Wesley Sundquist
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Wesley I. Sundquist (born 1959) is an American biochemist. Sundquist is known for studying the cellular, molecular and structural biology of retroviruses, particularly HIV. He is also known for studying the ESCRT pathway in cell division. Wesley Sundquist was born in St. Paul, Minnesota in 1959. He grew up in
St. Paul Minnesota Saint Paul (abbreviated St. Paul) is the capital of the U.S. state of Minnesota and the county seat of Ramsey County. Situated on high bluffs overlooking a bend in the Mississippi River, Saint Paul is a regional business hub and the cent ...
and Washington, DC. He received his bachelor’s degree in chemistry from
Carleton College Carleton College ( ) is a private liberal arts college in Northfield, Minnesota. Founded in 1866, it had 2,105 undergraduate students and 269 faculty members in fall 2016. The 200-acre main campus is between Northfield and the 800-acre Cowling ...
in Minnesota in 1981. During his time at Carleton Sundquist served as the coordinator of the Faribault Project, was elected to Sigma Xi and received a National Merit Scholarship (1977-81). Sundquist went on to complete a PhD at the Massachusetts Institute of Technology with
Stephen J. Lippard Stephen James Lippard (born October 12, 1940) is the Arthur Amos Noyes Emeritus Professor of Chemistry at the Massachusetts Institute of Technology. He is considered one of the founders of bioinorganic chemistry, studying the interactions of ...
in 1988. Following his PhD, he participated in postdoctoral research at the MRC Laboratory of Molecular in Cambridge, England under
Sir Aaron Klug Sir Aaron Klug (11 August 1926 – 20 November 2018) was a British biophysicist and chemist. He was a winner of the 1982 Nobel Prize in Chemistry for his development of crystallographic electron microscopy and his structural elucidation of bio ...
. In 1992 Sundquist joined the University of Utahbr>Department of Biochemistry
Sundquist is married to Nola Sundquist, with whom he lives with in Salt Lake City, Utah. They have two adult children, Chris and Emily.


Work and discoveries

Sundquist is Distinguished Professor and Chair of the Department of Biochemistry at the University of Utah, and he also directs a research lab. Th
Sundquist Lab
focuses on cellular, molecular and structural biology of retroviruses with a focus on Human Immunodeficiency Virus, HIV. Major projects in his lab include, 1) enveloped virus assembly 2) ESCRT pathway functions and regulation in cell division and cancer, and 3) HIV capsid structure, replication and restriction.


Enveloped virus assembly and budding

To leave a cell and spread infection, HIV viral particles must become enveloped within a membrane and bud from the cell. Sundquist found that retroviruses like HIV bud from infected cells using the host Endosomal Sorting Pathway Required for Transport or ESCRT pathway. HIV also uses the host proteins of the Angiomotin family to facilitate membrane envelopment prior to ESCRT- mediated budding. Sundquist's current research in this area focuses on understanding assembly and budding of HIV, characterizing the host and viral proteins involved, and testing innate immune restriction of viruses that use the ESCRT pathway. The Sundquist lab has also used their understanding of the requirements and principles of enveloped virus assembly to design and characterize new proteins that can assemble into nanocages, bud from cells, and carry cargoes into new target cells.


Selected publications

* Garrus JE, von Schwedler UK, Pornillos O, Morham SG, Zavitz KH, Wang HE, Wettstein DA, Stray KM, Cöté M, Rich RL, Myszka DG, Sundquist WI. (2001)
Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding
Cell, 107, 55-65. * von Schwedler U, Stuchell M, Müller B, Ward D, Chung H-Y, Morita E, Wang H, Davis T, Gong-Ping H, Cimbora DM, Scott AT, Kräusslich H-G, Kaplan J, Morham SG, and Sundquist WI. (2003)
The protein network of HIV budding
Cell, 114, 701-713. * Mercenne G, Alam SL, Arii J, Lalonde MS, Sundquist WI. (2015)
Angiomotin functions in HIV-1 assembly and budding
eLife, 4, e03778. * Votteler J, Ogohara C, Yi S, Hsia Y, Natterman U, Belnap DM, King NP, Sundquist WI. (2016)
Designed proteins induce the formation of nanocage-containing extracellular vesicles
Nature, 540, 292-5


ESCRT pathway functions and cell division

The ESCRT pathway facilitates formation of vesicles that bud into the endosome, neuronal pruning, reassembly of the post-mitotic nuclear envelope, final stage cell division (cytokinetic abscission). Cytokinetic abscission completes the separation of the two daughter cells, and also helps to coordinate a checkpoint that delays cell division until mitotic processes are completed successfully. In some cancer cells, this regulation doesn’t function correctly. Sundquist’s lab is studying these processes by determining the structures and functions of individual ESCRT proteins and the cofactors they recruit to help mediate abscission and the abscission checkpoint, and the signaling pathways that control their activities.


Selected publications

* Scott A, Gaspar J, Stuchell-Brereton MD, Alam SL, Skalicky JJ, Sundquist WI. (2005
Structure and ESCRT-III protein interactions of the MIT domain of human VPS4A
PNAS, 102(39), 13813-13818. * McCullough J, Clippinger AK, Talledge N, Skowyra ML, Saunders MG, Naismith TV, Colf LA, Afonine P, Arthur C, Sundquist WI, Hanson PI, Frost A. (2015
Structure and membrane remodeling activity of ESCRT-III helical polymers
Science, 350(6267), 1541-1551. * Stuchell-Brereton MD, Skalicky JJ, Kieffer C, Karren MA, Ghaffarian S, Sundquist WI. (2007
ESCRT-III recognition by VPS4 ATPases
Nature, 449, 740-744. * Morita E, Sandrin V, Chung HY, Morham SG, Gygi SP, Rodesch CK, Sundquist WI. (2007)
Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis
EMBO J, 26(19), 4215-27. * Caballe A, Wenzel DM, Agromayor M, Alam SL, Skalicky JJ, Kloc M, Carlton JG, Labrador L, Sundquist WI, Martin-Serrano J (2015)
ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins
eLife, 4, e06547.


HIV replication and restriction

The capsid of HIV facilitates viral
reverse transcription A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, ...
and protects the viral genome from the innate immune system. Sundquist defined the fullerene cone structure of the viral capsid, helping to set the stage for development of highly potent and long-lasting capsid inhibitors at Gilead Sciences. The Sundquist lab was also the first to reconstitute HIV reverse transcription and integration in a cell-free system. Sundquist and his collaborators also helped to define how the host restriction factor, TRIM5alpha recognizes and assembles around the capsid.


Selected publications

* Ganser BK, Li S, Klishko VY, Finch JT, Sundquist WI. (1999)
Assembly and analysis of conical models for the HIV-1 core
Science, 283(5398), 80-3. * Li S, Hill CP, Sundquist WI, Finch JT. (2000)
Image reconstructions of helical assemblies of the HIV-1 CA protein.
Nature, 407(6802), 409-13. *Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, Sundquist WI, Hill CP, Yeager M. (2009)
X-ray structures of the hexameric building block of the HIV capsid
Cell, 137(7), 1282-92. *Li Y-L, Chandrasekaran V, Carter SD, Woodward CL, Christensen DE, Dryden KA, Pornillos O, Yeager M, Ganser-Pornillos BK, Jensen GJ, Sundquist WI (2016)
Primate TRIM5 proteins form hexagonal nets on HIV-1 capsids
eLife, 5, e16269. *Christensen DE, Ganser-Pornillos BK, Johnson JS, Pornillos O, Sundquist WI, (2020)
Reconstitution and visualization of HIV-1 capsid dependent replication and integration in vitro. Science. 370(6513):eabc8420


Honors and scientific legacy

In 1993 Sundquist received the
Searle Scholars Award The Searle Scholars Program is a career development award made annually to the 15 young US professionals in biomedical research and chemistry considered most promising. The award was established in 1980 by a donation from the Searle family, and is ...
. In 2003 he received the ASBMB Amgen Award for the Application of Biochemistry and Molecular Biology to the understanding of disease. In 2004 he received both the
MERIT award The NIH MERIT award (Method To Extend Research in Time) Award (R37) was created by the National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary age ...
from the National Institutes of Health and the Bernard Fields award for Retrovirology. In 2017 he received the University of Uta
Rosenblatt Prize for Excellence
He has been elected to th
American Academy of Arts and Sciences
(2011) and the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
. (2014).


References

{{DEFAULTSORT:Sundquist, Wesley Massachusetts Institute of Technology School of Science alumni 20th-century American chemists Scientists from Saint Paul, Minnesota Carleton College alumni University of Utah faculty 1959 births Living people Scientists from Washington, D.C.