Research

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).

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.