Michael Grunstein

Position Titles

Distinguished Professor, Biological Chemistry
 

Biography

Michael Grunstein is Professor Emeritus in the Department of Biological Chemistry at the David Geffen School of Medicine at UCLA. He was born in Romania and obtained his Bachelor of Science degree from McGill University in Montreal and his doctorate from the University of Edinburgh, Scotland. He completed his post-doctoral training at Stanford University in Palo Alto, California, where he characterized histone mRNAs during sea urchin development with Larry Kedes and invented the colony hybridization screening technique of recombinant DNAs in David Hogness’ laboratory. Soon after coming to UCLA in 1975, he pioneered the genetic analysis of histones in yeast and showed for the first time that histones are regulators of gene activity in living cells. He has more recently studied the means by which histone modifications regulate gene activity in yeast and human cells.

Research Description

Michael Grunstein studies how histones and their post-translational modifications regulate chromosomal functions. It had been known since the 1960s that histone acetylation and gene activity were correlated, but it was not known whether changes in chromatin structure and in particular histone acetylation sites are a cause, or a result, of transcription. In the early 1980s, the Grunstein lab pioneered the use of genetics in analyzing histone protein function in yeast. This analysis showed that nucleosomes are repressors of transcription initiation in living cells and that acetylation sites at the histone N termini are required for gene activity. Moreover, his lab demonstrated in 1995 that non-histone regulatory proteins bind histones to regulate heterochromatin formation. This allowed the lab to determine how an acetylation site (histone H4 K16) at the H4 N terminus regulates the initiation and spread of heterochromatin, as well as how the site acts as a barrier to heterochromatin’s spread.

The Grunstein laboratory used genetics, as well as genome-wide and gene-specific biochemical approaches, to study how histones regulate the binding of regulatory enzymes and structural factors to chromatin. The lab’s findings include the role of histone deacetylation in regulating the timing of DNA replication, the role of deacetylation in gene activity and the genome-wide division of labor for histone deacetylases and histone acetylation sites in yeast. Studies from the Grunstein lab have uncovered the acetylation of a novel site – histone H3 K56 – in yeast and its role in transcription and heterochromatin silencing. The lab analyzed the  modification of this site – which also regulates yeast histone assembly, DNA replication and DNA repair – and its role in the differentiation of human stem cells.

Awards & Honors

2018 Albert Lasker Basic Medical Research Award (with David Allis)
2016 Gruber Genetics Prize (with David Allis)
2012 Thomson-Reuters Citation Laureate (with David Allis)
2011 Rosenstiel Award for Distinguished Work in Basic Medical Research (with David Allis)
2008 Benzon Symposium Speaker, Copenhagen, Denmark
2008 Elected to the National Academy of Sciences
2007 The 17th Beckman Symposium. The Changing Face of Chromatin
1998-2007 MERIT Award, National Institutes of Health
2006 Friedrich Miescher Institute, Basel, Science Colloquium Speaker
2005 Novum Lecture, Karolinska Institute, Stockholm
2004 Marian Koshland Lecturer, UC Berkeley
2001-2004 International Scientific Advisory Board Member. Wellcome Trust Center for Cell Biology, University of Edinburgh, Scotland
2003 Massry Prize (with Roger Kornberg and David Allis)
2001 Elected Fellow of the American Academy of Arts and Science
2000 Keynote Speaker, Euresco Conference, Gene Transcription in Yeast: Transcriptional Regulation and Chromatin Structure, Castelvecchio Pascoli, Italy
2000 Royal Swedish Society of Sciences Lecture
1999 Keynote Speaker, Chromatin Structure and Regulation, Keystone Symposium, Santa Fe, New Mexico
1998 Markey Distinguished Speaker, University of Southern California
1995 Keynote Speaker, Keystone Symposium, Epigenetic Regulation of Transcription, Hilton Head Island, South Carolina
1994 Chair, Gordon Conference, Nuclear Proteins
1985 Chair, Chromosome Structure and Expression Conference, Cold Spring Harbor
1979-1984 American Cancer Society Faculty Research Award
1976-1979 Awardee March of Dimes Basil O’Connor Starter Research Grant
1972-1974 Leukemia Society of America Fellow
1969-1971 Wellcome Trust Studentship Award