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School of Medicine
Department Affiliation: Primary: Oncology; Secondary: Pathology
Degree: Ph.D., Nagpur University
Telephone Number: 410-614-2473
Fax Number: 410-614-4073
E-mail address: firstname.lastname@example.org
Johns Hopkins Hospital Address: Breast Cancer Program, CRB1, Room 143, 1650 Orleans Street, Baltimore, MD 21231
Molecular alterations in breast cancer
Our lab is focused on using comprehensive gene expression, methylation and sequencing and metabolomics analysis to identify alterations in breast cancer, and exploiting these for early detection and therapy. Among differentially expressed genes, our lab has focused on the HOX genes. HOX genes are intimately involved in the development of resistance to both chemotherapy and to agents targeting the estrogen receptor. Our work explores the alternate pathways that are activated by HOX proteins leading to this resistance and novel treatments to overcome resistance in both tissue culture and xenograft models. In addition, epigenetically silenced genes and a metabolic reprogramming in tumors also trigger novel early detection and therapeutic strategies. We are testing the utility of differentiation therapy through reactivating RAR-beta in breast cancer using histone deacetylase inhibitors with great success. Also, we are targeting enzymes involved in gluconeogenesis and glycolysis with small molecule FDA-approved antimetabolites to achieve antitumor effects.
- Fackler, M.J., Umbricht, C., Williams, D., Argani, P., Cruz, L.A., Merino, V.F., Teo, W.W., Zhang, Z., Huang, P., Visvanathan, K., Marks, J., Gray, J.W., Ethier, S., Wolff, A.C., Cope, L.M., Sukumar, S. Genome-wide Methylation Analysis Identifies Genes Specific to Breast Cancer Hormone Receptor Status and Risk of Recurrence. Cancer Res 71(19):6195-6207, 2011. Pub Med Reference
Jin, K., Kong, X, Shah, T., Penet, M.F., Wildes, F., Sgroi, D.C., Ma, X.J., Huang, Y., Kallioniemi, A., Landberg, G., Bieche, I., Wu, X., Lobie, P.E., Davidson, N.E., Bhujwalla, Z.M., Zhu, T., Sukumar, S. The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. Proc Natl Acad Sci USA, 2011 Jun 20. Pub Med Reference [Epub ahead of print]
Maruyama, R., Choudhury, S., Kowalczyk, A., Bessarabova, M., Beresford-Smith, B., Conway, T., Kaspi, A., Wu, Z., Nikolskaya, T., Merino, V.F., Lo, P.K., Liu, X.S., Nikolsky, Y., Sukumar, S., Haviv, I., Polyak, K. Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium. PLoS Genet 2011 Apr;7(4). Pub Med Reference [Epub ahead of print].
Sabnis, G.J., Goloubeva, O., Chumsri, S., Nguyen, N., Sukumar, S., Brodie, A.M. Functional activation of the estrogen receptor-α and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res 71(5):1893-1903, 2011. Pub Med Reference
Maruyama, R., Shipitsin, M., Choudhury, S., Wu, Z., Protopopov, A., Yao, J., Lo, P.K., Bessarabova, M., Ishkin, A., Nikolsky, Y., Liu, X.S., Sukumar, S., Polyak, K. Altered antisense-to-sense transcript ratios in breast cancer. Proc Natl Acad Sci USA 2010 Nov 22 Pub Med Reference [Epub ahead of print]
- Marik, R., Fackler, M., Gabrielson, E., Zeiger, M.A., Sukumar, S., Stearns, V., Umbricht, C.B. DNA methylation-related vitamin D receptor insensitivity in breast cancer. Cancer Biol Ther 10(1):44-53, 2010. Pub Med Reference
Gupta, R.A., Shah, N., Wang, K.C., Kim, J., Horlings, H.M., Wong, D.J., Tsai, M.C., Hung, T., Argani, P., Rinn, J.L., Wang, Y., Brzoska, P., Kong, B., Li, R., West, R.B., van de Vijver, M.J., Sukumar, S., Chang, H.Y. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071-1076, 2010. Pub Med Reference
Other graduate programs in which Dr. Sukumar participates: