Project Details
Description
PROJECT SUMMARY
This Mentored Clinical Scientist Research Career Development Award (K08) proposal describes a three-year
career development and training plan for Dr. Forum Kamdar, a heart failure cardiovascular physician-scientist at
the University of Minnesota. Her long-term goal is to be an independent physician-scientist making significant
contributions in the field of neuromuscular cardiomyopathy. Her career development training plan encompasses
the following: (1) protected research time, (2) focused formal coursework and hands-on laboratory training in
cardiac tissue engineering and extracellular matrix dynamics, (3) rigorous training in the Responsible Conduct
of Research (4) a structured mentoring program with a multidisciplinary team of experienced scientists and
physician-scientists, and (5) focused research experience in basic science through the study of Duchenne
muscular dystrophy (DMD) cardiomyopathy utilizing cardiac tissue engineering to develop a DMD human
chambered muscle pump (hChaMP) culminating in the successful application for independent research funding.
DMD is the most common and deadly muscular dystrophy, and DMD-associated cardiomyopathy is ubiquitous
and significantly reduces survival in DMD patients. There are currently no effective treatment methods available
for DMD cardiomyopathy, and mechanisms defining DMD cardiomyopathy progression are not well understood.
The dystrophin glycoprotein complex (DGC) is a key component of cardiac mechanotransduction (MT) and the
loss of dystrophin in DMD results in loss of sarcolemmal integrity, which is a critical early event that ultimately
results in DMD cardiomyopathy. She and others have demonstrated that increased stress also exacerbates the
DMD phenotype, however a 3D model with progressive loading would allow for improved understanding of DMD
cardiomyopathy. The overall objective of the proposed research is to determine how progressive loading impacts
DMD cardiomyopathy disease progression and the impact of partial restoration of dystrophin using a 3D DMD
human chambered muscle pump (hChaMP). In Aim 1, Dr. Kamdar will evaluate the impact of altered MT on
DMD cardiomyopathy disease progression using a DMD hChaMP model system with increasing load. Next, in
Aim 2, she will determine the impact of dystrophin gene correction on cardiac remodeling mechanisms dictating
disease onset in DMD cardiomyopathy using dystrophin exon skipping. This research will provide novel insights
into DMD disease progression and ECM changes which will lay the foundation of her long term goal to identify
therapies to prevent or ameliorate DMD cardiomyopathy.
In summary, a comprehensive career development plan, in the context of a well-defined training, research and
mentorship structure, will allow Dr. Kamdar to emerge as a highly successful, independent physician-scientist in
DMD cardiomyopathy.
Status | Active |
---|---|
Effective start/end date | 9/1/22 → 8/31/24 |
Funding
- National Heart, Lung, and Blood Institute: $171,180.00
- National Heart, Lung, and Blood Institute: $171,180.00
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