Associate Professor
E-mail: sjmathew at rcb dot res dot in
Mammalian development, stem cells, regeneration and disease
We are interested in deciphering the mechanisms underlying mammalian embryonic development, stem cell mediated regeneration and diseases associated with abnormal development and regeneration. The cells in the developing embryo or regenerating tissues undergo processes such as specification, migration, proliferation, differentiation and apoptosis in a coordinated manner. We are trying to understand the signals controlling these cellular processes and their regulation. During the process of differentiation, cells undergo changes in morphology and cellular activity, based on their lineage and functional requirements. This is best illustrated in the case of the mammalian skeletal muscle, where the undifferentiated stem cells are small, round and mononuclear, whereas the mature, differentiated cells are large, elongated and multinuclear.
One gene family crucial to skeletal muscle differentiation are the skeletal muscle myosin heavy chains, expressed specifically by the skeletal muscle, with different members expressed at different developmental stages, adult life, and during muscle injury or disease. One such myosin heavy chain is myosin heavy chain-embryonic, encoded by the Myh3 gene. By generating knockout mice lacking Myh3 and employing mouse genetics, we have characterized the embryonic and perinatal functions of myosin heavy chain-embryonic in the skeletal muscle (Agarwal et al, Development 2020). Mutations in specific myosins have been reported to cause congenital diseases such as contracture syndromes, myopathies etc, and our studies using mouse models should lead to a mechanistic understanding of these diseases and possible therapeutic strategies to treat them.
Another major area of focus is to discover the transcriptional (e.g. transcriptional repressors), post-transcriptional (e.g. microRNAs), translational (e.g. signaling pathways like the Wnt/beta-Catenin pathway), and post-translational (e.g. protein modifications such as ubiquitylation) regulatory mechanisms that control differentiation, using in vitro and in vivo strategies. We have found that the corepressor Transducin-like Enhancer of Split 4 (TLE4) is a crucial regulator of muscle stem cell quiescence and its downregulation is required for the stem cells to enter differentiation (Agarwal et al, Journal of Cell Science 2022).
We are also interested in the biology of cancer, specifically investigating a tumor type called rhabdomyosarcoma, wherein the tumor cells exhibit characteristics of skeletal muscle cells. We are trying to identify and understand the roles of signaling pathways that are dysregulated in this type of cancer, which could lead to potential therapeutic interventions. Previously, we uncovered the role of the receptor tyrosine kinase MET and its interacting protein SPRY2 in rhabdomyosarcoma tumorigenic potential (Saini et al, Cell Death and Disease 2018).
Dr. Sam J Mathew
Associate Professor
Regional Centre for Biotechnology
NCR Biotech Science Cluster
3rd Milestone, Faridabad-Gurgaon Expressway
P.O. Box No. 3, Faridabad - 121 001
Haryana (NCR Delhi), India
E-mail: sjmathew at rcb dot res dot in
Phone: 91 129-2848822
