Peter J. Gruber, MD, PhD

Our lab is focused on understanding the genetic and molecular mechanistic structures that guide cardiac development and physiology, and how to translate these findings to clinical medicine.

Epigenetic control cardiac development and performance

Our lab is studies the epigenetic control of ischemic injury. This project attempts to unravel the histone deacetylase, isoform-specific basis for protection of the ischemic myocardium. Our long-term goal is to understand how epigenetic modulators such as histone deacetylase (HDAC) inhibition can alter the response of the heart to ischemic injury. Our focus is to characterize specific HDAC isoforms that mediate this effect to help understand the pathological process. This will provide a sound scientific basis for further investigations HDAC-mediated modulation of ischemic injury in an isoform specific manner. In a series of complimentary experiments, we are examining another series of murine mutants to identify the balancing pathways of histone acetyl transferases.

Cardiac development- ventricular maturation

A complementary effort in the lab investigates the molecular processes that underlie ventricular maturation and compaction in the heart. The inner myocardial layer consists of finger-like trabeculae that project radially towards the center of the heart. In humans, defects in this process (ventricular non-compaction) result in arrhythmias and heart failure. Previously, we identified an allelic series of Gata4, Gata5, and Gata6 mutants, and identified that redundancy in these locus is important in myocardial development. Using unbiased methods of laser capture micro dissection and micro genomic methods, further experiments allowed to identify other key players in the developmental process of ventricular maturation.

Genetics of congenital heart disease- using iPS cells to model patient-specific responses

An important parallel to these experiments in model systems is our focus on human congenital heart disease. To date, we have recruited a total of over 1700 patients to our studies and expanded out initiative to include patients from 5 countries on 3 continents. We have performed whole exome and whole genome sequencing on hundreds of patients. We have identified new genetic variants that our group interrogates with mechanistic, functional studies in model systems including human embryonic stem cells, human induced progenitor stem cells, fly, and gene targeted mice, pigs and non-human primates.