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Saraswati Sukumar

Saraswati Sukumar

Department Affiliation: Primary: Oncology;  Secondary: Pathology
Degree: Ph.D., Nagpur University
Rank: Professor
Telephone Number: 410-614-2473
Fax Number: 410-614-4073
E-mail address: saras@jhmi.edu
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.

Representative Publications:

  • Fackler, M.J., Cho, S., Cope, L., Gabrielson, E., Visvanathan, K., Wilsbach, K., Meir-Levi, D., Lynch, C.F., Marks, J., Geradts, J., Regan, M.M., Viale, G., Wolff, A.C., Sukumar, S., Umbricht, C.B. DNA methylation markers predict recurrence-free interval in triple-negative breast cancer. NPJ Breast Cancer, Jan 31;6:3, 2020.  Pub Med Reference
  • Downs, B.M., Mercado-Rodriguez, C., Cimino-Mathews, A., Chen, C., Yuan, J.P., Van Den Berg, E., Cope, L.M., Schmitt, F., Tse, G.M., Ali, S.Z., Meir-Levi, D., Sood, R., Li, J., Richardson, A.L., Mosunjac, M.B., Rizzo, M., Tulac, S., Kocmond, K.J., de Guzman, T., Lai, E.W., Rhees, B., Bates, M., Wolff, A.C., Gabrielson, E., Harvey, S.C., Umbricht, C.B., Visvanathan, K., Fackler, M.J., Sukumar, S. DNA Methylation Markers for Breast Cancer Detection in the Developing World. Clin. Cancer Res., Nov 1;25(21):6357-6367, 2019. Pub Med Reference
  • Teo, W.W., Merino, V.F., Cho, S., Korangath, P., Liang, X., Wu, R.C., Neumann, N.M., Ewald, A.J., Sukumar, S. HOXA5 determines cell fate transition and impedes tumor initiation and progression in breast cancer through regulation of E-cadherin and CD24. Oncogene, Oct 20;35(42):5539-5551, 2016. Pub Med Reference
  • Jin, K., Park, S., Teo, W.W., Korangath, P., Cho, S.S., Yoshida, T., Győrffy, B., Goswami, C.P., Nakshatri, H., Cruz, L.A., Zhou, W., Ji, H., Su, Y., Ekram, M., Wu, Z., Zhu, T., Polyak, K., Sukumar, S. HOXB7 Is an ERα Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance. Cancer Discov., Sep;5(9):944-959, 2015. Pub Med Reference
  • Liu, S., Jin, K., Hui, Y., Fu, J., Jie, C., Feng, S., Reisman, D., Wang, Q., Fan, D., Sukumar, S., Chen, H. HOXB7 promotes malignant progression by activating the TGFβ signaling pathway. Cancer Res., Feb 15;75(4):709-719, 2015.  Pub Med Reference
  • Shah, N., Jin, K., Cruz, L.A., Park, S., Sadik, H., Cho, S., Goswami, C.P., Nakshatri, H., Gupta, R., Chang, H.Y., Zhang, Z., Cimino-Mathews, A., Cope, L., Umbricht, C., Sukumar, S. HOXB13 mediates tamoxifen resistance and invasiveness in human breast cancer by suppressing ERα and inducing IL-6 expression. Cancer Res., Sep 1;73(17):5449-5458, 2013. 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, Feb 21;109(8):2736-2741, 2012.  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, Apr 15;464(7291):1071-1076, 2010. Pub Med Reference
  • Chen, H., Lee, J.S., Liang, X., Zhang, H., Zhu, T., Zhang, Z., Taylor, M.E., Zahnow, C., Feigenbaum, L., Rein, A., Sukumar, S. Hoxb7 inhibits transgenic HER-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. Cancer Res., May 15;68(10):3637-3644, 2008. Pub Med Reference

 


Other graduate programs in which Dr. Sukumar participates:

Cellular and Molecular Medicine Graduate Program
Human Genetics
Pathobiology