Current Methods in Melanocytic Biology

TOPICAL COLLECTIONS

Guest Editor

Sanjay Premi

H. Lee Moffitt Cancer Center

Dr. Premi started his research career during his PhD at the National Institute of Immunology, New Delhi, India where he investigated the genotoxicity of natural radioactivity. He pioneered in establishing a buffering effect of chromosomal alterations in offsetting the genotoxic effects of natural radioactivity. Dr. Premi’s research on the Y chromosome provides a base for several ongoing projects in the host laboratory. These findings motivated Dr. Premi to study the genotoxic stress from solar ultraviolet (UV) radiation at Yale University School of Medicine in the Department of Therapeutic Radiology. He discovered the carcinogenic role of melanin which is otherwise believed to be a potent shield against harmful effects of UV radiation. As an Associate Research Scientist at Yale Cancer Center, Dr. Premi developed adductSeq, a unique next-generation-sequencing based method to detect DNA damage at 1 bp resolution and identified hyperhotspots for UV-induced DNA damage. These hyperhotspots could be used as a dosimeter to assess a person’s history of UV exposure. As an Assistant Professor in the H. Lee Moffitt Cancer Center, Dr. Premi’s lab is interested in investigating the contradictory role of skin-pigmentation in skin-carcinogenesis. The idea is to re-sensitize the drug-resistant melanomas to the targeted therapies and immunotherapies by modulating the melanin-chemiexcitation pathway. Overall, Dr. Premi is an established and distinguished researcher in the field of skin tumorigenesis, the carcinogenicity of the skin pigmentary system, and photocarcinogenesis.

Collection Overview

Melanocytes are specialized skin cells that synthesize melanin and lead to the deadliest skin cancer ‘melanoma’. Keratinocytes receive melanin from melanocytes, leading to various skin color tones based upon the amount and type of melanin. Melanin is photoprotective, however, we discovered a melanin-chemiexcitation pathway that generates UV specific DNA damage in absence of UV. We believe that melanin in keratinocytes might lead to DNA damage and mutation through chemiexcitation, and ultimately to non-melanoma skin cancer types like squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). Melanin-synthesis is taxing because it produces huge amounts of superoxide and hydrogen peroxide. Accordingly, primary melanocytic cell-culture from the skin is arduous where melanocytes either lose pigment or simply die in response to minor changes in cell-culture conditions. This Methods Collection will focus on successful isolation and culturing of primary melanocytes and melanocytes-keratinocyte co-cultures, and alternate methods of feeding pigment to the non-pigmented keratinocytes to investigate the role of pigment in inducing SCC and BCC. To investigate the extent and type of UV- induced damage, this Methods Collection will also focus on the often-misconceived UV dosimetry, UV-wavelengths, and their potency in inducing DNA damage and mutations. Lastly, the type and amount of melanin greatly affect the potential of pre-conditioned melanocytes to induce melanoma. In this regard, this Methods Collection will also focus on analytical methods to investigate the chemical nature of the skin pigments.