Page 20 - CBAC Newsletter 2013

pursue a diverse range of research activities here at focused on the use of iPSC-derived cardiomyocytes and
Washington University. During my clinical training, I the study of disease associated ion channel mutations.
worked with Dr. Yoram Rudy’s lab to apply ECGI to the
study of patients with implanted cardiac pacemakers, Cardiac arrhythmias are complex diseases involving
which allowed us to characterize the electrical remod- multiple levels: molecule, cell, organ, and whole animal.
eling resulting from right ventricular pacing. In order to Ultimately, I hope to develop a research program in which
further explore the molecular and cellular mechanisms my lab and my collaborators work together using multiple
underlying pacemaker-induced remodeling, I began a approaches to understand these complex diseases and
collaboration with Dr. Igor Efimov’s lab which led to the develop novel therapies.
development of a miniaturized pacemaker amenable to
implantation in a mouse. This technology, in conjunction The CBAC brings together a wide variety of researchers
with the genetic tools available in the mouse, will open using a range of tools and approaches to the study of
the door to future studies of pacemaker - induced remod- cardiac arrhythmias, from single-cell electrophysiology
eling and tachycardia - induced heart failure. to multi-scale modeling. As a result, the seminar series
offers an invaluable opportunity to consider research
When I completed my clinical training, I joined Dr. Ner- questions from different perspectives. The greatest
bonne’s lab to focus on single-cell electrophysiology and strength of CBAC, as illustrated in the range of research
learn single-cell patch-clamp techniques. My first project projects I have pursued, is the opportunity to work with
was the characterization of a novel ion channel mutation mentors with expertise in a variety of techniques and
which had been identified in a patient seen by Dr. Phillip approaches.
Cuculich on the clinical EP service. We characterized the
physiology of the mutation and then used computation- Some papers that Dr. Scott Marrus has authored along
al modeling, in conjunction with the Rudy lab, to predict with other CBAC members include:
the effects of the mutation in human cells. This project
highlights the importance of productive collaborations Marrus, S.B., Andrews, C.M., Cooper, D.H., Faddis,
between clinical service and basic research and provides M.N. and Rudy, Y. (2012). Repolarization changes under-
a model which I envision for my future career, i.e. pro- lying long-term cardiac memory due to right ventricular
ductive collaborations with research-minded clinicians pacing: noninvasive mapping with ECGI. Circ. Arrhyth.
wherein novel clinical findings are explored in the lab and Electrophysiol. 2012; 5(4): 773-781.
the resulting discoveries ultimately translated back to the
clinic. Marrus, S.B., Cuculich, P.S., Wang, W. and Nerbonne,
J.M. (2011). Characterization of a novel, dominant
One of the challenges facing the study of diseases af- negative KCNJ2 mutation associated with Andersen-Taw-
fecting ion channels is the inaccessibility of native hu- il syndrome. Channels. 2011; 5(6): 500-509.
man cardiac tissue and the limitations of animal models.
Therefore, my recent focus has turned to the exploration Marrus, S.B. and Nerbonne, J.M. Mechanisms linking
of induced pluripotent stem cell (iPSC) derived cardiomy- short and long term electrical remodeling in the heart…is
ocytes. After reprogramming adult skin fibroblasts into it a stretch? Channels. 2008; 2: 1-8.
iPSCs, the cells are differentiated into cardiomyocytes
and offer a novel and exciting approach to study human
diseases by more accurately recapitulating the human
cellular environment. We anticipate that this method will
both provide a powerful research technique as well as
pave the way for patient-specific diagnostic and thera-
peutic strategies.

Over the next several years, I hope to continue to develop
the foundation for an independent research career

14 | CBAC Center Heartbeat