Alla Grishok, PhD

Associate Professor, Boston University School of Medicine 

Former RTI Lab: Doctoral candidate, Mello Lab
Training Period: 1996 - 2001

Grishok Lab

  Alla Grishok 

Analysis of RNA Interference in C. elegans: A Dissertation

Research in my laboratory investigates new mechanisms of gene regulation by short RNAs and chromatin-modifying complexes. A major focus of our work is the metazoan DOT1L methyltransferase complex. DOT1L is essential for development, it is an emerging oncoprotein implicated in numerous cancers, and it has recently been connected to control of mitochondrial genes and adipose tissue health. My lab studies gene regulation by the DOT1L complex in C. elegans, mammalian cells and zebrafish, including enhancer regulation, control of non-coding transcriptome, and cooperation with MYC. When investigating coordinate gene regulation by DOT1L and MYC we found a new biochemical function of DOT1L that we are actively studying now. Recently, we uncovered a long-sought link between DOT1L and RNAi by finding overactivation of  endogenous RNAi in dot-1 mutant worms. This likely leads to epigenetic inheritance of ectopic small RNAs and/or aberrant chromatin states and accounts for many developmental problems of the mutants. We are testing this possibility. Also, it would be interesting to know whether there are ectopic small RNAs in mammalian cells lacking DOT1L. Overall, we are interested in connecting our findings to the genetics and epigenetics of human disease.