Gene therapy, correction of genetic diseases by replacement or editing the defect, offers a specific and rational treatment and possible cure. Clinical trials in post-natal human gene therapy have been limited by several factors, including inefficient gene product delivery and host immune reactions against vectors and gene products.
Current projects include the development of in-utero gene therapy, which introduces gene therapy before the development of the immune system. The small size and gestational state of the fetus allows relatively higher doses of vector administration to a subject that has a higher proportion of stem cells.
Preliminary work in mice shows broad, high level expression of reporter genes following in utero injection to several tissues including brain, liver and muscle (up to 100% of cells in some organs). Translating this work in animals to the clinic is technically feasible: fetal surgeons and maternal fetal medicine specialists can already access and cannulate umbilical vessels in utero to administer cellular or gene therapy. In addition, advances in prenatal molecular screening have become sophisticated enough to sequence the whole genome of a human fetus as early as the first trimester from a simple blood test from the mother’s blood (analyzing cell free DNA). If successful, this line of research could revolutionize therapy for genetic diseases.
Yale University, with its strong foundation in molecular biology, biomedical engineering and medicine, allows us a unique and powerful opportunity to advance this line of research.
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The laboratory is funded from the NIH, the VA, as well as from the Yale Department of Surgery Ohse award. As part of Yale's Vascular Biology and Therapeutics program, the lab is located on the 4th floor of the Amistad building. Members of the Dardik laboratory include surgery residents from Yale and other programs as well as postdoctoral fellows and students from around the world.
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Under this theme the lab investigates issues associated with water and electrolyte transport in health and disease, such diverse themes from secretory diarrhea to microbiome to ischemic injury are studied in the ileum, and colon both at the cellular level, and in isolated intestinal loop. In this area we are also investigating alternative organ preservation solutions in collaboration with the transplant section.
Gastric Ion Secretion
This theme is associated with modulating levels of acid production in isolated gastric glands from animal and human models. We investigate alternative ways to prevent secretion, and further try to determine the reasons for the hypersecretion of acid and look for means to reduce or prevent this overproduction. Recently we have developed a series of natural products to prevent the secretion of acid that are fast acting and prevent secretion for extended times without the side effects of a PPI.
Renal Ion Transport
In this area we use isolated perfused renal tubules to investigate the production of renal stone disease and determine if activation of the Calcium Sensing Receptor can prevent recurrence of stone disease and also modulate calcium absorption.
The newest theme and perhaps the most exciting is the development of 3D printed tissues and organs using a Bioprinting technology. This technology allows for the rapid development of a replacement tissue using the printer. We are focusing our efforts on arteries and veins, intestine, and eventually liver. In a close collaboration with the leading commercial company that makes bioprinters; it is hoped that we will accelerate the actual printing time further and not be limited by the size of the print we wish to make. To date we have already begun to implant some of the printed vessels into rats in a collaboration with the Dardik laboratory.
Additional current projects are joint efforts with the Radiology Department including a study of sonographic features identifying appendicitis in otherwise ambiguous cases, and studying the impact of time under anesthesia on incidence and timing of postoperative pulmonary embolus. These studies are precursors to prospective studies that will also be done in cooperation with Radiology.
Resident Funding Opportunities
- National Clinical Scholars Program (NCSP)
- Yale University School of Medicine serves as one of four national sites (Yale, UCLA, University of Pennsylvania, University of Michigan) of the National Clinician Scholars Program aims to offer unparalleled training for clinicians as change agents driving policy-relevant research and partnerships to improve health and healthcare. The goal of the program is to cultivate health equity, eliminate health disparities, invent new models of care, and achieve higher quality health care at lower cost by training nurse and physician researchers who work as leaders and collaborators embedded in communities, health care systems, government, foundations, and think tanks in the U.S. and around the world.
- Partnerships at Yale University NCSP include the VA Connecticut Healthcare System, Yale School of Nursing, Yale-New Haven Hospital (YNHH), YNHH-Center for Outcomes Research and Evaluation (CORE), the Yale Center for Clinical Investigation, Columbus House, Integrated Refugee and Immigrant Services (IRIS), Project Access New Haven, and New Haven Family Alliance, among others.
- Departmental Grants
- Ohse Award- The Department of Surgery Ohse Research Grant Program supports a variety of awards for one year. The primary objectives of the OHSE awards are to promote research and to facilitate collaborations between physicians and scientists. Consistent with these objectives, the review process of the proposals will be collaborative among physicians and scientists from various sections within the Surgery Department.
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- Career Development Award with Faculty Sponsor
- Loan Repayment Program