Cynthia St. Hilaire, PhD
Assistant Professor of Medicine

Dr. Hilaire

Dr. Hilaire is Assistant Professor of Medicine, Division of Cardiology, Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine.

Office Location:
1744 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261

Contact Information:
Office Telephone: 412-648-9441
Fax: 412-624-6161
Email: sthilaire@pitt.edu

Education

  • BA - 2001, University of Vermont, 2001
  • PhD - 2008, Boston University School of Medicine

Research Interests

Research in the St. Hilaire Lab focuses on characterizing the underlying pathobiology of vascular disease, concentrating on mechanisms that drive vascular and valvular calcification and remodeling. Ectopic calcification in the cardiovascular system was once considered a passive and degenerative progression, but it is now appreciated that active biological processes drive this pathology, though the precise mechanisms inducing and propagating pathological calcification are not completely understood. Our overarching goal is to dissect the mechanisms that drive the transformation of a healthy vascular cell into a calcifying cell, in order to identify targets for the development of pharmacological therapies.

One avenue of research stems from the discovery by Dr. St. Hilaire and her colleagues at the NIH of the rare disease Arterial Calcification due to Deficiency of CD73 (ACDC). Patients with ACDC have inactivating mutations in the gene encoding for CD73, which catalyzes the breakdown of extracellular AMP to adenosine. ACDC patients exhibit severe medial-layer lower extremity vascular calcification and vessel tortuosity, which suggests that CD73 and adenosine signaling help to protect the vasculature from these pathologies. Vascular calcification and vessel tortuosity are phenotypes seen in a variety of diseases thus we aim to leverage what we learn from the study of this rare disease to identify novel mechanisms driving these pathologies in more common disorders.

Calcification in the aortic valves develops in roughly 30% of the aging population. Calcific aortic valve disease (CAVD) encompasses a spectrum of pathologic states that range from aortic sclerosis, the thickening and stiffening of the valve leaflets, to aortic stenosis, where blood flow to the aorta is obstructed and can lead to heart failure. We have created a human biospecimen bank of 150 control and CAVD valve specimens from which we obtain samples for pathology, biochemical, and gene expression analysis, as well as create primary cell lines that we use to study the process of how a healthy valve cell converts into a calcifying valve cell.

Please got to the St. Hilaire Lab website to learn more www.sthilairelab.pitt.edu

Selected Publications

  1. St Hilaire C, Ziegler SG, Markello TC, Brusco A, Groden C, Gill F, Carlson-Donohoe H, Lederman RJ, Chen MY, Yang D, Siegenthaler MP, Arduino C, Mancini C, Freudenthal B, Stanescu HC, Zdebik AA, Chaganti RK, Nussbaum RL, Kleta R, Gahl WA, Boehm M. NT5E mutations and arterial calcifications. N Engl J Med. 2011 Feb 3;364(5):432-42. PubMed PMID: 21288095; PubMed Central PMCID: PMC3049958.
  2. Mark ello TC, Pak LK, St Hilaire C, Dorward H, Ziegler SG, Chen MY, Chaganti K, Nussbaum RL, Boehm M, Gahl WA. Vascular pathology of medial arterial calcifications in NT5E deficiency: Implications for the role of adenosine in pseudoxanthoma elasticum. Mol Genet Metab. 2011 May;103:44-50. PMID 21371928.
  3. Cooley BC, Nevado J, Mellad J, Yang D, St Hilaire C, Negro A, Fang F, Chen G, San H, Walts AD, Schwartzbeck RL, Taylor B, Lanzer JD, Wragg A, Elagha A, Beltran LE, Berry C, Feil R, Virmani R, Ladich E, Kovacic JC, Boehm M. TGF-? signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling. Sci Transl Med. 2014 Mar 12;6(227):227ra34. PubMed PMID: 24622514; PubMed Central PMCID: PMC4181409.
  4. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS, Lee CC, DiMattia MA, Cowen EW, Gonzalez B, Palmer I, DiGiovanna JJ, Biancotto A, Kim H, Tsai WL, Trier AM, Huang Y, Stone DL, Hill S, Kim HJ, St Hilaire C, Gurprasad S, Plass N, Chapelle D, Horkayne-Szakaly I, Foell D, Barysenka A, Candotti F, Holland SM, Hughes JD, Mehmet H, Issekutz AC, Raffeld M, McElwee J, Fontana JR, Minniti CP, Moir S, Kastner DL, Gadina M, Steven AC, Wingfield PT, Brooks SR, Rosenzweig SD, Fleisher TA, Deng Z, Boehm M, Paller AS, Goldbach-Mansky R. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014 Aug 7;371(6):507-18. PubMed PMID: 25029335; PubMed Central PMCID: PMC4174543.
  5. P. Lanzer, M. Boehm, V. Sorribas, M. Thiriet, J. Janzen, T. Zeller, C. St. Hilaire, C. Shanahan. Medial vascular calcification revisited: review and perspectives. Eur Heart J. 2014 Jun 14;35(23):1515-1525. PMID 24740885.
  6. Boehm M, St. Hilaire C. Vascular Genetics. In: Lanzer P. (Ed.) PanVascular Medicine, 2nd edition, vol.x, pp 53-88. Springer Heidelberg New York Dordrecht London, 2015. DOI: 10.1007/978-3-642-37393-0_4-1