Peter J. Gruber, MD, PhD
Professor of Surgery (Cardiac)Cards
About
Research
Overview
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.
Academic Achievements & Community Involvement
Clinical Care
Overview
Peter J. Gruber, MD, PhD, is the chief of Pediatric Cardiac Surgery for Yale Medicine and Yale New Haven Children’s Hospital, and a pediatric cardiothoracic surgeon who treats patients from infancy—in some cases before they are born—to adults. He specializes in complex congenital heart disease, also known as structural heart disease, and performs a wide spectrum of procedures and complex surgeries, including pediatric heart transplant.
“Congenital heart diseases can be pretty scary because it’s your heart, and because the situation can turn serious very quickly,” Dr. Gruber says. “Some people want to know all the details. Other people find details just scare them. So, I read what the family or what the children want to know, and then try to communicate with them in whatever way is appropriate in that particular situation.”
“When a congenital heart problem is identified early, in one way or another, it may not be curable, but it’s usually treatable,” he says. “The overall mortality rate for those who have surgery is less than 1 percent, and patients who have surgery usually go on to enjoy a good quality of life.” Dr. Gruber works with a team of cardiologists and other specialists to determine the best approach for each patient.
A professor of surgery at Yale School of Medicine, Dr. Gruber has training as a developmental biologist and a geneticist, and he has a special interest in the molecular underpinnings of congenital heart disease. This work has impacted his work in the clinic as well. He had a patient with Wolff-Parkinson-White syndrome, characterized by abnormal electrical pathways in the heart, who needed a complex reconstruction inside of her heart. After the surgery, she developed an unusual irregular heartbeat, and she told Dr. Gruber that other members of her family had experienced the same thing. So, his research group sequenced and examined their DNA. “We identified a gene that was newly associated with this disease, all based on the generosity of the patient and their family,” he says. Committed to innovation, he said, “the research today is the clinical care of tomorrow.”
“Overall, it’s a highly rewarding combination of taking care of kids with lethal diseases, giving them a shot at a normal life. Figuring out how it happened is icing on the cake.”
Clinical Specialties
Fact Sheets
Adult Congenital Heart Disease
Learn More on Yale MedicineTruncus Arteriosus
Learn More on Yale MedicinePediatric Congenital Heart Surgery
Learn More on Yale MedicineReoperative Heart Surgery
Learn More on Yale Medicine
Board Certifications
Congenital Cardiac Surgery
- Certification Organization
- AB of Surgery
- Latest Certification Date
- 2020
- Original Certification Date
- 2010
Thoracic & Cardiac Surgery
- Certification Organization
- AB of Surgery
- Latest Certification Date
- 2023
- Original Certification Date
- 2004
Yale Medicine News
News & Links
Media
- Intraoperative image of patient with hypoplastic left heart syndrome during a Norwood repair.
- MicroCT of murine embryonic heart.
News
- April 26, 2024
Clancy Mullan Named 2024 Surgeon Scientist Training Program Scholar for Yale Department of Surgery
- March 11, 2024
Engineering a Heart Conduit: New $2M NIH Grant for Yale Research
- February 05, 2024
Surgical Education Solutions: Grant Recipients Announced
- October 31, 2023
2023 Academic Development Awards Focus on Surgical Education