DiGiovanni, John

DiGiovanni, John Ph.D.

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Research Interests

Epithelial carcinogenesis, oncogenes, growth factors, transgenic models

Current Research

Research interests in my laboratory focus on three major areas: i) identifying critical targets and mechanisms involved in the initiation, promotion and progression stages of chemical carcinogenesis; ii) identification of genetic determinants of susceptibility to chemically-induced cancer; iii) exploring novel chemoprevention strategies for inhibiting human cancer. There is an emphasis on growth factor signaling pathways and their role in multistage chemical carcinogenesis. In addition, transgenic mouse models are being developed to facilitate this research. Several of these research areas are summarized below.

Research in the area of mechanisms of tumor initiation involves studying polycyclic aromatic hydrocarbons (PAH's), which are ubiquitous environmental pollutants produced in cigarette smoke, automobile exhaust, and other combustion associated processes. These studies are providing information at the molecular level about mechanisms whereby PAH carcinogens induce the early events in cancer. Our current and future work in this area involves studies to determine the type(s) of DNA damage produced by environmental PAH carcinogens, the relationship to specific mutations in cancers linked to exposure to these carcinogens, and the role of DNA repair proteins.

Current research in understanding mechanism(s) of tumor promotion is elucidating growth factor signaling pathways involved in this process using the mouse skin carcinogenesis model system. We have recently developed several transgenic models based on overexpression of IGF-1, erbB2, c-src, STAT3 and Akt in skin epidermis. Ultimately, these studies will lead to the identification of new targets and model systems for chemoprevention/intervention studies.

In the area of chemoprevention research, we are currently examining naturally occurring coumarins that may have potential as chemopreventive agents. These compounds are ubiquitous in higher plants and are particularly rich in citrus oils and certain vegetables, such as cilantro and celery. The potential anticarcinogenic properties of these natural coumarin derivatives are being examined in preclinical studies using the multistage model of mouse skin tumorigenesis with promising results. In addition, we have developed novel mouse models for both human prostate cancer and biliary tract cancers. These mouse models are being used to study effective chemoprevention strategies for humans.

Selected Publications

  1. Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, Digiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model, Nat Med, 11 (1), 43-9, 2005
  2. Chan KS, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J, DiGiovanni J. Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis, J Clin Invest, 114 (5), 720-8, 2004
  3. Kleiner HE, Vulimiri SV, Hatten WB, Reed MJ, Nebert DW, Jefcoate CR, Digiovanni J. Role of cytochrome p4501 family members in the metabolic activation of polycyclic aromatic hydrocarbons in mouse epidermis, Chem Res Toxicol, 17 (12), 1667-74, 2004
  4. Matsumoto T, Kiguchi K, Jiang J, Carbajal S, Ruffino L, Beltran L, Wang XJ, Roop DR, DiGiovanni J. Development of transgenic mice that inducibly express an active form of c-Src in the epidermis, Mol Carcinog, 40 (4), 189-200, 2004
  5. 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

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9414