DiGiovanni, John

DiGiovanni, John Ph.D.

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Research Interests

Epithelial carcinogenesis, oncogenes, growth factors, transgenic models, cancer prevention

Current Research

Research interests in Dr. DiGiovanni’s laboratory focus on four major areas: i) identifying critical targets and mechanisms involved in the initiation and promotion stages of chemical as well as UV skin carcinogenesis; ii) identification of genetic determinants of susceptibility to chemically-induced skin cancer; iii) exploring novel prevention strategies for inhibiting chemical and UV skin carcinogenesis; and iv) development of new mouse models for cancer, including models for skin and head and neck cancers. Several of these research areas are briefly summarized below.

Research in the area of mechanisms of tumor initiation involves studying the target cells for tumor initiation. These cells are believed to be keratinocyte stem cells. Current research is aimed at identifying genes involved in survival and proliferation of keratinocyte stem cells following exposure to DNA damaging skin carcinogens.

Current research in understanding mechanism(s) of tumor promotion involves elucidating growth factor signaling pathways involved in this process using the mouse skin carcinogenesis model system. Our laboratory has 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, current studies are examining naturally occurring chemicals that may have potential as chemopreventive agents. Chemicals under study include resveratrol, capsaicin, ursolic acid and several others. These compounds target multiple pathways including inflammatory pathways (e.g. NFκB) and Akt, src and Stat3 signaling pathways.

A new research area involves studies of dietary energy balance and mechanisms that underly dietary energy related effects on epithelial carcinogenesis (including skin cancers). For example, current studies are examining growth factor signaling pathways that are modulated by both negative (calorie restriction) and positive (diet-induced obesity) energy balance that play a role in epithelial carcinogenesis using the mouse skin model. These studies will help to further identify potential targets for prevention strategies.

A final new area of research not mentioned above deals with the human skin disease psoriasis. We recently developed a new mouse model for human psoriasis based on overexpression of a constitutively active form of Stat3 (Stat3C). Current studies are examining the mechanisms underlying Stat3’s ability to elicit psoriatic lesions in skin of transgenic mice following mild forms of skin wounding.

Selected Publications

  1. Chan KS, Sano S, Kataoka K, Abel E, Carbajal S, Beltran L, Clifford J, Peavey M, Shen J, Digiovanni J. Forced expression of a constitutively active form of Stat3 in mouse epidermis enhances malignant progression of skin tumors induced by two-stage carcinogenesis, Oncogene, 27 (8), 1087-94, 2008
  2. Segrelles C, Lu J, Hammann B, Santos M, Moral M, Cascallana JL, Lara MF, Rho O, Carbajal S, Traag J, Beltran L, Martinez-Cruz AB, Garcia-Escudero R, Lorz C, Ruiz S, Bravo A, Paramio JM, DiGiovanni J. Deregulated activity of Akt in epithelial basal cells induces spontaneous tumors and heightened sensitivity to skin carcinogenesis, Cancer Res, 67 (22), 10879-88, 2007
  3. Lu J, Rho O, Wilker E, Beltran L, Digiovanni J. Activation of epidermal akt by diverse mouse skin tumor promoters, Mol Cancer Res, 5 (12), 1342-52, 2007
  4. Sano S, Chan KS, Kira M, Kataoka K, Takagi S, Tarutani M, Itami S, Kiguchi K, Yokoi M, Sugasawa K, Mori T, Hanaoka F, Takeda J, Digiovanni J. Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation, Cancer Res, 65 (13), 5720-9, 2005
  5. 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
  6. 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
  7. 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