Brian J. Nickoloff, M.D., Ph.D.
Director, Skin Cancer Research Laboratories
Professor

M.D., Wayne State University 
Ph.D., Wayne State University

Immunologist

Immunobiology of Skin Disease

The different areas of scientific inquiry being pursued in my laboratory include primarily three skin diseases: Kaposi's sarcoma, psoriasis, and basal cell carcinoma. For Kaposi's sarcoma, we are examining the immunobiologic role of costimulatory molecule expression (CD80/CD86) by tumor cells, as well as determining the etiologic and pathophysiologic roles of HHV-8 using SCID mice engrafted with human skin.

In our psoriasis-related work we are studying the role of the immune system, specifically the contribution of T cell-keratinocyte interactions in production of psoriadc lesions using a SCID mouse model.

We are investigating sunlight-induced basal cell carcinoma with respect to the importance of  Fas ligand (CD95L) expression. We are studying the ability of ultraviolet-B light to induce CD95L on keratinocytes in vitro and in vivo, and we are characterizing the functional role in which CD95L-positive keratinocytes induce apoptosis in CD95-positive cells. A common theme in many projects involves the regulation of apoptosis, cell cycle progression, and nuclear transcription factors. We use clinical and basic research approaches to better understand the genetic basis for benign and malignant proliferative disorders in the skin. Specific topics include determining the relative roles of p16, p21, and p27 in apoptosis induced by ultraviolet light, the caspase cascades and crosstalk between CDK inhibitors, caspases 3/8, and NF-kB-induced cell-survival proteins.

Selected Publications

Nickoloff BJ. (2006). Keratinocytes regain momentum as instigators of cutaneous inflammation. Trends Mol Med. 12(3):102-6.

Ito T, Ito N, Saathoff M, Stampachiacchiere B, Bettermann A, Bulfone-Paus S, Takigawa M, Nickoloff BJ, Paus R. (2005). Immunology of the human nail apparatus: the nail matrix is a site of relative immune privilege. J Invest Dermatol. 125(6):1139-48. 

Gordon KB, Bonish BK, Patel T, Leonardi CL, Nickoloff BJ. (2005). The tumour necrosis factor-alpha inhibitor adalimumab rapidly reverses the decrease in epidermal Langerhans cell density in psoriatic plaques. Br J Dermatol. 153(5):945-53. 

Nickoloff BJ, Ben-Neriah Y, Pikarsky E. (2005). Inflammation and cancer: is the link as simple as we think?
J Invest Dermatol. 124(6):x-xiv. 

Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, DiGiovanni, J. (2005). Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. 
Nat Med. 11(1):43-9. 

Nickoloff BJ, Nestle FO. (2004). Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest. 113(12):1664-75.

Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO. (2004). Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J Exp Med. 199(5):731-6.

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