果冻影院

果冻影院
果冻影院 果冻影院
Research Group Lab Hall
Pharmacology and Toxicology
John Baker, PhD

John E. Baker, PhD

Professor, Surgery (Pediatrics); Secondary Faculty

Locations

  • Biochemistry
    MFRC 4051

Contact Information

General Interests

Surgery/Cardiothoracic/Research

Education

PhD, Cardiac Biochemistry, 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 果冻影院 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

My research is focused on 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. Chronic hypoxia from birth results in erythropoiesis as manifest by an increase in hemoglobin and hematocrit. Erythropoietin activates protein kinase signaling pathways and can increase resistance to cerebral ischemia. Recently erythropoietin has been observed to increase resistance of the heart to regional ischemia in vivo. However the signal transduction pathway involved and the end effectors mediating cardioprotection were not examined. The role of erythropoietin in conferring immediate cardioprotection in the setting of cardiac surgery in children, where the heart is subjected to global ischemia, is unknown. John E. Baker, PhD, research interestTo determine a possible role for erythropoietin in cardioprotection during surgical ischemia and the underlying mechanisms we treated infant rabbit hearts with human recombinant erythropoietin prior to ischemia. The objectives of our study were to determine whether exposure of the heart to erythropoietin would immediately increase its resistance to subsequent ischemia, the erythropoietin concentration that confers optimal protection of the heart, the involvement and cellular location of protein kinase signaling pathways, and the role of potassium channels and nitric oxide synthase in mediating cardioprotection. Our study shows that erythropoietin exerts a concentration-and time-dependent cardioprotective effect. The mechanisms underlying erythropoietin-induced cardioprotection involves activation of PKC-epsilon, p38 MAP kinase and p42/44 MAP kinase with increased resistance to myocardial ischemia mediated by potassium channels but not by nitric oxide synthase. The optimal concentration of 1.0 U/ml needed to confer protection against cardiac ischemia is approximately 100 times above levels present during chronic hypoxia and 500 times above erythropoietin levels present in the circulation of normoxic rabbits. Increased resistance to myocardial ischemia is observed immediately after treatment with erythropoietin, indicating that induction of new genes is not necessary for its cardioprotective effect to be manifested. We believe our study is the first to demonstrate the biological effects of erythropoietin are mediated by a signal pathway that results in immediate activation of two potassium channels, the KATP and the KCa channel. These studies prompted us to hypothesize that erythropoietin would also be able to protect the infant human heart against injury during surgical repair of congenital heart disease. We plan to conduct a clinical trial to test this hypothesis in the setting of the cardiac operating room at Children's Wisconsin.

Publications

  • (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

  • (Lam V, Su J, Hsu A, Gross GJ, Salzman NH, Baker JE.) PLoS One. 2016;11(8):e0160840 PMID: 27505423 PMCID: PMC4978455 SCOPUS ID: 2-s2.0-84983638440 08/10/2016

Publications of from the