Office: JSCBB E132
Lab: JSCBB E130
Bachelor's: B. Tech, Indian Institute of Technology (IIT) Bombay, India
PhD: Biochemistry & Biophysics, University of Pennsylvania, Philadelphia
Postdoctoral Fellow: Helen Hay Whitney Foundation/NIH K99 Postdoctoral Fellow, University of California, Berkeley
Areas of Expertise
Chromatin, Electron Cryo-Microscopy (cryo-EM), Epigenetics, Gene Expression and Regulation, and Structural Biology.
Awards and Honors
How do cells retain their identity?
The human body has ~37 trillion cells and over 200 different cell types. We are interested in uncovering the molecular mechanisms that establish and maintain cellular identity during embryonic development and cellular differentiation. One elegant yet complex strategy utilized by the cells is to turn ON (active gene expression) or OFF (gene silencing) a select subset of genes. How does the cell know which subset of genes needs to be OFF? And how does the cell know to keep these in the OFF state to maintain cellular identity?
Our lab approaches these questions by utilizing a multi-disciplinary approach combining structural biology techniques such as single-particle cryo-electron microscopy (cryo-EM), cryo-electron tomography (cryo-ET) with chemical biology and biochemistry. We study chromatin modifier enzymes, which play critical roles in marking genes for either gene expression (ON) or gene silencing (OFF). We are particularly interested in gene-silencing enzymes such as Polycomb Repressive Complexes, DNA methyltransferase, and Histone deacetylases (HDACs), which play broad roles in cellular identity and genome integrity.
Our lab is at the forefront of utilizing new cryo-EM and cryo-ET methodologies to study these enzymatic processes in vitro and in situ. We are interested in understanding how RNA and nucleosomes regulate the activity of these enzymes, as well as developing new strategies to target these enzymes in diseases. Defects in these enzymes are found in almost all cancers and are fundamental to the disease pathology of many disorders, including neurodegenerative diseases.
Our research vision is to provide a molecular-level understanding of gene silencing. The outcomes from our research have broad implications in developing new avenues targeting diseases and understanding how these enzymes contribute to genome surveillance in the fight against foreign DNA invasion such as those from viruses.
See my NCBI bibliography for a full and up-to-date list
- Jansson-Fritzberg LI, Sousa CI, Smallegan MJ, Song JJ, Gooding AR, Kasinath V, Rinn JL, Cech TR. DNMT1 inhibition by pUG-fold quadruplex RNA. RNA. 2023 Mar;29(3):346-360. doi: 10.1261/rna.079479.122. Epub 2022 Dec 27. PubMed PMID: 36574982; PubMed Central PMCID: PMC9945446.
- Song J, Gooding AR, Hemphill WO, Kasinath V, Cech TR. Structural basis for inactivation of PRC2 by G-quadruplex RNA. bioRxiv. 2023 Feb 6;. doi: 10.1101/2023.02.06.527314. PubMed PMID: 36798278; PubMed Central PMCID: PMC9934548.
- Kasinath V, Beck C, Sauer P, Poepsel S, Kosmatka J, Faini M, Toso D, Aebersold R, Nogales E. JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Science. 2021 Jan 22;371(6527). doi: 10.1126/science.abc3393. PubMed PMID: 33479123; PubMed Central PMCID: PMC7993630.
- Kasinath, V, Faini M, Poepsel S, Reif, D., Feng, XA., Stjepanovic, G., Aebersold, R., and Nogales, E. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science (2018)