皇家华人

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Research Collaborate Lab Bench
Biochemistry
John E. Baker

John E. Baker, PhD

Professor

Locations

  • Biochemistry
    MFRC 4051

Contact Information

Education

PhD, University of London, 1984

Biography

Dr. Baker received his PhD degree in Biochemistry from the University of London in 1984 for studies on the mechanisms underlying the calcium paradox in the rat heart. Dr. Baker's postdoctoral training was carried out in Cardiothoracic Surgery at the 皇家华人 where in 1987 he joined the faculty. In 1992, Dr. Baker was appointed as a secondary faculty member in the Department of Biochemistry.

Research Experience

  • Cardiovascular Agents
  • Cardiovascular Diseases
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System
  • Microbiota
  • radiation effects
  • Radiation Effects
  • Radiation Genetics
  • Radiation Injuries
  • Radiation Injuries, Experimental
  • Radiation Tolerance
  • Radiation, Ionizing

Clinical Expertise

  • Clinical Trial
  • Clinical Trials, Phase II as Topic
  • Drugs, Investigational

Leadership Positions

  • Chair, Institutional Animal Care and Use Committee

Research Interests

The overall objective of my research program is to understand the mechanisms by which adaptation of the heart to chronic hypoxia increases resistance to subsequent ischemia. Many children undergoing cardiac surgery in the first year of life exhibit varying degrees of cyanotic heart disease where the myocardium is chronically perfused with hypoxic blood. Understanding the mechanisms by which cyanotic congenital heart disease modifies the myocardium and how that modification impacts on protective mechanics during ischemia may provide insight into developing treatments for limiting myocardial damage during surgery.

To investigate the effects of chronic hypoxia on myocardial function and the signal transduction mechanism responsible for subsequent cardioprotection, we have developed an animal model in which rabbits are raised in a hypoxic environment from birth. This model of chronic hypoxia simulates the essential characteristics of cyanotic heart disease and has been used to demonstrate that hypoxia from birth increases tolerance of the heart to ischemia.

Chronic hypoxia from birth increases the release of nitrite plus nitrate, the concentration of cGMP and the activity of a constitutive NOS isozyme in neonatal rabbit hearts. More importantly, increased NOS activity and nitric oxide production are essential for increasing resistance of the heart to global ischemia. The mechanisms by which chronic hypoxia increases NOS activity in hearts however, remain unknown. We have shown that chronic hypoxia induces major changes in NOS3 and caveolin-3 that may explain, in part, why chronic hypoxia increases resistance to subsequent ischemia. First, chronic hypoxia increases NOS3 protein without altering steady state message levels for any of the three NOS isoforms. Analysis and comparison of the autoradiogram of protected-fragment bands in ribonuclease protection assays demonstrate that NOS3 is the most abundant transcript of the three NOS isozymes. Second, chronic hypoxia decreases the amount of caveolin-3 in heart homogenates as well as the amount of caveolin-3 that can be co-precipitated with NOS3. Third, chronic hypoxia induces maximal increases in the biological nitric oxide index during perfusion that can not be enhanced further by perfusion with the nitric oxide donor, GSNO. These changes are consistent with the idea that nitric oxide increases resistance to global ischemia and that chronic hypoxia induces maximal NOS3 activity to increase resistance.

Chronic hypoxia from birth increases current through the sarcolemmal KATP channel and results in increased NO production from NOS3 in sarcolemmal caveolae. The relationship between NO and the KATP channel in normoxic and chronically hypoxic hearts however, remains unknown. We have shown that (i) intracellular NO, released from GSNO and NO released from spermine NONOate, in normoxic hearts and native NO, from increased nitric oxide synthase activity, in chronically hypoxic hearts, activates the sarcolemmal KATP channel, resulting in hyperpolarization and shortening of action potential duration (ii) activation of the KATP channel by NO in both normoxic and chronically hypoxic hearts occurs by a cGMP dependent mechanism and (iii) NO is released from GSNO in the intracellular environment.

Publications

  • (Raber J, Chaudhari M, De la Torre A, Holden S, Kessler K, Glaeser B, Lenarczyk M, Leonard SW, Borg A, Kwok A, Patel C, Kronenberg A, Olsen CM, Willey JS, Morré J, Choi J, Stevens JF, Bobe G, Minnier J, Baker J.) Front Physiol. 2024;15:1486767 PMID: 39605860 PMCID: PMC11598337 SCOPUS ID: 2-s2.0-85210519824 11/28/2024

  • (Lenarczyk M, Alsheikh AJ, Cohen EP, Schaue D, Kronenberg A, Geurts A, Klawikowski S, Mattson D, Baker JE.) Toxics. 2023 Feb 16;11(2) PMID: 36851074 PMCID: PMC9959763 SCOPUS ID: 2-s2.0-85149176377 03/01/2023

  • (Raber J, Holden S, Kessler K, Glaeser B, McQuesten C, Chaudhari M, Stenzel F, Lenarczyk M, Leonard SW, Morré J, Choi J, Kronenberg A, Borg A, Kwok A, Stevens JF, Olsen C, Willey JS, Bobe G, Minnier J, Baker JE.) Front Physiol. 2023;14:1316186 PMID: 38260101 PMCID: PMC10800373 01/23/2024

  • (Lenarczyk M, Kronenberg A, Mäder M, Komorowski R, Hopewell JW, Baker JE.) PLoS One. 2023;18(4):e0283877 PMID: 37099482 PMCID: PMC10132632 SCOPUS ID: 2-s2.0-85153985230 04/26/2023

  • (Ibrahim EH, Sosa A, Brown SA, An D, Klawikowski S, Baker J, Bergom C.) Tomography. 2022 Dec 22;9(1):36-49 PMID: 36648991 PMCID: PMC9844312 SCOPUS ID: 2-s2.0-85146484422 01/18/2023

  • (Lenarczyk M, Alsheikh AJ, Cohen EP, Schaue D, Kronenberg A, Geurts A, Klawikowski S, Mattson D, Baker JE.) Toxics. 2022 Dec 18;10(12) PMID: 36548630 PMCID: PMC9783591 12/23/2022

  • (Aufderheide TP, Engel TW 2nd, Saleh HO, Gutterman DD, Weston BW, Pepe PE, Baker JE, Labinski J, Debaty G, Tang L, Szabo A, Kalra R, Yannopoulos D, Colella MR.) Resuscitation. 2021 Dec;169:45-52 PMID: 34666124 SCOPUS ID: 2-s2.0-85118490179 10/20/2021

  • (Raber J, Holden S, Sudhakar R, Hall R, Glaeser B, Lenarczyk M, Rockwell K, Nawarawong N, Sterrett J, Perez R, Leonard SW, Morré J, Choi J, Kronenberg A, Borg A, Kwok A, Stevens JF, Olsen CM, Willey JS, Bobe G, Baker J.) Front Physiol. 2021;12:746509 PMID: 34646164 PMCID: PMC8503608 SCOPUS ID: 2-s2.0-85116920048 10/15/2021

  • (Borg AM, Baker JE.) Synth Biol (Oxf). 2021;6(1):ysab023 PMID: 34522784 PMCID: PMC8434797 09/16/2021

  • (Lenarczyk M, Laiakis EC, Mattson DL, Johnson BD, Kronenberg A, North PE, Komorowski R, Mäder M, Baker JE.) FASEB Bioadv. 2020 Dec;2(12):705-719 PMID: 33336158 PMCID: PMC7734425 12/19/2020

  • (Lenarczyk M, Kronenberg A, Mäder M, North PE, Komorowski R, Cheng Q, Little MP, Chiang IH, LaTessa C, Jardine J, Baker JE.) Radiat Res. 2019 Jul;192(1):63-74 PMID: 31095446 PMCID: PMC10654917 SCOPUS ID: 2-s2.0-85068362644 05/17/2019

  • (Malik M, Suboc TM, Tyagi S, Salzman N, Wang J, Ying R, Tanner MJ, Kakarla M, Baker JE, Widlansky ME.) Circ Res. 2018 Oct 12;123(9):1091-1102 PMID: 30355158 PMCID: PMC6205737 SCOPUS ID: 2-s2.0-85055600525 10/26/2018

Publications of from the

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