Assistant Professor, Pharmacology
Department of Pharmaceutical Sciences
College of Pharmacy
Oregon State University
203 Pharmacy Building
Corvallis, OR 97331-3507
Phone: 541-737-5775
Arup.Indra@oregonstate.edu
www.mcb.oregonstate.edu/faculty/indra
http://www.cgrb.oregonstate.edu/faculty/indra
IGBMC, France, Senior Research Scientist, 2002–2005
IGBMC, France, Postdoctoral Fellow, 1997–2001
Ph.D, Jadavpur University, Kolkata, India, 2001
M.S., Calcutta University, India, 1992
The research in our laboratory is focused on studying the role of nuclear receptors (NRs), particularly Retinoid-X-Receptors (RXR α, β and γ), in skin during development and in adult skin homeostasis and diseases like cancer using mice as a model system. NRs are ligand-dependent transcription factors, many of whose ligands are used for the treatment of different skin diseases and in the control of melanoma and non-melanoma skin cancer. In skin, RXRs and in particular RXRα plays a key role in transducing cellular signals through hetero-dimerisation with other NR members like Retinoic Acid Receptors (RARs), Vitamin-D-Receptor (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. The 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 bcteriophage 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 RXRα 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 temperature shock, solar UV induced skin tanning and photo aging, (iii) in various skin diseases and (iv) in melanoma and non-melanoma skin cancer.
The present research themes are:
• Studying RXRα 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 ageing and formation of melanoma and non-melanoma skin cancer.
• Generating humanized mouse models of human skin cancer.
• Identifying potential targets for therapeutic intervention against invasive squamous carcinoma and metastatic melanoma.
Other ongoing research projects include studying the in-vivo role in skin of transcription factors TAF10 & TAF4, co-repressors CTIP1 and CTIP2 and members of the mammalian SWI2/SNF2 chromatin remodeling complex such as BRM and BRG1.
Golonzhka, O., Leid, M., Indra, G*., Indra, A.K. *(2007). Expression of COUP-TF-interacting protein 2 (CTIP2) in mouse skin during development and in adulthood. [In press, Mechanism of Development (Gene Expression Pattern)].
Fadloun, A., Kobi, D., Pointud, J-C., Indra, A.K., Teletin, M., Bole-Feysot, C., Testoni, B., Mantovani, R., Metzger, D., Mengus, G. and Davidson, I. (2007). The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell autonomous tumor suppressor activity in mouse epidermis. [In press, Development].
Indra A.K.*, Castaneda, E., Antal, M.C., Jiang, M., Messaddeq, N., Meng, X., Loehr, C., Gariglio, P., Kato, S., Wahli, W., Desvergne, B., Metzger, D. and Chambon, P* (2007). Malignant transformation of DMBA/TPA-induced papillomas and melanocytic growths in th skin of mice selectively lacking Retinoid X Receptor alpha (RXRa) in epidermal keratinocytes. J Invest Dermatol. [NPG] May;127(5):1250-60.
*Corresponding author
Indra AK, Dupe V, Bornert JM, Messaddeq N, Yaniv M, Mark M, Chambon P, Metzger D. Temporally controlled targeted somatic mutagenesis in embryonic surface ectoderm and fetal epidermal keratinocytes unveils two distinct developmental functions of BRG1 in limb morphogenesis and skin barrier formation. Development. 2005;132(20):4533-44.
Indra AK, Mohan WS 2nd, Frontini M, Scheer E, Messaddeq N, Metzger D, Tora L. TAF10 is required for the establishment of skin barrier function in foetal, but not in adult mouse epidermis. Developmental Biology. 2005;285(1):28-37.
Metzger D, Li M, Indra AK, Ghyselinck G, Chambon P. Conditional knockouts: Cre-lox systems. In: Celis J, ed. CELL BIOLOGY: A Laboratory Handbook, 3rd Ed. San Diego: Elsevier Inc.; 2004
Metzger D, Indra AK, Li M, Chapellier B, Ghyselinck G, Chambon P. Targeted conditional somatic mutagenesis in the mouse: temporally controlled knock-out of the retinoid receptors in epidermal keratinocytes. Methods in Enzymology. Vol 364, 2003.
Indra AK, Li M, Brocard J, Warot X, Bornert JM, Gerard C, Messaddeq N, Chambon P, Metzger D. Targeted somatic mutagenesis in mouse epidermis. Hormone Research. 2000;54(5-6):296-300.
Indra AK, Li M, Warot X, Brocard J, Messaddeq N, Kato S, Metzger D, Chambon P. Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis. Nature. 2000;407(6804):633-6.
Indra AK, Warot X, Brocard J, Bornert JM, Xiao JH, Chambon P, Metzger D. Temporally controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Research. 1999;27(22):4324-7.
