|
|
|
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
|
|
|
