Kavitha Sarma, Ph.D.
Wistar Institute Assistant Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology
Graduate Group Affiliations
3601 Spruce St. Rm 234
Rutgers University, 2007.
Rutgers University, 2007.
Description of Research ExpertiseResearch Interests: RNA interactions in epigenetic gene regulation and genome organization.
Keywords: epigenetics, chromatin, polycomb, genome organization, non-coding RNA
We are interested in understanding the molecular mechanisms of RNA mediated epigenetic gene regulation. Aberrations in epigenetic gene silencing can be a causal mechanism of numerous human disease and developmental syndromes. We use a combination of biochemical, cell biological and functional genomics approaches in embryonic stem cell, neural stem cell, and cancer cell models to elucidate the molecular mechanisms and functional implications of RNA containing chromatin structures in gene regulation and in genome organization.
We are fascinated by triplex nucleic acid structures known as R-loops, that are comprised of a DNA:RNA hybrid and displaced ssDNA. R-loops are formed during transcription when the mRNA invades dsDNA (forming the DNA:RNA hybrid) and exposes a ssDNA that can then adopt a G quadruplex (G4) structure (Figure 4). Transcription from G rich repetitive regions results in the formation of G4 DNA that impedes the reannealing of DNA strands, promotes DNA:RNA hybridization, and stabilizes R-loops. In addition to known regulatory roles, R-loops are closely linked to increased DNA damage and genome instability. Stable aberrant R-loops have also been discovered in several neurological disorders, neurodegenerative diseases, and cancers. Discovering the genome-wide locations of R-loops is challenging because of the requirement for large sample size and inefficient enrichment using the monoclonal antibody that recognizes the RNA:DNA hybrid within R-loops. We have developed a new antibody independent approach, called MapR, to identify native R-loops genome-wide. Some questions that are interested in exploring are: Where do R-loops form in specific disease states? How do unscheduled R-loops contribute to neurodegenerative diseases and cancers? What are the protein factors that function in R-loop resolution and stabilization? How can R-loops impact gene regulation and genome organization in disease states?
Anna Bieluszewska Ph.D. - Postdoctoral Fellow
John Doherty B.S. - Research Assistant II
Bhanu Karisetty Ph.D. - Postdoctoral Fellow
Phillip Wulfridge Ph.D. - NRSA Postdoctoral Fellow
Qingqing Yan Ph.D. - Postdoctoral Fellow
Nicole Medeiros - Research Assistant III
Devinne Miller - Undergraduate Researcher
Joyce Bian - Undergraduate Researcher
Wenqing Ren- Postdoctoral Fellow Current Affiliation - Associate Researcher, Tongji University, China
Students who have been admitted to a graduate program at the University of Pennsylvania are encouraged to inquire about current rotation projects by sending an email to: firstname.lastname@example.org.
Selected PublicationsYan Q*, Wulfridge P*, Doherty J, Fernandez-Luna JL, Real PJ, Tang HY, Sarma K. : Proximity labeling identifies a repertoire of site-specific R-loop modulators. Nature Communications Jan 2022.
Shukla V*, Samaniego-Castruita D*, Dong Z, Gonzalez-Avalos E, Yuita H, Yan Q, Sarma K, Rao A: TET deficiency perturbs mature B cell homeostasis and promotes oncogenesis associated with accumulation of G-quadruplex and R-loop structures. Nature Immunology Jan 2022.
Wulfridge P and Sarma K: A nuclease- and bisulfite-based strategy captures strand-specific R-loops genome-wide. eLife Feb 2021.
Wenqing Ren*,Nicole Medeiros*, Robert Warneford-Thomson, Phillip Wulfridge, Qingqing Yan, Joyce Bian, Simone Sidoli, Benjamin A. Garcia, Emmanuel Skordalakes, Eric Joyce, Roberto Bonasio, Kavitha Sarma: Disruption of ATRX-RNA interactions uncovers roles in ATRX localization and PRC2 function. Nature Communications May 2020.
Qingqing Yan, Emily J. Shields, Roberto Bonasio, Kavitha Sarma: Mapping native R-loops genome-wide using a targeted nuclease approach. Cell Reports Oct 2019.
Sarma Kavitha, Cifuentes-Rojas Catherine, Ergun Ayla, Del Rosario Amanda, Jeon Yesu, White Forest, Sadreyev Ruslan, Lee Jeannie T: ATRX directs binding of PRC2 to Xist RNA and Polycomb targets. Cell 159(4): 869-83, Nov 2014.
Cifuentes-Rojas Catherine, Hernandez Alfredo J, Sarma Kavitha, Lee Jeannie T: Regulatory interactions between RNA and polycomb repressive complex 2. Molecular cell 55(2): 171-85, Jul 2014.
Simon Matthew D, Pinter Stefan F, Fang Rui, Sarma Kavitha, Rutenberg-Schoenberg Michael, Bowman Sarah K, Kesner Barry A, Maier Verena K, Kingston Robert E, Lee Jeannie T: High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 504(7480): 465-9, Dec 2013.
Zhao Jing, Ohsumi Toshiro K, Kung Johnny T, Ogawa Yuya, Grau Daniel J, Sarma Kavitha, Song Ji Joon, Kingston Robert E, Borowsky Mark, Lee Jeannie T: Genome-wide identification of polycomb-associated RNAs by RIP-seq. Molecular cell 40(6): 939-53, Dec 2010.
Sarma Kavitha, Levasseur Pierre, Aristarkhov Alexander, Lee Jeannie T: Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome. Proceedings of the National Academy of Sciences of the United States of America 107(51): 22196-201, Dec 2010.