Under the direction of physician-scientist Dr. James F. Martin, the Cardiomyocyte Renewal Laboratory (CRL) is focused
on understanding how specialized signaling pathways are connected to adult
tissue development and regeneration.
areas of research include atrial
fibrillation (genetic basis), heart development (and associated congenital
heart defects), and aortic valve disease (calcification process).
CRL is investigating genetic pathways (Hippo,
Wnt, and Bmp) that have not only been linked to severe and/or widespread heart
problems such as atrial fibrillation and pulmonary arterial hypertension, but
that also are associated with congenital heart defects and the calcification
process that leads to aortic valve disease.
Dr. Martin's goal is to obtain an
in-depth understanding of these pathways in order to develop ways to regenerate
heart muscle and prevent disorders such as atrial fibrillation and calcified
aortic valves. Ultimately, these studies are designed to identify therapeutic
options to promote normal tissue development and its regenerative capabilities.
Study areas in developmental
pathways and adult tissue regeneration include the following:
- Heart development. Heart growth is a developmental
process that is intricate and highly regulated. CRL has uncovered the
involvement of several pathways (Nodal, Pitx2c) influencing discrete steps in
heart formation (outflow and inflow tract development, cardiac septation and
ventricular growth). Pitx2c is associated with human diseases (Rieger Syndrome
I, atrial fibrillation). In addition, recent CRL discoveries indicate that
there are inhibitory pathways, such as the Hippo pathway, that control heart
size by regulating cardiomyocyte proliferation and may have a role in
cardiomyocyte renewal. CRL's studies are providing mechanistic insight into
these unique pathways in heart development and are focused on identifying new
avenues for therapeutic intervention to promote cardiac regeneration.
- Vascular and epithelial tissue
development. Bone morphogenetic protein (BMP) signaling has been implicated in human inherited disorders of blood vessel (vascular tissue) and tissues that line the structures of the body (epithelial tissue)
such as juvenile polyposis and pulmonary artery hypertension. CRL is studying BMP signaling during vertebrate development and their research has provided insight into BMP function in congenital heart malformations, with the long-term
goal of uncovering therapeutic avenues for human patients.
- Aortic valve disease. Aortic valve disease has become a
major medical problem that continues to increase as the population ages.
However, treatment options are currently very limited. The CRL research program
is investigating the mechanisms underlying the valve disease that begins with
narrowing of the aortic valve opening or "stenosis" due to deposition of calcium. This
"calcification" process limits blood flow through the heart and can lead to valve
hardening. CRL is focusing on the roles of the known regulators
of calcification, the BMPs, in heart valve calcification.
Dr. Martin's group was the first to provide genetic evidence that Bmp2 is
essential for atrioventricular valve development. CRL's recent discoveries
indicate BMP signaling is involved in maintaining healthy valve structure and
function (termed "homeostasis") by regulating poorly understood genes (Smad8
and microRNA 17-92). CRL's goal is to determine how BMPs regulate development
of valve calcification. CRL's studies are providing novel insights into the detailed
molecular mechanisms behind BMP function and how different proteins in this
pathway interact to either promote or block aortic valve calcification.
Contact Information and Location
Cardomyocyte Renewal Laboratory
James F. Martin, MD, PhD — Director
Texas Heart Institute
Houston, Texas 77030
Dr. Martin is also appointed as
Vivian L. Smith Professor
Baylor College of Medicine