- Investigator, Dalton Cardiovascular Research Center
- PhD: University of South Alabama
- Postdoctoral: University of Rochester, University of Louisville, Cincinnati Children’s Hospital
- Research: The role of mitochondria and programmed necrosis in cardiac disease
- Teaching: Cell Biology
- Office: 323 DCRC
- Email: email@example.com
- Phone: 573-884-8767 (office); 573-882-5052 (lab)
Mitochondrial dysfunction is often an underlying cause of myocardial disease. In particular, cardiac pathologies such as ischemia/reperfusion injury, heart failure, diabetic cardiomyopathy, anti-cancer agent-induced cardiotoxicity, etc., are associated with rapid and dramatic increases in mitochondrial permeability. These changes in permeability lead to ATP depletion, excessive production of reactive oxygen species, and ultimately swelling and rupture of the organelle, thereby instigating a molecular chain of events that leads to cardiomyocyte death. The long-range goal of our lab is to understand how specific mechanisms of mitochondrial-driven death can be targeted for the prevention of myocardial disease.
The mitochondrial permeability transition (MPT) pore, a large, non-specific channel thought to span both mitochondrial membranes, is known to mediate the lethal permeability changes that initiate mitochondrial-driven death. However, with the exception of a protein called cyclophilin-D (CypD), the precise molecular componentry of the MPT pore has still not been defined. In order to identify new putative elements of the MPT pore, we have conducted genomic and proteomic screens of CypD-containing complexes. We are now employing a combinatorial approach that ranges from molecular and biochemical methodologies, through cell culture techniques, to studies in genetically engineered mice to assess the role of each candidate in MPT, cardiomyocyte death, and the pathogenesis of cardiac disease.
In addition, MPT primarily drives necrotic cell death and thus another focus of our lab is studying mechanisms of programmed necrosis. In particular, we are concentrating on the so-called “necroptotic” pathway which is activated by TNF and induces a lethal kinase cascade consisting of RIP1, RIP3, and MLKL. We are examining the mechanisms by which this pathway is regulated and ultimately testing the role of these various components in the progression of cardiac disease. We are also studying how various necrotic pathways such as MPT, necroptosis, and PARP-driven necrosis are (or are not) coupled to one another.
Douglas DL, Baines CP. PARP1-Mediated Necrosis is Dependent on Parallel JNK and Ca2+/Calpain Pathways. J Cell Sci. 2014; 127:4134-45.
Hiemstra JA, Gutierrez-Aguilar M, Marshall KD, McCommis KS, Zgoda P, Cruz-Rivera N, Jenkins N, Krenz M, Domeier TL, Baines CP, Emter CA. A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini-swine with compensated heart failure. Physiol Rep. 2014; 2:e12050. (Co-corresponding Author).
Kalogeris TJ, Baines CP, Korthuis RJ. Adenosine prevents TNFα-induced decrease in endothelial mitochondrial mass through activation of eNOS-PGC1a regulatory axis. PLoS One. 2014; 9:e98459.
Gutierrez-Aguilar M, Douglas DL, Gibson AK, Domeier TL, Molkentin JD, Baines CP. Genetic manipulation of the mitochondrial phosphate carrier does not affect mitochondrial permeability transition in the heart. J Mol Cell Cardiol. 2014; 72:316-25.
Kwong JQ, Davis J, Baines CP, Sargent MA, Karch J, Wang X, Huang T, Molkentin JD. Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy. Cell Death Differ. 2014; 21:1209-17.
Marshall KD, Edwards MA, Krenz M, Davis JW, Baines CP. Proteomic mapping of the proteins released during necrosis and apoptosis from cultured neonatal cardiac myocytes. Am J Physiol Cell Physiol. 2014; 306:C639-47.
Brown DA, Hale SL, Baines CP, del Rio CL, Hamlin RL, Yueyama Y, Kijtawornrat A, Yeh ST, Frasier CR, Stewart LM, Moukdar F, Raza Shaikh S, Fisher-Wellman KH, Neufer PD Kloner RA. Reduction of early reperfusion injury with the mitochondria-targeting peptide Bendavia. J Cardiovasc Pharmacol Ther. 2014; 19:121-32.
Hiemstra JA, Liu S, Ahlman MA, Schuleri KH, Lardo AC, Baines CP, Dellsperger KC, Bluemke DA, Emter CA. A new twist on an old idea: a 2-dimensional strain assessment of cyclosporine as a therapeutic alternative for heart failure with preserved ejection fraction. Physiol Rep. 2013; 1:e00174.
McCommis KS, Douglas DL, Krenz M, Baines CP. Cardiac-specific hexokinase 2 overexpression attenuates hypertrophy by increasing pentose phosphate pathway flux. J Am Heart Assoc. 2013; 2:e000355.
McGee AM, Baines CP. Phosphate is not an absolute requirement for the inhibitory effects of cyclosporin A or cyclophilin D deletion on mitochondrial permeability transition. Biochem J. 2012; 443:185-91.
McGee AM, Douglas DL, Liang Y, Hyder S, Baines CP. Elevated C1qbp expression protects breast cancer cells against cell death and promotes their migration and proliferation. Cell Cycle. 2011; 10:4119-27.
Schwartz Longacre L, Kloner RA, Arai AE, Baines CP, Bolli R, Braunwald E, Downey JM, Gibbons RJ, Gottlieb RA, Heusch G, Jennings RB, Lefer DJ, Mentzer RM, Murphy E, Ovize M, Ping P, Przyklenk P, Sack MN, Vander Heide RS, Vinten-Johansen J, Yellon DM. New horizons in cardioprotection: recommendations from the 2010 National Heart, Lung, and Blood Institute workshop. Circulation. 2011; 124;1172-9.
McCommis KS, McGee AM, Laughlin MH, Bowles DK, Baines CP. Hypercholesterolemia increases mitochondrial oxidative stress and enhances the MPT response in the porcine myocardium: beneficial effects of chronic exercise. Am J Physiol. 2011; 301:R1250-8.
McGee AM, Baines CP. Complement 1q binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J. 2010; 433:119-25.
Ramachandran A, Lebofsky M, Baines CP, Lemasters JJ, Jaeschke H. Cyclophilin-D deficiency protects against acetaminophen-induced oxidant stress and liver injury. Free Radical Res. 2011; 45:156-64.
Emter CA, Baines CP. Low-intensity aerobic training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine. Am J Physiol. 2010; 299:H1348-56.
Baines CP, Molkentin JD. Adenine nucleotide translocase-1 induces cardiomyocyte death through upregulation of the pro-apoptotic protein Bax. J Mol Cell Cardiol. 2009;46:969-77 (Corresponding Author).
Millay DP, Sargent MA, Osinska H, Baines CP, Barton ER, Vuagniaux G, Sweeney HL, Robbins J, Molkentin JD. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat Med. 2008;14:442-7.
Nakayama N, Chen X, Baines CP, Klevitsky R, Zhang H, Jaleel N, Chua BHL, Zhang X, Hewett TE, Robbins J, Houser SR, Molkentin JD. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest. 2007; 117:2431-2444.
Diwan A, Koesters AG, Odley AM, Pushkaran S, Baines CP, Spike BT, Daria D, Jegga AG, Geiger H, Aronow BJ, Molkentin JD, Macleod KF, Kalfa TA, Dorn GW 2nd. Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci. 2007; 104:6794-6799.
Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD. VDACs are dispensable for mitochondrial permeability transition and mitochondrial-dependent cell death. Nat Cell Biol. 2007; 9:550-555.
Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005; 434:658-662.
A full list of Dr. Baines’ publications can be found here.
Stephanie Ferreira-Nichols – Research Technician
Kurt Marshall – Graduate Student
Linda Alex – Postdoctoral Fellow
Kari Deininger – Veterinary Student
Laci Peterson – Veterinary Student