Charles David Allis (March 22, 1951 – January 8, 2023) was an American

molecular biologist Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, and the Joy and

Jack Fishman Jack Fishman (September 30, 1930 – December 7, 2013), born Jacob Fiszman, was a Jewish-American pharmaceutical researcher from Kraków, Poland. In 1961, along with Mozes J. Lewenstein, he developed the medication naloxone, which can reverse ...

Professor at the

Rockefeller University The Rockefeller University is a private biomedical research and graduate-only university in New York City, New York. It focuses primarily on the biological and medical sciences and provides doctoral and postdoctoral education. It is classif ...

. He was also the Head of the Laboratory of

Chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

Biology and

Epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

, and a professor at the

Tri-Institutional MD–PhD Program The Tri-Institutional MD-PhD Program is an MD-PhD program based in New York City that was formed by combining earlier MD-PhD programs that had their inceptions in 1972. The current version of the program, which is operated by Weill Cornell Medicin ...

(the other two institutions being the

Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a cancer treatment and research institution in the borough of Manhattan in New York City, founded in 1884 as the New York Cancer Hospital. MSKCC is one of 52 National Cancer Institute– ...

and

Weill Cornell Medicine The Joan & Sanford I. Weill Medical College of Cornell University is Cornell University's biomedical research unit and medical school located in Upper East Side, Manhattan, New York City, New York. Weill Cornell Medicine is affiliated with NewY ...

Early life and education

Allis was born and raised in

Cincinnati Cincinnati ( ) is a city in the U.S. state of Ohio and the county seat of Hamilton County. Settled in 1788, the city is located at the northern side of the confluence of the Licking and Ohio rivers, the latter of which marks the state line wit ...

Ohio Ohio () is a state in the Midwestern region of the United States. Of the fifty U.S. states, it is the 34th-largest by area, and with a population of nearly 11.8 million, is the seventh-most populous and tenth-most densely populated. The sta ...

. His father was a

city planner An urban planner (also known as town planner) is a professional who practices in the field of town planning, urban planning or city planning. An urban planner may focus on a specific area of practice and have a title such as city planner, town ...

and his mother an

elementary school A primary school (in Ireland, the United Kingdom, Australia, Trinidad and Tobago, Jamaica, and South Africa), junior school (in Australia), elementary school or grade school (in North America and the Philippines) is a school for primary ed ...

teacher A teacher, also called a schoolteacher or formally an educator, is a person who helps students to acquire knowledge, competence, or virtue, via the practice of teaching. ''Informally'' the role of teacher may be taken on by anyone (e.g. whe ...

. He entered the

University of Cincinnati The University of Cincinnati (UC or Cincinnati) is a public research university in Cincinnati, Ohio. Founded in 1819 as Cincinnati College, it is the oldest institution of higher education in Cincinnati and has an annual enrollment of over 44,00 ...

in 1969, majoring in

biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

. He had his first experience of

basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied resear ...

in his

senior Senior (shortened as Sr.) means "the elder" in Latin and is often used as a suffix for the elder of two or more people in the same family with the same given name, usually a parent or grandparent. It may also refer to: * Senior (name), a surname ...

(or fourth) year of

BSc A Bachelor of Science (BS, BSc, SB, or ScB; from the Latin ') is a bachelor's degree awarded for programs that generally last three to five years. The first university to admit a student to the degree of Bachelor of Science was the University of ...

. The experience attracted him to research, and he went to

Indiana University Indiana University (IU) is a system of public universities in the U.S. state of Indiana. Campuses Indiana University has two core campuses, five regional campuses, and two regional centers under the administration of IUPUI. *Indiana Universit ...

for graduate studies. He graduated with an

MSc MSC may refer to: Computers * Message Sequence Chart * Microelectronics Support Centre of UK Rutherford Appleton Laboratory * MIDI Show Control * MSC Malaysia (formerly known as Multimedia Super Corridor) * USB mass storage device class (USB MSC ...

in 1975 and a

PhD PHD or PhD may refer to: * Doctor of Philosophy (PhD), an academic qualification Entertainment * '' PhD: Phantasy Degree'', a Korean comic series * ''Piled Higher and Deeper'', a web comic * Ph.D. (band), a 1980s British group ** Ph.D. (Ph.D. albu ...

three years later, under the supervision of

Anthony Mahowald Anthony Mahowald (born November 24, 1932) is a molecular genetics and cellular biologist who served as the department chair of the molecular genetics and cellular biology department at the University of Chicago. His lab focused on the Drosophila ...

Career

Allis undertook a

postdoctoral fellowship A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). The ultimate goal of a postdoctoral research position is to p ...

in the

University of Rochester The University of Rochester (U of R, UR, or U of Rochester) is a private research university in Rochester, New York. The university grants undergraduate and graduate degrees, including doctoral and professional degrees. The University of Roc ...

after obtaining his

. In 1981, he joined the

Baylor College of Medicine Baylor College of Medicine (BCM) is a medical school and research center in Houston, Texas, within the Texas Medical Center, the world's largest medical center. BCM is composed of four academic components: the School of Medicine, the Graduate Sc ...

as an

assistant professor Assistant Professor is an academic rank just below the rank of an associate professor used in universities or colleges, mainly in the United States and Canada. Overview This position is generally taken after earning a doctoral degree and general ...

in the Department of

Biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

and Department of

Cell Biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...

, and was promoted to

associate professor Associate professor is an academic title with two principal meanings: in the North American system and that of the ''Commonwealth system''. Overview In the ''North American system'', used in the United States and many other countries, it is a ...

in 1986 and

full professor Professor (commonly abbreviated as Prof.) is an academic rank at universities and other post-secondary education and research institutions in most countries. Literally, ''professor'' derives from Latin as a "person who professes". Professors ...

in 1989. He joined the Department of

Biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

Syracuse University Syracuse University (informally 'Cuse or SU) is a Private university, private research university in Syracuse, New York. Established in 1870 with roots in the Methodist Episcopal Church, the university has been nonsectarian since 1920. Locate ...

College of Arts and Sciences A College of Arts and Sciences or School of Arts and Sciences is most commonly an individual institution or a unit within a university that focuses on instruction of the liberal arts and pure sciences, although they frequently include programs and ...

in 1990. Allis returned to the

in 1995, and became the Marie Curran Wilson and Joseph Chamberlain Wilson Professor of Biology two years later. In 1998, Allis went to the Department of Biochemistry and

Molecular Genetics Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...

at the

University of Virginia The University of Virginia (UVA) is a Public university#United States, public research university in Charlottesville, Virginia. Founded in 1819 by Thomas Jefferson, the university is ranked among the top academic institutions in the United S ...

School of Medicine A medical school is a tertiary educational institution, or part of such an institution, that teaches medicine, and awards a professional degree for physicians. Such medical degrees include the Bachelor of Medicine, Bachelor of Surgery (MBBS, MB ...

. He joined the

in 2003 as the Joy and

Professor and Head of the Laboratory of

Biology and

. Allis had been treated for cancer. He died January 8, 2023, at a hospital in

Seattle Seattle ( ) is a seaport city on the West Coast of the United States. It is the seat of King County, Washington. With a 2020 population of 737,015, it is the largest city in both the state of Washington and the Pacific Northwest regio ...

Washington Washington commonly refers to: * Washington (state), United States * Washington, D.C., the capital of the United States ** A metonym for the federal government of the United States ** Washington metropolitan area, the metropolitan area centered on ...

Research

Allis was known for his research of

histone modifications In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn ar ...

and their relation to

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

structure. He started working on ''

Tetrahymena ''Tetrahymena'', a Unicellular organism, unicellular eukaryote, is a genus of free-living ciliates. The genus Tetrahymena is the most widely studied member of its phylum. It can produce, store and react with different types of hormones. Tetrah ...

'', a

ciliated The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...

unicellular A unicellular organism, also known as a single-celled organism, is an organism that consists of a single cell, unlike a multicellular organism that consists of multiple cells. Organisms fall into two general categories: prokaryotic organisms and ...

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

. ''Tetrahymena'' is an ideal candidate to study

histone acetylation Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an ...

due to its dual nucleus. It has a larger

macronucleus A macronucleus (formerly also meganucleus) is the larger type of nucleus in ciliates. Macronuclei are polyploid and undergo direct division without mitosis. It controls the non-reproductive cell functions, such as metabolism. During conjugation, t ...

that is transcriptionally active and

somatic Somatic may refer to: * Somatic (biology), referring to the cells of the body in contrast to the germ line cells ** Somatic cell, a non-gametic cell in a multicellular organism * Somatic nervous system, the portion of the vertebrate nervous sys ...

, and a smaller

micronucleus Micronucleus is the name given to the small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal i ...

that is transcriptionally silent and

germline In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...

. Chromatin biology at the time was not a popular topic; nor was the use of ciliated organisms. In 1996, his group isolated the

histone acetyltransferase Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-''N''-acetyllysine. DNA is wrapped around histones, and, by transferring an ...

p55 from ''Tetrahymena'', an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that acetylates

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...

s, and found the enzyme was homologous to Gcn5p, a known transcriptional

co-activator A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA p ...

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

. This was the first time that histone acetyltransferases were connected to DNA

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

activation Activation, in chemistry and biology, is the process whereby something is prepared or excited for a subsequent reaction. Chemistry In chemistry, "activation" refers to the reversible transition of a molecule into a nearly identical chemical or ...

, verifying Vincent Allfrey's hypothesis in the 1960s that histone acetylation regulates transcription. Following this seminal report, Allis continued studying histone acetylation, discovering more histone acetyltransferases, including

TAF1 Transcription initiation factor TFIID subunit 1, also known as transcription initiation factor TFIID 250 kDa subunit (TAFII-250) or TBP-associated factor 250 kDa (p250), is a protein that in humans is encoded by the ''TAF1'' gene. Function Init ...

(part of the

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

TF_IID needed to initiate transcription). Allis also branched off to researching histone phosphorylation and

histone methylation Histone methylation is a process by which methyl groups are transferred to amino acids of histone proteins that make up nucleosomes, which the DNA double helix wraps around to form chromosomes. Methylation of histones can either increase or decrea ...

. He linked histone phosphorylation to

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

and

mitogen A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a ...

stimulation, and established a synergistic relationship between histone phosphorylation and acetylation. He also determined the role of methylation at

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

9 of

histone H3 Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a stri ...

, identified

SET domain Set, The Set, SET or SETS may refer to: Science, technology, and mathematics Mathematics *Set (mathematics), a collection of elements * Category of sets, the category whose objects and morphisms are sets and total functions, respectively Electr ...

-containing proteins as

histone methyltransferase Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of ...

, and found that histone

ubiquitylation Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fou ...

regulates histone methylation. In 2000, Allis and Brian Strahl proposed the "

histone code The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications (known as ''histone marks'') to histone proteins, primarily on their unstructured ends. Together with sim ...

hypothesis", which states that DNA

is largely regulated by

. Later, Allis (together with

Thomas Jenuwein Thomas Jenuwein (born 1956) is a Germans, German scientist working in the fields of epigenetics, chromatin biology, gene regulation and genome function. Biography Thomas Jenuwein received his Ph.D. in molecular biology in 1987 from the Europea ...

) explicitly associated the histone code with

epigenetics In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

, and recognized the clinical significance of histone modifications, especially in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s. In more recent years, his attention turned to "oncohistones", which are histones with

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s that distort normal histone modifications, leading to cancers.

Honors and awards

* Member of the

American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and ...

(2001) *

Dickson Prize in Medicine The Dickson Prize in Medicine and the Dickson Prize in Science were both established in 1969 by Joseph Z. Dickson and Agnes Fischer Dickson. Dickson Prize in Medicine The Dickson Prize in Medicine is awarded annually by the University of Pittsburg ...

(2002) *

Massry Prize The Massry Prize was established in 1996, and until 2009 was administered by the Meira and Shaul G. Massry Foundation. The Prize, of $40,000 and the Massry Lectureship, is bestowed upon scientists who have made substantial recent contributions in ...

(2003) *

Wiley Prize in Biomedical Sciences The Wiley Prize in Biomedical Sciences is intended to recognize breakthrough research in pure or applied life science research that is distinguished by its excellence, originality and impact on our understanding of biological systems and processes. ...

(2004) *

Member Member may refer to: * Military jury, referred to as "Members" in military jargon * Element (mathematics), an object that belongs to a mathematical set * In object-oriented programming, a member of a class ** Field (computer science), entries in ...

of the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...

(2005) * Distinguished Alumnus Award,

(2007) *

Gairdner Foundation International Award The Canada Gairdner International Award is given annually by the Gairdner Foundation at a special dinner to five individuals for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a p ...

(2007) * ASBMB-

Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...

Award (2008) * Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research (2010) *

Japan Prize is awarded to people from all parts of the world whose "original and outstanding achievements in science and technology are recognized as having advanced the frontiers of knowledge and served the cause of peace and prosperity for mankind." The P ...

(2014) *

Grand Prix Charles-Leopold Mayer The Grand Prix Charles-Léopold Mayer (Charles-Léopold Mayer Prize) is awarded annually by the Académie des Sciences (French Academy of Sciences) de l'Institut de France (the French Institute) to researchers who have performed outstanding work in ...

(2014) *

Breakthrough Prize in Life Sciences The Breakthrough Prize in Life Sciences is a scientific award, funded by internet entrepreneurs Mark Zuckerberg and Priscilla Chan of Facebook; Sergey Brin of Google; entrepreneur and venture capitalist Yuri Milner; and Anne Wojcicki, one of the ...

(2015) *

Gruber Prize in Genetics The Gruber Prize in Genetics, established in 2001, is one of three international awards worth US$500,000 made by the Gruber Foundation, a non-profit organization based at Yale University in New Haven, Connecticut. The Genetics Prize honors leadi ...

(2016) *

March of Dimes Prize in Developmental Biology The March of Dimes Prize in Developmental Biology is awarded once a year by the March of Dimes. It carries a $250,000 award "to an investigator whose research brings us closer to the day when all babies will be born healthy." It also includes a ...

(2017) *

Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...

(2018) * Member of the

National Academy of Medicine The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, En ...

(2019) *

Albany Medical Center Prize The Albany Medical Center Prize in Medicine and Biomedical Research is the United States' second highest value prize in medicine and biomedical research, awarded by the Albany Medical Center. Among prizes for medicine worldwide, the Albany Medical ...

(2022) Allis was a member of

Phi Beta Kappa The Phi Beta Kappa Society () is the oldest academic honor society in the United States, and the most prestigious, due in part to its long history and academic selectivity. Phi Beta Kappa aims to promote and advocate excellence in the liberal a ...

when he graduated from the

. The C. David Allis Mentorship Fund for Young Scientists at the

was established in his honor.

References

{{DEFAULTSORT:Allis, Charles David 1951 births 2023 deaths Scientists from Cincinnati American molecular biologists Fellows of the American Academy of Arts and Sciences Members of the United States National Academy of Sciences University of Cincinnati alumni Indiana University alumni University of Rochester faculty Rockefeller University faculty Syracuse University faculty Baylor College of Medicine faculty Massry Prize recipients University of Virginia School of Medicine faculty Members of the National Academy of Medicine Recipients of the Albert Lasker Award for Basic Medical Research