Professor, Department of Molecular and Human Genetics
Director, Biochemical Genetics Laboratory

B.S., Mississippi State University, 1965
Ph.D., University of Georgia, 1971
Postdoc, Case Western Reserve University, 1974

RESEARCH INTERESTS:

For many years, my laboratory has had as its major focus on various aspects of the genes and the enzymes involved in the metabolism of arginine. In addition to the role of arginine in the synthesis of protein, it is a precursor for the formation of many other amino acids, creatine, and polyamines and plays a major role in the urea cycle where it is involved in the metabolism of ammonia. Of great interest now is the role of arginine as the precursor molecule for the formation of nitric oxide (NO). Nitric oxide has been shown to be a very significant messenger molecule involved in various physiological processes including neurotransmission, blood pressure homeostasis, and as an antimicrobial and antitumor agent. In order to further our understanding of these processes, we have developed and are utilizing mice that are deficient for the various genes that may potentially play a role in the production of nitric oxide. Currently our work has focused on the role of arginase I and II in the homeostasis of intracellular arginine. Arginase I is hypothesized to play a significant role in limiting the supply of arginine for nitric oxide synthesis. We are utilizing transgenic mouse technology to overproduce arginase I and ES cells technology to prepare mice with regulated arginase I expression.

In this same area, we are studying the role of a relatively newly recognized gene, arginase II. So far, the exact role of this enzyme in metabolism is undefined. We have recently characterized the murine gene and have constructed a murine line that is deficient in this enzyme. Until recently, we had not identified any significant phenotype but it now appears that on some mouse backgrounds the lack of this gene leads to infertility in males. This is currently being evaluated.

We are also involved in a major mouse mutagenesis project within the Department that will produce large numbers of randomly mutagenized mice. Breeding schemes allow us to screen for recessive mutations affecting development. My laboratory's role in this project is to conduct large-scale metabolite screens that will enable us to identify mutations in numerous metabolic pathways. This project utilizes the power of the tandem mass spectrometer to analyze literally thousands of mutagenized mice per year. Mutants identified in the large screen will be available to the laboratory and the scientific community at large for further investigation.

SELECTED PUBLICATIONS:

1. Scaglia F, Carter S, O'Brien WE, Lee B (2004). Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol. Genet. Metab. 81: Suppl. 79-85.

2. Singer JB, Hill AE, Burrage LC, Olszens KR, Song J, Justice M, O'Brien WE, Conti DV, Witte JS, Lander ES, Nadeau JH (2004). Genetic dissection of complex traits with chromosome substitution strains of mice. Science 304: 445-448.

3. Sutton VR, O’Brien WE, Clark GD, Kim J, Wanders RJA (2003). 3-Hydroxy-2-methylbutyrl-CoA dehydrogenase deficiency. J. Inherit. Metab. Dis. 26: 69-71.

4. Song J, Wadhwa L, Bejjani BA, O'Brien WE (2003). Determination of 3-keto-4-ene steroids and their hydroxylated metabolites catalyzed by recombinant human cytochrome P450 1B1 enzyme using gas chromatography-mass spectroscopy with trimethylsilyl derivatization. J. Chromatogr. B. 791: 127-135.

5. Iyer RK, Yoo PK, Kern RM, Rozengurt N, Tsoa R, O'Brien WE, Yu H, Grody WW, Cederbaum SD (2002). Mouse model for human arginase deficiency. Mol. Cell Biol. 22: 4491-4498.

6. Scaglia F, Zheng Q, O'Brien WE, Henry J, Rosenberger J, Reeds P, Lee B (2002). An integrated approach to the diagnosis and perspective management of partial ornithine transcarbamylase deficiency. Pediatrics 109: 150-152.

7. Bodamer OA, Bloesch SM, Gregg AR, Stockler-Ipsiroglu S, O'Brien WE (2001). Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass spectrometry. Clin. Chem. Acta. 308: 173-176.

8. Ochoa JB, Bernard AC, O'Brien WE, Griffen MM, Maley ME, Rockich AK, Tsuei BJ, Boulanger BR, Kearney PA, Morris SM Jr. (2001). Arginase I Expression and Activity in Human Mononuclear Cells After Injury. Ann. Surg. 233: 393-399.

9. Lee B, Yu H, Jahoor F, O'Brien W, Beaudet AL, Reeds P (2000). In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorders of the urea cycle. Proc. Natl. Acad. Sci. USA 97: 8021-8026.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

William E. O'Brien, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, NABS 270
Houston, Texas 77030, U.S.A.
Mail Stop: NAB 2015

Phone: 713-798-5484
Fax: 713-798-6584
E-mail:

Back to top