Faculty ProfilesAnthony Baker, PhD
4150 Clement St
San Francisco, CA 94121
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.
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Recent Articles (55)
Cowley PM, Wang GY, Joshi SK, Swigart PM, Lovett DH, Simpson PC, Baker AJ. Î±1A-Subtype Adrenergic Agonist Therapy for Failing Right Ventricle. Am J Physiol Heart Circ Physiol. 2017 Aug 19; ajpheart.00153.2017.
Ceron CS, Baligand C, Joshi SK, 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. Am J Physiol Renal Physiol. 2017 Mar 22; ajprenal.00461.2016.
Myagmar BE, Flynn JM, Cowley PM, Swigart P, Montgomery M, Thai K, Nair DR, Gupta R, 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. Circ Res. 2017 Feb 20.
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. JACC Basic Transl Sci. 2016 Apr; 1(3):155-167.
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. Am J Physiol Heart Circ Physiol. 2015 Sep; 309(5):H888-96.
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. J Biol Chem. 2015 Apr 24; 290(17):10703-16.
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. Am J Physiol Heart Circ Physiol. 2014 Oct 15; 307(8):H1150-8.
O'Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2014; 66(1):308-33.
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. PLoS One. 2013; 8(7):e68154.
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. Ann Thorac Surg. 2013 May; 95(5):1619-25.
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. Am J Physiol Heart Circ Physiol. 2013 Apr 1; 304(7):H946-53.
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. J Cell Biochem. 2010 Apr 15; 109(6):1185-91.
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. Am J Physiol Heart Circ Physiol. 2010 Mar; 298(3):H913-20.
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. J Biomech Eng. 2009 Nov; 131(11):111001.
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. Am J Physiol Heart Circ Physiol. 2008 Jan; 294(1):H205-12.
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. Biochem Biophys Res Commun. 2007 Jun 22; 358(1):189-95.
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. Am J Physiol Heart Circ Physiol. 2006 Oct; 291(4):H2013-7.
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. J Clin Invest. 2006 Apr; 116(4):1005-15.
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. Am J Physiol Heart Circ Physiol. 2006 Mar; 290(3):H1103-9.
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. Cardiovasc Res. 2006 Feb 15; 69(3):688-96.
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. Physiol Genomics. 2005 Jun 16; 22(1):118-26.
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. J Mol Cell Cardiol. 2003 Oct; 35(10):1207-16.
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. Am J Physiol Heart Circ Physiol. 2003 Apr; 284(4):H1104-9.
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. J Mol Cell Cardiol. 2002 Aug; 34(8):1007-17.
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. Am J Physiol Heart Circ Physiol. 2001 Apr; 280(4):H1653-9.
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. Proc Natl Acad Sci U S A. 2000 Apr 25; 97(9):4826-31.
Figueredo VM, Chang KC, Baker AJ, Camacho SA. Chronic alcohol-induced changes in cardiac contractility are not due to changes in the cytosolic Ca2+ transient. Am J Physiol. 1998 Jul; 275(1 Pt 2):H122-30.
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+. Biophys J. 1996 Jun; 70(6):2571-80.
Miller RG, Carson PJ, Moussavi RS, Green A, Baker A, Boska MD, Weiner MW. Factors which influence alterations of phosphates and pH in exercising human skeletal muscle: measurement error, reproducibility, and effects of fasting, carbohydrate loading, and metabolic acidosis. Muscle Nerve. 1995 Jan; 18(1):60-7.
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. Am J Physiol. 1994 Mar; 266(3 Pt 1):C825-31.
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. J Bone Joint Surg Am. 1992 Oct; 74(9):1358-66.
Weiner MW, Moussavi RS, Baker AJ, Boska MD, Miller RG. Constant relationships between force, phosphate concentration, and pH in muscles with differential fatigability. Neurology. 1990 Dec; 40(12):1888-93.