Basic and Translational Science Research

Dr. Gruber is a Professor of Surgery at the Yale School of Medicine and a Pediatric Cardiothoracic Surgeon at Yale New Haven Children’s Hospital. Over the past two decades, his clinical practice has focused on surgical repair of complex congenital heart disease; and research on understanding it’s molecular and genetic underpinnings and developing innovative therapies to improve cardiac function. He has contributed to discoveries that have shown the importance of epigenetic factors, especially histone deacetylases, in cardiac development and its response to ischemia-reperfusion injury. He earned his B.A. in Biochemistry from the University of Pennsylvania (1985), M.D. from the University of Pennsylvania School of Medicine (1992), and Ph.D. from the University of Pennsylvania, in Biochemistry and Biophysics (1992). He completed his dissertation in Laboratory of Biochemical Genetics and Metabolism at Rockefeller University. His post-doctoral fellowship in Cardiac Development was completed at the American Heart Association-Bugher Foundation Center for Molecular Biology at the University of California, San Diego (1994-1996). His clinical training in General and Cardiothoracic Surgery was completed at the Johns Hopkins Hospital (1992-1999) and Pediatric Cardiothoracic Surgery at The Children’s Hospital of Philadelphia (2002). He has held faculty appointments as Assistant Professor of Surgery at the University of Pennsylvania School of Medicine and Surgeon, Children’s Hospital of Philadelphia (2002-2011); Associate Professor, the D. Rees and Eleanor T Jensen Presidential Chair of Surgery, and Chief, Section of Pediatric Cardiothoracic Surgery at the University of Utah School of Medicine (2011-2014); and the Johann L.F. Ehrenhaft Professor and Chairman, Department of Cardiothoracic of Surgery at the University of Iowa (2014-2017). He is a member of the American Society of Clinical Investigation and the American Surgical Association and has contributed over 150 scientific publications.

Dr. Ahuja has a wide-reaching laboratory with a broad focus on various aspects of surgical oncology, particularly epigenetics. Her lab utilizes techniques involving animals models, human cells, in vitro organoid models, precision medicine, and systems biology allowing the lab to span from clinical data mining to translational studies to basic science projects. Recently, the lab has published on a range of topics including population trends in sarcomas, surgical training and education, and early markers of pancreatic cancer. A strong focus in the lab is on the genetic and epigenetic basis/changes that occur in GI cancers (gastric, colorectal, pancreatic, etc.). The lab is answering questions such as which epigenetic changes lead to rapid cancer progression compared to long term survival. In addition, some projects focus more on treatment such as nanoparticle based drug delivery to solid tumors. A final focus is on the tumor microenvironment, particularly through collaborations across Yale labs to develop co-cultures of organoids and mesenchymal cells to study epithelial-mesenchymal interactions.

The Dardik laboratory focuses on working to understand he healing and function of blood vessels and synthetic blood vessel substitutes and patches that are used in vascular reconstruction. Work is underway to understand fundamental molecular mechanisms by which vein graft adaptation and arteriovenous fistula maturation result in positive remodeling and successful adaptation to the arterial and fistula environments, yet often proceed, in the long-term, to neointimal hyperplasia and graft failure. Dr. Dardik is deeply committed to the training and mentoring of young investigators, especially those interested in becoming surgeon-scientists; he has been a mentor to over 25 predoctoral students for MD, PhD, MD/PhD, and masters? degrees, and to over 50 postdoctoral fellows, many of whom have entered academic surgical careers.

George Tellides, MD, PhD, earned his medical degree from the University of Witwatersrand, Johannesburg, and his PhD from the University of Oxford. Dr. Tellidies is dedicated to saving and improving the lives of patients with cardiac disease and heart failure and concentrates his clinical practice at the Veterans Affairs Medical Center, West Haven, CT.

The Cowles laboratory is interested in the relationship between the enteric nervous system (ENS) and intestinal mucosal homeostasis. The ENS controls nearly every function of the bowel via a variety of neurotransmitters and peptide hormones. Understanding these actions has the potential to lead to new treatments for intestinal disorders. Our laboratory has found that serotonin (5-HT) is a regulator of enterocyte turnover in the small intestine. Mouse models of 5-HT excess result in taller villi, deeper crypts, increased crypt cell division and increased enterocyte apoptosis in the ileum. Pharmacologic enhancement of 5-HT signaling has similar effects. The neural and cellular mechanisms that are involved in this process are under active investigation.Other studies include understanding how the enteric nervous system (ENS) responds to injury. The ENS is equivalent to the central nervous system (CNS) but its layers of protection from injury are significantly less. This suggests that it must have an ability to replace injured and dead components. Preliminary studies have demonstrated a novel finding of intestinal ischemic injury resulting in neurogenesis in the ENS

The goal of the Khan lab is to improve our understanding of the biology and treatment of gastrointestinal cancers. We use a combination basic science investigation, translational research, and clinical outcomes research to achieve this goal. The basic science and translational focus of our lab is in obtaining a deep understanding of the transcriptional and metabolic biology of colorectal cancer and liver metastases. We have identified genes correlating with clinical outcome in patients with colorectal liver metastases. Our lab work has also led to the identification of metabolic pathways in colorectal cancer which are specific to sex, ethnicity and race. The lab translates our clinical findings to the bench, through development of animal models of metastasis to enable the study of tumor clonality and the interaction of cancer with the immune system. Leveraging data via large national databases, we also perform clinical outcomes research for cancers which arise from the stomach, liver, pancreas, bile duct, small intestine, colon, and, appendix. Recent clinical projects have helped define the rise of early onset colorectal cancer in the United States, explain trends of palliative care utilization in surgical oncology, and understand current surgical management of appendiceal carcinoid tumors. The Khan lab is federally funded.

The Park Laboratory focuses on isolating tumor infiltrating lymphocytes (TILs) from primary breast cancers with a goal of utilizing these cell lines in adoptive cell therapy for patients with advanced breast cancer. We have generated a PDX mouse model whereby we have successfully implanted tumor cells from primary breast cancers in order to monitor responsiveness of these tumors to TIL populations generated ex vivo.

David H. Stitelman, MD, is a surgeon in the Division of Pediatric Surgery within the Department of Surgery at Yale.As a clinician, Dr. Stitelman cares for children of all ages. He is the surgical director of the Yale Fetal Care Center. Such a program allows families who are given a fetal diagnosis based on prenatal testing an opportunity to meet with surgeons, pediatric medical specialists, obstetricians and neonatologists to plan for the management of their babies before and after birth.Dr. Stitelman also runs a basic science laboratory with a focus on prenatal therapy. The hope of this line of research is to treat and cure genetic and structural diseases before birth.