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词条 Draft:Jonathan S. Stamler
释义

  1. Early life and education

  2. Career and research

     Academic appointments  Research findings 

  3. References

  4. External links

{{User sandbox}}{{Connected contributor|User1=RPremont |U1-declared=yes| U1-otherlinks=Affiliated with BLP subject. Page needs external editor to assess and edit for neutrality.}}{{Use American English|date=February 2019}}{{Infobox scientist
| name = Jonathan S. Stamler
| image = Jonathan Stamler.jpg
| image_size =
| alt =
| caption = Jonathan Stamler in his laboratory
| birth_name = Jonathan Solomon Stamler
| birth_date = {{Birth date and age|1959|06|23}}
| birth_place = Wallingford, Oxfordshire, England
| death_date =
| death_place =
| nationality = American
|fields = {{Plainlist|
  • Biochemistry
  • Cardiology and Vascular biology
  • Redox biology }}

| workplaces = {{Plainlist|
  • Case Western Reserve University
  • Harrington Discovery Institute
  • University Hospitals Cleveland Medical Center
  • Duke University
  • Harvard University }}

| alma_mater = {{Plainlist|
  • Brandeis University
  • Icahn School of Medicine at Mount Sinai }}

| academic_advisors =
| doctoral_students =
| notable_students =
| known_for = Identification of S-nitrosylation as a protein post-translational modification, characterizing its regulatory enzymes, and defining its physiological and disease relevance
| awards = {{Plainlist|
  • Pew Scholar (1993)
  • HHMI Investigator (1997)
  • Outstanding Investigator Award in Basic Science (American Federation for Medical Research Foundation) (2001)
  • Coulter Translational Partnership Research Award (2009)
  • American Heart Association Distinguished Scientist Award (2013) }}

}}

Jonathan Solomon Stamler (born June 23, 1959) is an English-born American physician-scientist known for his discovery of protein S-nitrosylation, the addition of a nitric oxide (NO) group to the sulfur thiol on cysteine residues in proteins, as a post-translational modification to regulate enzymatic activity and other protein functions, and particularly in transporting NO as S-nitrosothiol on hemoglobin as the third gas in the respiratory cycle. [1] [2] [3] He is author of over 300 scientific papers and holds over 125 approved or pending biotechnology patents, and is also a co-founder of multiple biotechnology companies focused on improving health through modifying S-nitrosylation or its physiological targets.

[4]

Early life and education

Stamler was born in Wallingford, England on June 23, 1959 [4] to a British father and American mother, and lived in multiple countries (United Kingdom, Switzerland, Israel, United States) as a youth due to his father’s global career. He played on the Israeli national (under 18) tennis team.

He graduated with a Bachelor’s Degree from Brandeis University in 1981, and earned his M.D. degree from Icahn School of Medicine at Mount Sinai in 1985 [4]. His residency and fellowship training in pulmonary medicine and in cardiovascular medicine was at Brigham and Women’s Hospital at Harvard Medical School. [4]

Career and research

Academic appointments

Stamler was appointed Assistant Professor in Medicine at Harvard Medical School in 1993, and Associate Professor then Professor in Medicine at Duke University School of Medicine in 1993 and 1996, respectively, with recognition as the George Barth Geller Professor for Research in Cardiovascular Diseases in 2004. [4]

He was an Investigator with the Howard Hughes Medical Institute from 1997 to 2005. [4] [5]

In 2009, Stamler became Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation at University Hospitals Cleveland Medical Center, and Professor of Medicine, Professor of Biochemistry and founding Director of the Institute for Transformative Molecular Medicine at Case Western Reserve University School of Medicine. [4] [6]

In 2012, Stamler founded and became Director of the Harrington Discovery Institute at University Hospitals Cleveland Medical Center, and in 2016 was named Harrington Discovery Institute President. [4] [7] [8] He is a founder of the Harrington Project, a tripartite collaboration among non-profit and for-profit organizations to shepherd laboratory discovery through translation and into biotechnology commercialization and approved therapy. [4]

Research findings

At the start of Stamler’s research career, nitric oxide (NO) gas recently had been identified as a signaling molecule that mediated control of blood pressure, a finding that was recognized by awarding the Nobel Prize in Medicine or Physiology in 1998 to Louis J. Ignarro, Robert F. Furchgott, and Ferid Murad. [9] In their canonical pathway, NO gas released from blood vessel endothelial cells travels into nearby vascular smooth muscle cells to relax them (thereby increasing vessel diameter and decreasing blood pressure) by binding to the heme cofactor in the enzyme soluble guanylyl cyclase to produce cyclic guanosine monophosphate (cGMP) and thus activate the cGMP-dependent protein kinase to phosphorylate proteins regulating muscle contraction, among other targets. [10]

NO gas is unsuited to widespread signaling throughout the body due to its high affinity binding to the heme cofactors in red blood cell hemoglobin, whose vast quantity should prevent NO activity from traversing the bloodstream. [10] Furthermore, while many biological actions were being discovered for NO, guanylyl cyclase/cGMP did not mediate some of these actions. [11] Stamler recognized that NO also can be activated to bind to thiol groups, including those of free cysteine residues present in most proteins, by conversion to nitrosonium ion NO+, to form an S-nitrosothiol that is no longer subject to inactivation by heme, and first demonstrated that modification by S-nitrosylation can regulate the activity of proteins including enzymes by modifying active site or allosteric site cysteines. [12] [13] He went on to show that protein S-nitrosylation is a widespread mechanism for NO bioactivity to be carried by proteins, including by hemoglobin itself; [14] [1] that is, NO in the form of a nitrosyl group is a cellular signal that acts through post-translational modification of target proteins, akin to protein phosphorylation or ubiquitination. [15] In addition to proteins, Stamler demonstrated that low molecular weight metabolic thiols (e.g., glutathione, coenzyme A) also can be S-nitrosylated, and that these molecules can act as carriers of NO bioactivity. [16] Whereas it was initially assumed by many researchers that NO operated under principles of redox biology where NO modified thiols randomly (as do reactive oxygen species), Stamler demonstrated that there exist specific enzymes to convert NO to the nitrosyl state (S-nitrosyl synthases), to transfer S-nitrosyl groups to specific residues in proteins (transnitrosylases), and to remove specific S-nitrosyl groups (S-nitrosyl reductases). [16][17]

Stamler’s studies have identified several specific physiological and pathophysiological roles for protein S-nitrosylation and its regulation, demonstrating that S-nitrosyl NO bioactivity accounts for many physiological actions originally attributed to NO gas, as well mediating previously unknown actions.

His work has established that hemoglobin in red blood cells not only carries oxygen and carbon dioxide to support cellular respiration, but also carries NO as an S-nitrosothiol that is critical for autoregulation of blood flow through tissue microcapillaries, establishing the circulatory system as a 3-gas system where oxygen delivery to tissue by hemoglobin (acting as a S-nitrosyl synthase and nitrosyltransferase) is linked to oxygen-dependent R- and T-state conformational changes of hemoglobin to load NO on Cysteine 93 of beta-globin in high oxygen and to deliver S-nitrosothiol bioactivity to tissues in low oxygen. [14]

[18] [19] [1] [2] [3] [20] The ability of hemoglobin to undergo conformation-dependent S-nitrosylation is impaired in red blood cells from sickle cell disease patients, impairing blood microcirculation and tissue oxygen delivery beyond that caused by red blood cell sickling. [21] [22] Since hemoglobin S-nitrosylation is rapidly lost upon blood storage, the lack of S-nitrosylation within stored red blood cells limits the effective oxygen delivery capability of transfused blood, which can be improved by treating stored red blood cells to replace lost S-nitrosyl groups. [23] [24] [25]

Examining the hemoglobin of the parasitic worm Ascaris, Stamler found that this ancient form of hemoglobin utilizes NO to eliminate oxygen from its anaerobic environment. [26] [27] Physiological studies have shown that S-nitrosylation of specific proteins is important during diseases including asthma, [28] [29] heart failure, [30] [31] and acute kidney injury. [32] [33]

References

1. ^1 2 {{cite news |last=Blakeslee |first=Sandra |date=1996-03-21 |title= Surprise Discovery in Blood: Hemoglobin Has Bigger Role |url=https://www.nytimes.com/1996/03/21/us/surprise-discovery-in-blood-hemoglobin-has-bigger-role.html |dead-url= |work= |location= |website= www.nytimes.com |publisher=New York Times |archive-url= |archive-date= |access-date=2019-01-11}}
2. ^1 {{cite news |last=Blakeslee |first=Sandra |date=1997-07-22 |title= What Controls Blood Flow? Blood |url=https://www.nytimes.com/1997/07/22/science/what-controls-blood-flow-blood.html |dead-url= |work= |location= |website=www.nytimes.com |publisher=New York Times |archive-url= |archive-date= |access-date=2019-01-11}}
3. ^1 {{cite news |last=Saunders |first=Fenella |date=1997-01-01 |title=The NO & SNO Cycle |url= http://discovermagazine.com/1997/jan/thenosnocycle981 |dead-url= |work= |location= |website=www.discovermagazine.com |publisher=Kalmbach Media |archive-url= |archive-date= |access-date=2019-01-11}}
4. ^1 2 3 4 5 6 7 8 {{ cite |url=https://www.uhhospitals.org/-/media/Files/HDI/Harrington-Investigators/stamler-cv-full-july-2018.pdf |title= Jonathan Stamler curriculum vitae |accessdate=2019-01-11}}
5. ^{{cite web |url= https://www.hhmi.org/scientists/jonathan-s-stamler |title=Jonathan S. Stamler |author= |date= |website=www.hhmi.org/ |publisher=Howard Hughes Medical Institute |access-date=2019-01-11 |quote=}}
6. ^{{cite web |url=http://blog.case.edu/case-news/2009/09/17/jonathanstamler |title=”Director of Institute for Transformative Molecular Medicine, Inaugural Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation Announced” |author= |date=2009-09-17 |website=www.case.edu |publisher=Case Western Reserve University |access-date=2019-01-11 |quote=}}
7. ^{{cite web |url= https://www.cleveland.com/healthfit/index.ssf/2012/02/jonathan_stamler_named_directo.html |title=Jonathan Stamler named director, Bob Keith to head drug development of Harrington project |last=Zeitner |first=Brie |date=2012-02-29 |website=www.cleveland.com |publisher=Cleveland.com |access-date= |quote=}}
8. ^{{cite news |last=Rosenblum |first=Jonah |date=2016-02-11 |title=”Stamler gains ‘genius’ tag as Harrington Discovery Institute director” |url=https://www.clevelandjewishnews.com/features/health/stamler-gains-genius-tag-as-harrington-discovery-institute-director/article_5a6b60c6-d0e2-11e5-a1c1-5fd5ac712f22.html |dead-url= |website=www.clevelandjewishnews.com |publisher=Cleveland Jewish Publication Company |work= |location= |archive-url= |archive-date= |access-date=2019-01-11 }}
9. ^{{cite web |url= https://www.nobelprize.org/prizes/medicine/1998/7543-the-nobel-prize-in-physiology-or-medicine-1998 |title=1998 Nobel Prize in Medicine or Physiology |author= |date= |website=www.nobelprize.org |publisher=Nobel Media |access-date=2019-01-11 |quote=}}
10. ^1 {{cite journal |last1=Murad |first1=Ferid |date=1994 |title= The nitric oxide-cyclic GMP signal transduction system for intracellular and intercellular communication. |url= https://www.ncbi.nlm.nih.gov/pubmed/7511827 |journal= Recent Prog Horm Res |volume= 49|issue= |pages=239-248 |doi= |access-date=2019-01-11}}
11. ^{{cite journal |last1=Garg |first1=UC |last2=Hasid |first2=A |date=August 1990 |title=Nitric oxide-generating vasodilators inhibit mitogenesis and proliferation of BALB/C 3T3 fibroblasts by a cyclic GMP-independent mechanism |url=https://www.ncbi.nlm.nih.gov/pubmed/1697465 |journal=Biochem Biophys Res Commun |volume=171 |issue=1 |pages=474-479 |doi= |access-date=2019-01-11 }}
12. ^{{cite journal |last1=Stamler |first1=JS |last2=Simon |first2=DI |last3=Osborne |first3=JA |last4=Mullins |first4=ME |last5=Jaraki |first5=O |last6=Michel |first6=T |last7=Singel |first7=DJ |last8=Loscalzo |first8=J |date=1992-01-01 |title=S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds |url=https://www.ncbi.nlm.nih.gov/pubmed/1346070 |journal=Proc Natl Acad Sci U S A |volume=89 |issue=1 |pages=4444-448 |doi= |access-date=2019-01-11 }}
13. ^{{cite journal |last1=Stamler |first1=JS |last2=Simon |first2=DI |last3=Jaraki |first3=O |last4=Osborne |first4=JA |last5=Francis |first5=S |last6=Mullins |first6=M |last7=Singel |first7=D |last8=Loscalzo |first8=J |date=1992-09-01 |title=S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme |url=https://www.ncbi.nlm.nih.gov/pubmed/1325644 |journal=Proc Natl Acad Sci U S A |volume=89 |issue=17 |pages=8087-8091 |doi= |access-date=2019-01-11 }}
14. ^1 {{cite journal |last1=Jia |first1=L |last2=Bonaventura |first2=C |last3=Bonaventura |first3=J |last4=Stamler |first4=JS |date=1996-03-21 |title=S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control |url= https://www.ncbi.nlm.nih.gov/pubmed/8637569 |journal=Nature |volume=380 |issue=6571 |pages=221-226 |doi=10.1038/380221a0 |access-date=2019-01-11 }}
15. ^{{cite journal |last1=Hess |first1=DT |last2=Stamler |first2=JS |date=2012-02-10 |title=Regulation by S-nitrosylation of protein post-translational modification |url= https://www.ncbi.nlm.nih.gov/pubmed/22147701 |journal= J Biol Chem |volume=287 |issue=7 |pages=4411-4418 |doi=10.1074/jbc.R111.285742 |access-date=2019-01-11 }}
16. ^1 {{cite journal |last1=Benhar |first1=M |last2=Forrester |first2=MT |last3=Stamler |first3=JS |date=October 2009 |title=Protein denitrosylation: enzymatic mechanisms and cellular function |url= https://www.ncbi.nlm.nih.gov/pubmed/19738628 |journal= Nat Rev Mol Cell Biol |volume=10 |issue=10 |pages=721-732 |doi=10.1038/nrm2764 |access-date=2019-01-11 }}
17. ^{{cite news |author= |date=2018-01-19 |title=New Nitric Oxide-Converting Enzymes Discovered |url=https://www.genengnews.com/news/new-nitric-oxide-converting-enzymes-discovered/ |dead-url= |work= |location= |website=www.genengnews.com |publisher=Mary Ann Liebert Inc |archive-url= |archive-date= |access-date= }}
18. ^{{cite journal |last1=Stamler |first1=JS |last2=Jia |first2=L |last3=Eu |first3=JP |last4=McMahon |first4=TJ |last5=Demchenko |first5=IT |last6=Bonaventura |first6=J |last7=Gernert |first7=K |last8= Piantadosi |first8=CA |date=1997-06-27 |title= Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient |url=https://www.ncbi.nlm.nih.gov/pubmed/9197264 |journal=Science |volume=276 |issue=5321 |pages=2034-2037 |doi= |access-date=2019-01-11 }}
19. ^{{cite journal |last1=Zhang |first1=R |last2=Hess |first2=DT |last3=Qian |first3=Z |last4=Hausladen |first4=A |last5=Fonseca |first5=F |last6=Chaube |first6=R |last7=Reynolds |first7= JD|last8=Stamler |first8=JS |date=2015-05-19 |title= Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia |url= https://www.ncbi.nlm.nih.gov/pubmed/25810253 |journal= Proc Natl Acad Sci U S A |volume=112 |issue=20 |pages=6425-6430 |doi=10.1073/pnas.1502285112 |access-date=2019-01-11}}
20. ^{{cite news |last=Paddock |first=Catherine |date=2015-04-13 |title=Study shows blood cells need nitric oxide to deliver oxygen |url= https://www.medicalnewstoday.com/articles/292292.php |dead-url= |work= |location= |website=www.medicalnewstoday.com |publisher=Healthline Media UK |archive-url= |archive-date= |access-date=2019-01-11}}
21. ^{{cite journal |last1=Pawloski |first1=JR |last2=Hess |first2=DT |last3=Stamler |first3=JS |date=2005-02-15 |title=Impaired vasodilation by red blood cells in sickle cell disease |url= https://www.ncbi.nlm.nih.gov/pubmed/15699345 |journal=Proc Natl Acad Sci U S A |volume=102 |issue=7 |pages=2531-2536 |doi= |access-date=2019-01-11 }}
22. ^{{cite news |last=Leary |first=Warren E |date=1996-04-23 |title=Findings Intrigue Sickle Cell Experts |url=https://www.nytimes.com/1996/04/23/science/findings-intrigue-sickle-cell-experts.html |dead-url= |work= |location= |website=www.nytimes.com |publisher=New York Times |archive-url= |archive-date= |access-date=2019-01-11 }}
23. ^{{cite journal |last1=Reynolds |first1=JD |last2=Ahearn |first2=GS |last3=Angelo |first3=M |last4=Zhang |first4=J |last5=Cobb |first5=F |last6=Stamler |first6=JS |date= October 2007 |title=S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood |url=https://www.ncbi.nlm.nih.gov/pubmed/17940022 |journal=Proc Natl Acad Sci U S A |volume=104 |issue=43 |pages=17058-17062 |doi=10.1073/pnas.0707958104 |access-date=2019-01-11 }}
24. ^{{cite journal |last1=Reynolds |first1=JD |last2=Bennett |first2=KM |last3=Cina |first3=AJ |last4=Diesen |first4=DL |last5=Henderson |first5=MB |last6=Matto |first6=F |last7=Plante |first7=A |last8=Williamson |first8=RA |last9=Zandinejad |first9=K |last10=Demchenko |first10=IT |last11=Hess |first11=DT |last12=Piantadosi |first12=CA |last13=Stamler |first13=JS |date=2013-07-09 |title=S-nitrosylation therapy to improve oxygen delivery of banked blood |url=https://www.ncbi.nlm.nih.gov/pubmed/23798386 |journal=Proc Natl Acad Sci U S A |volume=110 |issue=28 |pages=11529-11534 |doi=10.1073/pnas.130648911 |access-date=2019-01-11 }}
25. ^{{cite news |last=Park |first=Alice |date=2007-10-08 |title=Why Banked Blood Goes Bad |url=http://content.time.com/time/health/article/0,8599,1669438,00.htm |dead-url= |work= |location= |website=www.time.com |publisher=TIME Media |archive-url= |archive-date= |access-date=2019-01-11 }}
26. ^{{cite journal |last1=Minning |first1=DM |last2=Gow |first2=AJ |last3=Bonaventura |first3=J |last4=Braun|first4=R |last5=Dewhirst |first5=M |last6=Goldberg |first6=DE |last7=Stamler |first7=JS |date=1999-09-30 |title=Ascaris haemoglobin is a nitric oxide-activated 'deoxygenase' |url= https://www.ncbi.nlm.nih.gov/pubmed/10519555 |journal=Nature |volume=401 |issue=6752 |pages=497-502 |doi=10.1038/46822 |access-date=2019-01-11 }}
27. ^{{cite news |last=Blakeslee |first=Sandra |date=1999-10-05 |title=Thanks to a 'Horrible Worm,' New Ideas on Hemoglobin |url=https://archive.nytimes.com/www.nytimes.com/library/national/science/100599sci-hemoglobin.html |dead-url= |work= |location= |website=www.nytimes.com |publisher=New York Times |archive-url= |archive-date= |access-date=2019-01-11 }}
28. ^{{cite journal |last1=Gaston |first1=B |last2=Sears |first2=S |last3=Woods |first3=J |last4=Hunt |first4=J |last5=Ponaman |first5=M |last6=McMahon |first6=T |last7=Stamler |first7=JS |date=1998-05-02 |title=Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure |url= https://www.ncbi.nlm.nih.gov/pubmed/9643794 |journal=Lancet |volume=351 |issue=9112 |pages=1317-1319 |doi=10.1016/S0140-6736(97)07485-0 |access-date=2019-01-11 }}
29. ^{{cite journal |last1=Que |first1=LG |last2=Liu |first2=L |last3=Yan |first3=Y |last4=Whitehead |first4=GS |last5=Gavett |first5=SH |last6= Schwartz|first6=DA |last7=Stamler |first7=JS |date=2005-06-10 |title=Protection from experimental asthma by an endogenous bronchodilator. |url=https://www.ncbi.nlm.nih.gov/pubmed/15919956 |journal=Science |volume=308 |issue=5728 |pages=1618-1621 |doi=10.1126/science.1108228 |access-date=2019-01-11 }}
30. ^{{cite journal |last1=Hayashi |first1=H |last2=Hess |first2=DT |last3=Zhang |first3=R |last4=Sugi |first4=K |last5=Gao |first5=H |last6=Tan |first6=BL |last7=Bowles |first7=DE |last8=Milano |first8=CA |last9=Jain |first9=MK |last10=Koch |first10=WJ |last11=Stamler |first11=JS |date=2018-05-03 |title=S-Nitrosylation of β-Arrestins Biases Receptor Signaling and Confers Ligand Independence |url=https://www.ncbi.nlm.nih.gov/pubmed/29727618 |journal=Mol Cell |volume=70 |issue=3 |pages=473-487 |doi=10.1016/j.molcel.2018.03.034 |access-date=2019-01-11 }}
31. ^{{cite news |author= |date=2018-05-14 |title= Heart disease severity may depend on nitric oxide levels |url=https://www.sciencedaily.com/releases/2018/05/180514132501.htm |dead-url= |work= |location= |website=www.sciencedaily.com |publisher=ScienceDaily |archive-url= |archive-date= |access-date=2019-01-11}}
32. ^{{cite journal |last1=Zhou |first1=HL |last2=Zhang |first2=R |last3=Anand |first3=P |last4=Stomberski |first4=CT |last5=Qian |first5=Z |last6=Hausladen |first6=A |last7=Wang |first7=L |last8=Rhee |first8=EP |last9=Parikh |first9=SM |last10=Karumanchi |first10=SA |last11=Stamler |first11=JS |date=2019-01-10 |title= Metabolic reprogramming by the S-nitroso-CoA reductase system protects against kidney injury |url= https://www.ncbi.nlm.nih.gov/pubmed/30487609 |journal=Nature |volume=565 |issue=7737 |pages=96-100 |doi=10.1038/s41586-018-0749-z |access-date=2019-01-11}}
33. ^{{cite news |author= |date=2018-11-28 |title=Re-programming the body's energy pathway boosts kidney self-repair |url=https://medicalxpress.com/news/2018-11-re-programming-body-energy-pathway-boosts.html |dead-url= |work= |location= |website=medicalexpress.com |publisher=Science X |archive-url= |archive-date= |access-date=2019-01-11 }}

External links

[https://www.uhhospitals.org/harrington-discovery-institute/harrington-investigators/jonathan-stamler Stamler lab website]

[https://www.uhhospitals.org/harrington-discovery-institute/about-us/team/jonathan-s-stamler-md Harrington Discovery Institute website]

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