Research Interests

Chromatin Biology, Cytoskeleton Signaling in Cancer Cells, Nuclear Receptor Biology, Breast Cancer, and Roles of Infection and Inflammation in Cancer.

Research Program

The high mortality rate associated with breast cancer (of other cancers) is due to a propensity for the tumor to metastasize to distinct organs while the primary tumor is small and undetected. Research in Kumar’s research is directed at defining the phenotypic signaling leading to cancer progression, how and why normal and cancer cells spread, the significance of cytoskeleton signaling in the sequestration of critical molecules with roles in life and death cellular decisions. These scientific questions are centered on p21-activated kinase 1 (PAK1). His group was the first to show the hyper-activation and -expression of PAK in human cancer (i.e. breast cancer), discovered novel PAK1 substrates and functions in cancer cells, made conceptual advancement in establishing the nuclear localization and functions of PAK1, and allowed the PAK family to make in-roads into diverse systems such as trafficking, microtubule biogenesis and mitosis.

The second major focus of Kumar’s laboratory is directed at defining the mechanisms of estrogen receptor action in breast cancer, with a special focus on master chromatin coregulators. Over the years, the Kumar lab has discovered over half-dozen coregulators and put the MTA family of nuclear receptor coregulators in the mainstream research in the areas of genomic and non-genomic estrogen signaling. Since MTA1 and its targets are widely deregulated in human cancer, this work has laid down the foundation of therapeutic approaches targeting these molecules in breast and other hormone-responsive human cancer. More recently, the laboratory have recently discovered a mechanistic role of MTA1/NuRD family of complexes in DNA-damage response as it is a required component of cellular responses to a variety of cellular stress. Further, the research team has now established that MTA1 is a target of inflammation and its expression is induced stimulation of lipopolysaccharide, a major byproduct of bacterial infection, and thus, required to manifest some aspects of cellular responses of inflammation. The laboratory is seeking more evidence to implicate MTA1 in the process of inflammation-driven cancers. Collectively, research in Kumar’s group has defined the biochemistry and molecular biology of PAK and MTA molecules, and put them on the scientific map, opened new research directions in biomedical research

Selected Publications

• Molli, P., Li, D-Q., Bagheri-Yarmand, R., Katayama, H., Sen, S, Iyer, J., Chernoff, J., Tsai, M.Y., Nair, S. S. and Kumar, R.  Apc1b, a new centrosomal protein, is both an activator and substrate of Aurora A.    Journal of Cell Biology 190: 101-114, 2010.
• Li, D-Q., Ohshiro, K, Reddy, SDN, Pakala, S.B., Lee, M-H., Zhang, Y., Rayala, S.K., Kumar, R. E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1. Proc. Nat. Acad. Sci. USA  116: 17493-17498, 2009.
• Vadlamudi, R.K., Badheri-Yarmand, R., Yang, Z., Balasenthil, S., Nygen, D.,Sahin, A.A, den Hollander, P., Kumar, R. Dynein light chain 1, a PAK1 Interacting substrate, promotes cancerous phenotypes. Cancer Cell, 5, 575-585, 2004.
• Barnes, C.J., Vadlamudi, R.K., Mishra, S.K., Jacobson, R.H., Li, F., and Kumar, R. Functional inactivation of a transcriptional corepressor by a signaling kinase. Nature Structural Biology 10, 662-628, 2003.
• Kumar, R., Wang, R-W, Mazumdar, A., Talukder, A.H., Mandal, M., Yang, Z. et al. A naturally occurring MTA1 variant sequesters estrogen receptor in the cytoplasm, Nature 418, 654-657, 2002.
• Mazumdar A, Wang RW, Mishra SK, Adam L, Yarmand RB, Mandal M, Vadlamudi R, and Kumar R. Transcriptional repression of estrogen receptor by MTA1. Nature Cell Biology 3, 30-37, 2001.