Administration & Faculty

Sigrid C. Roberts, PhD

Associate Professor

503-352-7289
sroberts@pacificu.edu

 

Education

2003 Postdoctoral Fellowship,

National Research Service Award, OHSU

2003 Postdoctoral Training,

Oregon Health & Science University

1997 Postdoctoral Fellowship,

Deutsche Forschungsgemeinschaft,

Universitaet Konstanz, Germany

1994 Doctor of Philosophy,

Biochemistry, University of Iowa

1989 Diplom, Biology

(equivalent to Master of Science degree),

Universitaet Oldenburg, Germany

1988 Fulbright Fellowship

1988 Master of Science, Biochemistry,

University of Wyoming, Laramie

 

Teaching

Block coordinator for:

PHRM 561 Biochemistry II

PHRM 582 Hematology and Oncology

Teaching in:

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 vitro macrophage 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 potential therapeutic 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.

 

Selected publications

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 of Leishmania 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.

 

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