Gehred, Natalie

Mentor: Dr. Tom Vondriska

Research project:

Cardiac fibroblasts are the cells responsible for extracellular matrix deposition and maintenance in the healthy adult heart.  In injured hearts, cardiac fibroblasts differentiate into cells known as myofibroblasts in an effort to repair damage.  Unlike cardiac fibroblasts, myofibroblasts are capable of proliferation and migration to the areas of damage, where they are able to support the structure and mechanical function of the heart with their contractile ability and increased production of collagen and extracellular matrix components.  While this remodeling is required to preserve heart function in the short term, the prolonged activity of myofibroblasts can lead to the overall stiffening of the heart, called fibrosis.  Maladaptive fibrosis, along with cardiomyocyte cell death and hypertrophy in injured hearts, leads to heart failure, the leading cause of death in the United States.

My research focuses on characterizing the transcriptional changes that occur in subpopulations of cardiac fibroblasts in response to pressure overload-induced hypertrophy.  I plan to use scRNA-seq data from adult mouse hearts to identify key driving transcription factors or other chromatin remodeling proteins involved in the differentiation of subpopulations of myofibroblasts, especially those that may express anti-fibrotic transcriptional profiles and ameliorate fibrosis.  These targets will be examined using loss of function approaches in vivo in future studies.  Understanding the dynamics of these cell populations in the heart will allow me to begin to identify targets for pharmacological intervention to prevent or reverse maladaptive fibrosis.