David Allis, a molecular biologist whose research greatly advanced scientific understanding of how proteins interact with genes and helped set the foundations for potential new drug treatments for lymphomas and other diseases, died Jan. 8 at a hospital in Seattle. He was 71.
Dr. Allis’s discoveries reshaped knowledge of the genetic “on-off” and “volume” switches known as gene expression, in which information encoded in a gene is turned into a function such as making proteins and ribonucleic acid, or RNA, molecules that help regulate body functions. Any flaws in the process, such as not triggering a gene or stimulating it too much, can open the way for biological imbalances and possible disease.
Medical researchers had long known that external factors such as diet, exercise and smoking could influence gene expression, but they had less clarity on how it was happening at a molecular level. Dr. Allis led teams that filled in the gaps and literally wrote new chapters in the field of epigenetics, studying how genes can be affected by lifestyle, environment and other outside influences.
Dr. Allis peered into proteins, known as histones, that are nature’s shrink wrap: squeezing the long DNA threads into cellular packets. The National Institutes of Health described it as the equivalent of “packing 24 miles of extremely fine thread into a tennis ball.”
Beginning with research in the 1980s with a single-celled aquatic creature called a tetrahymena, Dr. Allis found that histone proteins were more than mere wrappers or spools, as long thought. Instead, histones are important pathways — via a “tail” on the histone protein — to regulate genes and could become a critical part of new medical therapies.
The link between histones and gene expression “wasn’t given so much as a grain of salt” for decades, Dr. Allis said in 2001. For biotech firms and the medical community, he said, it was like going from “one book in the library” to setting up “an entire shelf.”
“This really suggests promising new drug targets,” said Joanna Wysocka, a researcher and professor of developmental biology at Stanford University, who did postgraduate work with Dr. Allis.
A handful of drugs known as histone deacetylase inhibitors — basically regulating the histone messaging to genes — have been developed to treat melanomas, lymphoma and other blood-borne cancers. Researchers also have pursued histone-targeting drugs as potential therapies for heart disease and HIV infection.
A 2022 paper in the Journal of the American Chemical Society noted that the histone-gene interplay “may provide novel insight” into the development of neurodegenerative diseases such as dementia. Other avenues of study include how influences on histone-gene interplay could have roles in autism and premature labor and birth.
Dr. Allis “transformed our understanding of gene regulation with a discovery whose impact was wholly unanticipated,” said Richard Lifton, president of Rockefeller University, where Dr. Allis was a professor and researcher from 2003 until moving to the Seattle area last year.
“These discoveries,” he added, “have had a profound impact on our fundamental understanding of biology.”
Charles David Allis was born on March 22, 1951, in Cincinnati, where his father was a city planner and his mother was an elementary school teacher.
He started at the University of Cincinnati with plans for medical school but became fascinated with cellular research during his senior year when a professor suggested he spend some time in the laboratory before a decision on medical studies.
Dr. Allis graduated in 1973 with a degree in biology and received his doctorate in 1978 from the Indiana University. As a postdoctoral fellow at the University of Rochester — and later as a professor at the Baylor College of Medicine and Syracuse University — Dr. Allis left lab colleagues puzzled at his deep interest in the tetrahymena, what he called his “pond water critter.”
For Dr. Allis, it was a perfect specimen for its mix of high levels of histones and gene expression activity.
Dr. Allis’s “major work was in a strange organism, and he was criticized for it,” recalled Robert Roeder, a professor of biochemistry at Rockefeller University.
One reviewer on one of Dr. Allis’s grant applications asked why he didn’t just work with “something important,” said Roeder.
Dr. Allis’s breakthrough came in 1996 by showing the links between histones and gene expression. It built on earlier experiments by Michael Grunstein, a professor at the University of California at Los Angeles, that explored how the histone tail-receptors activated or silenced gene expression in yeast cells.
In 2018, Dr. Allis and Grunstein shared an Albert Lasker award, one of the most prestigious honors in medicine.
Besides his wife of 48 years, survivors include three children; a sister; and two grandchildren.
Dr. Allis liked to call himself a “scientific dad” to the many postdoctoral students who passed through his labs over the decades.
“His passion for the research was contagious,” Wysocka said. “He would always say, ‘every amino acid matters.’ But then he would add, ‘But people matter more.’”