The focus of my laboratory is:
- The study of myocardial ischemia-reperfusion injury, cardiac remodeling and heart failure
- The interactions between inflammatory mediators, cardiac myocytes and fibroblasts play an important
role in the pathophysiology of ischemia reperfusion injury and cardiac remodeling
- My laboratory uses state-of-the-art physiological monitoring, molecular biology, primary cell culture, transgenic animals, gene therapy, immunohistochemistry and electron microscopy to address novel therapeutic mechanisms for cardiac injury and remodeling
- Over the past year, we have described a new paradigm for cardiac protection that involves the
interaction of signaling molecules with microdomains within cardiac myocytes known as caveolae
- We have documented the importance of caveolae in the cardiac protection produced by ischemia reperfusion, opioids and volatile anesthetics
- We have created a unique line of transgenic mice with cardiac specific overexpression of caveolin-3
to test hypotheses regarding our ability to augment cardiac protection from ischemia reperfusion injury
- We study the importance of adenylyl cyclase in the cardiac myocyte and the cardiac fibroblast, key players in the
inflammatory phase of cardiac repair and remodeling
- We are examining mice with genetic overexpression of the adenylyl cyclase isoform six (ACVI). We are involved in a clinical trial to test the efficacy of gene transfer of adenylyl cyclase to patients with congestive heart failure that has recently been funded by the NIH
- We have documented that adenylyl cyclase is an important molecule in determining the phenotype of cardiac fibroblasts and the ability of the cardiac fibroblast to produce collagen
- These studies have implications to cardiac inflammation, fibrosis and development of diastolic dysfunction and congestive heart failure
- The trainees would be involved in exploring hypotheses and mechanisms of myocardial ischemia reperfusion injury, cardiac inflammation and remodeling
Drummond JC, Dao AV, Roth DM, Cheng CR, Atwater BI, Minokahdeh A, Pasco LC, Patel PM. Effect of dexmedetomidine on
cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans Anesthesiol.
Patel HH, Head BP, Petersen HN, Niesman IR, Huang D, Gross GJ, Insel PA, Roth DM. Protection of adult rat cardiac
myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors Am J Physiol Heart Circ
Physiol. 291:H344-350, 2006.
Insel PA, Head BP, Ostrom RS, Patel HH, Swaney JS, Tang CM, Roth DM. Caveolae and lipid rafts: G protein-coupled
receptor signaling microdomains in cardiac myocytes Ann NY Acad Sci. 1047:166-172. 2005.
Roth DM, Lai NC, Gao MH, Fine S, McKirnan MD, Roth DA, Hammond HK. Nitroprusside increases gene transfer
associated with intracoronary delivery of adenovirus. Hum Gene Ther.;15:989-94, 2004
Kaspar BK, Roth DM, Chin Lai N, Drumm JD, Erickson DA, McKirnan MD, Hammond HK. Myocardial gene transfer and
long-term expression following intracoronary delivery of adeno-associated virus.J Gene Med. 2004 Oct 28 (epub
ahead of print).
Roth DM, Lai NC, Gao MH, Drumm JD, Jimenez J, Feramisco JR, Hammond HK. Indirect intracoronary delivery of
adenovirus encoding adenylyl cyclase increases left ventricular contractile function in mice. Am J Physiol Heart
Circ Physiol 287:H172-177, 2004.
Lai NC, Roth DM, Gao MH, Tang T, Dalton N, Lai YY, Spellman M, Clopton P, Hammond HK: Intracoronary adenovirus
encoding adenylyl cyclase VI increases left ventricular function in heart failure. Circulation 110:330-336, 2004.
Ander AN, Duggirala SK, Drumm JD, Roth DM: Natriuretic peptide gene expression after beta-adrenergic stimulation
in adult mouse cardiac myocytes. DNA Cell Biol 23:586-591, 2004.
Roth DM, Drumm JD, Bhargava V, Swaney JS, Gao MH, Hammond HK: Cardiac-directed expression of adenylyl cyclase and
heart rate regulation. Basic Res Cardiol 98:380-387, 2003.