Michael N. Hall

Last updated

Michael Nip Hall [1]
Michael N Hall 2014.jpg
Michael N. Hall in 2014
Born (1953-06-12) June 12, 1953 (age 70) [2]
Puerto Rico [3]
NationalitySwiss
American
Education University of North Carolina at Chapel Hill (BS)
Harvard University (PhD)
Known forDiscovery and research of TOR
Awards Louis-Jeantet Prize for Medicine
Sir Hans Krebs Medal
Breakthrough Prize in Life Sciences
Szent-Györgyi Prize for Progress in Cancer Research
Albert Lasker Award for Basic Medical Research
Canada Gairdner International Award
Scientific career
Fields Molecular biology
Institutions University of Basel
University of California, San Francisco
Pasteur Institute
Thesis Genetic studies on the regulation of the major outer membrane porin proteins of Escherichia coli K-12  (1981)
Doctoral advisor Thomas J. Silhavy

Michael Nip Hall (born 12 June 1953) is an American-Swiss molecular biologist and professor at the Biozentrum of the University of Basel, Switzerland. [4] He discovered TOR , a protein central for regulating cell growth.

Contents

Early life and education

Hall was born in Puerto Rico. His parents liked Latin American culture, so they moved to Peru when he was three years old, and then to Venezuela a few years later. [5] When Hall was 13, he went to the United States for boarding school, at St. Mark's School in Southborough, Massachusetts. [4] [5]

Hall entered the University of North Carolina at Chapel Hill as an arts major, but switched to zoology as he wanted to study medicine, [5] earning his BSc in 1976. [2] He found out he was not attracted to medicine after working at a local hospital, and turned to research when working on his undergraduate honors thesis in a molecular genetics laboratory. [5] Hall obtained his PhD from Harvard University in 1981. [2]

Career

Hall has been intrigued with the research of François Jacob and Jacques Monod with bacterial genetics, and so he went to the Pasteur Institute in Paris as a research fellow in 1981 for eight months. [5] He then joined Ira Herskowitz's group at the University of California, San Francisco as a postdoctoral fellow. He became a principal investigator in 1984, leading his own research group. [4]

In 1987, Hall moved to Basel, Switzerland, and joined the Division of Biochemistry of the Biozentrum, University of Basel, as an assistant professor. [4] He was promoted to professor in 1992. [2]

Hall was twice appointed Vice Director of the Biozentrum, from 2002 to 2009 and again from 2013 to 2016. [4] He was also Chairman of the European Molecular Biology Organization Council between 2021 and 2022, and served on the Council from 2017 to 2019 and again from 2020 to 2022. [6]

Currently, Hall serves on the Board of Trustees of the Louis-Jeantet Foundation. [7]

Research

Hall is a pioneer in the fields of the PI3K/AKT/mTOR pathway and cell growth control, and is best known for discovering mTOR. In 1991, Hall seminally discovered two genes that, when mutated, made rapamycin unable to inhibit cell growth in yeasts. [8] Hall named them TOR1 and TOR2, short for "Target of Rapamycin", [9] which his group also sequenced and characterized. [10] [11]

Three years later, Stuart Schreiber identified the mammalian counterpart of TOR, known as the "mammalian target of rapamycin" (mTOR). [12] The gene and the protein it encodes are later renamed the "mechanistic target of rapamycin", while the short form remains mTOR. [13]

The protein encoded by the TOR (and mTOR) gene is a protein kinase activated by growth factors, nutrients, and insulin. It is a central controller of cell growth and metabolism. The TOR protein plays a key role in aging and the development of diseases such as cancer, obesity, diabetes, and cardiovascular disease. [14]

After the discovery of TOR, Hall continued studying the function and regulation of TOR and mTOR in yeasts and humans. His group was the first to recognize that yeast TOR1 and TOR2 proteins can form two protein complexes (known as TORC1 and TORC2) with distinct function and composition. [15] They went on to show the mammalian counterpart of TORC2 (named mTORC2) is not inhibited by rapamycin and regulates a different signalling pathway from mTORC1. [16]

Hall also identified many roles of mTORC1 and mTORC2, including ribosomes physically interact with and activate mTORC2, [17] glutamine breakdown stimulates mTORC1, [18] and mTORC2 promotes lipid synthesis and cancer. [19] Collaborating with Nenad Ban and Timm Maier, Hall reported the structures of mTORC1 in 2016 [20] and mTORC2 in 2018. [21]

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Sirolimus</span> Pharmaceutical drug

Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumor (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin (mTOR) kinase inhibitor that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity.

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

Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours.

mTOR Mammalian protein found in humans

The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases.

<span class="mw-page-title-main">Folliculin</span> Protein-coding gene

The tumor suppressor gene FLCN encodes the protein folliculin, also known as Birt–Hogg–Dubé syndrome protein, which functions as an inhibitor of Lactate Dehydrogenase-A and a regulator of the Warburg effect. Folliculin (FLCN) is also associated with Birt–Hogg–Dubé syndrome, which is an autosomal dominant inherited cancer syndrome in which affected individuals are at risk for the development of benign cutaneous tumors (folliculomas), pulmonary cysts, and kidney tumors.

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

RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mTOR pathway and the regulation of the cell cycle.

<span class="mw-page-title-main">P70-S6 Kinase 1</span> Protein-coding gene in the species Homo sapiens

Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase, is an enzyme that in humans is encoded by the RPS6KB1 gene. It is a serine/threonine kinase that acts downstream of PIP3 and phosphoinositide-dependent kinase-1 in the PI3 kinase pathway. As the name suggests, its target substrate is the S6 ribosomal protein. Phosphorylation of S6 induces protein synthesis at the ribosome.

<span class="mw-page-title-main">RPTOR</span> Protein-coding gene in humans

Regulatory-associated protein of mTOR also known as raptor or KIAA1303 is an adapter protein that is encoded in humans by the RPTOR gene. Two mRNAs from the gene have been identified that encode proteins of 1335 and 1177 amino acids long.

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

Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) is a protein that in humans is encoded by the RICTOR gene.

Kun-Liang Guan, is a Chinese and American biochemist. He won the MacArthur Award in 1998.

AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1. It is essential for the initial building of the autophagosome and Cvt vesicles. In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR kinase, a sensor for nutrient availability.

mTOR inhibitors Class of pharmaceutical drugs

mTOR inhibitors are a class of drugs that inhibit the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs, which have shown tumor responses in clinical trials against various tumor types.

mTORC1 Protein complex

mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.

mTOR Complex 2 (mTORC2) is an acutely rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodeling. The complex itself is rather large, consisting of seven protein subunits. The catalytic mTOR subunit, DEP domain containing mTOR-interacting protein (DEPTOR), mammalian lethal with sec-13 protein 8, and TTI1/TEL2 complex are shared by both mTORC2 and mTORC1. Rapamycin-insensitive companion of mTOR (RICTOR), mammalian stress-activated protein kinase interacting protein 1 (mSIN1), and protein observed with rictor 1 and 2 (Protor1/2) can only be found in mTORC2. Rictor has been shown to be the scaffold protein for substrate binding to mTORC2.

<span class="mw-page-title-main">David M. Sabatini</span> American scientist who co-discovered mTOR

David M. Sabatini is an American scientist and a former professor of biology at the Massachusetts Institute of Technology. From 2002 to 2021, he was a member of the Whitehead Institute for Biomedical Research. He was also an investigator of the Howard Hughes Medical Institute from 2008 to 2021 and was elected to the National Academy of Sciences in 2016. He is known for his contributions in the areas of cell signaling and cancer metabolism, most notably the co-discovery of mTOR.

<span class="mw-page-title-main">Joseph Heitman</span>

Joseph Heitman is an American physician-scientist focused on research in genetics, microbiology, and infectious diseases. He is the James B. Duke Professor and Chair of the Department of Molecular Genetics and Microbiology at Duke University School of Medicine.

Immunometabolism is a branch of biology that studies the interplay between metabolism and immunology in all organisms. In particular, immunometabolism is the study of the molecular and biochemical underpinninngs for i) the metabolic regulation of immune function, and ii) the regulation of metabolism by molecules and cells of the immune system. Further categorization includes i) systemic immunometabolism and ii) cellular immunometabolism. Immunometabolism includes metabolic inflammation:a chronic, systemic, low grade inflammation, orchestrated by metabolic deregulation caused by obesity or aging.

<span class="mw-page-title-main">WYE-687</span> Chemical compound

WYE-687 is a drug which acts as an inhibitor of both subtypes of the mechanistic target of rapamycin (mTOR), mTORC1 and mTORC2. It is being researched for potential applications in the treatment of various forms of cancer.

<span class="mw-page-title-main">HY-124798</span> Chemical compound

HY-124798 (Rheb inhibitor NR1) is the first compound to be developed that acts as a potent and selective inhibitor of Rheb, a GTP-binding protein which acts as an endogenous activator of the mechanistic target of rapamycin (mTOR) subtype mTORC1. Since many of the side effects of rapamycin and its analogues are thought to result from binding to the other subtype mTORC2, it is hoped that selective inhibition of mTORC1 should have a more selective effects profile. As mTORC1 and mTORC2 have binding sites that are very similar in structure, it has been challenging to develop highly subtype selective inhibitors, making indirect inhibition via modulation of other messenger proteins such as Rheb an attractive approach. However, since HY-124798 has a relatively weak IC50 of 2.1μM, and Rheb also has other targets in addition to mTORC1, it remains to be established whether it will deliver the hoped for improvements in pharmacological profile.

<span class="mw-page-title-main">Torin-1</span> Chemical compound

Torin-1 is a drug which was one of the first non-rapalog derived inhibitors of the mechanistic target of rapamycin (mTOR) subtypes mTORC1 and mTORC2. In animal studies it has anti-inflammatory, anti-cancer, and anti-aging properties, and shows activity against neuropathic pain.

Phosphatidylinositol 3-phosphate-binding protein 2 (Pib2) is a yeast protein involved in the regulation of TORC1 signaling and lysosomal membrane permeabilization. It is essential for the reactivation of TORC1 following exposure to rapamycin or nutrient starvation.

References

  1. 1 2 "Debrecen Award for Molecular Medicine 2016". University of Debrecen. Archived from the original on February 24, 2023. Retrieved February 24, 2023.
  2. 1 2 3 4 "Charles Rodolphe Brupbacher Prize for Cancer Research 2019" (PDF). Charles Rodolphe Brupbacher Foundation. Archived from the original (PDF) on February 23, 2023. Retrieved February 23, 2023.
  3. 1 2 "Michael N. Hall". National Academy of Sciences. Archived from the original on February 24, 2023. Retrieved February 24, 2023.
  4. 1 2 3 4 5 "CV of Prof. Dr. Michael N. Hall". Biozentrum University of Basel . Retrieved May 15, 2023.
  5. 1 2 3 4 5 Neill, Ushma S. (2017). "A conversation with Michael Hall". Journal of Clinical Investigation . 127 (11): 3916–3917. doi:10.1172/JCI97760. PMC   5663369 . PMID   29091075. Archived from the original on March 2, 2023. Retrieved March 2, 2023.
  6. ↑ "Council". European Molecular Biology Organization. March 22, 2021. Archived from the original on November 29, 2022. Retrieved November 29, 2022.
  7. ↑ "The members of the Board of Trustees". Louis-Jeantet Foundation. December 7, 2017. Archived from the original on March 7, 2023. Retrieved March 7, 2023.
  8. ↑ Heitman, Joseph; Movva, N. Rao; Hall, Michael N. (1991). "Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast" . Science . 253 (5022): 905–909. Bibcode:1991Sci...253..905H. doi:10.1126/science.1715094. PMID   1715094. S2CID   9937225.
  9. ↑ Hall, Michael N. (2017). "An Amazing Turn of Events". Cell . 171 (1): 18–22. doi: 10.1016/j.cell.2017.08.021 . PMID   28888325. S2CID   26247385.
  10. ↑ Kunz, Jeannette; Henriquez, Ruben; Schneider, Ulrich; Deuter-Reinhard, Maja; Movva, N. Rao; Hall, Michael N. (1993). "Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression" . Cell. 73 (7): 585–596. doi:10.1016/0092-8674(93)90144-F. PMID   8387896. S2CID   42926249 . Retrieved March 13, 2023.
  11. ↑ Helliwell, Stephen B.; Wagner, Philipp; Kunz, Jeannette; Deuter-Reinhard, Maja; Henriquez, Ruben; Hall, Michael N. (1994). "TOR1 and TOR2 Are Structurally and Functionally Similar but not Identical Phosphatidylinositol Kinase Homologues in Yeast". Molecular Biology of the Cell . 5 (1): 105–118. doi:10.1091/mbc.5.1.105. PMC   301013 . PMID   8186460.
  12. ↑ Brown, Eric J.; Albers, Mark W.; Shin, Tae Bum; Ichikawa, Kazuo; Keith, Curtis T.; Lane, William S.; Schreiber, Stuart L. (1994). "A mammalian protein targeted by G1-arresting rapamycin-receptor complex". Nature . 369 (6483): 756–8. Bibcode:1994Natur.369..756B. doi:10.1038/369756a0. PMID   8008069. S2CID   4359651 . Retrieved March 10, 2023.
  13. ↑ Kennedy, Brian K.; Lamming, Dudley W. (2016). "The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging". Cell Metabolism . 23 (6): 990–1003. doi:10.1016/j.cmet.2016.05.009. PMC   4910876 . PMID   27304501.
  14. ↑ Saxton, Robert A.; Sabatini, David M. (2017). "mTOR Signaling in Growth, Metabolism, and Disease". Cell. 168 (6): 960–976. doi:10.1016/j.cell.2017.02.004. PMC   5394987 . PMID   28283069.
  15. ↑ Loewith, Robbie; Jacinto, Estela; Wullschleger, Stephan; Lorberg, Anja; Crespo, José L.; Bonenfant, Débora; Oppliger, Wolfgang; Jenoe, Paul; Hall, Michael N. (2002). "Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control". Molecular Cell . 10 (3): 457–468. doi: 10.1016/S1097-2765(02)00636-6 . PMID   12408816.
  16. ↑ Jacinto, Estela; Loewith, Robbie; Schmidt, Anja; Lin, Shuo; Rüegg, Markus A.; Hall, Alan; Hall, Michael N. (2004). "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive". Nature Cell Biology . 6 (11): 1122–1128. doi:10.1038/ncb1183. PMID   15467718. S2CID   13831153 . Retrieved March 13, 2023.
  17. ↑ Zinzalla, Vittoria; Stracka, Daniele; Oppliger, Wolfgang; Hall, Michael N. (2011). "Activation of mTORC2 by Association with the Ribosome". Cell. 144 (5): 757–768. doi: 10.1016/j.cell.2011.02.014 . PMID   21376236. S2CID   6454568.
  18. ↑ Durán, Raúl V.; Oppliger, Wolfgang; Robitaille, Aaron M.; Heiserich, Lisa; Skendaj, Roswitha; Gottlieb, Eyal; Hall, Michael N. (2012). "Glutaminolysis Activates Rag-mTORC1 Signaling". Molecular Cell. 47 (3): 349–358. doi: 10.1016/j.molcel.2012.05.043 . PMID   22749528.
  19. ↑ Guri, Yakir; Colombi, Marco; Dazert, Eva; Hindupur, Sravanth K.; Roszik, Jason; Moes, Suzette; Jenoe, Paul; Heim, Markus H.; Riezman, Isabelle; Riezman, Howard; Hall, Michael N. (2017). "mTORC2 Promotes Tumorigenesis via Lipid Synthesis". Cancer Cell . 32 (6): 807–823. doi: 10.1016/j.ccell.2017.11.011 . PMID   29232555.
  20. ↑ Aylett, Christopher H. S.; Sauer, Evelyn; Imseng, Stefan; Boehringer, Daniel; Hall, Michael N.; Ban, Nenad; Maier, Timm (2016). "Architecture of human mTOR complex 1" . Science. 351 (6268): 48–52. Bibcode:2016Sci...351...48A. doi:10.1126/science.aaa3870. PMID   26678875. S2CID   32663149 . Retrieved March 14, 2023.
  21. ↑ Stuttfeld, Edward; Aylett, Christopher H. S.; Imseng, Stefan; Boehringer, Daniel; Scaiola, Alain; Sauer, Evelyn; Hall, Michael N.; Maier, Timm; Ban, Nenad (2018). "Architecture of the human mTORC2 core complex". eLife . 7: e33101. doi: 10.7554/eLife.33101 . PMC   5837792 . PMID   29424687.
  22. ↑ "Michael N. Hall". European Molecular Biology Organization. Archived from the original on November 27, 2022. Retrieved February 26, 2023.
  23. ↑ Hall, Michael N. "TOR SIGNALLING: FROM BENCH TO BEDSIDE" (PDF). Max Cloëtta Foundation. Archived from the original (PDF) on February 26, 2023. Retrieved February 26, 2023.
  24. ↑ "Elected Fellows". American Association for the Advancement of Science. Archived from the original on February 26, 2023. Retrieved February 26, 2023.
  25. ↑ "Professor Michael N. HALL". Louis-Jeantet Foundation. October 2017. Archived from the original on February 26, 2023. Retrieved February 26, 2023.
  26. ↑ "Past laureates". Marcel Benoist Prize. Archived from the original on February 26, 2023. Retrieved February 26, 2023.
  27. ↑ "Senate of the SAMS: Individual members since 1992" (PDF). Swiss Academy of Medical Sciences. Archived from the original (PDF) on February 27, 2023. Retrieved February 27, 2023.
  28. ↑ "Plenary Lectures". Federation of European Biochemical Societies. Archived from the original on December 16, 2014. Retrieved December 16, 2014.
  29. ↑ "Michael N. Hall". Breakthrough Prize in Life Sciences. Archived from the original on January 16, 2023. Retrieved January 16, 2023.
  30. ↑ "Michael N. Hall". Gairdner Foundation. Archived from the original on February 28, 2023. Retrieved February 28, 2023.
  31. ↑ "2017 Prize: Michael N. Hall, Ph.D." National Foundation for Cancer Research. April 26, 2016. Archived from the original on February 28, 2023. Retrieved February 28, 2023.
  32. ↑ "2017 Albert Lasker Basic Medical Research Award". Lasker Foundation. Archived from the original on February 28, 2023. Retrieved February 28, 2023.
  33. ↑ "2019 - Michael Hall". Human Frontier Science Program. Archived from the original on March 1, 2023. Retrieved March 1, 2023.
  34. ↑ "Michael N. Hall". BBVA Foundation Frontiers of Knowledge Award. Archived from the original on March 1, 2023. Retrieved March 1, 2023.
  35. ↑ "Sjöberg Prize awarded for decisive discoveries about cell growth" (Press release). Royal Swedish Academy of Sciences. February 3, 2020. Archived from the original on March 1, 2023. Retrieved March 1, 2023.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.