John Digiovanni, Ph.D.
Research interests in my laboratory focus on 6 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, prostate and head and neck cancers; v) impact of dietary energy balance, especially obesity on development and progression of both skin and prostate cancer; and finally vi) role of Stat3 psoriasis.
Selected peer-reviewed publications (Selected from a list of over 230)
- Sano S, Chan KS, Carbajal S, Clifford J, Peavy M, Kiguchi K, Itami S, Nickeloff BJ, DiGiovanni J. Stat3 links activated keratinocytes and immunocytes for development of psoriasis in a novel transgenic mouse model. Nat Med 11:43-49, 2005.
- Sano S, Chan KS, Kira M, Takagi S, Tarutani M, Itami S, Kiguchi K, Yokoi M, Sugusawa K, Mori T, Hanaoka F, Takeda J, DiGiovanni J. Stat3 is a key regulator of keratinocyte survival and proliferation following ultraviolet irradiation. Cancer Res 65:5720-5729, 2005
- Kiguchi K, Ruffino L, Kawamoto T, Franco E, Kurakata S-i, Fujiwara K, Hanai M, Rumi M, DiGiovanni J. Therapeutic effect of CS-706, a specific COX-2 inhibitor, on gallbladder carcinoma in BK5.ErbB-2 mice. Mol Cancer Therapeutics 6:1709-1717, 2007.
- Segrelles C, Lu J, Hammann B, Santos M, Moral M, Cascallana J, Lara M, 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 67:10879-10888, 2007.
- Chan K, 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. Oncogene14:1087-1094, 2008.
- Moore T, Beltran L, Carbajal S, Strom S, Hursting SD, DiGiovanni J. Dietary energy balance modulates signaling through Akt/mTOR pathways in multiple epithelial tissues. Cancer Prev Res 1:65-76, 2008.
- Moore T, Carbajal S, Beltran L, Perkins SN, Yakar S, LeRoith D, Hursting SD, DiGiovanni J. Reduced susceptibility to two-stage skin carcinogenesis in mice with low circulating IGF-1 levels. Cancer Res 68:3680-3688, 2008.
8. Kataoka K, Kim DJ, Carbajal S, Clifford J, DiGiovanni J. Stage-specific disruption of Stat3 demonstrates a direct requirement during both the initiation and promotion stages of mouse skin tumorigenesis. Carcinogenesis 29:1108-1114, 2008.
- Segrelles C, Moral M, Lorz C, Santos M, Lu J, Cascallana JL, Lara MF, Carbajal S, Martinez-Cruz AB, Garcia-Escudero R, Beltran L, Segovia JC, Bravo A, DiGiovanni J, Paramio JM. Constitutively active Akt induces ectodermal defects and impaired bone morphogenetic protein signaling. Mol Biol Cell 19:137-49, 2008.
- Wang G, Carbajal S, Vijg J, DiGiovanni J., Vasquez KM. DNA structure-induced genomic instability in
vivo. JNCI 100:1815-1817, 2008.
- Kleiner H, Xia X, Sonoda J, Zhang J, Pontius E, Abey J, Evans RM, Moore D, DiGiovanni J. Effects of naturally occurring coumarins on hepatic drug metabolizing enzymes in mice. Tox Applied Pharm 232:337-50, 2008.
- Liu B, Xia X, Carbajal S, DiGiovanni J, Fischer S, Hu Y. IKKa deletion in keratinocytes causes cell- autonomous epidermal hyperplasia that is rescued by inactivation of the EGF receptor. Cancer Cell 14:212-225, 2008.
- Moral M, Segrelles C, Lara MF, Martinez AB, Lorz C, Santos M, Garcia R, Lu J, Kiguchi K, Buitrage A, Costa C, Saiz D, Rodriguez JL, Martinez-Tello FJ, Rodriguez-Pinilla M, Sanchez M, Garin M, Grande T, Bravo A, DiGiovanni J, Paramio J. Akt activation synergizes with Tp53 loss in oral epithelium to produce novel mouse model for head and neck squamous cell carcinoma. Cancer Res 69:1099-1108, 2009.
- Kim DJ, Angel JM, Sano S, DiGiovanni J. Constitutive activation and targeted disruption of signal transducer and activator of transcription 3 (Stat3) in mouse epidermis reveal its critical role in UVB- induced skin carcinogenesis. Oncogene 28:950-960, 2009.
- Kim DJ, Kataoka K, Rao D, Cotsarelis G, DiGiovanni J. Targeted disruption of Stat3 reveals a major role for follicular stem cells in skin tumor initiation. Cancer Res, 69:7587-7594, 2009.
- Kim, D.J., Tremblay, M.L., DiGiovanni, J. UVB-mediated nuclear translocation of protein tyrosine phosphatase TC-PTP is required for rapid Stat3 dephosphorylation in skin. PloSOne, 5(4): e10290, 2010.
- Kiguchi, K., Kitamura, T., Moore, T., Rumi, M., Chang, H., Treece, D., Ruffino, L., Connolly, K., DiGiovanni, J. Dual inhibition of both the EGFR and erbB2 effectively inhibits promotion of skin tumors during two-stage carcinogenesis. Cancer Prevention Research, 2010 Aug;3(8):940-52.
- Miyoshi,K.,Takaishi,M.,Nakajima,K.,Ikeda,M.,Asao,N.,DiGiovanni,J.,Sano,S.,Stat3isa therapeutic target for psoriasis. J. Invest. Dermatol, 2010, Sep 2. [Epub ahead of print].
Evidence That Gsta4 Modifies Susceptibility to Skin Tumor Development in Mice and Humans. JNCI, in press, 2010.
Director of Center for Molecular Carcinogenesis and Toxicology
Associate Director of Basic Science Research, LiveSTRONG Cancer Institutes
Professor of Pharmacology & Toxicology
Ph.D., Pharmacology, The University of Washington, 1978
B.S., Pharmacy, The University of Washington, 1974