Angel, Joe M.

Angel, Joe M. Ph.D.

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Research Interests

Disease modifier genes, complex trait genetics, tumor genetics, carcinogenesis

Current Research

The overall goal of my research is to study the genetics of susceptibility to carcinogen exposure using mouse models. Susceptibility to environmental carcinogens is a function of multiple poorly penetrant genes that modify the propensity for tumor development. Mouse models of genetic susceptibility for development of specific tumors have been proven to be useful experimental tools for identifying and characterizing such genetic factors.

We are using 2 tumor model systems to identify, clone, and characterize genes that influence susceptibility to carcinogen-induced cancer in mice. One of our models examines the genetics of susceptibility of mice to N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas. MNU susceptibility is a multigenic trait involving at least three genes. Studies in genetic crosses of sensitive AKR mice with resistant C57L/J mice have demonstrated that a locus mapping to the central region of chromosome 7 influences susceptibility. The dominant allele is inherited from C57L/J and confers relative resistance to MNU. We have designated the locus Tlag1 (T-lymphoma attenuation gene 1). Tlag1 has been mapped to an approximately 350-kb region of mouse chromosome 7, and we are characterizing candidate MNU-susceptibility genes. A second MNU-susceptibility locus, Tlag2, has been mapped to chromosomes 4 in AKR x (AKR x C57L)F1 mice and confirmed in other crosses. We are currently conducting studies to delimit the map location of this locus.

The other mouse model that we have used to identify tumor-susceptibility loci is the 2-stage mouse skin tumor model. The 2-stage model of skin carcinogenesis involves an initiation step in which mice are treated with a single subcarcinogenic dose of a carcinogen followed by a promotion step in which initiated mice are exposed to multiple applications of a promoting stimulus such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Sensitive mice develop premalignant papillomas. Studies indicate that genetic factors that influence papilloma formation primarily act at the promotion step. To identify genes that control promotion susceptibility, we have examined TPA sensitivity in genetic crosses of sensitive DBA/2 or C3H mice with resistant C57BL/6 mice. The results indicate that TPA susceptibility is a multigenic trait. We have mapped 4 susceptibility loci in this model. We have developed congenic mouse strains for one of these loci, Psl1 (promotion susceptibility locus 1), and have narrowed the map location of this locus to a 15 cM region of distal chromosome 9. Several genes mapping within this region are attractive candidate TPA-susceptibility genes. We are conducting studies characterize these candidate genes for their roles in TPA skin tumor promotion.

Selected Publications

  1. Benavides F, Gomez G, Venables-Griffith A, Lambertz I, Flores M, Angel JM, Fuchs-Young R, Richie ER, Conti CJ. Differential susceptibility to chemically induced thymic lymphomas in SENCARB and SSIN inbred mice, Mol Carcinog, 45 (7), 543-8, 2006
  2. Riggs PK, Angel JM, Abel EL, DiGiovanni J. Differential gene expression in epidermis of mice sensitive and resistant to phorbol ester skin tumor promotion, Mol Carcinog, 44 (2), 122-36, 2005
  3. Angel JM, Caballero M, DiGiovanni J. Identification of novel genetic loci contributing to 12-O-tetradecanoylphorbol-13-acetate skin tumor promotion susceptibility in DBA/2 and C57BL/6 mice, Cancer Res, 63 (11), 2747-51, 2003
  4. Angel JM, Richie ER. Tlag2, an N-methyl-N-nitrosourea susceptibility locus, maps to mouse chromosome 4, Mol Carcinog, 33 (2), 105-12, 2002
  5. Richie ER, Schumacher A, Angel JM, Holloway M, Rinchik EM, Magnuson T. The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas, Oncogene, 21 (2), 299-306, 2002
  6. Angel JM, Caballero M, DiGiovanni J. Confirmation of the mapping of a 12-O-tetradecanoylphorbol-13-acetate promotion susceptibility locus, Psl1, to distal mouse chromosome 9, Mol Carcinog, 32 (4), 169-175, 2001

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9425