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Heads of Laboratories

Head shot of C. David Allis
C. David Allis, Ph.D.
Tri-Institutional Professor
Joy and Jack Fishman Professor
Laboratory of Chromatin Biology and Epigenetics

Dr. Allis studies the DNA-histone protein complex called chromatin, which packages genetic information within each cell. Chromatin can facilitate or restrict access to specific genes, enabling the cell to efficiently manage expression of its genome and serving as a means of gene regulation outside of DNA — the basis of epigenetics.

Although every gene exists within every cell in the human body, only a small percentage of genes is activated in any given cell. To manage this genetic information efficiently, nature has evolved a sophisticated system that facilitates access to specific genes. Dr. Allis studies the DNA-histone protein complex called chromatin, which packages the genetic information that exists within each cell and serves as a means of gene regulation that lies outside of the DNA itself — the basis of epigenetics.

Chromatin is the physiological template of the human genome. Elaborate mechanisms have evolved to introduce meaningful variation into chromatin to alter gene expression and other important biological processes. Three major mechanisms of this are covalent histone modifications, chromatin remodeling by ATP-dependent complexes and use of histone variants. Dr. Allis and his colleagues hypothesize that distinct patterns of covalent histone modifications form a histone or epigenetic “code” that is read by effector proteins to bring about distinct downstream events. Histone proteins, their posttranslational modifications and the enzyme systems responsible for generating them are highly conserved through evolution. The Allis lab is currently investigating different histone modifications and their biological roles in a variety of unicellular and multicellular eukaryotic models. Through such enzymatic processes as acetylation, methylation, phosphorylation and ubiquitylation, histones are believed to function like master on/off switches and determine whether particular genes are active or inactive. Knowing how to turn particular genes on or off could reduce the risk of certain diseases.

The frequent, high-density posttranslational modifications (PTMs) in histone proteins have led members of the Allis laboratory to hypothesize that PTMs are located in strategic locations along the histone tail as a way for the cell to deal, reversibly, with gene silencing or, in contrast, gene activation. The lab has been a front-runner in deciphering elaborate cross talk relationships in the same histone tails (cis) or across distinct histone tails (trans). It appears that these regulatory pathways govern chromatin function during DNA replication and repair, chromosome segregation and chromatin compaction as cells undergo apoptosis. The combinatorial readout of distinct histone modifications that lead to the specification of unique downstream biological processes has been termed the “histone or epigenetic code” — a widely cited and influential hypothesis.

More recently, researchers in the Allis lab proposed that the mammalian genome is indexed by H3 variants in a nonrandom fashion reflecting the assembly mechanisms of dedicated, personalized chaperone proteins and exchange factors that control whether genes are constitutively expressed or remain silent. The Allis lab produced the first genome-wide maps of H3.3 localization, first in mammalian embryonic stem cells and then again after the cells had differentiated to become neurons. Biochemical approaches have led them to chaperone complexes that engage H3.3 selectively, depositing it into distinct regions of the genome. One of these chaperone systems (ATRX/Daxx targeting H3.3 to telomeres and other heterochromatic loci) has been shown to be mutated in a significant fraction of patients who suffer from pancreatic neuroendocrine tumors. Remarkably, H3.3 mutations are also highly specific to pediatric gliomas, a disease that is clinically and molecularly distinct from its adult counterpart. Dr. Allis and his colleagues hypothesize that these mutations can alter the recruitment and activity of histone-modifying complexes and therefore alter the epigenetic landscape and dysregulate gene expression. Given the restricted distribution of H3.3 mutations to pediatric gliomas, they further hypothesize that cell lineage-specific cellular context is crucial for the ability of these mutations to mediate oncogenesis. Active investigations are under way to test these hypotheses with collaborators in more clinically relevant settings, including human patients.


B.S. in biology, 1973
University of Cincinnati

M.S. in biology, 1975
Ph.D. in biology, 1978
Indiana University 


University of Rochester, 1978–1981 


Assistant Professor, 1981–1986
Associate Professor, 1986–1989
Professor, 1989–1990
Baylor College of Medicine

Professor, 1990–1995
Syracuse University

Professor, 1995–1998
University of Rochester

Professor, 1998–2003
University of Virginia Health System

Professor, 2003–
The Rockefeller University


Dickson Prize, 2002

Massry Prize, 2003

Wiley Prize, 2004

Canada Gairdner International Award, 2007

ASBMB-Merck Award, 2008

Lewis S. Rosenstiel Award, 2011

Japan Prize, 2014

Charles Leopold-Mayer Prize, 2014

Breakthrough Prize, 2015


National Academy of Sciences
American Academy of Arts and Sciences
French Academy of Sciences


Lewis, P.W. et al. Inhibition of PRC2 activity by gain-of-function mutations in pediatric glioblastoma. Science 340, 867–861 (2013).

Banaszynski, L.A. et al. Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells. Cell 155, 107–120 (2013).

Goldberg, A.D. et al. Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140, 678–691 (2010).

Wang, G.G. et al. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 459, 847–851 (2009).

Wysocka, J. et al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442, 86–90 (2006).