Department of Biochemistry
School of Medicine & Biomedical Sciences
Faculty

SATRAJIT SINHA, Ph.D.
Associate Professor

email: ssinha2@buffalo.edu

 

Dr. Sinha's Lab Page

 

Transcriptional control of epidermal differentiation

The epidermis is stratified squamous epithelium found at the skin surface. The basal cells of the epidermis tucked away in the innermost layer constitute the proliferative compartment of epidermis. In a balanced and carefully orchestrated differentiation program, basal cells periodically withdraw from the cell cycle and migrate towards the skin surface. As these cells differentiate, they progress through distinct stages and unique sets of genes are turned on and off. Temporally and spatially compartmentalized, the epidermis thus provides a unique system to study the molecular switches that control tissue-specific and differentiation-specific gene expression. Study in our laboratory focuses on the identification and characterization of transcription factors that govern this program of control of developmental and differentiation decisions of the epidermal cells.

1.  The first area of interest of the lab includes analysis of promoters/enhancers of genes that are unique to the different differentiation stages of epidermis. These studies involve DNAse I hypersensitive site mapping, gel-shifts, footprints, ChIP (chromatin immunoprecipitation) assays, keratinocyte cell culture and transgenic mice analysis. To complement these studies we are also using genomic tools and in silico analysis to characterize putative cis-elements common for epidermal specific genes.

2.  The second area of interest centers on two families of transcription factors (AP-2 and Ets) that play key role in governing keratinocyte-specific gene expression. Studies include expression and biochemical analysis of newly discovered family members as well as gain-of-function and loss-of function studies using transgenic mice. We are also in the process of identifying and characterizing additional new transcription factors that are unique to the epidermis. In future our goal is to identify the target genes for these factors and to gain insights into the process of how epidermal-specific patterns of gene expression is established.

Selected Recent Publications

Romano, R, K, Ortt, B. Birkaya, K. Smalley, and S. Sinha. 2009. An active role of the DN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS ONE in press

Choi, Y.S., R. Chakrabarti, R. Escamilla-Hernandez, and S. Sinha. 2009 Elf5 conditional knockout mice reveal its role as a master regulator in mammary alveolar development: failure of Stat5 activation and functional differentiation in the absence of Elf5. Developmental Biology 329, 227-241. [PDF]

Nagarajan, P., Parikh, N., Garrett-Sinha, LA., Sinha, S. 2009 Ets1 Induces Dysplastic Changes When Expressed in Terminally-Differentiating Squamous Epidermal Cells PLoS ONE. 4(1):e4179.  [PDF]

Parikh, N., Nagarajan, P., Sei-ichi, M., Sinha, S., and Garrett-Sinha, L. A. (2008) Isolation and characterization of an immortalized oral keratinocyte cell line of mouse origin. Arch Oral Biol 53: 1091-1100. [PDF]

Landesberg, R., Cozin, M., Cremers, S., Woo, V., Kousteni, S., Sinha, S., Garrett-Sinha, L., Raghavan, S. (2008) Inhibition of oral mucosal cell wound healing by biphosphonates. J. Oral Maxillofac Surg 66, 839-847.

Ortt, K., Raveh, E., Gat, U., Sinha, S. (2008) A chromatin immunoprecipitation screen in mouse keratinocytes reveals Runx1 as a direct transcriptional target of DeltaNp63. J Cell Biochem 104, 1204-19. [PDF]

Nagarajan, P., Romano, R. A and Sinha, S. (2008) Transcriptional control of the differentiation program of interfollicular epidermal keratinocytes. Crit Rev Eukaryot Gene Expr. 18 57-79

Choi, Y.S., Cheng, J., Segre, J., and Sinha, S. (2008) Generation and analysis of Elf5-LacZ mouse: Unique and dynamic expression of Elf5 (ESE-2) in the inner root sheath of cycling hair follicle. Histochem Cell Biol. 129, 85-94 [PDF]

Nagarajan, P., and Sinha, S. (2008) Development of an inducible gene expression system for primary murine keratinocytes. J Dermatol Sci 49, 73-84 [PDF]

Birkaya, B., Ortt, K. and Sinha, S. (2007). Novel in vivo targets of ΔNp63 identified by a modified and improved chromatin immunoprecipitation approach. BMC Molecular Biology May; 8:43 [PDF]

Romano, R. A., Birkaya, B. and Sinha, S. (2007). A functional enhancer of keratin14 is a direct transcriptional target of ΔNp63. J Invest Dermatol May;127(5):1175-86. [PDF]

Nair, M., Bilanchone, V., Ortt, K., Sinha, S., and Dai, X. (2007). Ovol1 represses its own transcription by competing with transcription activator c-Myb and by recruiting histone deacetylase 1. Nucleic Acid Research Mar 1; 35(5):1687-1697 [PDF]

Ortt, K, and Sinha, S. Derivation of the consensus DNA-binding sequence for p63 reveals unique requirements that are distinct from p53. FEBS Letters 580, Issue 18, 4544-4550

Choi, Y. S. and Sinha, S. (2006). Determination of the consensus DNA-binding sequence and a transcriptional activation domain for ESE-2. Biochem J. 398, 497-507

Romano, R. A., Birkaya, B. and Sinha, S. (2006). Defining the Regulatory Elements in the Proximal Promoter of DeltaNp63 in Keratinocytes: Potential Roles for Sp1/Sp3, NF-Y, and p63. J Invest Dermatol. 126, 1469-79.

Djalilian, A. R., McGaughey, D., Patel, S., Seo, E. Y., Yang, C., Cheng, J., Tomic, M, Sinha, S. Ishida-Yamamoto, A, Segre, J. A. (2006). Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response. J Clin Invest 116, 1243-1253.

Tummala, R. and Sinha, S. (2006). Differentiation-specific transcriptional regulation of the ESE-2 gene by a novel keratinocyte-restricted factor. J Cell Biochem 97, 766-81.

Romano, R. A., Li, H., Tummala, R., Maul, R. and Sinha, S. (2004). Identification of Basonuclin2, a DNA-binding zinc-finger protein expressed in germ tissues and skin keratinocytes. Genomics 83, 821-33.

Sinha, S. Regulation of Intermediate Filament Gene Expression. 2004. “Intermediate Filament Cytoskeleton, Editors Omary and Coulombe.” Methods in Cell Biology 78.

Tummala, R., Romano, R. A., Fuchs, E. and Sinha, S. (2003). Molecular cloning and characterization of AP-2 epsilon, a fifth member of the AP-2 family. Gene 321, 93-102.

Sinha, S. and Fuchs, E. (2001). Identification and dissection of an enhancer controlling epithelial gene expression in skin. Proc Natl Acad Sci USA 98, 2455-60.

Sinha, S., Degenstein, L., Copenhaver, C. and Fuchs, E. (2000). Defining the regulatory factors required for epidermal gene expression. Mol Cell Biol 20, 2543-55.

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