Gregg L. Semenza

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Gregg L. Semenza
Gregg L. Semenza (cropped).jpg
Semenza in Stockholm, December, 2019
Born
Gregg Leonard Semenza

(1956-07-12) July 12, 1956 (age 68)
New York City, U.S.
Education Harvard University (AB)
University of Pennsylvania (MD, PhD)
Known for Hypoxia-inducible factors
SpouseLaura Kasch-Semenza
Awards Albert Lasker Award for Basic Medical Research (2016)
Nobel Prize in Physiology or Medicine (2019)
Scientific career
Institutions Johns Hopkins School of Medicine
Thesis Molecular genetic analysis of the silent carrier of beta thalassemia (haplotype)  (1984)
Doctoral advisors Elias Schwartz
Saul Surrey

Gregg Leonard Semenza (born July 12, 1956) is an American 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 thirteen research papers retracted due to falsified data. [5]

Contents

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. [7] As an undergraduate at Harvard University, he studied medical genetics and mapped genes on chromosome 21. [7] For his MD-PhD at the University of Pennsylvania, he sequenced genes linked to the recessive genetic disorder, beta-thalassemia. [7] [8] [9] Semenza subsequently completed his Pediatrics residency at Duke University [10] before completing a postdoctoral fellowship at Johns Hopkins University. [7] Semenza became the founding director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering following his post-doctorate. [7]

Research

Illustration of how cells sense and adapt to oxygen availability HIF Nobel Prize Physiology Medicine 2019 Hegasy ENG.png
Illustration of how cells sense and adapt to oxygen availability

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 2024, Semenza has had 13 of his research papers retracted due to data falsification via improper manipulation and/or duplication of images. [17] [18] [19] [20]

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

Related Research Articles

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References

  1. ↑ "Gregg L. Semenza, M.D., Ph.D."
  2. ↑ Foundation, Lasker. "Oxygen sensing – an essential process for survival – The Lasker Foundation". The Lasker Foundation.
  3. ↑ "The Nobel Prize in Physiology or Medicine 2019". NobelPrize.org. Retrieved October 7, 2019.
  4. 1 2 Kolata, Gina; Specia, Megan (October 7, 2019). "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". The New York Times . Retrieved October 8, 2019.
  5. ↑ "Nobel prize-winner tallies two more retractions, bringing total to 13". Retraction Watch. September 13, 2024. Retrieved September 22, 2024.
  6. ↑ "Gregg L. Semenza: Facts". nobelprize.org. Retrieved October 9, 2019.
  7. 1 2 3 4 5 6 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. Bibcode:2010PNAS..10714521A. doi: 10.1073/pnas.1009481107 . PMC   2930469 . PMID   20679204.
  8. ↑ "Johns Hopkins geneticist Gregg Semenza wins Lasker Award for insights into how cells sense oxygen". September 13, 2016.
  9. ↑ Semenza, Gregg Leonard (1984). Molecular genetic analysis of the silent carrier of beta thalassemia (haplotype) (Ph.D. thesis). University of Pennsylvania. OCLC   1049531609 – via ProQuest.
  10. ↑ "Gairdner Award". October 7, 2019.
  11. 1 2 3 4 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. doi:10.1172/JCI90055. ISSN   0021-9738. PMC   5096796 . PMID   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. ↑ Ledford, Heidi; Callaway, Ewen (October 7, 2019). "Biologists who decoded how cells sense oxygen win medicine Nobel". Nature . 574 (7777): 161–162. Bibcode:2019Natur.574..161L. doi: 10.1038/d41586-019-02963-0 . PMID   31595071.
  13. ↑ "Nobel Prize winner Gregg Semenza retracts four papers". Retraction Watch . September 3, 2022.
  14. ↑ Else, Holly (October 21, 2022). "Dozens of papers co-authored by Nobel laureate raise concerns". Nature. 611 (7934). Springer Science and Business Media LLC: 19–20. Bibcode:2022Natur.611...19E. doi:10.1038/d41586-022-03032-9. ISSN   0028-0836. PMID   36271037. S2CID   253063290.
  15. ↑ "Retraction for Lee et al., Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization". Proceedings of the National Academy of Sciences. 120 (18): e2305537120. May 2, 2023. Bibcode:2023PNAS..12005537.. doi:10.1073/pnas.2305537120. ISSN   0027-8424. PMC   10160985 . PMID   37099630.
  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. (May 23, 2023). "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. doi:10.1038/s41388-023-02720-8. ISSN   1476-5594. PMC   10330742 . PMID   37221224.
  17. ↑ "Retraction Watch Database".
  18. ↑ Ellie Kincaid (October 2, 2023). "Nobel Prize winner Gregg Semenza tallies tenth retraction". Retraction Watch. Retrieved October 21, 2023.
  19. ↑ "Retraction Watch Database". Retraction Watch. Center for Scientific Integrity. Retrieved November 7, 2023.
  20. ↑ "Nobel Prize winner Gregg Semenza retracts another study". Chemical & Engineering News. Retrieved November 7, 2023.
  21. 1 2 "Gregg L. Semenza, M.D., Ph.D." Johns Hopkins Medicine. Retrieved October 8, 2019.
  22. ↑ "Gregg L. Semenza, MD, PhD". American Society for Clinical Investigation. Retrieved October 7, 2019.
  23. ↑ "E. Mead Johnson Award in Pediatric Research". Archived version of American Pediatric Society website. Archived from the original on December 15, 2014. Retrieved October 7, 2019.
  24. ↑ "72 New Members Chosen By Academy". nationalacademies.org. Retrieved October 7, 2019.
  25. ↑ "2008 Elected Members". Association of American Physicians. December 20, 2019. Archived from the original on December 20, 2008. Retrieved October 8, 2019.
  26. ↑ "Nobel Prize in Physiology or Medicine awarded to 2010 Gairdner Laureates". gairdner.org. October 7, 2019. Retrieved October 7, 2019.
  27. ↑ "Two NAM Members Receive Albert Lasker Basic Medical Research Award". nam.edu. September 15, 2016. Retrieved October 7, 2019.
  28. ↑ "Gregg L. Semenza". Institut de France. Grands Prix des Fondations. April 21, 2015. Retrieved December 12, 2017.
  29. ↑ "The 2012 Stanley J. Korsmeyer Award: William G. Kaelin, Jr., MD, and Gregg L. Semenza, MD, PhD". www.the-asci.org. Archived from the original on August 15, 2017. Retrieved October 7, 2019.
  30. ↑ "Wiley: The 13th Annual Wiley Prize in Biomedical Sciences Awarded for Advancements in Oxygen Sensing Systems". www.wiley.com. Retrieved October 7, 2019.
  31. ↑ Foundation, Lasker. "Oxygen sensing – an essential process for survival". The Lasker Foundation. Retrieved October 7, 2019.
  32. ↑ Gallagher, James (October 7, 2019). "How cells sense oxygen wins Nobel prize" . Retrieved October 7, 2019.
  33. ↑ "The Nobel Prize in Physiology or Medicine 2019". NobelPrize.org. Retrieved October 8, 2019.
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