Research & Publications
Dr. Dardik is a surgeon-scientist who seeks to use the power of molecular biology to achieve a modern understanding of vascular disease, and to use the basic science laboratory to perform cutting edge research to ultimately benefit patients with vascular disease. The Dardik laboratory studies how vascular interventions heal and can be improved. We are currently trying to understand the fundamental molecular mechanisms by which venous remodeling results in successful adaptation to the arterial or fistula environment, yet often proceeds, in the long-term, to graft failure or failure of arteriovenous fistula (AVF) maturation. We are also studying how patches heal after angioplasty or venoplasty. We are also using a new biomimetic scaffold to deliver stem cells to diabetic wounds and improve limb ischemia.
Extensive Research Description
The Dardik laboratory uses modern molecular techniques to study the diseases and therapeutics that vascular surgeons care for in their patients. As part of Yale’s Vascular Biology and Therapeutics program, we take advantage of our rich collaborative environment to push our field forward, focusing on basic and translational research that is relevant to our patients.
A major focus of our laboratory is to understand the healing and function of blood vessels and synthetic blood vessel substitutes and patches that are used in vascular reconstruction. We are currently trying to understand the 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. We are focusing on the role of vascular identity in controlling the response to vascular intervention; the laboratory made the original observation that vein graft adaptation is associated with diminished Eph-B4 expression without increased Ephrin-B2 expression, e.g. vein grafts lose venous identity without gaining arterial identity (Kudo et al., ATVB 27:1562, 2007; Muto et al., J Exp Med 208:561, 2011). However, arteriovenous fistula maturation is characterized by retention of venous identity with gain of arterial identity (Protack et al., Sci Rep 7:15386, 2017). We are currently exploring downstream mechanisms by which vessel identity regulates vessel remodeling and the success or failure of vascular therapeutics (Sadaghianloo et al., Ann Vasc Surg 41:225, 2017) as well as the role of the extracellular matrix in controlling vascular remodeling (Kuwahara et al., ATVB 37:1147, 2017). This work has led to the new RADAR procedure that shows improved outcomes compared to the conventional radial-cephalic AV fistula (Bai & Sadaghianloo et al., Science Transl Med 12(557):eaax7613, 2020).
Our work describing a role for vascular identity during adaptive remodeling has led us to investigate the response to fast-flow hemodynamic milieus such as those found in arteriovenous malformations and fistulae. We are also investigating the biomolecular pathways implicated in the pathogenesis of isolated slow-flow vascular malformations with focus on local, sustained delivery of inhibitory agents.
Studying mechanisms of vascular remodeling has also led us to examination of vascular patch remodeling, including demonstration that patches heal by infiltration of vascular stem cells according to their environment (Li et al., PLoS ONE 7:e38844, 2012; Bai et al., Physiol Rep 4:e12841, 2016; Bai et al., J Biomed Mater Res A 105:3422, 2017). This work led to the first description of a mechanism of pseudoaneurysm formation after patch angioplasty (Bai et al., ATVB epub Nov 16 2017) as well as description of a novel drug delivery system (Bai et al., Sci Rep 7:40142, 2017). We also study remodeling of tissue engineered vascular grafts using both in vivo and in vitro models.
Selected Awards for Dardik Laboratory Trainees:
- 2003 Jacek Paszkowiak: Connecticut Chapter of the American College of Surgeons, 1st place prize for best talk
- 2004 Desarom Teso: Society for Clinical Vascular Surgery, Allastair Karmody Award
- 2006 Tamara Fitzgerald: Ohse award, Dept. of Surgery, Yale University School of Medicine
- 2006 Tamara Fitzgerald: NIH F32 Research Fellowship Award
- 2007 Dania Magri: Doris Duke Clinical Fellowship
- 2008 Tormod Westvik: American Vascular Association, Lifeline Resident Research Prize
- 2009 Amanda Feigel: American College of Surgeons, Surgical Forum Excellence in Research Award
- 2009 Lynn Model: NIH T32 Research Fellowship Award
- 2011 Clay Quint: American Vascular Association, Lifeline Resident Research Prize
- 2011 Caroline Jadlowiec: American College of Surgeons, Surgical Forum Excellence in Research Award
- 2011 Sammy Eghbalieh: Society for Vascular Surgery Basic Science Poster competition winner
- 2011 Lynn Model: Research Resident of the Year award, Dept. of Surgery, Yale University School of Medicine
- 2011 Clinton Protack: Ohse award, Dept. of Surgery, Yale University School of Medicine
- 2012 Robert Brenes: Society for Vascular Surgery Foundation, Resident Research Prize
- 2012 Michael Collins: Association of VA Surgeons, 1st place Basic Science Presentation
- 2015 Jeans Santana: Sarnoff Fellowship, Sarnoff Cardiovascular Research Foundation
- 2016 Trenton Foster: Society for Vascular Surgery Foundation, Resident Research Prize
- 2016 Tambudzai Kudze: HHMI Medical Student Research Fellowship, Howard Hughes Medical Institute
- 2017 Jeans Santana: the Association of VA Surgeons, Lloyd S Rogers award
- 2017 Katharine Wolf: Sarnoff Fellowship, Sarnoff Cardiovascular Research Foundation
- 2018 Jolanta Gorecka: Association of VA Surgeons Resident Research Award
- 2018 Arash Fereydooni: HHMI Medical Student Research Fellowship, Howard Hughes Medical Institute
- 2018 Shin Rong Lee: NIH T32 Research Fellowship Award
- 2018 Shirley Liu: NIH T32 Research Fellowship Award
- 2019 Jolanta Gorecka: Association of VA Surgeons Resident Research Award
- 2019 John Langford: NIH T32 Research Fellowship Award
- 2020 Luis Gonzalez: NIH F30 Predoctoral NRSA Fellowship
Aorta; Arterial Occlusive Diseases; Arteriosclerosis; Arteriovenous Anastomosis; Arteriovenous Fistula; Arteriovenous Shunt, Surgical; Cardiovascular System; Carotid Arteries; Endothelium; Endothelium, Vascular; Graft Occlusion, Vascular; Jugular Veins; Molecular Biology; Research; Stem Cells; Vascular Diseases; Vascular Surgical Procedures; Vena Cava, Inferior; Reperfusion Injury; Vascular Fistula; Peripheral Vascular Diseases; Carotid Stenosis; Diabetic Foot; Surgically-Created Structures; Tissue Engineering; Receptor, EphB4; Ephrin-B2; Vascular Endothelial Growth Factors; Adult Stem Cells; Induced Pluripotent Stem Cells; Vascular Remodeling; Analytical, Diagnostic and Therapeutic Techniques and Equipment
Public Health Interests