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)
Switzer Prize (2023)
Scientific career
Fields Pulmonology, physiology
Institutions University of California, San Francisco
University of Texas, Houston
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 physiological defects in 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 in 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 across the 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. 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> Genetic disorder affecting mostly the lungs

Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably Staphylococcus aureus. CF is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. The hallmark feature of CF is the accumulation of thick mucus in different organs. 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.

The sweat test measures the concentration of chloride that is excreted in sweat. It is used to screen for cystic fibrosis (CF). Due to defective chloride channels (CFTR), the concentration of chloride in sweat is elevated in individuals with CF.

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

Sodium phenylbutyrate, sold under the brand name Buphenyl among others, is a salt of an aromatic fatty acid, 4-phenylbutyrate (4-PBA) or 4-phenylbutyric acid. The compound is used to treat urea cycle disorders, because its metabolites offer an alternative pathway to the urea cycle to allow excretion of excess nitrogen.

<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">Sodium-hydrogen antiporter 3 regulator 1</span> Protein-coding gene in the species Homo sapiens

Sodium-hydrogen antiporter 3 regulator 1 is a regulator of Sodium-hydrogen antiporter 3. It is encoded by the gene SLC9A3R1. It is also known as ERM Binding Protein 50 (EBP50) or Na+/H+ Exchanger Regulatory Factor (NHERF1). It is believed to interact via long-range allostery, involving significant protein dynamics.

<span class="mw-page-title-main">CLCN3</span> Protein-coding gene in the species Homo sapiens

H+/Cl− exchange transporter 3 is a protein that in humans is encoded by the CLCN3 gene.

<span class="mw-page-title-main">Channel blocker</span> Molecule able to block protein channels, frequently used as pharmaceutical

A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel.

The Wiley Prize in Biomedical Sciences is intended to recognize breakthrough research in pure or applied life science research that is distinguished by its excellence, originality and impact on our understanding of biological systems and processes. The award may recognize a specific contribution or series of contributions that demonstrate the nominee's significant leadership in the development of research concepts or their clinical application. Particular emphasis will be placed on research that champions novel approaches and challenges accepted thinking in the biomedical sciences.

Transepithelial potential difference (TEPD) is the voltage across an epithelium, and is the sum of the membrane potentials for the outer and inner cell membranes.

<span class="mw-page-title-main">Ivacaftor</span> Cystic fibrosis treatment drug

Ivacaftor is a medication used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis. It is also included in combination medications, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor which are used to treat people with cystic fibrosis.

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

Denufosol (INN) is an inhaled drug for the treatment of cystic fibrosis, being developed by Inspire Pharmaceuticals and sponsored by the Cystic Fibrosis Foundation. It was tested in two Phase III clinical trials, TIGER-1 and TIGER-2. Initially, in the first Phase III trial, TIGER-1, the compound showed significant results as compared with placebo. In the second Phase III trial, TIGER-2, the compound did not meet the primary endpoint, a significant change in baseline FEV1 at the week 48 endpoint as compared to placebo. As of 2011, no additional clinical studies are being conducted with the compound.

Everett Peter Greenberg is an American microbiologist. He is the inaugural Eugene and Martha Nester Professor of Microbiology at the Department of Microbiology of the University of Washington School of Medicine. He is best known for his research on quorum sensing, and has received multiple awards for his work.

<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.

Chloride channel openers refer to a specific category of drugs designed to modulate chloride channels in the human body. Chloride channels are anion-selective channels which are involved in a wide variety of physiological functions and processes such as the regulation of neuroexcitation, transepithelial salt transport, and smooth muscle contraction. Due to their distribution throughout the body, diversity, functionality, and associated pathology, chloride channels represent an ideal target for the development of channel modulating drugs such as chloride channel openers.

Phyllis I. Gardner is a Professor of Medicine at the Stanford University School of Medicine, and former Dean of Education. Gardner was one of the first people to be publicly skeptical of Elizabeth Holmes, the founder of blood testing company Theranos, who was later found guilty of investor fraud.

Elexacaftor/tezacaftor/ivacaftor, sold under the brand names Trikafta and Kaftrio, 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 a Senior Vice President at 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
  29. ↑ "Medical School | Switzer Prize". UCLA Medical School. August 11, 2022. Retrieved February 4, 2025.
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