Vipul Shukla, PhD
Assistant Professor, Cell and Developmental Biology
Research Program
- Cancer Epigenetics and Nuclear Dynamics (CEND)
- Translational Research in Malignancy (TRIM)
Cancer-Focused Research
My research broadly focuses on understanding the roles of cytosine modifications and alternative DNA structures in normal and cancer genomes. I am currently investigating the functions of G-quadruplexes and R-loops, two of the most common secondary DNA structures in regulation of normal cellular functions and cancer pathogenesis. This research stems from the work I performed during my post-doctoral training investigating the functions of Ten-Eleven-Translocation (TET) family of enzymes in normal and malignant hematopoiesis. TET enzymes are methyl-cytosine directed dioxygenases that mediate the DNA demethylation process and are required for normal development. Mutational as well as functional inactivation of TET enzymes occurs frequently in many hematological malignancies and solid cancers. While studying the role of TET loss-of-function in development of B cell lymphomas, my studies identified accumulation of G-quadruplexes and R-loops as a novel feature of TET deficiency in multiple cell types. G-quadruplexes and R-loops occupy evolutionarily conserved sites, are implicated in modulation of gene expression, alterations in chromatin function and maintenance of genomic stability. While our knowledge regarding the biology of G-quadruplexes and R-loops, as well as other secondary DNA structures, is still in its infancy, my current research strongly suggests a central role for these structures in impacting many established paradigms in genome biology. As first-steps towards gaining a clear understanding, I am studying the abundance of G-quadruplexes and R-loops in normal and cancer genomes, mechanisms regulating their dynamics and cellular pathways controlled by these structures.