|
John Hollander, Ph.D. |
Director of Graduate Studies, Exercise Physiology
Assistant Professor of Exercise Physiology
Graduate Training: University of Wisconsin-Madison
Fellowship:
University of California San Diego |
|
Office: 3040A-HSN
Lab: 3040-HSN
PO Box 9227
Morgantown, WV 26506 |
Email: Jhollander@hsc.wvu.edu
Phone: 304-293-3683
Fax: 304-293-5513 |
Research Interests:
 |
| Figure 1: Mitochondrial subpopulation subcellular spatial arrangement indicating SSM beneath the cell membrane (sarcolemma) and IFM between contractile fibers. |
|
Figure 2: Mitochondrial subpopulation electron microscopy. Ultrathin section (70 nm) of heart tissue imaged at X 10,000. |
|
Figure 3: Isolated perfused mouse heart model utilized for global ischemia and reperfusion heart studies. |
Significance: Nearly 80 million adults in the U.S. have one or more types of cardiovascular disease (approximately 1 in 3 individuals). These
numbers
are
staggering, and they point to the importance of research dedicated to understanding cardiovascular disease progression, as well as
therapeutic treatment
design.
The specific research interests of our laboratory focus on understanding the pathogenesis of cardiovascular disease with an emphasis on the development
of therapeutic interventions. Specific research projects focus on understanding the role played by the mitochondrion during cardiovascular pathologies
including diabetes mellitus and ischemic heart disease.
1. Diabetic Cardiomyopathy
Cardiovascular complications, including diabetic cardiomyopathy, are the leading cause of mortality among diabetic patients, in the United States. The persistent hyperglycemia associated with diabetes mellitus, contributes to increased reactive oxygen species (ROS) generation, and tissue damage.
Because the mitochondrion is the primary site for ROS generation, determining how mitochondria are affected by diabetes mellitus is crucial for understanding the disease. Examination of mitochondria is complicated by the fact that two distinct mitochondrial subpopulations are present in the cardiac myocyte, interfibrillar mitochondria (IFM), which situate between the contractile proteins and subsarcolemmal mitochondria (SSM) that exist beneath the cell membrane (Figures 1 and 2).
Currently, it is unclear how individual cardiac mitochondrial subpopulations are differentially effected by diabetes mellitus making it difficult to determine their specific contribution to the pathogenesis of diabetic cardiomyopathy. Our long-term goal is to determine the specific contributions of these spatially distinct mitochondrial subpopulations during diabetic cardiomyopathy as a prerequisite to the development of therapeutic interventions designed to lessen cardiac complications associated with diabetes mellitus.
2. Cardiac Ischemia/Reperfusion (I/R) Injury
Ischemia occurs when the supply of blood to the heart is inadequate to maintain normal oxidative metabolism. Additionally, restitution of coronary flow to the heart, or reperfusion, causes adverse effects that include tissue damage. Reactive oxygen species (ROS) play a central role in the tissue damage resulting from ischemia and reperfusion (I/R) injury. Mitochondria are particularly susceptible to the oxidative environment presented by I/R because they are a main site of ROS generation. These studies utilize molecular gene manipulation of proteins (transgenic, viral vectors) in an effort to develop cardioprotective therapeutic strategies for treating the heart during ischemia and the subsequent reperfusion event (Figure 3). These studies focus on preserving mitochondrial function.
Approaches and Techniques: The laboratory employs a mixture of molecular biology, physiology, and biochemistry to address the research questions
posed. Techniques utilized include:
- Molecular gene manipulation (transgenic mice, conditional knockout mice, viral vectors)
- Proteomics
- Flow cytometry
- Confocal microscopy
- Working heart preparations
- Enzyme kinetics
- EPR spectroscopy
- Cell culture
Selected Publications:
-
Hollander, J. M., K. M. Lin, B. T. Scott, W. H. Dillmann. Protection against simulated ischemia-reoxygenation damage with overexpression
of phospholipid hydroperoxide glutathione peroxidase and HSP 60 and HSP 10. Free Rad. Biol. Med. 35(7):742-751, 2003.
-
Hollander, J. M., K. M. Lin, B. T. Scott, W. H. Dillmann. Protection against simulated ischemia-reoxygenation damage with overexpression
of phospholipid hydroperoxide glutathione peroxidase and HSP 60 and HSP 10. Free Rad. Biol. Med. 35(7):742-751, 2003.
-
Hollander, J. M., J. L. Martin, D. D. Belke, B. T. Scott, W. H. Dillmann. Overexpression of wild type HSP27 and a HSP27 nonphosphorylatable
mutant protects against ischemia/reperfusion injury in a transgenic mouse model. Circulation. 110:3544-3552, 2004.
-
Dieterle, T., M. Meyer, Y. Gu, D. D. Belke, E. Swanson, M. Iwatate, J. M. Hollander, K. L. Peterson, J. Ross, W. H. Dillmann. Gene transfer
of a phospholamban-targeted antibody improves calcium handling and cardiac function in heart failure. Cardiovasc. Res. 67:678-688, 2005.
-
Belke, D. D., B. Gloss, J. M. Hollander, E. A. Swanson, H. Duplain and W. H. Dillmann. In vivo gene delivery of hsp70i adenovirus and
adeno-associated virus preserves contractile function in mouse heart following ischemia-reperfusion. Am. J. Physiol. 291:H2905-2910, 2006.
-
Williamson, C. L., E. R. Dabkowski, W. H. Dillmann, and J. M. Hollander. Mitochondria protection from hypoxia/reoxygenation injury with mitochondrial heat shock protein 70 (mthsp70) overexpression. Am. J. Physiol. 294:H249-H256, 2008.
-
Dabkowski, E. R., C. L. Williamson, and J. M. Hollander. Mitochondria-Specific Transgenic Overexpression of Phospholipid
Hydroperoxide Glutathione Peroxidase (GPx4) Attenuates Ischemia/Reperfusion Associated Cardiac Dysfunction. Free Rad. Biol. Med.
45:855-865, 2008.
-
Dabkowski, E. R., C. L. Williamson, V. C. Bukowski, R. S. Chapman, S. S. Leonard, and J. Hollander. Diabetic
cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations. Am. J. Physiol. 296:H359-H369, 2009 .
|
Lab Personnel:
Dharendra Thapa - Graduate Student
Sara Lewis - Biology Technician
Tara Croston - Graduate Student
Walter Baseler – Graduate Student
Danielle Shephard - Graduate Student
Cody Nichols - Graduate Student
Raja Jagannathan - Scientist
|  |
|
| |
Dharendra Thapa, Sara Lewis, Danielle Shephard, Tara Croston, John Hollander, Walt Baseler, Cody Nichols, Raja Jagannathan |
|
For information about the Exercise Physiology Curriculum and the Faculty Research Areas
Click this link: Research and Graduate Education Exercise Physiology Web Page |
|
|
