Vignesh Kasinath, Ph.D.

Research

The human genome is riddled with transposons, DNA sequences that promote genetic instability by replicating and integrating into additional chromosomal locations. My lab will explore how cells “silence” transposons, genetic elements whose movement within the genome can disrupt the function of genes. To maintain genomic integrity, cells have surveillance systems that distinguish between transposons and normal genes and epigenetically silence the transposons to prevent their replication. Recently, my group has found that one such system, human silencing hub (HUSH), interacts with specific RNA-binding proteins that have known roles in combating retroviral integrations in the human genome. Now, using cutting-edge techniques in cryo-electron microscopy, biochemistry, and RNA-protein interaction mapping, we will determine how RNA-binding proteins aid HUSH in the recognition of transcriptionally active transposons, how HUSH interacts with chromatin and RNA to silence these elements, and how mutations in HUSH perturb these interactions. Since HUSH functions as an RNA-mediated gene silencer, my work could lead to novel therapeutic strategies for treating cancers and other human diseases associated with transposon invasion, by epigenetically silencing such translocations that often result in oncofusions.