U Biochemist Receives National Honor for Outstanding Contributions in Basic Research
In a ceremony held last month, the 2024 Louisa Gross Horwitz Prize was awarded to Wesley Sundquist, PhD, Leo T. and Barbara K. Samuels Presidential Chair and a distinguished professor of biochemistry at the University of Utah, and Scott Emr, PhD, director of the Weill Institute for Cell and Molecular Biology at Cornell University.
The Louisa Gross Horwitz Prize is awarded for outstanding contributions in basic research in the fields of biology or biochemistry. The prize is regarded as a potential precursor of a future Nobel Prize, with 51 of the 113 previous winners subsequently being awarded a Nobel in Physiology or Medicine or Chemistry.
“Dr. Sundquist’s research has been instrumental in understanding the inner workings and vulnerabilities of HIV,” says Bob Carter, MD, PhD, Senior Vice President for Health Sciences and CEO for University of Utah Health. “We’re proud that this world-class scientist chooses to do his work at U of U Health and are honored that he has been recognized in this way.”
Sundquist and Emr were honored for discovering the ESCRT (Endosomal Sorting Complexes Required for Transport) pathway and revealing how it works. Sundquist’s early research in this area focused on determining how HIV assembles in a host cell, leading to the discovery that ESCRT complexes are required for HIV replication.
ESCRT complexes deform the cell membrane and bend parts of it away from the cytoplasm, the space that houses all material inside a cell. This process plays an essential role in packaging and sorting molecules, removing waste, and performing important functions such as cell division and membrane repair.
Dr. Sundquist’s research has been instrumental in understanding the inner workings and vulnerabilities of HIV. We’re proud that this world-class scientist chooses to do his work at U of U Health and are honored that he has been recognized in this way.
Many viruses, including HIV, hijack ESCRT machinery to exit an infected host cell and spread infection throughout the body. Defects in ESCRT function can also contribute to cancer, neurodegeneration, and Parkinson’s disease.
“Viruses have been very good at exploring cellular machinery and exploiting it for their own purposes,” says Sundquist, whose work has been funded by the National Institutes of Health for 30 years. “You can learn a lot about the cell by just following the viruses.”
Over the years, Sundquist and his colleagues have identified new human ESCRT proteins, mapped their interactions with one another, determined the three-dimensional structures and mechanisms of several key ESCRT complexes, and contributed to the understanding of how the ESCRT pathway mediates the final step of cell division.
“It’s fascinating to think about how a virus can make a particle to cross the cell membrane, get into a new cell, and commandeer its machinery to replicate,” says Sundquist, Director of the CHEETAH Center, a multi-institute collaboration devoted to understanding HIV structure and dynamics. “This collaborative Center structure has turned out to be much richer than even we appreciated.”
Sundquist’s studies of HIV assembly, that are separate from his ESCRT research, have helped lay the foundation for a new highly effective, long-lasting anti-HIV drug developed by Gilead Sciences that has been shown to prevent HIV transmission in large phase 3 clinical trials. The drug, Lenacapavir, was named the 2024 Breakthrough of the Year by Science, a top scientific journal.
Emr developed a genetic strategy in yeast to search for ESCRT proteins and went on to define the first ESCRT complex, ESCRT-I, in 2001. His lab also discovered how the cell uses ESCRT to sort membrane proteins for destruction, a vital process in regulating cell signals and clearing waste from the cell.
“People have an innate desire to understand how the world works, from the universe down to molecules in a cell,” Sundquist says. “It's very satisfying when you get to the stage where you understand something that you didn't understand before.”
Sundquist completed his BA in chemistry at Carleton College and obtained his PhD in chemistry from the Massachusetts Institute of Technology. Sundquist has also held a research position at the MRC Laboratory of Molecular Biology, Cambridge, UK. He has been elected to the American Academy of Arts and Sciences and the National Academy of Sciences.