PHRM 561 | Biochemistry II
PHRM 582 | Hematology and Oncology
PHRM 562 | Pharmacodynamics & Pharmacokinetics
PHRM 564 | Pulmonary, Cardiovascular & Renal III
PHRM 586 | Infectious diseases
Areas of Research & Specialization
The overall objective of my research is to characterize and therapeutically validate the polyamine pathway of the protozoan parasite Leishmania, which causes devastating and often fatal diseases in humans worldwide. Polyamines are essential cations that are especially important for rapidly proliferating cells such as parasites. The polyamine biosynthetic pathway in Leishmania is essential for parasite survival and significantly disparate from the host’s mechanism of polyamine production. A variety of genetic, cell and molecular biology, as well as biochemical techniques are being used to dissect the pathway. In addition, in vitromacrophage infectivity studies and in vivo murine infectivity models are being utilized to assess the importance of the polyamine pathway for host-parasite interactions and infectivity.
Previous research has focused on the role of ornithine decarboxylase (ODC) for parasite infectivity. Parasites missing this enzyme were generated by targeted gene replacement techniques and the LdDodc gene deletion mutants exhibited dramatically reduced infectivity in mice compared to wild type parasites. These studies have validated ODC as a potentialtherapeutic target. More recent research focuses on arginine metabolism in parasite infections. In Leishmania, arginase is a vital enzyme that converts the amino acid arginine to ornithine, which is then directly funneled into polyamine biosynthesis. Arginine is a key amino acid for two competing pathways in host macrophages: it can be converted to ornithine by the action of host arginase or alternatively to the potent anti-leishmanial agent nitric oxide by the inducible nitric oxide synthase. An increased activity of host arginase has been found associated with increased parasitemia and disease exacerbation, and inhibition of host arginase has been shown to reduce but not eradicate parasite numbers in infected macrophages and mice. Similarly, arginase deficient Leishmania parasites are still capable of eliciting an infection, albeit at lower levels than wild type parasites, suggesting that parasites are able to scavenge at least some ornithine from the host. Thus, it appears that both host arginase and parasite arginase play key roles in Leishmania infections and a dual inhibition of host and parasite arginase may be a novel therapeutic strategy for the treatment of leishmaniasis.
Singh, AK, Roberts SC, Ullman B, Madhubala, R. A Quantitative Proteomics Screen to Identify Potential Drug Resistance Mechanism in a α-deflouromethylornithine (DFMO) Resistant Leishmania donovani. J. Proteomics. 2014 Mar 12. [Epub ahead of print]
Roberts SC. Introduction to Pharmacogenomics. In: Karimi R., Biomedical and Pharmaceutical Sciences with Patient Care Correlations. 2014. Jones & Bartlett Learning, Burlington, MA,
Estrada F, Kim E, Olenyik T, Panozzo-Zenere EA, Labadie GR, Roberts SC. The Polyamine Pathway as a Potential Therapeutic Target against Leishmaniasis. Oregon Bio 2013 Annual Conference, Marylhurst, OR, September, 2013
Panozzo-Zenere E, Benitez D, Roberts S, Comini M, Tekwani B, Labadie G. Diferentes aproximaciones en la búsqueda del blanco molecular del metabolismo de las poliaminas en tripanosomátidos. Instituto de Química Rosario-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Suipacha 531, S2002LRK, Rosario, Argentina, 2013
Paradis D, Olenyk T, Harrelson J, Roberts S. The Effect of Polyamine Depletion on Parasite Proliferation. Pacific University Undergraduate Research Conference, Nov 2013
D'Antonio EL, Ullman B, Roberts SC, Gaur Dixit U, Wilson ME, Hai Y, and Christianson DW.Crystal structure of arginase from Leishmania mexicana and implications for the inhibition of polyamine biosynthesis in parasitic infections. Arch Biochem Biophys. 2013 Apr 9;535(2):163-176
Roberts SC. Genetic Manipulation of Leishmania Parasites Facilitates the Exploration of The Polyamine Biosynthetic Pathway as a Potential Therapeutic Target. In: Advances in Genetics Research. 2013. Volume 10. Editor: Urbano KV. Nova Science Publishers, Inc., ISBN: 978-1-62417-928-0
Roberts SC. The genetic toolbox for Leishmania parasites. Bioengineered Bugs. 2011 Nov-Dec;2(6):320-6.
Gilroy C, Olenyik T, Roberts SC, Ullman B. Spermidine synthase is required for virulence ofLeishmania donovani. Infect Immun. 2011 Jul;79(7):2764-9.
Roberts SC, Kline C, Liu W, Ullman B. Generating knock-in parasites: integration of an ornithine decarboxylase transgene into its chromosomal locus in Leishmania donovani. Exp Parasitol. 2011 Jun;128(2):166-9.
Riley E, Roberts SC, Ullman B. Inhibition profile of Leishmania mexicana arginase reveals differences with human arginase I. Int J Parasitol. 2011 Apr;41(5):545-52.
Karimi R, Arendt CS, Cawley P, Buhler AV, Elbarbry F, Roberts SC. Learning bridge: curricular integration of didactic and experiential education. Am J Pharm Educ. 2010 Apr 12;74(3):48.
Chawla B, Jhingran A, Singh S, Tyagi N, Park MH, Srinivasan N, Roberts SC, Madhubala R.Identification and characterization of a novel deoxyhypusine synthase in Leishmania donovani.J Biol Chem. 2010 Jan 1;285(1):453-63.
Darlyuk I, Goldman A, Roberts SC, Ullman B, Rentsch D, Zilberstein D. Arginine homeostasis and transport in the human pathogen Leishmania donovani. J Biol Chem. 2009 Jul 24;284(30):19800-7.
Boitz JM, Yates PA, Kline C, Gaur U, Wilson ME, Ullman B, Roberts SC. Leishmania donovani ornithine decarboxylase is indispensable for parasite survival in the mammalian host. Infect Immun. 2009 Feb;77(2):756-63.
Gaur U, Roberts SC, Dalvi RP, Corraliza I, Ullman B, Wilson ME. An effect of parasite-encoded arginase on the outcome of murine cutaneous leishmaniasis. J Immunol. 2007 Dec 15;179(12):8446-53.
Roberts SC, Jiang Y, Gasteier J, Frydman B, Marton LJ, Heby O, Ullman B. Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs. Antimicrob Agents Chemother. 2007 Feb;51(2):438-45.
Roberts SC., Tancer MJ, Polinsky MR., Gibson KM, Heby O, Ullman B. Arginase plays a pivotal role in polyamine precursor metabolism in Leishmania. Characterization of gene deletion mutants. J Biol Chem. 2004 May 28;279(22):23668-78.
Heby O, Roberts SC, Ullman B. Polyamine biosynthetic enzymes as drug targets in parasitic protozoa. Biochem Soc Trans. 2003 Apr;31(2):415-9.