Dr. Jeannette Tenthorey of Seattle’s Fred Hutchinson Cancer Research Center has been named as one of 15 “exceptional early career scientists” by the Howard Hughes Medical Institute and will receive eight years of financial support through its Hanna H. Gray Fellows Program.
Now in its second year, the Hanna H. Gray program was designed by HHMI to spot and support future leaders in academic research. The grants of up to $1.4 million are designed to help research centers recruit and retain young women as well as underrepresented minorities pursuing careers in the life sciences.
“I’m delighted by this huge honor conferred on Jeannette. She is completely deserving of it,” said Fred Hutch evolutionary biologist Dr. Harmit Malik, who hired Tenthorey as a postdoctoral research fellow last year. Malik and his team study how the competition between microbes, such as bacteria and viruses, and the hosts they infect drives evolutionary changes in the genes involved in these contests.
“She is creating an ambitious research program in exploring new frontiers in host–pathogen interactions,” Malik said. “I am excited that we will get a front-row seat for her discoveries over the next few years.”
In her first four years of the Gray fellowship, Tenthorey will study a family of proteins believed to be part of the natural defenses, or innate immunity, of mammalian cells. Hard-wired into our genes, the innate immune system is a kind of first-responder network that reacts quickly to threats from invaders.
The molecules Tenthorey studies, known as guanylate-binding proteins, are inactive most of the time but are churned out inside cells that are under microbial attack. They are thought to block several different bacterial species and show an ability to prevent their growth and limit their mobility.
“Other than that, we don’t really understand how they work,” Tenthorey said. “We know they are important, but we don’t know exactly what they do or how they do it.”
By dissecting the rapid evolution of these proteins as they encounter bacterial challenges, she hopes to find out how specific mutations enable cells to withstand assault or to counteract efforts by bacteria to evade ever-changing defenses.
Tenthorey received a Ph.D. in molecular and cell biology from the University of California, Berkeley, in 2017. Working in the laboratory of Dr. Russell Vance, she was the lead author of a paper published last November in Science. It showed how a protein inside mammalian cells undergoes a shape-changing routine to grab onto flagella, hair-like structures that some invading bacteria — such as salmonella — use to propel themselves. Once it clings to one of these propelling hairs, the immune protein sets off a chain reaction that causes that cell to sacrifice itself, trapping the bacterium and releasing a flood of signals that warn neighboring cells of a microbial threat.
“It’s another part of the arsenal to detect and respond to infection,” Tenthorey said.
The Gray fellowship will pay Tenthorey’s salary for the next four years; then it can directly cover her research for up to four more years in a future faculty position.
Tenthorey is particularly appreciative that the Gray fellowships were set up to help women and minorities. Tenthorey said she was inspired as a youngster by her mother, who grew up in a conservative home where she was told she could only go to secretarial or nursing school. Her mother went to college as a nursing major, and eventually switched to biology.
“She somehow convinced her mother that it was close enough,” said Tenthorey. “She taught me, ‘Hey, do what you want to do, and don’t listen to what others say you can or cannot do.’” Her mother and father both work for pharmaceutical companies in Connecticut.
The Gray fellowship is funded by HHMI, the nation’s largest private supporter of biomedical research in academic settings. Dr. Gray is the former president of the University of Chicago and former chair of the HHMI trustees.
Tenthorey’s mentor Malik was an HHMI early career scientist from 2009 to 2013, when he was named a HHMI investigator. Her UC Berkeley adviser Vance was also named an HHMI investigator in 2013.
Sabin Russell is a former staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and he wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT and a freelance writer for the New York Times and Health Affairs.