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Cell's ‘power plants’ focus of conference

by Roby Hill
South Carolina College of Pharmacy
As the eye of the medical world turns increasingly to mitochondria, it is focusing more and more on South Carolina.
MUSC President Dr. Ray Greenberg speaks to researchers during the Charleston Conference on Mitochondrial Physiology and Pathobiology.

John Lemasters, M.D., Ph.D., and Craig Beeson, Ph.D., faculty in the Department of Pharmaceutical and Biomedical Sciences (PBS) at the South Carolina College of Pharmacy, illustrated the point during the Charleston Conference on Mitochondrial Physiology and Pathobiology. The conference, which took place Nov. 15-18, 2009, featured some of the most well-known and respected “mitochondriacs” in the world.
“John and Craig put together a very compelling program on a topic that not only has great currency and resonance, but also one in which MUSC is recognized as being an international leader,” said Rick Schnellmann, Ph.D., chair of the PBS department. “Our faculty, our research, our Centers in Drug Discovery and Cell Death, Injury and Regeneration make Charleston a natural hub for this kind of conference.”
In addition to researchers from MUSC, conference presenters included top people from Stockholm University, Universidade due Sao Paulo, Harvard Medical School, National Institutes of Health, University of Florida, Johns Hopkins University, University of Ottawa, University of Geneva, University of Michigan, University of Kansas, Cornell University, Boston University, University of Pittsburg School of Medicine and Pfizer. Attendees included more than 100 scientists from the public and private sectors at institutions all over the world.
“Mitochondrial damage may be the most common cause of pathophysiologies,” said Beeson, PBS associate professor. “Neurodegenerative diseases, metabolic diseases, adverse drug events—mitochondria play a major role in all of these. It had been long recognized as the powerhouse of the cell because it makes energy, but now it is also known as the ‘executioner’ of the cell because it coordinates cell death and is the ultimate arbiter of cell fate in response to stress.”
The PBS department has a number of mitochondrial experts and is home to significant breakthroughs in assay technologies. Lemasters is a nationally-known expert on the mitochondrial permeability transition, which triggers cell death in many diseases and pathological states. A world-renowned pioneer in laser scanning confocal microscopy—a powerful research tool allowing the visualization of the functioning of single cells with an unprecedented degree of clarity—Lemasters holds five patents, has edited four textbooks and authored more than 400 articles in peer-reviewed journals. In addition to serving as full professor in the PBS department, Lemasters is a South Carolina Center of Economic Excellence Endowed Chair in Advanced Cellular Technologies and director of the Center of Cell Death, Injury, and Regeneration.
Seahorse Biosciences, with which Beeson helped develop the extracellular flux analyzer, collaborated with PBS faculty to establish the Seahorse Biosciences/MUSC Academic Development Core, the first academic core utilizing this technology. An extracellular flux analyzer is a fully-integrated instrument that simultaneously measures the two major energy yielding pathways—aerobic respiration and glycolysis—in a convenient, microplate format. It enables a researcher to conduct high-throughput testing of biologically relevant samples, which had never before been possible. More than 15 research groups at MUSC routinely use the instrument to study cancer cells, primary liver and kidney cells, zebrafish embryos, and tissue biopsies. The flux analyzer allows near instant study of mitochondrial health, and dysfunction, as it pertains to mutation, disease, or clinical status. MUSC is home to four XF24 and one XF96 Extracellular Flux Analyzers, meaning the University now has more of the instruments than any other institution in the world.
Virtually all presentations at the Charleston conference described new, unpublished research. Some of the research described by MUSC faculty included Zhi Zhong’s “Ethanol-Induced Mitochondrial Depolarization in Liver” in the session on Mechanisms of Uncoupling; Lemaster’s “Mitochondrial Permeability Transition, Mitophagy and Hepatocyte Remodeling” and Eduardo Maldonado’s “Free Tubulin and cAmp-Dependent Phosphorylation Modulate Mitochondrial Membrane Potential in HEPG2 Cells: Is VDAC the Target?” during the session on Mitochondrial Dynamics and Autophagy; Schnellmann’s “Glucose Regulation of Calpain 10 in Renal Proximal Tubular Cells and Streptozotocin-induced Diabetic Kidneys” in the session on Oxidative Stress and Aging and Baerbel Rohrer’s “New Drug Leads as Potential Treatments for Calcium Induced Retinal Degeneration” in the session on Mitochondrial Mechanisms in Toxicity.
This last presentation provided a case study in efficient collaboration at a medical research university.
Beeson and Rohrer, along with postdoctoral scientists Nathan Perron from the College of Pharmacy and Mausumi Bandyopadhyay from the College of Medicine, leveraged two of the college’s Centers for Economic Excellence core units to discover drug leads that may prevent animal blindness.
The team screened 50,000 molecules in the Center for Drug Discovery, directed by pharmacy professor and CoEE chair, Chuck Smith, and discovered a dozen ‘hits.’ Transitioning to the Center for Cell Death, Injury and Regeneration, they were able to screen those hits down to three by using the extracellular flux analyzers in the MUSC/Seahorse Biosciences Academic Development Core. Finally, they translated the discovery to animal models where they identified two new drug leads.  
The ability of the South Carolina College of Pharmacy and MUSC to create an opportunity for dialogue among the world’s foremost mitochondrial experts could open many doors of discovery in the future. The NIH is considering creating an Office of Mitochondrial Medicine to coordinate all ongoing mitochondrial research efforts within the NIH.
In a letter published Jan. 6 in The Hill, Howard Zucker, former assistant director-general of the World Health Organization and former U.S. deputy assistant secretary of health, called for support of such an office given the growing importance of mitochondrial research: “We may be at the threshold of what could be a paradigm shift in our theories of the medical universe. Perhaps there is a universal biologic theory for why cells fail to function properly and it rests within the mitochondria.”

Friday, Jan. 22, 2010

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