Education & Training
- B.S., Molecular Genetics, University of Vermont- 2001
- Ph.D.,Biochemistry, Program in Cell and Molecular Biology, Boston University School of Medicine- 2008
- Postdoctoral Fellowship, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD-2008-2015
Research Interest Summary
Cardiovascular disease is the leading cause for mortality worldwide. Vascular calcification is an independent co-morbidity seen in many cardiovascular disease states and itself is a well-established marker indicative of disease severity. The overarching goal of the research conducted in the St. Hilaire Lab focuses on identifying and characterizing the mechanisms underlying the development of vascular and valvular calcification pathologies, with specific interest in defining the mechanisms by which inflammation and mechanical stress drive the transformation of a healthy vascular cell into a calcifying cell. Through collaborations with UPMC Heart and Vascular Institute surgeons, Dr. St. Hilaire's lab built a biobank of human arterial and valvular tissues and and creates cell lines from healthy and diseased patients for in vitro and ex vivo studies and next-generation sequencing technologies. Using these human samples, they discovered a novel non-canonical role for telomerase in regulating the phenotypic switching of a healthy valve cell into an osteogenic calcifying cell in calcific aortic valve disease. Leveraging their experience in vascular inflammation they have embarked on a project exploring how activation of the innate immune system and signaling pathways drives transcriptional activation of osteogenic pathways and promotes endothelial cell dysfunction, ectopic calcification, and extracellular matrix remodeling. Additional ongoing projects stem from Dr. St. Hilaire's discovery of the genetic cause of a rare disease in which patients develop non-atherosclerotic vascular calcification in their lower-extremity arteries due to mutations in the gene NT5E/CD73. Projects in this line of research aim to understand how mutations in CD73 lead to lower-extremity non-atherosclerotic vascular calcification and to define the role of CD73 and adenosine signaling in regulating extracellular matric homeostatis and vessel tortuosity.
Moorhead WJ 3rd, Chu CC, Cuevas RA, Callahan J 4th, Wong R, Regan C, Boufford CK, Sur S, Liu M, Gomez D, MacTaggart JN, Kamenskiy A, Boehm M, St Hilaire C. Dysregulation of FOXO1 (Forkhead Box O1 Protein) Drives Calcification in Arterial Calcification due to Deficiency of CD73 and Is Present in Peripheral Artery Disease. Arterioscler Thromb Vasc Biol. 2020 Jul;40(7):1680-1694. doi: 10.1161/ATVBAHA.119.313765. Epub 2020 May 7. PubMed PMID: 32375544; PubMed Central PMCID: PMC7310306.
Joolharzadeh P, St Hilaire C. CD73 (Cluster of Differentiation 73) and the Differences Between Mice and Humans. Arterioscler Thromb Vasc Biol. 2019 Mar;39(3):339-348. doi: 10.1161/ATVBAHA.118.311579. Review. PubMed PMID: 30676071; PubMed Central PMCID: PMC6446586.
Gomez D, Baylis RA, Durgin BG, Newman AAC, Alencar GF, Mahan S, St Hilaire C, Müller W, Waisman A, Francis SE, Pinteaux E, Randolph GJ, Gram H, Owens GK. Interleukin-1β has atheroprotective effects in advanced atherosclerotic lesions of mice. Nat Med. 2018 Sep;24(9):1418-1429. doi: 10.1038/s41591-018-0124-5. Epub 2018 Jul 23. PubMed PMID: 30038218; PubMed Central PMCID: PMC6130822.
Hortells L, Sur S, St Hilaire C. Cell Phenotype Transitions in Cardiovascular Calcification. Front Cardiovasc Med. 2018;5:27. doi: 10.3389/fcvm.2018.00027. eCollection 2018. PubMed PMID: 29632866; PubMed Central PMCID: PMC5879740.
Xue Y, St Hilaire C, Hortells L, Phillippi JA, Sant V, Sant S. Shape-Specific Nanoceria Mitigate Oxidative Stress-Induced Calcification in Primary Human Valvular Interstitial Cell Culture. Cell Mol Bioeng. 2017 Oct;10(5):483-500. doi: 10.1007/s12195-017-0495-6. Epub 2017 Jul 25. PubMed PMID: 30319717; PubMed Central PMCID: PMC6178984.
Jin H*, St Hilaire C*, Huang Y*, Yang D, Dmitrieva NI, Negro A, Schwartzbeck R, Liu Y, Yu Z, Walts A, Davaine JM, Lee DY, Donahue D, Hsu KS, Chen J, Cheng T, Gahl W, Chen G, Boehm M. Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC. Sci Signal. 2016 Dec 13;9(458):ra121. doi: 10.1126/scisignal.aaf9109. PubMed PMID: 27965423; PubMed Central PMCID: PMC5489239. *co-authorship
Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS, Lee CR, 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):507-518. doi: 10.1056/NEJMoa1312625. Epub 2014 Jul 16. PubMed PMID: 25029335; PubMed Central PMCID: PMC4174543.
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-β signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling. Sci Transl Med. 2014 Mar 12;6(227):227ra34. doi: 10.1126/scitranslmed.3006927. PubMed PMID: 24622514; PubMed Central PMCID: PMC4181409.
Markello 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(1):44-50. doi: 10.1016/j.ymgme.2011.01.018. Epub 2011 Feb 3. PubMed PMID: 21371928; PubMed Central PMCID: PMC3081917.
Kovacic JC, Gupta R, Lee AC, Ma M, Fang F, Tolbert CN, Walts AD, Beltran LE, San H, Chen G, St Hilaire C, Boehm M. Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice. J Clin Invest. 2010 Jan;120(1):303-14. doi: 10.1172/JCI40364. Epub 2009 Dec 28. PubMed PMID: 20038813; PubMed Central PMCID: PMC2798694.