Last Updated: 2/12/2009

Research Interests
The Fry lab uses toxicogenomic and systems biology approaches to reveal molecular mechanisms of metal-induced carcinogenesis. A primary focus of our laboratory includes the study of mechanisms of arsenic-induced disease. A broad goal of the laboratory is to identify the genes and their encoded proteins that control human susceptibility to metal-induced disease. Active and proposed studies include:

Determining the role of NF-kB in arsenic-induced disease.
Arsenic exposure in humans is associated with increased risk for many types of cancers, but the mechanism for this is unclear. In addition, arsenic is a known co-carcinogen with DNA damaging agents. We have shown that prenatal arsenic exposure in humans results in significant transcriptional modulation of the NF-kB pathway. We hypothesize that this modulation may impact cellular responses upon exposure to DNA damaging agents. Specifically, we are using a lymphoblastoid cell culture model to determine the impact of low dose arsenic exposure on modulation of the NF-kB pathway. As our research is also aimed at identifying mechanisms by which arsenic acts as a co-carcinogen, we are examining how low dose arsenic exposure impacts responses to subsequent exposure to DNA damaging agents. Our work in vitro is complemented by our studies in human populations where we examine the impact of exposure on NF-kB activation. These studies examine a mechanism by which arsenic exposure could modulate cellular responses to other damaging agents and be linked to cancer.

Identifying proteins that protect against arsenic-induced killing; application of arsenic as a chemotherapeutic.
Arsenic trioxide is used as a chemotherapeutic to treat leukemia. In these studies we perform computational analysis that integrates tumor cell responses to arsenic with genome-wide expression profiles. These analyses are used to identify genes that influence tumor cell sensitivity to against arsenic-induced cytotoxicity. Using these approaches, we have identified pathways that are associated with cellular resistance to arsenic. These pathways are being targeted to generate knockdown cells to determine if altered expression impacts tumor cell survival. These studies have direct application in the clinic where arsenic could be used to treat other types of tumors.

Recent Accomplishments and Honors
2005 Infinite Mile Award, MIT
1995 Phi Beta Kappa (William Smith College)
1995 Magna Cum Laude (William Smith College)

Training
William Smith College B.Sc. 1991-1995 Biology
Tulane University MS 1995-1997 Biology
Tulane University (Degree)/Yale University Ph.D. 1997-2000 Biology
Massachusetts Institute of Technology Post-Doctoral Associate 2000-2002 Genomics

Publications
1. Fry, RC, J Peter Svensson, JP Chandni Valiathan, C Emma Wang, E Brad J. Hogan, BJ Sanchita Bhattacharya, S, James M. Bugni, JM, Charles A. Whittaker, CA and Samson, LD. Genomic Predictors of Inter-Individual Differences in Response to DNA Damaging Agents. Genes and Development, Oct 2008; 22: 2621 - 2626.

2. Borenshtein D, Fry RC, Groff EB, Nambiar PR, Carey VJ, Fox JG, Schauer DB. Diarrhea as a cause of mortality in a mouse model of infectious colitis. Genome Biol. 2008. Aug 4;9(8):R122

3. Liu S, Bhattacharya S, Han A, Suragani RN, Zhao W, Fry RC, Chen JJ. Haem-regulated eIF2alpha kinase is necessary for adaptive gene expression in erythroid precursors under the stress of iron deficiency. Br J Haematol. 2008. Jul 28.

4. Garca A, Ihrig MM, Fry RC, Feng Y, Xu S, Boutin SR, Rogers AB, Muthupalani S, Samson LD, Fox JG. Genetic susceptibility to chronic hepatitis is codominantly inherited in Helicobacter hepaticus-infected AB6F1 and B6AF1 hybrid male mice and progression to hepatocellular carcinoma is linked to hepatic expression of lipogenic genes and immune associated networks. Infect Immun. 2008 Feb 19.

5. Rogers AB, Theve EJ, Feng Y, Fry RC, Taghizadeh K, Clapp KM, Boussahmain C, Cormier KS, Fox JG. Hepatocellular carcinoma associated with liver-gender disruption in male mice. Cancer Res. 2007 Dec 15;67(24):11536-46.

6. Fry RC, Navasumrit P, Valiathan C, Svensson JP, Hogan, BJ, Luo M, Bhattacharya S, Kandjanapa K, Soontararuks S, Nookabkaew S, Mahidol C, Ruchirawat M and Samson LD. Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic Exposed Mothers. PLOS Genetics. 2007. 3(11): e207.

7. Rusyn I, Fry RC, Begley TJ, Klapacz J, Svensson JP, et al. Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates. 2007. PLoS ONE 2(11): e1252.

8. Beyer RP, Fry RC, Lasarev MR, McConnachie LA, Meira LB, Palmer VS, Powell CL, Ross PK, Bammler TK, Bradford BU, Cranson AB, Cunningham ML, Fannin RD, Higgins GM, Hurban P, Kayton RJ, Kerr KF, Kosyk O, Lobenhofer EK, Sieber SO, Vliet PA, Weis BK, Wolfinger R, Woods CG, Freedman JH, Linney E, Kaufmann WK, Kavanagh TJ, Paules RS, Rusyn I, Samson LD, Spencer PS, Suk W, Tennant RJ, Zarbl H; Members of the Toxicogenomics Research Consortium. Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses. Toxicol Sci. 2007 Sep;99(1):326-37.

9. Hwa AJ, Fry RC, Sivaraman A, So PT, Samson LD, Stolz DB, Griffith LG. Rat liver sinusoidal endothelial cells survive without exogenous VEGF in 3D perfused co-cultures with hepatocytes. FASEB J. 2007 Apr 10.

10. Fry, R.C., DeMott, M.S., Cosgrove, J.P., Begley, T.J., Samson, L.D., Dedon, P.C. The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA. BMC Genomics 2006, 7:313.

11. Benn J., Hu J., Hogan B..J, Fry R.C., Samson, L.D. and Thorsen, T. 2006. Comparative modeling and analysis of microfluidic and conventional DNA microarrays. Analytical Biochemistry, 15;348(2):284-93.

12. Sivaraman, A., Leach, J.K., Townsend, S., Iida, T., Hogan, B.J., Stolz, D.B., Fry, R.C., Samson, L.D., Tannenbaum, S.R. and Griffith, L.G. A Microscale In Vitro Physiological Model of the Liver: Predictive Screens for Drug Metabolism and Enzyme Induction. Current Drug Metabolism, Volume 6, No. 6, 2005.

13. Fry, R.C., Begley, T., and Samson, L.D. 2005. Genome-Wide Responses to DNA-damaging agents. Annual Reviews of Microbiology, 59:357-77.

14. Fry, R. and Members of the Toxicogenomics Research Consortium (listed alphabetically). 2005. Standardizing Global Gene Expression Analysis Between Laboratories and Across Platforms. Nature Methods. May;2(5):351-6.

15. Boutin, S.R., Rogers A.B., Shen, Z, Fry, R.C., Love JA, Nambiar, P.R, Suerbaum S., Fox, J.G. 2004 Hepatic temporal gene expression profiling in Helicobacter hepaticus-infected A/JCr mice. Toxicol Pathol. Nov-Dec;32(6):678-93.

16. Qin, L.X., Kerr K.F.; Contributing Members of the Toxicogenomics Research Consortium (Fry, RC and Samson, LD). 2004. Empirical evaluation of data transformations and ranking statistics for microarray analysis. Nucleic Acids Res. Oct 12;32

17. Fry, R., and Samson, L.D. 2003. Methods of Microarray Data Analysis II. DNA Repair, 21; 2 (11):1289-91.

18. Fry, R., Sambandan, T.G., and Rha, C.K. 2003. DNA damage and stress transcripts in Saccharomyces cerevisiae mutant sgs1. Mechanisms of Aging and Development, 124: 839-846.

19. Fry, R., Habashi, J., Okamoto, H., and Deng, X.W. 2002. Characterization of a strong dominant phyA mutation unique to phytochrome A signal propagation. Plant Physiology, 130: 457-465.

20. Fry, R., Champion, H., Lawrence, T., Murphy, W., Coy, D., and Kadowitz, P. 1997 Proadrenomedullin NH2-terminal peptide (PAMP) 12-20 has vasodepressor activity in the rat and cat. Life Sciences Journal. 60 (10): 161-167.

21. Champion, H., Fry, R., Murphy, W., Coy, D., and Kadowitz, P. 1996 Catecholamine release mediates pressor effects of adrenomedullin (15-22) in the rat. Hypertension. 28 (6): 1041-1046.

22. Fry, R., Kolmes-Fergusson, L., Kolmes, S., and Villani, M. 1997 Radiographic study of the response of Japanese beetle larvae (Coleoptera: Scarabaeidae) to soil-incorporated mycelial particles of Metarhizium anisopliae (Deuteromycetes). Journal of New York Entomological Society. 105 (1-2): 113-120.

E-mail: rfry@email.unc.edu
Telephone: 843-6864
Address: MHRC 0032 Chapel Hill, NC 27599

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