Gregg L. Semenza Explained

Gregg L. Semenza
Birth Name:Gregg Leonard Semenza
Birth Date:12 July 1956
Birth Place:New York City. New York, U.S.
Spouse:Laura Kasch-Semenza
Education:Harvard University (AB)
University of Pennsylvania (MD, PhD)
Known For:Hypoxia-inducible factors
Workplaces:Johns Hopkins School of Medicine
Thesis Title:Molecular genetic analysis of the silent carrier of beta thalassemia (haplotype)
Thesis Url:https://search.proquest.com/docview/303306495/
Thesis Year:1984
Doctoral Advisors:Elias Schwartz
Saul Surrey

Gregg Leonard Semenza (born July 12, 1956) is a pediatrician and Professor of Genetic Medicine at the Johns Hopkins School of Medicine. He serves as the director of the vascular program at the Institute for Cell Engineering.[1] He is a 2016 recipient of the Albert Lasker Award for Basic Medical Research.[2] He is known for his discovery of HIF-1, which allows cancer cells to adapt to oxygen-poor environments. He shared the 2019 Nobel Prize in Physiology or Medicine for "discoveries of how cells sense and adapt to oxygen availability" with William Kaelin Jr. and Peter J. Ratcliffe.[3] [4] Semenza has had ten research papers retracted due to falsified data.[5]

Early life

Semenza was born on July 12, 1956,[6] in Flushing, New York City; he and his four siblings grew up in Westchester County, New York.[7]

Education and career

Semenza grew up in Westchester County, New York and attended Washington Irving Intermediate School in Tarrytown, New York. He then attended Sleepy Hollow High School where he was a mid-fielder on the soccer team and graduated in 1974. As an undergraduate at Harvard University, he studied medical genetics and mapped genes on chromosome 21. For his MD-PhD at the University of Pennsylvania, he sequenced genes linked to the recessive genetic disorder, beta-thalassemia.[8] [9] Semenza subsequently completed his Pediatrics residency at Duke University[10] before completing a postdoctoral fellowship at Johns Hopkins University. Semenza became the founding director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering following his post-doctorate.

Research

While a post-doctorate researcher at Johns Hopkins, Semenza evaluated gene expression in transgenic animals to determine how this affected the production of erythropoietin (EPO), known to be part of the means for the body to react to hypoxia, or low oxygen levels in the blood.[11] Semenza identified the gene sequences that expressed hypoxia-inducible factors (HIF) proteins. Semenza's work showed that the HIF proteins consisted of two parts; HIF-1β, a stable base to most conditions, and HIF-1α that deteriorated when nominal oxygen levels were present. HIF-1α was further found essential to the EPO production process, as test subjects modified to be deficient in HIF-1α were found to have malformed blood vessels and decreased EPO levels. These HIF proteins were found across multiple test animals.[11] Semenza further found that HIF-1α overproduction could lead to cancer in other subjects.[11]

Semenza's research overlapped with that of William Kaelin and Peter J. Ratcliffe on determining the mechanism of oxygen detection in cells, and how EPO production is regulated by HIF and other factors. This has led to the development of drugs that help regulate these processes for patients with anaemia and kidney failure.[12]

Retractions

In 2011 Semenza retracted from Biochemical Journal one paper coauthored with Naoki Mori (and other collaborators), and in 2022 retracted four papers from PNAS according to Retraction Watch.[13] As of 2022, concerns about the integrity of images in 52 articles coauthored by Semenza have been raised on PubPeer. This has led to investigations by the journals where these articles appeared, resulting in many corrections, retractions and expressions of concern.[14]

In 2023, additional papers in PNAS[15] and Oncogene[16] were retracted.

As of 2023, Semenza has had 10 of his research papers retracted due to data falsification via improper manipulation and/or duplication of images.[17] [18] [19]

Personal life

Semenza is married to Laura Kasch-Semenza, whom he had met while at Johns Hopkins, and who currently operates one of the university's genotyping facilities.[7]

Awards

External links

Notes and References

  1. Web site: Gregg L. Semenza, M.D., Ph.D..
  2. Web site: Oxygen sensing – an essential process for survival – The Lasker Foundation. Lasker. Foundation. The Lasker Foundation.
  3. Web site: The Nobel Prize in Physiology or Medicine 2019. NobelPrize.org. en-US. October 7, 2019.
  4. News: Kolata . Gina . Specia . Megan . Nobel Prize in Medicine Awarded for Research on How Cells Manage Oxygen – The prize was awarded to William G. Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza for discoveries about how cells sense and adapt to oxygen availability. . October 7, 2019 . . October 8, 2019 .
  5. Web site: Kincaid . Ellie . 2023-10-02 . Nobel Prize winner Gregg Semenza tallies tenth retraction . 2024-02-15 . Retraction Watch . en-US.
  6. Web site: Gregg L. Semenza: Facts . nobelprize.org . October 9, 2019.
  7. Ahmed, Farooq . August 17, 2010 . Profile of Gregg L. Semenza . Proceedings of the National Academy of Sciences of the United States of America . 107 . 33 . 14521–14523 . 10.1073/pnas.1009481107 . 2930469 . 20679204 . 2010PNAS..10714521A . free .
  8. Web site: Johns Hopkins geneticist Gregg Semenza wins Lasker Award for insights into how cells sense oxygen. September 13, 2016.
  9. Molecular genetic analysis of the silent carrier of beta thalassemia (haplotype) . 1984 . . Ph.D. . Semenza . Gregg Leonard . . subscription . 1049531609.
  10. Web site: Gairdner Award. October 7, 2019.
  11. Hurst. Jillian H.. September 13, 2016. William Kaelin, Peter Ratcliffe, and Gregg Semenza receive the 2016 Albert Lasker Basic Medical Research Award. The Journal of Clinical Investigation. 126. 10. 3628–3638. 10.1172/JCI90055. 0021-9738. 5096796. 27620538. Further support for an oxygen-sensing mechanism was provided by the discovery of erythropoietin (EPO), a glycoprotein hormone that stimulates erythrocyte production [...] During the same time period in which Semenza was developing EPO-transgenic mice, Peter Ratcliffe, a physician and kidney specialist, was establishing a laboratory in Oxford University’s Nuffield Department of Medicine to study the regulation of EPO.
  12. Biologists who decoded how cells sense oxygen win medicine Nobel . Heidi . Ledford . Ewen . Callaway . October 7, 2019 . . 574 . 7777 . 161–162 . 10.1038/d41586-019-02963-0 . 31595071 . 2019Natur.574..161L . free .
  13. Web site: Nobel Prize winner Gregg Semenza retracts four papers . 2022-09-03. Retraction Watch.
  14. Else . Holly . Dozens of papers co-authored by Nobel laureate raise concerns . Nature . Springer Science and Business Media LLC . 2022-10-21 . 611 . 7934 . 19–20 . 0028-0836 . 10.1038/d41586-022-03032-9 . 36271037 . 2022Natur.611...19E . 253063290 .
  15. 2023-05-02 . Retraction for Lee et al., Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization . Proceedings of the National Academy of Sciences . en . 120 . 18 . e2305537120 . 10.1073/pnas.2305537120 . 0027-8424 . 10160985 . 37099630. 2023PNAS..12005537. .
  16. Zhang . H. . Wong . C. C. L. . Wei . H. . Gilkes . D. M. . Korangath . P. . Chaturvedi . P. . Schito . L. . Chen . J. . Krishnamachary . B. . Winnard . P. T. . Raman . V. . Zhen . L. . Mitzner . W. A. . Sukumar . S. . Semenza . G. L. . 2023-05-23 . Retraction Note: HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs . Oncogene . 42 . 28 . 2234 . en . 10.1038/s41388-023-02720-8 . 37221224 . 1476-5594. 10330742 .
  17. Web site: Nobel Prize winner Gregg Semenza tallies tenth retraction . October 2, 2023 . Ellie Kincaid . Retraction Watch . October 21, 2023.
  18. Web site: Retraction Watch Database . Retraction Watch . Center for Scientific Integrity . 2023-11-07.
  19. Web site: Nobel Prize winner Gregg Semenza retracts another study . 2023-11-07 . Chemical & Engineering News . en.
  20. Web site: Gregg L. Semenza, M.D., Ph.D.. Johns Hopkins Medicine . October 8, 2019.
  21. Web site: Gregg L. Semenza, MD, PhD. American Society for Clinical Investigation. October 7, 2019.
  22. Web site: E. Mead Johnson Award in Pediatric Research. Archived version of American Pediatric Society website. October 7, 2019. https://web.archive.org/web/20141215105829/https://www.aps-spr.org/SPR/Awards/EMJ/PastRecipients.asp. December 15, 2014.
  23. Web site: 72 New Members Chosen By Academy. nationalacademies.org. October 7, 2019.
  24. Web site: 2008 Elected Members. Association of American Physicians . December 20, 2019 . October 8, 2019. https://web.archive.org/web/20081220193643/http://aap-online.org/. December 20, 2008.
  25. Web site: Nobel Prize in Physiology or Medicine awarded to 2010 Gairdner Laureates. gairdner.org. October 7, 2019. October 7, 2019.
  26. Web site: Two NAM Members Receive Albert Lasker Basic Medical Research Award. nam.edu. September 15, 2016. October 7, 2019.
  27. News: Gregg L. Semenza. April 21, 2015. Institut de France. Grands Prix des Fondations. December 12, 2017.
  28. Web site: The 2012 Stanley J. Korsmeyer Award: William G. Kaelin, Jr., MD, and Gregg L. Semenza, MD, PhD. www.the-asci.org. October 7, 2019. August 15, 2017. https://web.archive.org/web/20170815102115/https://www.the-asci.org/awards/korsmeyer/2012-william-g-kaelin-jr-and-gregg-l-semenza/. dead.
  29. Web site: Wiley: The 13th Annual Wiley Prize in Biomedical Sciences Awarded for Advancements in Oxygen Sensing Systems. www.wiley.com. October 7, 2019.
  30. Web site: Oxygen sensing – an essential process for survival. Foundation. Lasker. The Lasker Foundation. en. October 7, 2019.
  31. News: How cells sense oxygen wins Nobel prize. Gallagher. James. October 7, 2019. October 7, 2019. en-GB.
  32. Web site: The Nobel Prize in Physiology or Medicine 2019. NobelPrize.org. October 8, 2019.

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