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Personal History
Education
Ph.D., Biochemistry, University of Madras, Madras, India, 1996
M.S., Biochemistry, University of Madras, Madras, India, 1991
B.S. Zoology, Bharathidasan University, Trichy, India 1989
Academic Appointments
6/2007-present: Assistant professor, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, Maryland 21201.
1997-2007: Senior Research Associate, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio 44106.
Research Interests
Cancer begins with a normal cell that, due to persistent environmental insult, is transformed, via a series of progressively more insidious steps, into a cancer cell. A major goal of chemopreventive therapy is to alter the normal cell response to the environmental stress agent in order to inhibit disease progression. These agents act via a variety of different mechanisms. Some chemopreventive agents enhance cell differentiation. (-)-Epigallocatechin-3-gallate (EGCG) is an important bioactive antioxidant, derived from tea, which possesses remarkable cancer preventive properties. Our studies clearly indicate that EGCG markedly increases keratinocyte differentiation. Based on these results, we argue that EGCG acts to prevent cancer development by forcing neoplastic cells to undergo differentiation. This is an important hypothesis, as it indicates that green tea may act to prevent disease before it develops (Balasubramanian et al., J Biol Chem 277:1828-1836, 2002). In addition, our studies show that all chemopreventive agents are not created equal, and that these agents can antagonize each others action (Balasubramanian et al., J Biol Chem 281:36162-36172, 2006; Balasubramanian et al., J Biol Chem 282:6707-6715, 2007). This implies that the use of these compounds for cancer prevention must be carefully considered. An immediate goal is to examine how these agents influence epigenetic regulation.
Publications
Zhu L, Brodie C, Balasubramanian S, Eckert RL. (2007) Multiple PKCdelta Tyrosine Residues Are Required for PKCdelta-Dependent Activation of Involucrin Expression-a Key Role of PKCdelta-Y (311). J Invest Dermatol. (In Press).
Lee K, Adhikary G, Balasubramanian S, Gopalakrishnan R, McCormick T, Dimri GP, Eckert RL, Rorke EA. (2007) Expression of Bmi-1 in Epidermis Enhances Cell Survival by Altering Cell Cycle Regulatory Protein Expression and Inhibiting Apoptosis. J Invest Dermatol. (In Press).
Balasubramanian S, Eckert RL. (2007) Keratinocyte proliferation, differentiation, and apoptosis- Differential mechanisms of regulation by curcumin, EGCG and apigenin. Toxicol Appl Pharmacol. 1, 224:214-219.
Balasubramanian S, Eckert RL. (2007) Curcumin suppresses AP1 transcription factor-dependent differentiation and activates apoptosis in human epidermal keratinocytes. J Biol Chem, 282: 6707-6715.
Balasubramanian S, Zhu L, Eckert RL. (2006) Apigenin inhibition of involucrin gene expression is associated with a specific reduction in phosphorylation of PKC delta-Y311. J. Biol. Chem, 281:36162- 36172.
Eckert RL, Crish JF, Efimova T, and Balasubramanian S (2006) Opposing action of curcumin and green tea polyphenol in human keratinocytes. Mol. Nutr. Food Res. 50, 123-129.
Balasubramanian S, Chandraratna RA, and Eckert RL (2005) A novel retinoid related molecule inhibits pancreatic cancer cell proliferation by a retinoid receptor independent mechanism via suppression of cell cycle regulatory protein function and induction of caspase-associated apoptosis. Oncogene, 24: 4257-4270.
Balasubramanian S, Sturniolo MT, Dubyak GR, and Eckert RL (2005) Human epidermal keratinocytes undergo (-)-epigallocatechin-3-gallate-dependent differentiation but not apoptosis. Carcinogenesis, 26: 1100-1107.
Eckert RL, Crish JF, Efimova T, Dashti SR, Deucher A, Bone F, Adhikary G, Huang G, Gopalakrishnan R, and Balasubramanian S (2004) Regulation of involucrin gene expression. Journal of Investigative Dermatology, 123:13-22.
Eckert RL, Crish JF, Efimova F, and Balasubramanian S (2004) Antioxidants regulate normal keratinocyte differentiation. Biochemical Pharmacology, 68: 1125-1131.
Balasubramanian S, and Eckert RL (2004) Green tea polyphenol and curcumin inversely regulate human involucrin promoter activity via opposing effects on CCAAT/enhancer binding protein function. Journal of Biological Chemistry, 279:24007-24014.
Balasubramanian S, Chandraratna RA, and Eckert RL (2004) Suppression of human pancreatic cancer cell proliferation by AGN194204, an RXR-selective retinoid. Carcinogenesis, 25:1377-1385.
Sah JF, Balasubramanian S, Eckert RL, Rorke EA (2004) Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases. Journal of Biological Chemistry, 279:12755-12762.
Eckert RL, Efimova T, Balasubramanian S, Crish JF, Bone F, and Dashti SR (2003) p38 Mitogen-activated protein kinases on the body surface-a function for p38 delta. Journal Investigative Dermatology, 120:823-828.
Eckert RL, Efimova T, Dashti SR, Balasubramanian S, Deucher A, Crish JF, Sturniolo M, Bone F (2002) Keratinocyte survival, differentiation, and death: many roads lead to mitogen-activated protein kinase. Journal of Investigative Dermatology, 7: 36-40.
Balasubramanian S, Efimova T, and Eckert RL (2002) Green tea polyphenol stimulates a Ras, MEKK1, MEK3, and p38 cascade to increase activator protein 1 factor-dependent involucrin gene expression in normal human keratinocytes. Journal of Biological Chemistry, 277:1828-36.
Crish J, Bone F, Balasubramanian S, Zaim T, Wagner J, Yun J, Rorke E, and Eckert RL (2000) Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins. Carcinogenesis 21, 1031-1037.
Eckert RL, Crish JF, Balasubramanian S, and Rorke EA (2000) Transgenic animal models for human papillomavirus diseases. International Journal of Oncology, 16, 853-70.
Balasubramanian S, Agarwal, C, Efimova T, Dubyak GR, Banks, E, Welter J, and Eckert RL (2000) Thapsigargin suppresses phorbol ester-dependent human involucrin promoter activity by suppressing CCAAT-enhancer-binding protein alpha (C/EBPalpha) DNA binding. Biochemical Journal, 350, 791-796.
Balasubramanian S, Kim KH, Ahmad N, and Mukhtar H (1999) Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. Oncogene, 18, 1297-1302.
Balasubramanian S, Ahmad N, and Mukhtar H (1999) Upregulation of E2F transcription factors in chemically induced mouse skin tumors. International Journal of Oncology, 15, 387-390.
Dhawan D, Balasubramanian S, Amonkar AJ, and Singh N (1999) Chemopreventive effect of 4-demethyl epipodophyllotoxin on DMBA/TPA induced mouse skin carcinogenesis. Carcinogenesis, 20, 997-1003.
Sharma ND, Balasubramanian S, Khanna N, Bahadur S, Chattopadhyay TK, and Singh N (1999) Telomerase activity in Indian patients with carcinomas of the aerodigestive tract. Tumor Biology, 20, 225-32.
Balasubramanian S, Ahmad N, Jeedigunta S, and Mukhtar H (1998) Alterations in cell cycle regulation in mouse skin tumors. Biochemical Biophysical Research Communication, 243, 744-748.