Dileep Varma
Assistant Professor of Cell and Molecular Biology
Department of Cell & Molecular Biology
Northwestern University Feinberg School of Medicine
United States of America
Biography
The broad area of my research interest is in the cytoskeleton and intracellular motility. The cytoskeletal polymer that I am most interested in is the microtubules and the cytoskeletal process that I am most excited about is the accurate segregation of chromosomes during mitosis. A dividing cell assembles mitotic kinetochores and a mitotic spindle at the onset of mitosis. The kinetochores serve as sites where the microtubules of the mitotic spindle comes in physical contact with the chromosomes, and are hence extremely important for accurate chromosome segregation. Improper kinetochore microtubule (kMT) attachments lead to erroneous chromosome segregation, chromosome loss and aneuploidy in turn, which is the leading cause of cancer in tissue cells and of birth defects and miscarriages during human embryonic development. Over a decade of research had identified the kinetochore-bound Ndc80 complex as the key requirement for the direct physical contact with microtubules of the spindle. But what is still not understood well is how the kinetochores and the Ndc80 complex remains stably attached to the highly dynamic microtubule plus-ends during mitotic metaphase and subsequent chromosome segregation in anaphase. Work is yeast model system had provided us with important insights into the possible mechanism governing this process, but we still do not have a clear mechanistic picture in vertebrate systems. Work in my lab focusses on understanding the molecular mechanisms that are involved the controlling and regulating kinetochore microtubule attachments in vertebrate cells. We are also very interested to delineate the intricate mechanism that link this event with the activation and silencing of the spindle assembly checkpoint which is also absolutely critical for accurate chromosome segregation.
Research Interest
Cell Division, Chromosome Segregation, Biochemistry: Proteins, Cell Imaging
Publications
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Cell division: Molecular pathways for KMN kinetochore recruitment Afreen S, Varma D Current Biology. 2015 Apr 20; 25(8): R332-R335. doi:http://dx.doi.org/10.1016/j.cub.2015.02.041. PMID: 25898103 ISSN: 0960-9822
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Sequential replication-coupled destruction at G1/S ensures genome stability Coleman KE, Grant GD, Haggerty RA, Brantley K, Shibata E, Workman BD, Dutta A, Varma D, Purvis JE, Cook JG Genes and Development. 2015 Aug 15; 29(16): 1734-1746. doi:http://dx.doi.org/10.1101/gad.263731.115. PMID: 26272819 PMCID: 26272819 ISSN: 0890-9369
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The RZZ complex requires the N-terminus of KNL1 to mediate optimal Mad1 kinetochore localization in human cells Calda GV, Lynch TR, Anderson R, Afreen S, Varma D, De Luca JG Open Biology. 2015 Nov; 5(11): doi:http://dx.doi.org/10.1098/rsob.150160. PMID: 26581576 PMCID: 26581576 ISSN: 2046-2441