Michael J. Welsh (biologist)

Last updated

Michael J. Welsh
Born
Michael James Welsh

Marshalltown, Iowa [1]
Education University of Iowa (BSc, MD)
Known forResearch of cystic fibrosis
Awards Warren Alpert Foundation Prize (2018)
George M. Kober Medal (2020)
Shaw Prize in Life Science & Medicine (2022)
Wiley Prize (2023)
Scientific career
Fields Pulmonology
Institutions University of California, San Francisco
University of Texas
University of Iowa
Howard Hughes Medical Institute

Michael James Welsh is an American pulmonologist. He is the current Roy J. Carver Chair in Biomedical Research, [2] the Professor of Internal Medicine in Pulmonary, Critical Care and Occupational Medicine at the Department of Internal Medicine, and the Director of Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa. [3] He is also a professor at the Department of Neurosurgery, Department of Neurology, and Department of Molecular Physiology and Biophysics. [3] He received the 2022 Shaw Prize in Life science and Medicine, together with Paul A. Negulescu, for their work that uncovered the etiology of cystic fibrosis and developed effective medications. [4]

Contents

Early life and education

Welsh was born and raised in Marshalltown, Iowa, and went to Loras College in Dubuque. [1] He has 3 siblings. [5] He obtained his BSc from the University of Iowa, then his MD from College of Medicine of the same university (now the Roy J. and Lucille A. Carver College of Medicine) in 1974. [1] [3] He completed his residency in Internal Medicine at the University of Iowa Hospitals and Clinics, [3] during which the attending physicians supervising him induced his interest in research. [5]

Career

After his residency, Welsh spent 3 years at the University of California, San Francisco and then University of Texas Medical School at Houston as a research fellow, returning to the University of Iowa in 1981 and becoming an assistant professor at the Department of Internal Medicine, eventually promoted to Professor of Internal Medicine and Professor of Molecular Physiology and Biophysics. [1]

Welsh was the President of the American Society for Clinical Investigation between 1996 and 1997, [6] and has been the President of the Association of American Physicians. [7] Currently, Welsh is an investigator at the Howard Hughes Medical Institute (since 1989) [8] and sits on the Scientific Advisory Board of the Harrington Discovery Institute at University Hospitals Cleveland Medical Center. [7]

Research

Welsh's research centered on cystic fibrosis, specifically the CFTR protein, an ion channel that allows chloride ions to pass through. His studies helped answer questions about why defects in the protein emerge and how these defects affect the protein's function. [9] [10] In 1989, Lap-Chee Tsui, Francis Collins, and their team discovered the gene that encodes the CFTR protein and found that changes in the protein caused cystic fibrosis. [11] Welsh's group discovered in 1991 that the CFTR protein is a chloride channel, meaning it allows chloride ions to pass through cell membrane. [12] The same year, his group reported how the activity of the CFTR protein could be regulated. [13] He later categorized the four classes of CFTR mutations that are still in use today in an expanded format. [14] Crucially, Welsh and his group found that when the CFTR protein contains F508del mutation, the most common mutation in cystic fibrosis patients, it could be transported to the cell surface under low temperature but not at body temperature. [15] His study also showed F508del-mutated CFTR protein can function properly if it reached cell surface, [16] paving the way for cystic fibrosis therapies. In recent years, Welsh has developed animal models of cystic fibrosis, most notably in pigs, allowing for the study of the disease in an in vivo setting. [17]

Personal life

Welsh married twice. He met his first wife, who died in 2006 from cancer, when she was a college student. They had 3 children. Welsh married his second wife in 2013. [5]

Honors and awards

Related Research Articles

<span class="mw-page-title-main">Cystic fibrosis</span> Autosomal recessive disease mostly affecting the lungs

Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.

<span class="mw-page-title-main">Cystic fibrosis transmembrane conductance regulator</span> Mammalian protein found in humans

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the CFTR gene.

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<span class="mw-page-title-main">Epithelial sodium channel</span> Group of membrane proteins

The epithelial sodium channel(ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na+). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.

<span class="mw-page-title-main">MT-ND4</span> Mitochondrial gene coding for a protein involved in the respiratory chain

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<span class="mw-page-title-main">GOPC</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Ivacaftor</span> Pharmaceutical medication used to treat cystic fibrosis

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<span class="mw-page-title-main">Denufosol</span> Chemical compound

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<span class="mw-page-title-main">Lumacaftor/ivacaftor</span> Cystic fibrosis drug

Lumacaftor/ivacaftor, sold under the brand name Orkambi among others, is a combination of lumacaftor and ivacaftor used to treat people with cystic fibrosis who have two copies of the F508del mutation. It is unclear if it is useful in cystic fibrosis due to other causes. It is taken by mouth.

<span class="mw-page-title-main">Chloride channel opener</span>

A chloride channel opener is a type of drug which facilitates ion transmission through chloride channels.

<span class="mw-page-title-main">Tezacaftor</span> Chemical compound

Tezacaftor is a drug used for the treatment of cystic fibrosis (CF) in people six years and older, who have a F508del mutation, the most common type of mutation in the CFTR gene. It is sold as a fixed-dose combination with ivacaftor under the brand name Symdeko. It was approved by the U.S. FDA in 2018. The combination of elexacaftor, tezacaftor, and ivacaftor is being sold as Trikafta.

Elexacaftor/tezacaftor/ivacaftor, sold under the brand names Trikafta (US) and Kaftrio (EU), is a fixed-dose combination medication used to treat cystic fibrosis. Elexacaftor/tezacaftor/ivacaftor is composed of a combination of ivacaftor, a chloride channel opener, and elexacaftor and tezacaftor, CFTR modulators.

Batsheva Kerem, is an Israeli geneticist who was on the research team that identified and cloned the CFTR gene, which when mutated, is responsible for causing cystic fibrosis (CF). She later established the Israel National Center for CF Genetic Research. She discovered the most prevalent cystic fibrosis-causing mutations among the Israeli population, allowing for the establishment of nationwide genetic screening programs to identify carriers of these mutations and enabling prenatal diagnoses. She researches how some CF mutations prevent CFTR protein production by causing nonsense-mediated decay and abnormal mRNA splicing, and how therapies might be able to counteract those problems. She also studies the role of genetic instability in cancer. She is currently a professor at the Hebrew University.

<span class="mw-page-title-main">Cystic fibrosis and race</span>

Underrepresented populations, especially black and hispanic populations with cystic fibrosis are often not successfully diagnosed. This is in part due to the minimal dissemination of existing data on patients from these underrepresented groups. While white populations do appear to experience a higher frequency of cystic fibrosis, other ethnicities are also affected and not always by the same biological mechanisms. Thus, many healthcare and treatment options are less reliable or unavailable to underrepresented populations. This issue affects the level at which public health needs are being met across the world.

Paul Adrian Negulescu is an American-Romanian cell biologist. He is the Senior Vice President and Site Head of the San Diego Research Center of American pharmaceutical company Vertex Pharmaceuticals. He received the 2022 Shaw Prize in Life science and medicine, together with Michael J. Welsh, for their work that uncovered the etiology of cystic fibrosis and developed effective medications.

References

  1. 1 2 3 4 5 Abboud, François M. (2009). "Introduction of Gordon Wilson Medal recipient Dr. Michael Welsh". Transactions of the American Clinical and Climatological Association. 120: 147–148. PMC   2744533 . PMID   19768172.
  2. ↑ "Welsh Lab - Contact Us". Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa. Archived from the original on October 22, 2022. Retrieved October 23, 2022.
  3. 1 2 3 4 "Michael J. Welsh, MD". Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa. Archived from the original on October 22, 2022. Retrieved October 23, 2022.
  4. ↑ "Press Release" (Press release). Shaw Prize Foundation. May 24, 2022. Archived from the original on October 12, 2022. Retrieved October 12, 2022.
  5. 1 2 3 "Autobiography of Michael J Welsh". Shaw Prize Foundation. Archived from the original on October 22, 2022. Retrieved October 23, 2022.
  6. ↑ "Michael J. Welsh, MD". American Society for Clinical Investigation. Archived from the original on October 25, 2022. Retrieved October 25, 2022.
  7. 1 2 "Michael Welsh, MD". Harrington Discovery Institute at University Hospitals Cleveland Medical Center. Archived from the original on October 23, 2022. Retrieved October 26, 2022.
  8. ↑ "Michael J. Welsh, MD". Howard Hughes Medical Institute. Archived from the original on October 25, 2022. Retrieved October 25, 2022.
  9. ↑ "DR. MICHAEL WELSH". Sanford Lorraine Cross Award. Archived from the original on October 29, 2022. Retrieved October 29, 2022.
  10. ↑ "Essay". Shaw Prize Foundation. Archived from the original on October 28, 2022. Retrieved October 28, 2022.
  11. ↑ Riordan, John R.; Rommens, Johanna M.; Kerem, Bat-Sheva; Alon, Noa; Rozmahel, Richard; Grzelczak, Zbyszko; Zielenski, Julian; Lok, Si; Plavsic, Natasa; Chou, Jia-Ling; Drumm, Mitchell L.; Iannuzzi, Michael C.; Collins, Francis S.; Tsui, Lap-Chee (1989). "Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA". Science . 245 (4922): 1066–1073. doi:10.1126/science.2570460. PMID   2475911. S2CID   86352511 . Retrieved October 27, 2022.
  12. ↑ Anderson, Matthew P.; Gregory, Richard J.; Thompson, Simon; Souza, David W.; Paul, Sucharita; Mulligan, Richard C.; Smith, Alan E.; Welsh, Michael J. (1991). "Demonstration that CFTR is a chloride channel by alteration of its anion selectivity". Science. 253 (5016): 202–205. Bibcode:1991Sci...253..202A. doi:10.1126/science.1712984. PMID   1712984 . Retrieved October 27, 2022.
  13. ↑ Cheng, Seng H.; Rich, Devra P.; Marshall, John; Gregory, Richard J.; Welsh, Michael J.; Smith, Alan E. (1991). "Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel". Cell . 66 (5): 1027–1036. doi:10.1016/0092-8674(91)90446-6. PMID   1716180. S2CID   25208449 . Retrieved October 28, 2022.
  14. ↑ Welsh, Michael J.; Smith, Alan E. (1993). "Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis" (PDF). Cell. 73 (7): 1251–1254. doi:10.1016/0092-8674(93)90353-r. PMID   7686820. S2CID   36691109. Archived from the original (PDF) on October 29, 2022. Retrieved October 29, 2022.
  15. ↑ Denning, Gerene M.; Anderson, Matthew P.; Amara, Jane F.; Marshall, John; Smith, Alan E.; Welsh, Michael J. (1994). "Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive". Nature . 358 (6389): 761–764. doi:10.1038/358761a0. PMID   1380673. S2CID   4365756 . Retrieved October 28, 2022.
  16. ↑ Cheng, S. H.; Fang, S. L.; Zabner, J.; Marshall, J.; Piraino, S.; Schiavi, S. C.; Jefferson, D. M.; Welsh, M. J.; Smith, A. E. (1995). "Functional activation of the cystic fibrosis trafficking mutant delta F508-CFTR by overexpression". American Journal of Physiology . 268 (1): L615-624. doi:10.1152/ajplung.1995.268.4.L615. PMID   7733303 . Retrieved October 28, 2022.
  17. ↑ Rogers, Christopher S.; Stoltz, David A.; Meyerholz, David K.; Ostedgaard, Lynda S.; Rokhlina, Tatiana; Taft, Peter J.; Rogan, Mark P.; Pezzulo, Alejandro A.; Karp, Philip H.; Itani, Omar A.; Kabel, Amanda C.; Wohlford-Lenane, Christine L.; Davis, Greg J.; Hanfland, Robert A.; Smith, Tony L.; Samuel, Melissa; Wax, David; Murphy, Clifton N.; Rieke, August; Whitworth, Kristin; Uc, Aliye; Starner, Timothy D.; Brogden, Kim A.; Shilyansky, Joel; McCray, Jr., Paul B.; Zabner, Joseph; Prather, Randall S.; Welsh, Michael J. (2008). "Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs". Science. 321 (5897): 1837–1841. Bibcode:2008Sci...321.1837R. doi:10.1126/science.1163600. PMC   2570747 . PMID   18818360.
  18. ↑ "Amberson Lecturers". American Thoracic Society. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  19. ↑ "Michael J. Welsh, M.D." National Academy of Medicine. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  20. ↑ "Michael J. Welsh". American Academy of Arts and Sciences. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  21. ↑ "Michael J. Welsh". National Academy of Sciences. Archived from the original on October 22, 2022. Retrieved October 31, 2022.
  22. ↑ "APS 2017 Distinguished Lectureship Award Winners to Present Talks at Experimental Biology". American Physiological Society. April 18, 2017. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  23. ↑ "Steven C. Beering Award". Indiana University. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  24. ↑ "Michael Welsh". Warren Alpert Foundation Prize. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  25. ↑ "Welsh receives Kober Medal". Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa. April 15, 2021. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  26. ↑ "George M. Kober Medal and Lectureship". Association of American Physicians. Archived from the original on October 31, 2022. Retrieved October 31, 2022.
  27. ↑ "The 2022 Prize in Life Science & Medicine". Shaw Prize Foundation. Archived from the original on October 5, 2022. Retrieved October 5, 2022.
  28. ↑ Wiley Prize 2023
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