Alan Dardik MD-PhD, FACS

Associate Professor of Surgery (Vascular); Chief, Vascular Surgery, VA Connecticut Healthcare Systems, West Haven, CT

Research Interests

Vein graft adaptation; Fistula adaptation; Markers of blood vessel identity during vein graft and AVF adaptation; How understanding the mechanisms of vein graft adaptation lead to improved tissue engineering; Effects of aging on vein graft adaptation; Bioengineering a "better" blood vessel

Current Projects

  • Dr. Clinton Protack is currently examining the role of Eph-B4 phosphorylation and downstream signaling in vein graft adaptation.
  • Dr. Kota Yamamoto is currently examining the role of Eph-B4 and eNOS expression in AVF maturation.
  • Dr. Chenzi Yang is currently examining the role of VEGF-A in downstream regulation of vein graft identity.
  • Dr. Michael Hall is currently building a novel organ perfusion model of vein graft adaptation.
  • Dr. Taylor Williams is currently examining eNOS and TGF-beta signaling during vein graft adaptation.
  • Dr. Roland Assi is currently understanding the role of flow in Eph-B4 activation.

Research Summary

The Dardik laboratory studies the healing and function of blood vessels and synthetic blood vessel substitutes that are used in patients having vascular bypass surgery. We are currently trying to understand the fundamental molecular mechanisms by which vein graft adaptation results in positive remodeling and successful adaptation to the arterial environment, yet often proceeds, in the long-term, to neointimal hyperplasia and graft failure. The laboratory has made the original observation that vein graft adaptation is associated with diminished Eph-B4 expression (Kudo et al., ATVB 27:1562, 2007). We are currently investigating the importance of modulating Eph-B4 function in vein graft adaptation, and have recently published that Eph-B4 is active in adult veins, regulates venous remodeling, and that Eph-B4 function depends on receptor phosphorylation and association with caveolin-1 signaling (Muto et al., J Exp Med 208:561, 2011). We are currently investigating the importance of modulating Eph-B4 function in vein graft adaptation. The laboratory is R01 funded from the NIH NHLBI and, as part of Yale's Interdepartmental Program in Vascular Biology and Therapeutics, is located on the 4th floor of the Amistad building. Members of the Dardik laboratory include surgery residents from Yale, UConn, and St. Mary’s Hospital as well as postdoctoral fellows from Japan, China, and India.

Extensive Research Description

We previously published that Eph-B4, a determinant of venous identity during embryonic development that persists as a venous marker, decreases expression and immunodetectable protein during vein graft adaptation in both humans and aged rats. We have extended our findings to a mouse model and have found similar results. Based on this work we hypothesize that Eph-B4 is a critical negative regulator of multiple SMC layer development.
We are currently manipulating Eph-B4 in vivo to test our hypothesis that Eph-B4 remains functional during adult life and is a regulator of vein graft identity and adaptation to the arterial environment. We are collaborating with the Sessa laboratory to test the importance of caveolin-1 binding and phosphorylation to Eph-B4 activation. We are collaborating with the Breuer laboratory to test the importance of Eph-B4 and Ephrin-B2 in the development of tissue engineered vascular grafts.

Honors & Awards for Dardik Laboratory Trainees:

  • 2002 Masae Haga: Eastern Vascular Society, the William J. von Liebig Foundation Second Place Poster Award
  • 2002 Jacek Paszkowiak: Connecticut Chapter of the American College of Surgeons, 2nd place prize for best poster, resident’s competition
  • 2003 Jacek Paszkowiak: Connecticut Chapter of the American College of Surgeons, 1st place prize for best talk, resident’s competition
  • 2004 Desarom Teso: Society for Clinical Vascular Surgery, Allastair Karmody Award
  • 2004 Desarom Teso: New England Surgical Society, 2nd place prize for best talk, resident’s competition
  • 2006 Tamara Fitzgerald: Ohse award, Dept. of Surgery, Yale University School of Medicine
  • 2006 Tamara Fitzgerald: NIH F32 Research Fellowship Award
  • 2007 Jose Pimiento: New England Surgical Society’s Surgical Resident and Fellow Research Presentation Day, 2nd place prize for best talk, resident’s competition
  • 2007 Dania Magri: Lifeline Student Research Fellowship, American Vascular Association
  • 2008 Tiffany Fancher: Connecticut Chapter of the American College of Surgeons, 1st place Resident Research Prize
  • 2008 Tormod Westvik: American Vascular Association, Lifeline Resident Research Prize
  • 2009 Akihito Muto: International Academic Encouragement Award, Nagoya Surgery Support Organization, Nagoya, Japan
  • 2009 Amanda Feigel: American College of Surgeons, Surgical Forum Excellence in Research Award
  • 2009 Amanda Feigel: Connecticut Chapter of the American College of Surgeons, 1st place Resident Research Prize
  • 2009 Kenneth Ziegler: New England Society for Vascular Surgery – Attendance Grant: Student Initiative Program
  • 2010 Akihito Muto: Society for Vascular Surgery Travel Scholarship to Research Initiatives / ATVB conference
  • 2010 Sammy Eghbalieh: Society for Vascular Surgery Travel Scholarship to 2010 Vascular Annual conference
  • 2010 Amanda Feigel: Society for Vascular Surgery Travel Scholarship to 2010 Vascular Annual conference
  • 2010 Lynn Model: Society for Vascular Surgery Travel Scholarship to 2010 Vascular Annual conference
  • 2010 Kenneth Ziegler: New England Society for Vascular Surgery – Attendance Grant: Student Initiative Program
  • 2010 Lynn Model: New England Society for Vascular Surgery – Attendance Grant: Student Initiative Program
  • 2011 Clay Quint: American Vascular Association, Lifeline Resident Research Prize
  • 2011 Kenneth Ziegler: Society for Vascular Surgery Travel Scholarship to 2011 Vascular Annual conference
  • 2011 Sammy Eghbalieh: Society for Vascular Surgery Travel Scholarship to 2011 Vascular Annual Conference
  • 2011 Caroline Jadlowiec: American College of Surgeons, Surgical Forum Excellence in Research Award
  • 2011 Mike Collins: New England Surgical Society’s Surgical Resident and Fellow Research Presentation Day, 2nd place prize, basic science
  • 2011 Robert Brenes: Waterbury Resident Research Day, 1st place Poster Presentation
  • 2011 Sammy Eghbalieh: Society for Vascular Surgery Basic Science Poster competition winner, 2011 Vascular Annual Meeting
  • 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

Selected Publications

  • Li X, Jadlowiec C, Guo Y, Protack C, Ziegler K, Lv W, Yang C, Shu C, Dardik A. Pericardial patch angioplasty heals via an Ephrin-B2 and CD34 positive cell mediated mechanism. PLoS ONE 7(6):e38844 (2012)
  • Muto A, Panitch A, Kim N, Park K, Komalavilas P, Brophy CM, Dardik A. Inhibition of Mitogen Activated Protein Kinase Activated Protein Kinase II with MMI-0100 reduces intimal hyperplasia ex vivo and in vivo. Vascular Pharmacology 56:47-55 (2012)
  • Dardik A and Gaunt M. Outpatient Surgery. Clinical decision making and board review. Radcliffe Publishing, London (2012).
  • Eghbalieh SDD, Chowdhary P, Muto A, Ziegler KR, Kudo FA, Pimiento JM, Mirmehdi I, Model LS, Kondo Y, Nishibe T, Dardik A. Age-related neointimal hyperplasia is associated with monocyte infiltration after balloon angioplasty. Journal of Gerontology Series A: Biological Sciences 67(2):109-117 (2012)
  • Muto A, Yi T, Harrison KD, Dávalos A, Fancher TT, Ziegler KR, Feigel A, Kondo Y, Nishibe T, Sessa WC, Dardik A. Eph-B4 prevents venous adaptive remodeling in the adult arterial environment. Journal of Experimental Medicine 208(3):561-575 (2011).
  • Muto A, Model L, Ziegler K, Eghbalieh SDD, Dardik A. Mechanisms of vein graft adaptation to the arterial circulation: Insights into the neointimal algorithm and management strategies. Circulation Journal 74(8):1501-1512 (2010).

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