Arup Indra
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Assistant Professor, College of Pharmacy |
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Education
Ph.D. 2001, Jadavpur UniversityResearch
Micronutrients such as Vitamin A (Retinoid) and Vitamin D are used for treatment of different types of skin diseases, and as chemopreventive agents in cancer. They function as ligands for the nuclear receptors Retinoic Acid Receptors (RARs) and Vitamin-D-Receptor (VDR), which belong to the nuclear receptor superfamily and are ligand dependent transcription factors.The research in our laboratory is focused to study the role of Nuclear Receptors (NRs) particularly Retinoid-X-Receptors (RXR a, b and g ) in skin ontogenesis, tissue homeostasis and in diseases like cancer. In skin, RXRs and in particular RXR a plays a key role in transducing cellular signals through hetero-dimerisation with other NR members like RARs, VDR, Peroxisome-Proliferator Activated Receptors (PPARs) and Liver-X-Receptors (LXRs) in presence of their cognate ligands.
Skin, which acts as a protective shield from outside, has several vital functions. It has a complex multicellular structure made up of epidermal keratinocytes, dermal fibroblasts, hair follicle melanocytes, and subcutaneous fat cells, beside endothelial, nerve, muscle and some other cell types. Conventional gene knock-out approach for many NRs had several drawbacks like in-utero or postnatal lethality, complex pleiotrophic gene effects and compensation by other members of the gene family. To circumvent that we developed a spatio temporally controlled somatic mutagenesis technique based on the bacteriophage P1-Cre/ lox strategy. Using that genetic tool one can selectively ablate any gene, in any cell of a given tissue, and at any timepoint in the life of an animal.
Through selective ablation of NRs and in particular RXRa in keratinocytes, melanocytes and in fibroblast we want to address its role (i) in skin ontogenesis and in adult skin homeostasis, (ii) in stress responses like solar UV induced skin tanning and photo aging, and (iii) in melanoma and non-melanoma skin cancer.
The present research themes are:
- Studying RXRa mediated change in gene expression and alteration in signal transduction between similar or diverse cell types in skin.
- Understanding the molecular mechanism of NR dependent skin tanning, photo aging and formation of melanoma and non-melanoma skin cancer.
- Generating humanized mouse models of human skin cancer.
- Identifying potential drug targets for therapeutic intervention against invasive squamous carcinoma and metastatic melanoma.