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CDB Seminar - David Virshup, Duke-NUS Medical School, Singapore

08 April 2022, 12:00 pm–1:00 pm

photo of David Virshup

Title: Upstream Regulation of Wnt Signaling: Biology and Therapy

This event is free.

Event Information

Open to

All

Availability

Yes

Cost

Free

Organiser

Michael Wright – Cell and Developmental Biology

Host: Patricia Salinas

Abstract: Wnt are lipoproteins made in stromal cells called telocytes that utilize specialized molecules to travel short distances to regulate development and stem cell proliferation. Getting these highly hydrophobic signaling proteins from their site of synthesis to the plasma membrane of a specific nearby cell is an interesting and complex task. In this talk I will discuss recent findings including:

  • Structural insights into the dedicated proteins PORCN and WLS/ Evi in sending cells that acylate and deliver Wnts to the plasma membrane.
  • How telocytes from the intestinal stroma deliver Wnts to stem cells in organoids.
  • Insights into downstream Wnt signaling gleaned from studies of small molecule PORCN inhibitors in Wnt-addicted cancers.

Suggested references:

  1. Kaur A, Lim JYS, Sepramaniam S, Patnaik S, Harmston N, Lee MA, Petretto E, Virshup DM, Madan B. WNT inhibition creates a BRCA‐like state in Wnt‐addicted cancer. Embo Mol Med. 2021;13(4):e13349. PMID: 33660437
  2. Harmston N, Lim JYS, Arqués O, Palmer HG, Petretto E, Virshup DM, Madan B. Widespread Repression of Gene Expression in Cancer by a Wnt/β-Catenin/MAPK Pathway. Cancer Res. 2020 Nov 17;81(2):464–475. PMID: 33203702
  3. Nygaard R, Yu J, Kim J, Ross DR, Parisi G, Clarke OB, Virshup DM, Mancia F. Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion. Cell. 2021 Jan 7;184(1):194-206.e14. PMID: 33357447

Join Zoom Meeting https://ucl.zoom.us/j/99153820525?pwd=Ym5GTmw2cjErL1pNUDRETTlYbVZsZz09

Meeting ID: 991 5382 0525

Passcode: 307689

About the Speaker

David Virshup

at Duke-NUS Medical School, Singapore

David Virshup, M.D., is Director of the Programme in Cancer and Stem Cell Biology (CSCB) and Professor at Duke-NUS Medical School and is jointly appointed as Professor of Pediatrics at Duke University in North Carolina. Dr. Virshup received his B.A. magna cum laude from Beloit College, majoring in chemistry. He received his M.D. from Johns Hopkins University in Baltimore, followed by clinical residency in Pediatrics and a fellowship in Pediatric Hematology/Oncology. He credits his research training and mentoring to William Zinkham, Vann Bennett, and Tom Kelly in the departments of Pediatrics, Cell Biology and Anatomy, and Molecular Biology and Genetics, all at Hopkins. Dr. Virshup established his first independent laboratory at the University of Utah in Salt Lake City, where over the course of 17 years he rose to Professor of Pediatrics and Oncological Sciences with an endowed chair as an investigator at the Huntsman Cancer Institute. He moved to Duke-NUS in Singapore in 2007 to help establish CSCB. He has been elected to several honorific societies including the American Society for Clinical Investigation (ASCI), the American Association for the Advancement of Science (AAAS) and the Association of American Physicians (AAP). He is board certified in both Pediatrics and Pediatric Hematology/Oncology in the USA. His research has focused on signal transduction, with an emphasis on both Wnt signaling and circadian rhythms. Early work examined the roles of Protein Phosphatase 2A and Casein Kinase 1 play in these processes. In Singapore, studies of phosphorylation of the PERIOD protein lead to the elucidation of the phosphoswitch model controlling circadian clock speed. In addition, his laboratory collaborated to develop a small molecule inhibitor of Wnt secretion, ETC-159, a drug now in human clinical trials.

More about David Virshup