• using inbred strains of mice to model the natural human variation in genetic susceptibility to disease and environmental exposure
• integrating experimental, computational and bioinformatic approaches to understand the architecture of gene regulatory networks in eukaryotes.

How an organism is affected by changes in its environment depends in part on its genetic background. The Voy lab uses inbred strains of mice to model natural human variation in genetic susceptibility to disease and environmental exposure. Mouse genetics, high throughput gene expression profiling, computational biology and physiological tools are integrated to probe the net effects of gene-environment interactions. Three areas of research are currently under study.

1. Genetic variation in the health outcome of exposure to low doses of ionizing radiation. The detrimental effects of high doses of radiation are well-known, but the physiological consequences of lower doses are poorly defined. Standard and recombinant inbred strains of mice are used to dissect robust responses to low dose exposures from those that depend on genetic background. Transcriptome profiling is combined with functional responses and pathway mining tools to identify the molecular mechanisms that underlie low dose radiation effects.
2. Interactions between an obesigenic environment and the renin-angiotensin system. Adipose tissue produces an increasing repertoire of adipokines with both local and systemic actions. Levels of many of these factors are modulated by diet and energy balance. Mouse models of altered production of one such adipokine, angiotensin II, are used to probe the extent to which adipose tissue directly contributes to conditions that are co-morbid with obesity, such as type II diabetes.
3. Health effects of inhaled nanoparticles. Nanoparticles are both manufactured for their own value in a growing range of applications and produced as byproducts of manufacturing processes. Despite their rapidly increasing use, the health effects of inhaled nanoparticles have not been well-characterized. Mouse models are used to explore the potential consequences of exposure to a variety of types of engineered particles of nano scale.

• Liu Y, Das S, Olszewski RE, Carpenter DA, Culiat CT, Sundberg JP, Liu X, Soteropoulos P, Doktycz MJ, Michaud EJ and Voy BH. The Near Naked Hairless (HrN) mutation disrupts hair formation but is not due to a mutation in the hairless coding region. In preparation.
• Liu Y, Das S, Carpenter DA, Cain KT, Sundberg JP, Michaud EJ and Voy BH. Molecular basis for hair loss in mice carrying a novel nonsense mutation (Hrrh-R) in the Hairless gene (Hr) In preparation
• Voy BH, Scharff JA, Perkins AD, Saxton AM, Borate B, Chesler EJ, Branstetter LK, and Langston MA. Extracting gene networks for low dose radiation using graph theoretical algorithms. In review, PLoS Computational Biology.
• Scharff J, Voy BH, Perkins A, Saxton A, Langston MA. Graph theoretical approach to eludicating gene networks underlying the response to low dose ionizing radiation. Proceedings, The 21st Annual ACM Symposium on Applied Computing, Dijon, FR, May 2006 (in press).
• Kim S, Voy BH, Huang T, Koontz JW, Quignard-Boulange A, Harp JB, Moustaid-Moussa N. Angiontesin II (Ang II) uses insulin signaling pathways in 3T3-L1 adipocytes. Adipocytes, In press
• Baldwin NE, Collins RI, Langston MA, Leuze MR, Symons CT, and Voy BH. High performance computational tools for motif discovery. Proceedings, The Third IEEE International Workshop on High Performance Computational Biology, Santa Fe, New Mexico, April, 2004 (in press).
• Voy BH, Kim S, Urs S, Joshi R, and Moustaid-Moussa N. The adipose renin angiotensin system: genetics, regulation and physiological function (In Genomics and Proteomics in Nutrition, N Moustaid-Moussa and CD Berdanier, eds.) Marcel Dekker, New York, NY. In press.
• Moustaid-Moussa N, Urs S, Campbell B, Kim HY, Kim S, Giannone R, Wortmann P, Zhang B, Snoddy J, and Voy BH. Gene expression profiling in adipose tissue (In Genomics and Proteomics in Nutrition, N Moustaid-Moussa and CD Berdanier, eds.) Marcel Dekker, New York, NY. In press.
• Wang Y, Jones-Voy BH, Urs S, Kim S, Quigley N, Heo Y-R, Standridge M, Andersen A, Dhar M, Joshi R, Taylor JW, Chun J, Leuze MR, Claycombe KJ, & Moustaid-Moussa N. The human fatty acid synthase gene and lipogenesis are coordinately regulated in human adipose tissue. J of Nutr. 134: 1032-8, 2004.
• Urs S, Smith C, Campbell B, Taylor J, Jones-Voy BH, and Moustaid-Moussa N, Gene expression profiling in human preadipocytes and adipocytes by microarray. J of Nutr. 134: 762-70, 2004
• Kim S, Urs S, Massiera F, Joshi R, Heo YR, Kobayashi H, Jones BH, Teboul M, Ailhaud G, Kim JH, and Moustaid-Moussa, N. Effect of agt gene inactivation and high fat diet on adipocyte metabolism and renal gene expression. Horm. Metab. Res. 34: 721-725, 2003.
• Heo YR, Claycombe K, Truett GE, Wright P, Banz W, Maher M, Zemel M, Jones BH, and Moustaid-Moussa N. Effects of fatty (fa) allele on adipose tissue leptin and lipid metabolism. Horm. Metab. Res. 34: 686-690, 2003.
• Hoyt PR, Tack L, Jones BH, Van Dither J, Staat S, Doktycz MJ. Automated high-throughput probe production for DNA microarray analysis. Biotechniques 34(2): 402-7, 2003.

• Claycombe KJ, Wang Y, Jones BH, Kim S, Wilkison WO, Zemel MB, Chun J, Moustaid-Moussa N. Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: interaction with insulin. Physiol Genomics. 2000 Sep 8;3(3):157-62.
• Claycombe KJ, Jones BH, Standridge MK, Guo Y, Chun JT, Taylor JW, Moustaid-Moussa N. Insulin increases fatty acid synthase gene transcription in human adipocytes. Am J Physiol. 1998 May;274(5 Pt 2):R1253-9.
• Jones BH, Standridge MK, Claycombe KJ, Smith PJ, Moustaid-Moussa, N. Glucose induces expression of stearoyl CoA desaturase in 3T3-L1 adipocytes. Biochem. J. 335:405-408, 1998.
• Jones BH, Standridge MK, Taylor,JW, Moustaid N. Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control in adipocytes. Am. J. Phys. 273:R236-R242, 1997.
• Jones BH, Standridge MK, Moustaid N. Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells. Endocrinology 138:1512-1519, 1997.
• Jones BH, Maher MA, Banz WJ, Zemel MB, Whelan J, Moustaid N. Adipose tissue stearoyl CoA desaturase mRNA is increased by obesity and decreased by polyunsaturated fatty acids. Am. J. Phys. 270:E192-E196, 1996.
• Jones BH, Kim JH, Zemel MB, Woychik RP, Michaud EJ, Wilkison WO, Moustaid N. Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity. Am. J. Phys. 270:E192-E196, 1996.
• Moustaid N, Jones BH, Taylor JW. Lipogenic activity and insulin responsiveness of primary cultured human adipocytes. J. of Nutr. 126:865-870, 1996.

• Functional Analysis of Gene Regulatory Networks Underlying Skin Biology and Environmental Susceptibility. Brynn H. Jones, Jay R. Snoddy, Cymbeline T. Culiat, Mitchel J. Doktycz, Peter R. Hoyt, Denise D. Schmoyer, Erich J. Baker, Douglas P. Hyatt, Line C. Pouchard, Michael R. Leuze, Eugene M. Rinchik, and Edward J. Michaud. DOE Human Genome Program Contractor-Grantee Workshop, Oakland, California, January 27-30, 2002.

• Comparative Methods for Identification of Genomic Regulatory Regions. Michael R. Leuze and Brynn H. Jones. C. Warren Neel Conference on Statistical Data Mining and Knowledge Discovery, University of Tennessee, Knoxville, June 22-25, 2002.
• Hairy Issues: Using mouse models of skin and hair pathophysiology to understand complex genetic networks. Centers for Bioinformatics & Computational Biology and Genome Technology Seminar Series; Duke University, April 3, 2002.