-funded multi-institution Systems Biology program centered on Enteropathogens. This combined computational-experimental approach is expected to yield novel, systems-level insights into the biology of these bacteria that are not readily apparent when the data are analyzed in isolation.
Fong NL, Lerman JA, Lam I, Palsson BO, Charusanti P. (2013) Reconciling a Salmonella enterica metabolic model with experimental data confirms that overexpression of the glyoxylate shunt can rescue a lethal ppc deletion mutant. FEMS Microbiol Lett. 342: 62. Link
Seo J-H, Hong JSJ, Kim D, Cho B-K, Huang T-W, Tsai S-F, Palsson BO, Charusanti P. (2012) Multiple-omic data analysis of Klebsiella pneumoniae MGH 78578 reveals its transcriptional architecture and regulatory features. BMC Genomics 13: 679. Link
Charusanti P, Fong NL, Nagarajan H, Pereira AR, Li HJ, Abate EA, Su Y, Gerwick WH, Palsson BO. (2012) Exploiting adaptive laboratory evolution of Streptomyces clavuligerus for antibiotic discovery and overproduction. PLoS One 7: e33727. Link
Charusanti P, Chauhan S, McAteer K, Lerman JA, Hyduke DR, Motin VL, Ansong C, Adkins JN, Palsson BO. (2011) An experimentally-supported genome-scale metabolic network reconstruction for Yersinia pestis CO92. BMC Syst Biol. 5: 163. Link
Liao Y-C, Huang T-W, Chen F-C, Charusanti P, Hong JSJ, Tsai S-F, Palsson BØ, Hsiung CA. (2011) An experimentally validated genome-scale metabolic reconstruction of Klebsiella pneumoniae MGH 78578, iYL1228. J. Bacteriol. 193: 1710-7. Link
Thiele I, Hyduke D, Steeb B, Fankam G, Allen DK, Bazzani S, Charusanti P, et al. (2011) A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2. BMC Syst Biol. 5: 8. Link
Charusanti P, Conrad TM, Knight EM, Venkataraman K, Fong NL, Xie B, Gao Y, Palsson BØ. (2010) Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene. PLoS Genet. 6: e1001186. Link
Lewis NE, Hixson KK, Conrad TM, Lerman JA, Charusanti P, Polpitiya AD, Adkins JN, Schramm G, Purvine SO, Lopez-Ferrer D, Weitz KK, Eils R, König R, Smith RD, Palsson BØ. (2010) Omic data from evolved E. coli are consistent with computed optimal growth from genome-scale models. Mol Syst Biol. 6: 390. Link
Cho BK, Charusanti P, Herrgård MJ, Palsson BØ. (2007) Microbial regulatory and metabolic networks. Curr Opin Biotechnol. 18: 360-4. Link
Charusanti P, Hu X, Chen LN, Neuhauser D, DiStefano JJ (2004) A mathematical model of BCR-ABL autophosphorylation, signaling through the CRKL pathway, and Gleevec dynamics in chronic myeloid leukemia. Discrete Cont Dyn-B. 4: 99-114. Link
Ansong C, Deatherage BL, Hyduke D, Schmidt B, McDermott JE, Jones MB, Chauhan S, Charusanti P, et al. (2012) Studying Salmonellae and Yersiniae Host-Pathogen Interactions Using Integrated Omics and Modeling. Curr Top Microbiol Immunol.
A Method to Generate Novel Bioactive Molecules. Inventors: Bernhard Palsson and Pep Charusanti. US provisional patent application filed.
Platform Strain for Metabolic Engineering of Bioactive Compounds. Inventors: Bernhard Palsson, Pep Charusanti, and Harish Nagarajan. US provisional patent application filed.
Email Address: pcharusanti-at-ucsd.edu
Phone: (858) 822-3180
Fax: (858) 822-3120
Mailing Address: UCSD Dept. of Bioengineering, 9500 Gilman Drive, Mail Code 0412, La Jolla, CA 92093-0412