David Allis, biologist who found protein-to-gene pathways, dies at 71

David Allis, a molecular biologist whose research greatly advanced scientific understanding of how proteins interact with genes and helped lay the foundation for potential new drug treatments for lymphomas and other diseases, died Jan. 8 at a New York hospital. Seattle. He was 71 years old.

His wife, Barbara, said that Dr. Allis had been treated for cancer.

Dr. Allis’s discoveries reshaped understanding of the genetic “on-off” and “volume” switches known as gene expression, in which the information encoded in a gene is turned into a function, such as making proteins and ribonucleic acid, or RNA, molecules that help regulate bodily functions. Any failure in the process, such as not turning on a gene or stimulating it too much, can lead the way to biological imbalances and possible disease.

Medical researchers have known for a long time that external factors such as diet, exercise and smoking can affect gene expression, but they were less clear about how it was happening at the molecular level. Dr. Allis led teams that filled the gaps and literally wrote new chapters in the field of epigeneticsstudying how genes can be affected by lifestyle, environment and other external influences.

Dr. Allis examined the proteins, known as histones, which are nature’s shrink wrap: compressing the long strands of DNA into cellular packages. He National Institutes of Health he 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 discovered that histone proteins were more than just wrappers or spools, as was long thought. Instead, histones are important pathways, through a “tail” on the histone protein, for regulating genes and could become a critical part of new medical therapies.

The link between histones and gene expression “hasn’t been given a grain of salt” for decades, Dr. Allis said in 2001. For biotech companies and the medical community, he said, it was like going from “a book in the library” to the creation of “a complete shelf”.

“This really suggests promising new drug targets,” said Joanna Wysocka, a researcher and professor of developmental biology at Stanford University, who did graduate work with Dr. Allis.

A handful of drugs known as histone deacetylase inhibitors -basically regulating histone messaging to genes- have been developed to treat melanomas, lymphomas and other blood-borne cancers. Researchers have also looked at histone-targeting drugs as potential therapies for heart disease and HIV infection.

A 2022 article in the journal American Chemical Society noted that histone-gene interaction “may provide novel insight” into the development of neurodegenerative diseases such as dementia. Other avenues of study include how influences on histone-gene interaction might play a role in autism and preterm labor and birth.

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“[Dr. Allis] transformed our understanding of gene regulation with a discovery whose impact was totally unexpected,” said Richard Lifton, president of rockefeller University, where Dr. Allis was a professor and researcher from 2003 until he moved 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 an elementary school teacher.

He started at the University of Cincinnati with plans for medical school, but became fascinated with cell research during his senior year when a professor suggested he spend some time in the lab before making a decision about medical studies.

Dr. Allis graduated in 1973 with a BS in Biology and received his Ph.D. in 1978 from Indiana University. As a postdoctoral fellow at the University of Rochester, and later as a professor at Baylor School of Medicine and Syracuse University, Dr. Allis left his laboratory colleagues baffled by his deep interest in tetrahymena, which he called his “pond water bug”.

For Dr. Allis, it was a perfect specimen for its combination of high histone levels and gene expression activity.

“[Dr. Allis’s] The main work was on a foreign organism, and it was criticized for it,” recalled Robert Roeder, a professor of biochemistry at Rockefeller University.

A reviewer of one of Dr. Allis’s grant applications asked why he didn’t just work on “something important,” Roeder said.

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, Los Angeles, who explored how histone-tail receptors turned gene expression on or off in yeast cells.

In 2018, Dr. Allis and Grunstein shared an Albert Lasker award, one of the most prestigious honors in medicine.

In addition to his wife of 48 years, Dr. Allis is survived by three children; a sister; and two grandchildren.

Dr. Allis liked to call himself a “scientist father” to the many post-doctoral students who passed through his labs over the decades.

“His passion for research was contagious,” Wysocka said. “He always said, ‘every amino acid matters.’ But he later added: ‘But the people matter more’”.

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