NEW YORK, NY (September 18, 2024)-Columbia University will award the 2024 Louisa Gross Horwitz Prize to Scott Emr and Wesley Sundquist for discovering the ESCRT (Endosomal Sorting Complexes Required for Transport) pathway and revealing how it works.
ESCRT (pronounced "escort") complexes deform the cell membrane and bend parts of it away from the cytoplasm, the space that houses all material inside a cell. This unique process plays an essential role in keeping cells healthy by packaging and sorting molecules, removing waste, and regulating important functions such as cell division, neuron remodeling, and immune responses. Defects in ESCRT function can lead to uncontrolled cell growth and tumor formation, contributing to cancer, neurodegeneration, and Parkinson's disease. In addition, many viruses, including HIV, hijack ESCRT machinery to exit an infected host cell.
Scott Emr discovered the first ESCRT complex, ESCRT-I, in 2001. Emr developed a genetic strategy in yeast to search for more ESCRT proteins and, since the initial discovery, his lab has published a series of papers identifying more than 20 genes that comprise all five known ESCRT complexes. Emr also made several important discoveries about how ESCRT complexes function. He showed that lipids in the membrane act like shipping labels that can be read by ESCRT complexes to send molecules to precise destinations. Emr also found that ESCRT complexes recognize proteins that are tagged with a molecule called ubiquitin and sends them to the lysozyme, a component of the cell that breaks down biomolecules. This groundbreaking discovery explained how the cell sorts proteins for destruction, a vital process in regulating cell signals and clearing waste from the cell.
Wes Sundquist's early work focused on determining how HIV assembles in a host cell, which led to the discovery that ESCRT complexes are required for HIV replication. Sundquist showed how HIV and other enveloped viruses hijack the host cell's ESCRT machinery to envelope their own viral components within a membrane to escape the cell and spread infection. He and his colleagues also identified new human ESCRT proteins; mapped their interactions with one another and with ubiquitin; determined the three-dimensional structures and mechanisms of several key ESCRT complexes; and contributed to our understanding of how the ESCRT pathway mediates the final step of cell division. Sundquist's studies of HIV assembly also helped set the stage for an important new class of anti-HIV drugs.
Emr and Sundquist are the 114th and 115th winners of the Horwitz Prize, which is awarded annually by Columbia University for groundbreaking work in medical science. Of the 113 previous Horwitz Prize winners, 51 have gone on to receive Nobel Prizes.
Awardee biographies
Scott Emr, PhD, is the Nancy M. and Samuel C. Fleming Professor Emeritus in the Department of Molecular Biology and Genetics, Cornell University, USA. Emr received his BS degree in biology from the University of Rhode Island, USA, and completed his PhD in microbiology and molecular genetics at Harvard University, USA. Emr has also held research positions at the California Institute of Technology, USA; the University of California, Berkeley, USA; the University of California, San Diego, USA; and the Howard Hughes Medical Institute, USA. He has been elected to the American Association for the Advancement of Science, European Molecular Biology Organization, American Academy of Arts and Sciences, and the National Academy of Sciences.
Wesley Sundquist, PhD, is the Samuels Professor in the Department of Biochemistry at the University of Utah, USA. Sundquist completed his BA degree in chemistry at Carleton College, USA, and obtained his PhD degree in chemistry from the Massachusetts Institute of Technology, USA. Sundquist has also held research positions at MRC Laboratory of Molecular Biology, Cambridge, UK, and Department of Biochemistry at the University of Wisconsin, USA. He has been elected to the American Academy of Arts and Sciences and the National Academy of Sciences.
References
The Louisa Gross Horwitz Prize
The Louisa Gross Horwitz Prize was established in 1967 by the late S. Gross Horwitz. It is named in honor of the donor's mother, Louisa Gross Horwitz, who was the daughter of Dr. Samuel David Gross (1805-89), a prominent Philadelphia surgeon who served as president of the American Medical Association and wrote "Systems of Surgery." Of the 115 Horwitz Prize winners to date, 51 have gone on to receive Nobel Prizes. Most recently, 2014 Horwitz Prize winner James P. Allison, PhD, of the University of Texas MD Anderson Cancer Center, shared the 2018 Nobel Prize in Physiology or Medicine with Tasuku Honjo, MD, PhD, of Kyoto University. For a list of previous Horwitz Prize awardees, please click here.
The 2024 Louisa Gross Horwitz Prize lectures and dinner will take place early next year (2025), with a date to be shared on the Horwitz Prize lecture website.
