Two Fred Hutchinson Cancer Research Center investigators have been elected to the American Academy of Arts and Sciences. Evolutionary biologist Dr. Harmit Malik and molecular biologist Dr. Steven Henikoff were honored for their innovative contributions to our understanding of fundamental biological processes. Malik studies how conflicts between genes with opposing functions shape how genes evolve, while Henikoff focuses on the structure, function and evolution of chromosomes, which are structures cells use to help organize and regulate their DNA.
One of the oldest learned societies in the U.S., the Academy was founded in 1780 to honor excellence, convene leaders to examine new ideas, address issues of importance to the nation and the world, and advance the public good. This year, the Academy recognizes the accomplishments and leadership of 261 new members who hail from academia, the arts, industry, public policy and research.
“We are celebrating a depth of achievements in a breadth of areas,” said Academy President David Oxtoby. “These individuals excel in ways that excite us and inspire us at a time when recognizing excellence, commending expertise, and working toward the common good is absolutely essential to realizing a better future.”
Henikoff, a Howard Hughes Medical Institute Investigator since 1990, studies how chromosomes, composed of long structures of DNA and other molecules, evolve and function. He works to understand mechanisms of inheritance that don’t depend on DNA sequence, examining how DNA-packaging proteins and the molecules that turn genes on and off and read out their information shape these processes. Henikoff also develops tools for comparing gene sequences, determining the arrangement of genes in living cells, and understanding the biological functions of genes and how cells regulate them.
He realized early on that computing and the internet could revolutionize biological research and helped build the infrastructure for analyzing the human genome, the entire collection of DNA in a single cell. In 1992, Henikoff and his wife, Jorja Henikoff, developed a computational method that enables researchers to compare the relatedness among all living things and uncover the roots of human diseases by studying simpler organisms.
Henikoff and his colleagues have also developed techniques that allow scientists to map features of chromosomes that are altered when genes are switched on or off. Applied to the study of fruit fly cells, these methods have already offered new insight into how gene activity patterns may persist for many generations of cells. The techniques also may eventually help scientists determine how an embryo develops into an adult animal or how healthy cells become cancerous.
“It’s a special honor to be elected with Harmit,” Henikoff said.
For his part, Malik said his own election underscores how well Henikoff deserves a place in the Academy:
“I’m Steve’s former trainee and current junior colleague, so this should count twice for him!” he said.
Malik, himself an HHMI Investigator since 2013, got his start as a postdoctoral fellow in Henikoff’s lab. Malik’s interest was caught by an offbeat idea: He wanted to understand why certain genes evolve rapidly, and suspected it was due to genetic conflict, in which competition between genes with opposing functions drives their evolution. Henikoff gave Malik the freedom to pursue the notion, and the foundation for a career was laid.
Malik’s interest in the push-pull between different genes and the proteins they encode — sometimes within the same organism, and sometimes between organisms — has helped him reveal fundamental processes occurring within a variety of biological systems. With Hutch colleague and HIV expert Dr. Michael Emerman, he pioneered paleovirologry, or the study of extinct viruses. Malik theorized (correctly) that long-past viral infections would leave imprints on host DNA that would allow him and Emerman to infer how the viruses influenced the evolution of host antiviral proteins.
Malik also studies genetic conflicts occurring within a single species. For example, he has studied the evolution of the centromere, a specialized region of the chromosome that’s essential for proper cell division, and the centromere-specific, DNA-packaging proteins. His work showed that these proteins and the centromere’s DNA sequence evolve in concert, shedding light on how evolution helps cells balance competing forces at work during the cell divisions that occur during egg cell development.
Since he set off to follow the evolutionary trail that genetic conflicts leave in DNA, Malik has helped his lab members gain insights into subjects as wide-ranging as bacteria’s antiviral mechanisms and male fertility.
Malik and Henikoff have continued to collaborate since Malik established his own laboratory at the Hutch in 2003. Recently, their teams worked together to better understand why some unusual DNA-packaging proteins evolve rapidly, and how cancer may co-opt them. The work gave new insights into the factors at play during embryonic development and how tumor cells can turn normal biological processes to their own ends.
With Henikoff and Malik, 14 Hutch scientists have been elected to the Academy, including Nobel Prize winners Drs. Linda Buck and Lee Hartwell and fellow HHMI Investigator Dr. Sue Biggins.
On April 1, 2022, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance became Fred Hutchinson Cancer Center, a single, independent, nonprofit organization that is also a clinically integrated part of UW Medicine and UW Medicine’s cancer program. Read more about the restructure.
Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at email@example.com.