Shiv I. Grewal

National Institutes of Health


Election Year: 2014
Primary Section: 26, Genetics
Secondary Section: 21, Biochemistry
Membership Type: Member

Biosketch

Shiv Grewal is a Distinguished Investigator at the National Cancer Institute (NCI) recognized for groundbreaking research in the field of epigenetics. His work provided fundamental insight into heterochromatin formation, a compact form of chromatin that inhibits inappropriate gene expression and ensures genome stability. He obtained his PhD from the University of Cambridge in 1992, where he held the prestigious Cambridge-Nehru scholarship. As a post-doctoral fellow at NCI he discovered that heterochromatic gene silencing can be stably propagated as epigenetic states through meiosis and inherited in cis. Grewal joined Cold Spring Harbor Laboratory faculty in 1998, where he uncovered a surprising connection between RNAi and heterochromatin assembly that was named “Breakthrough of the Year 2002” by Science. In 2003, Grewal returned to the NCI as a Senior Investigator and was appointed Chief of the Laboratory of Biochemistry and Molecular Biology in 2011. His work has elucidated how heterochromatin is assembled in different parts of the genome and revealed its diverse genome regulatory functions. Three of his papers are judged historic discoveries in the past 50 years by Nature. Grewal is the recipient of the Newcomb-Cleveland Prize, NIH Merit Award, and the NIH Directors’ award. In 2014, he was elected to the National Academy of Sciences and the American Academy of Arts and Sciences.

Research Interests

Shiv Grewal’s laboratory investigates conserved pathways involved in epigenetic genome control and assembly of heterochromatin, a specialized form of chromatin that impacts diverse cellular processes, including trans-generational inheritance of gene expression states, chromosome architecture, and the maintenance of genome stability. His early discovery that heterochromatic structures can be epigenetically inherited in cis illustrated that the unit of inheritance sometimes constitutes DNA plus associated protein complexes. Grewal’s work uncovered the paradigm of molecular signatures, such as distinct histone methylation patterns, which denote alternative chromatin states. He defined mechanisms in which histone modifiers both “write” and “read” methylated histones to promote epigenetic inheritance of heterochromatin. His laboratory discovered pathways in which heterochromatin proteins recruit effectors that preclude nucleosome turnover to promote gene silencing. Recently, Grewal expanded their earlier work linking RNAi to heterochromatin formation. They discovered conserved nuclear RNA processing machinery, including MTREC (Mtl1-Red1 complex) and its associated factors, which mediate assembly of facultative heterochromatin to reprogram the genome in response to environmental and developmental signals. These studies are beginning to yield insights into the roles that RNA processing factors and heterochromatin play in adaptive regulation of eukaryotic genomes. Additional areas of investigation are also elucidating the critical function of heterochromatin in three-dimensional organization of the chromosomes.

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