Anthony Baker, PhD

Professor

Anthony J. Baker, Ph.D. has a longstanding interest in the cellular and molecular mechanisms that regulate cardiac muscle contraction in health and disease. We use multiple approaches to monitor cardiac function in experimental preparations that span a range of complexity from contraction of myofilaments in-vitro, intact single cells, electrically stimulated intact cardiac muscle, intact hearts in-vitro, and intact hearts in-vivo. A major goal is to investigate new therapies to treat heart failure.

Heart failure is a leading cause of death and disability and new therapies are needed to treat this devastating disease. Research in the Baker lab focuses on both of the major pumping chambers of the heart, the left ventricle (LV) and right ventricle (RV).

We are investigating the mechanisms causing failure of the LV subsequent to a heart attack, where blood flow stops to a region of the heart resulting in death of muscle cells in that region, termed a myocardial infarction (MI). We are studying the weakened border-zone immediately adjacent to the MI. We are investigating the mechanisms that cause gradual enlargement of this weakened border-zone, ultimately leading to dilation of the heart and LV failure. We are investigating treatments to stabilize the border-zone to slow or halt the progression to heart failure after MI.

We are also investigating the mechanisms involved in failure of the RV. RV failure is relatively understudied and poorly understood. It has been assumed that an understanding of RV failure can be extrapolated from studies of LV failure. In contrast, we have found that the RV has distinctive properties compared to the LV, and the regulation of RV contraction in heart failure differs compared to the failing LV, suggesting that treatment strategies for the failing RV should be tailored to the distinctive biology of the RV.

Education
1986 - Biophysics, University of California, San Francisco
PhD, 1984 - Physiology, University of Bristol
BA, 1979 - Biology, University of York
Publications
  1. Izu L, Shimkunas R, Jian Z, Hegyi B, Kazemi-Lari M, Baker A, Shaw J, Banyasz T, Chen-Izu Y. Emergence of Mechano-Sensitive Contraction Autoregulation in Cardiomyocytes. 2021. PMID: 34072584


  2. Shimkunas R, Hegyi B, Jian Z, Shaw JA, Kazemi-Lari MA, Mitra D, Leach JK, Li X, Jaradeh M, Balardi N, Chen YJ, Escobar AL, Baker AJ, Bossuyt J, Banyasz T, Chiamvimonvat N, Lam KS, Bers DM, Izu LT, Chen-Izu Y. Mechanical Load Regulates Excitation-Ca2+ Signaling-Contraction in Cardiomyocyte. 2021. PMID: 33601939


  3. Spaulding KA, Zhu Y, Takaba K, Ramasubramanian A, Badathala A, Haraldsson H, Collins A, Aguayo E, Shah C, Wallace AW, Ziats NP, Lovett DH, Baker AJ, Healy KE, Ratcliffe MB. Myocardial injection of a thermoresponsive hydrogel with reactive oxygen species scavenger properties improves border zone contractility. 2020. PMID: 32270584


  4. Myagmar BE, Ismaili T, Swigart P, Raghunathan A, Baker AJ, Sahdeo S, Blevitt JM, Milla ME, Simpson PC. Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist. 2019. PMID: 31426700


  5. Cowley PM, Wang G, Swigart PM, Raghunathan A, Reddy NP, Dulam P, Lovett DH, Simpson PC, Baker AJ. Reversal of Right Ventricular failure by Chronic α1A-Subtype Adrenergic Agonist Therapy. 2018. PMID: 30412439


  6. Janssen PML, Canan BD, Kilic A, Whitson BA, Baker AJ. Human Myocardium Has a Robust a1A-Subtype Adrenergic Receptor Inotropic Response. 2018. PMID: 29923888


  7. Pewowaruk RJ, Philip JL, Tewari SG, Chen CS, Nyaeme MS, Wang Z, Tabima DM, Baker AJ, Beard DA, Chesler NC. Multiscale Computational Analysis of Right Ventricular Mechanoenergetics. 2018. PMID: 30003251


  8. Spaulding K, Takaba K, Collins A, Faraji F, Wang G, Aguayo E, Ge L, Saloner D, Wallace AW, Baker AJ, Lovett DH, Ratcliffe MB. Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. 2018. PMID: 29432443


  9. Cowley PM, Wang G, Joshi S, Swigart PM, Lovett DH, Simpson PC, Baker AJ. a1A-Subtype adrenergic agonist therapy for the failing right ventricle. 2017. PMID: 28822963


  10. Baligand C, Qin H, True-Yasaki A, Gordon JW, von Morze C, Santos JD, Wilson DM, Raffai R, Cowley PM, Baker AJ, Kurhanewicz J, Lovett DH, Wang ZJ. Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model. 2017. PMID: 28708304


  11. Ceron CS, Baligand C, Joshi S, Wanga S, Cowley PM, Walker JP, Song SH, Mahimkar R, Baker AJ, Raffai RL, Wang ZJ, Lovett DH. An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury. 2017. PMID: 28331061


  12. Myagmar BE, Flynn JM, Cowley PM, Swigart PM, Montgomery MD, Thai K, Nair D, Gupta R, Deng DX, Hosoda C, Melov S, Baker AJ, Simpson PC. Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent. 2017. PMID: 28219977


  13. Thomas RC, Cowley PM, Singh A, Myagmar BE, Swigart PM, Baker AJ, Simpson PC. The Alpha-1A Adrenergic Receptor in the Rabbit Heart. 2016. PMID: 27258143


  14. Thomas RC, Singh A, Cowley P, Myagmar BE, Montgomery MD, Swigart PM, De Marco T, Baker AJ, Simpson PC. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart. 2016. PMID: 27453955


  15. Cowley PM, Wang G, Chang AN, Makwana O, Swigart PM, Lovett DH, Stull JT, Simpson PC, Baker AJ. The a1A-adrenergic receptor subtype mediates increased contraction of failing right ventricular myocardium. 2015. PMID: 26116709


  16. Chang AN, Battiprolu PK, Cowley PM, Chen G, Gerard RD, Pinto JR, Hill JA, Baker AJ, Kamm KE, Stull JT. Constitutive phosphorylation of cardiac myosin regulatory light chain in vivo. 2015. PMID: 25733667


  17. Shimkunas R, Makwana O, Spaulding K, Bazargan M, Khazalpour M, Takaba K, Soleimani M, Myagmar BE, Lovett DH, Simpson PC, Ratcliffe MB, Baker AJ. Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone. 2014. PMID: 25128171


  18. Lovett DH, Mahimkar R, Raffai RL, Cape L, Zhu BQ, Jin ZQ, Baker AJ, Karliner JS. N-terminal truncated intracellular matrix metalloproteinase-2 induces cardiomyocyte hypertrophy, inflammation and systolic heart failure. 2013. PMID: 23874529


  19. Shimkunas R, Zhang Z, Wenk JF, Soleimani M, Khazalpour M, Acevedo-Bolton G, Wang G, Saloner D, Mishra R, Wallace AW, Ge L, Baker AJ, Guccione JM, Ratcliffe MB. Left ventricular myocardial contractility is depressed in the borderzone after posterolateral myocardial infarction. 2013. PMID: 23523189


  20. Chu C, Thai K, Park KW, Wang P, Makwana O, Lovett DH, Simpson PC, Baker AJ. Intraventricular and interventricular cellular heterogeneity of inotropic responses to a(1)-adrenergic stimulation. 2013. PMID: 23355341


  21. Zhang Z, Sun K, Saloner DA, Wallace AW, Ge L, Baker AJ, Guccione JM, Ratcliffe MB. The benefit of enhanced contractility in the infarct borderzone: a virtual experiment. 2012. PMID: 22509168


  22. Oishi PE, Cholsiripunlert S, Gong W, Baker AJ, Bernstein HS. Myo-mechanical analysis of isolated skeletal muscle. 2011. PMID: 21403622


  23. Yeh CC, Li H, Malhotra D, Turcato S, Nicholas S, Tu R, Zhu BQ, Cha J, Swigart PM, Myagmar BE, Baker AJ, Simpson PC, Mann MJ. Distinctive ERK and p38 signaling in remote and infarcted myocardium during post-MI remodeling in the mouse. 2010. PMID: 20186881


  24. Wang GY, Yeh CC, Jensen BC, Mann MJ, Simpson PC, Baker AJ. Heart failure switches the RV alpha1-adrenergic inotropic response from negative to positive. 2009. PMID: 20035030


  25. Sun K, Stander N, Jhun CS, Zhang Z, Suzuki T, Wang GY, Saeed M, Wallace AW, Tseng EE, Baker AJ, Saloner D, Einstein DR, Ratcliffe MB, Guccione JM. A computationally efficient formal optimization of regional myocardial contractility in a sheep with left ventricular aneurysm. 2009. PMID: 20016753


  26. McCloskey DT, Turcato S, Wang GY, Turnbull L, Zhu BQ, Bambino T, Nguyen AP, Lovett DH, Nissenson RA, Karliner JS, Baker AJ. Expression of a Gi-coupled receptor in the heart causes impaired Ca2+ handling, myofilament injury, and dilated cardiomyopathy. 2007. PMID: 17965283


  27. Zhou HZ, Ma X, Gray MO, Zhu BQ, Nguyen AP, Baker AJ, Simonis U, Cecchini G, Lovett DH, Karliner JS. Transgenic MMP-2 expression induces latent cardiac mitochondrial dysfunction. 2007. PMID: 17475219


  28. Wang GY, McCloskey DT, Turcato S, Swigart PM, Simpson PC, Baker AJ. Contrasting inotropic responses to alpha1-adrenergic receptor stimulation in left versus right ventricular myocardium. 2006. PMID: 16731650


  29. O'Connell TD, Swigart PM, Rodrigo MC, Ishizaka S, Joho S, Turnbull L, Tecott LH, Baker AJ, Foster E, Grossman W, Simpson PC. Alpha1-adrenergic receptors prevent a maladaptive cardiac response to pressure overload. 2006. PMID: 16585965


  30. Turcato S, Turnbull L, Wang GY, Honbo N, Simpson PC, Karliner JS, Baker AJ. Ischemic preconditioning depends on age and gender. 2006. PMID: 16450074


  31. Turnbull L, Zhou HZ, Swigart PM, Turcato S, Karliner JS, Conklin BR, Simpson PC, Baker AJ. Sustained preconditioning induced by cardiac transgenesis with the tetracycline transactivator. 2005. PMID: 16243914


  32. Wang GY, Bergman MR, Nguyen AP, Turcato S, Swigart PM, Rodrigo MC, Simpson PC, Karliner JS, Lovett DH, Baker AJ. Cardiac transgenic matrix metalloproteinase-2 expression directly induces impaired contractility. 2005. PMID: 16183043


  33. McCloskey DT, Turnbull L, Swigart PM, Zambon AC, Turcato S, Joho S, Grossman W, Conklin BR, Simpson PC, Baker AJ. Cardiac transgenesis with the tetracycline transactivator changes myocardial function and gene expression. 2005. PMID: 15797971


  34. McCloskey DT, Turnbull L, Swigart P, O'Connell TD, Simpson PC, Baker AJ. Abnormal myocardial contraction in alpha(1A)- and alpha(1B)-adrenoceptor double-knockout mice. 2003. PMID: 14519431


  35. Turnbull L, McCloskey DT, O'Connell TD, Simpson PC, Baker AJ. Alpha 1-adrenergic receptor responses in alpha 1AB-AR knockout mouse hearts suggest the presence of alpha 1D-AR. 2002. PMID: 12595294


  36. McCloskey DT, Rokosh DG, O'Connell TD, Keung EC, Simpson PC, Baker AJ. Alpha(1)-adrenoceptor subtypes mediate negative inotropy in myocardium from alpha(1A/C)-knockout and wild type mice. 2002. PMID: 12234770


  37. Baker AJ, Redfern CH, Harwood MD, Simpson PC, Conklin BR. Abnormal contraction caused by expression of G(i)-coupled receptor in transgenic model of dilated cardiomyopathy. 2001. PMID: 11247776


  38. Redfern CH, Degtyarev MY, Kwa AT, Salomonis N, Cotte N, Nanevicz T, Fidelman N, Desai K, Vranizan K, Lee EK, Coward P, Shah N, Warrington JA, Fishman GI, Bernstein D, Baker AJ, Conklin BR. Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. 2000. PMID: 10781088


  39. Halow JM, Figueredo VM, Shames DM, Camacho SA, Baker AJ. Role of slowed Ca(2+) transient decline in slowed relaxation during myocardial ischemia. 1999. PMID: 10471357


  40. Baker AJ, Figueredo VM, Keung EC, Camacho SA. Ca2+ regulates the kinetics of tension development in intact cardiac muscle. 1998. PMID: 9724275


  41. Shames DM, Baker AJ, Weiner MW, Camacho SA. Ca(2+)-force relationship of frog skeletal muscle: a dynamic model for parameter estimation. 1996. PMID: 8997209


  42. Schreur JH, Figueredo VM, Miyamae M, Shames DM, Baker AJ, Camacho SA. Cytosolic and mitochondrial [Ca2+] in whole hearts using indo-1 acetoxymethyl ester: effects of high extracellular Ca2+. 1996. PMID: 8744296


  43. Zhao L, Pate E, Baker AJ, Cooke R. The myosin catalytic domain does not rotate during the working power stroke. 1995. PMID: 8519999


  44. Baker AJ, Brandes R, Schreur JH, Camacho SA, Weiner MW. Protein and acidosis alter calcium-binding and fluorescence spectra of the calcium indicator indo-1. 1994. PMID: 7819496


  45. Baker AJ, Carson PJ, Miller RG, Weiner MW. Metabolic and nonmetabolic components of fatigue monitored with 31P-NMR. 1994. PMID: 8065387


  46. Baker AJ, Brandes R, Schendel TM, Trocha SD, Miller RG, Weiner MW. Energy use by contractile and noncontractile processes in skeletal muscle estimated by 31P-NMR. 1994. PMID: 8166246


  47. Brandes R, Figueredo VM, Camacho SA, Baker AJ, Weiner MW. Investigation of factors affecting fluorometric quantitation of cytosolic [Ca2+] in perfused hearts. 1993. PMID: 8298028


  48. Brandes R, Figueredo VM, Camacho SA, Baker AJ, Weiner MW. Quantitation of cytosolic [Ca2+] in whole perfused rat hearts using Indo-1 fluorometry. 1993. PMID: 8298027


  49. Baker AJ, Longuemare MC, Brandes R, Weiner MW. Intracellular tetanic calcium signals are reduced in fatigue of whole skeletal muscle. 1993. PMID: 8460665


  50. Gordon L, Levinsohn DG, Borowsky CD, Manojlovic RD, Sessler DI, Weiner MW, Baker AJ. Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study. 1992. PMID: 1429791


  51. Baker AJ, Carson PJ, Green AT, Miller RG, Weiner MW. Influence of human muscle length on energy transduction studied by 31P-NMR. 1992. PMID: 1506363


  52. Miller RG, Carson PJ, Moussavi RS, Green AT, Baker AJ, Weiner MW. Fatigue and myalgia in AIDS patients. 1991. PMID: 1922802


  53. Weiner MW, Moussavi RS, Baker AJ, Boska MD, Miller RG. Constant relationships between force, phosphate concentration, and pH in muscles with differential fatigability. 1990. PMID: 2247239


  54. Baker AJ, Carson PJ, Miller RG, Weiner MW. Investigations of muscle bioenergetics with 31P NMR. 1989. PMID: 2691438