Department Collaboration Leads
to Groundbreaking Discoveries
When patients look for innovative
clinical care, they turn to the teams at
One patient in particular searched
across the globe for cardiac arrhythmia
treatment. He was in his late thirties
with recurrent ventricular fibrillation and
cardiac arrest. His condition was severe
and unique: neither surgical therapies
nor standard pharmaceutical therapies
had been effective.
In a typical patient with a potentially
lethal cardiac arrhythmia, an
implantable cardioverter defibrillator is
a common treatment method. However
for this patient, his defibrillator fired well
over 100 times over just a few months,
making it difficult to perform daily
activities such as driving, working and
spending time with his young child.
That is until he came to Ohio State for
our groundbreaking treatment.
Researchers at The Ohio State
University College of Medicine,
Pharmacy and Engineering joined
forces with clinicians in the Ohio State
Heart and Vascular Center to undertake
a cross-disciplinary collaboration. Peter
Mohler, PhD, director of the Dorothy
M. Davis Heart and Lung Research
Institute (DHLRI), chair of the Department
of Physiology and Cell Biology, and
associate dean for Basic Research at the
Ohio State College of Medicine was a
member of the research team that paved
the path in defining a new genetic cause
and treatment for arrhythmia.
“We have an incredible team of bright,
but more importantly selfless people at
Ohio State. At every step of this story,
very busy people dropped what they
were doing to accelerate the pace of
discovery,” Dr. Mohler said.
For their first step, the team turned
to innovative new genetic platforms.
Instead of examining only the handful
of known cardiovascular disease
genes, they utilized an innovative
new research platform called “whole
exome sequencing” to test the DNA
sequence of all of the approximately
20,000 genes in the patient. To the
team’s surprise, the group identified
a completely new gene isoform and
found a new potential disease variant
with that novel DNA sequence.
Enlisting the help of expert cardiologists,
surgeons, physiologists, molecular
biologists and undergraduate students
was the best way to treat a disease
caused by a mutation in a gene
with unknown function. The team
determined that the new form of the
gene was responsible for regulating the
flux of potassium across the heart cell
membrane, and more importantly that
the novel human variant disrupted this
flow of potassium.
To translate the findings to patient
treatment, the team utilized
computational simulations to define
a new therapeutic strategy based on
altered cell electrical function. From
this work, a new therapeutic regimen
was devised based on an experimental
compound used for patients with
“While this is one great example
related to heart disease, these types of
stories and collaborations are now the
norm at Ohio State. I am most excited
that I could just as easily tell you a
similar story related to translational
research focused on diabetes, cancer,
neuroscience, infectious disease or
muscular dystrophy. While it is an
exciting time to be a scientist, it is an
especially exciting time to be a scientist
at Ohio State,” Dr. Mohler explained.
Thus, the therapy worked to treat
the arrhythmia, and the information
generated from this study is now being
used to design new genetic tests and
potential treatments for patients with
similar arrhythmias around the world.
The untreatable patient is now treatable.
As shown by Ohio State, cross-disciplinary collaborations are the future
of innovative research solutions.
Magnified image of individual heart cells.