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Cancer progression is not only driven by uncontrolled proliferation, acquisition of inappropriate invasiveness, but also by deregulation of signaling cascades and chromatin dynamics feeding into defective control of transcription. Laboratory research program consists of two major areas - cytoskeleton and chromatin remodeling and a possible regulatory trans-regulation of these two major biologic processes. Our team was the first to show the hyper-activation and deregulated expression of p21-activated kinase 1 in human cancer (i.e. breast cancer) contributing to a huge interest in other laboratories and widespread documentation of PAK overexpression in human cancer, discovered multiple novel PAK1 substrates and functions in cancer cells, made conceptual advancement in establishing the nuclear localization and functions of PAK1, allowing the PAK family to make in-roads into diverse systems such as mitosis and hormone independence. 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 the nuclear receptor coregulators in the nucleus and in the cytoplasm, with a particular focus on the metastatic tumor antigens (MTA) family of chromatin modifiers and its targets. Over the years, the Kumar lab has discovered over half-dozen new nuclear receptor coregulators including, BCAS3, PELP1, DLC1 etc and put the MTA family of nuclear receptor coregulators in the genomic and non-genomic estrogen signaling. Since MTA1 and its targets are widely deregulated in human cancer and may have a causative role in breast cancer, this work has laid down the foundation of therapeutic approaches targeting these molecules in breast and other hormone-responsive human cancer. Collectively, our laboratory has defined the molecular biology and functions of the two important molecules in human cancer, paved the way for new research opportunities new research directions in biomedical research, and provided two major bona-fide cancer therapeutic targets.
More recently, the laboratory has decoded the digital transcriptome of breast cancer for the first time using RNA-sequencing and computational genomic-centered unbiased approach. The work revealed specific global breast cancer transcriptomic adaptations in triple-negative breast, estrogen receptor positive, and HER2 positive breast cancers. The significance of this study has implications beyond the current digital transcriptome of breast cancer as this work is influencing the breast cancer genomics, the transcriptional regulation of cancer, and helped us discovered new differentially spliced transcripts and mutations in functionally relevant molecules.
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Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the healthcare related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.