Last Updated: 7/13/2009

Arlin B Rogers, DVM, PhD Assistant Professor Molecular Carcinogenesis

Research Interests

The main objective of our laboratory is to determine mechanisms of sexually dimorphic liver cancer risk in humans and mouse models. Men develop primary liver cancer, hepatocellular carcinoma (HCC), more than three times as often as women. Using an infectious model of liver cancer (Helicobacter hepaticus) in mice, we demonstrated that loss of sex-specific liver function is associated with tumor promotion, a process we termed liver-gender disruption. Liver-gender disruption is driven by proinflammatory cytokines as evidenced by the fact that interferon-γ alone will reproduce many of the same alterations. This corroborates recent reports from other laboratories on the important role of cytokines, including IL-6 and IFN-γ, in male-predominant liver carcinogenesis. We are actively engaged in dissecting the molecular mechanisms that link inflammation to cancer in the liver, and how sex impacts the rate of tumor progression.

Recently our laboratory discovered that H. hepaticus does not even have to translocate to the liver to promote liver cancer. The natural niche of H. hepaticus is the lower bowel; only in select strains of mice does the organism migrate to the liver and induce hepatitis. We found in mice initiated with the food-borne liver carcinogen aflatoxin B1, or in mice bearing a hepatitis C virus (HCV) transgene, that H. hepaticus promoted HCC merely by colonizing the gut. From its remote intestinal location, the bacteria upregulated innate and Th1-type immune responses converging on NF-κB in both the lower bowel and liver. This is the first demonstration that gut microbiota can influence cancer beyond the intestinal tract. We are pursuing mechanisms to explain this connection, which has significant implications for human cancer risk assessment and prevention.

Finally, our laboratory discovered and is characterizing a novel mouse model of nonalcoholic fatty liver disease (NAFLD) associated with insulin resistance but not obesity. We found that male offspring of A/JCr and C57BL/6 mice develop spontaneous NAFLD that may progress to HCC. Intriguingly, there is a parent-specific mode of inheritance. F1 males with an A/J dam and B6 sire (ABF1) develop early and severe lesions, whereas those with a B6 dam and A/J sire (BAF1) develop late and self-limiting disease. Female offspring are resistant. Our initial survey revealed disease associations with X-linked but not mitochondrial, imprinted or Y-linked genes. However, subsequent investigation showed that somatic chromosomes also were involved. We are interrogating this model to determine the genetic basis for NAFLD risk, and to identify signaling networks disrupted during progression to cancer.

Recent Accomplishments and Honors

2009 Aspen Cancer Conference, Theodore Puck Award for Outstanding Abstract
2008 North Carolina Translational and Clinical Sciences Institute, NCTraC$10K
2005 MIT Center for Environmental Health Sciences Pilot Award

Training

2003 Diplomate, American College of Veterinary Pathologists
2001 PhD, Experimental Pathology, Colorado State University
1992 MS, Veterinary Pathobiology, University of Illinois at Urbana-Champaign
1990 DVM, Veterinary Medicine, University of Illinois at Urbana-Champaign
1988 BS, Veterinary Science, University of Illinois at Urbana-Champaign

Publications

1. Rogers AB, Houghton J. Helicobacter-Based Mouse Models of Digestive System Carcinogenesis. Methods Mol Biol. 2009;511:267-295.
2. Longato L, de la Monte S, Kuzushita N, Horimoto M, Rogers AB, Slagle BL, Wands JR. Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver. Hepatology. 2009 Jun;49(6):1935-43.
3. Lemke LB, Rogers AB, Nambiar PR, Fox JG. Obesity and non-insulin-dependent diabetes mellitus in Swiss-Webster mice associated with late-onset hepatocellular carcinoma. J Endocrinol. 2008 Oct;199(1):21-32.
4. Theve EJ, Feng Y, Taghizadeh K, Cormier KS, Bell DR, Fox JG, Rogers AB. Sex hormone influence on hepatitis in young male mice infected with Helicobacter hepaticus. Infect Immun. 2008 Sep;76(9):4071-8.
5. Fremont JJ, Marini RP, Fox JG, Rogers AB. Acute respiratory distress syndrome in two rhesus macaques (Macaca mulatta). J Am Assoc Lab Anim Sci. 2008 Sep;47(5):61-6.
6. Meira LB, Bugni JM, Green SL, Lee CW, Pang B, Borenshtein D, Rickman BH, Rogers AB, Moroski-Erkul CA, McFaline JL, Schauer DB, Dedon PC, Fox JG, Samson LD. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest. 2008 Jul;118(7):2516-25.
7. Bridgeford EC, Fox JG, Nambiar PR, Rogers AB. Agammaglobulinemia with Staphylococcus aureus botryomycosis in a cohort of related sentinel Swiss Webster mice. J Clin Microbiol. 2008 May;46(5):1881-4.
8. 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.
9. Dai C, Whitesell L, Rogers AB, Lindquist S. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell. 2007 Sep 21;130(6):1005-18.
10. Rogers AB, Cormier KS, Fox JG. Thiol-reactive compounds prevent nonspecific antibody binding in immunohistochemistry. Lab Invest. 2006 May;86(5):526-33.
11. Rogers AB, Taylor NS, Whary MT, Stefanich ED, Wang TC, Fox JG. Helicobacter pylori but not high-salt induces gastric intraepithelial neoplasia in B6129 mice. Cancer Res. 2005 Dec;65(23):10709-15.
12. Rogers AB, Boutin SR, Whary MT, Sundina N, Ge Z, Cormier K, Fox JG. Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus infected A/JCr mice. Toxicol Pathol. 2004 Nov-Dec;32(6):668-77.
13. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science. 2004 Nov 26;306(5701):1568-71.
14. Rogers AB, Fox JG. Inflammation and Cancer I. Rodent models of infectious gastrointestinal and liver cancer. Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G361-6.
15. Maurer KJ, Marini RP, Fox JG, Rogers AB. Polycystic kidney syndrome in New Zealand White rabbits resembling human polycystic kidney disease. Kidney Int. 2004 Feb;65(2):482-9.
16. Levenberg S, Huang NF, Lavik E, Rogers AB, Itskovitz-Eldor J, Langer R. Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12741-6.
17. Rogers AB, Hoover EA. Fetal feline immunodeficiency virus is prevalent and occult. J Infect Dis. 2002 Oct 1;186:895-904.
18. Rogers AB, Mathiason CK, Hoover EA. Cellular localization of feline immunodeficiency virus using native species antibodies. Am J Pathol. 2002 Oct;161(4):1143-51.
19. Rogers AB, Smith RD, Kakoma I. Serologic cross-reactivity of antibodies against Borrelia theileri, Borrelia burgdorferi, and Borrelia coriaceae in cattle. Am J Vet Res. 1999 Jun;60(6):694-7.
20. Rogers AB, Hoover EA. Maternal-fetal feline immunodeficiency virus transmission: timing and tissue tropisms. J Infect Dis. 1998 Oct;178:960-7.

E-mail: abr@med.unc.edu
Telephone: 843-8088
FAX: 966-8212
Address: CB #7431, 355 Rosenau Hall Chapel Hill, NC 27599

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