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Claudette Marie St. Croix, PhD

Contact

Room 220.1 BSTS, 3500 Terrace Street
R-znvy: pyf68@cvgg.rqh
Primary Phone: 967-179-5635


Personal Statement

In the St. Croix laboratory, we employ emerging optical imaging technologies to address fundamental concepts in vascular endothelial cell biology, specifically the role of the endothelium in regulating blood flow distribution in the lung. We have focused our efforts on investigating the physiological of nitric oxide (NO) mediated changes in intracellular zinc on endothelial cell signaling. In particular: 1) the cellular regulation of transition metal (zinc) homeostasis by metallothionein S-nitrosylation in pulmonary endothelium; 2) the role of NO-zinc mediated in the regulation of hypoxic pulmonary vasoconstriction; and 3) the role for NO-released zinc in promoting phosphorylation of key signaling proteins that activate contractile pathways in endothelial cells. In collaboration with Michael Tsang (Developmental Biology) and Beth Roman (Biological Sciences) we recently adopted the embryonic zebrafish (Daniorerio) model to study zinc-mediated control of vascular function. We have since expanded this program to encompass the development and validation of the system-based microscopic approaches to assess endothelial dysfunction. A third, related research focus is a funded collaborative effort with Drs. Marcel Bruchez and Alan Waggoner from Carnegie Mellon University directed towards development and application of novel genetically encoded fluorescent biosensors for calcium, and reactive oxygen and nitrogen species (ROS and RNS, respectively), to establish the role of ROS and RNS based signaling in the regulation of vascular tone and barrier function in cell culture and in zebrafish models of vascular disease.





Education

1988 University of Guelph, Guelph, ON, Canada BSc (Hons)
1991 University of Toronto, Toronto, Canada MSc (Exercise Sciences)
1995 University of Western Ontario, London, Canada PhD (Kinesiology)
2000 University of Wisconsin-Madison, WI Postdoctoral Fellow (cardiopulmonary physiology)
2002 University of Pittsburgh, Pittsburgh, PA  Postdoctoral Fellow (Pharmacology)


Teaching

EOH 3210 Pathophysiology of Environmental Disease (Director)
EOH 2314  Molecular Fundamentals of Environmental Health
MSCBMP 2860 Multiparametric Microscopic Imaging (co-Director)
Quantitative Fluorescence Microscopy (QFM), Mount Desert Island Biologic Laboratory, Maine





Translational Program Project: Vascular Sub-Phenotypes of Lung Disease

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute

Translational Program Project: Vascular Sub-Phenotypes of Lung Disease


Selected Publications

Since 2008 (of 64 Total):
1.       Bernal, PJ, Leelavanichkul, K, Bauer, EM, Cao, R, Wilson, A, Wasserloos, KJ, Watkins,SC, Watkins, SC, Pitt, BR,Watkins, SC and St.Croix, C.M. Nitric oxide mediated zinc release contributes to hypoxic regulation of pulmonary vascular tone. Circ Res. 102(12):1575-83, 2008. PMID: 18483408
2.       Garner AL, St Croix CM, Pitt BR, Leikauf GD, Ando S and Koide K. Specific fluorogenic probes for ozone in biological and atmospheric samples. Nature Chemistry1: 316 – 321, 2009.
3.       Tang JB, Goellner EM, Wang XH, Trivedi RN, St Croix CM, Jelezcova E, Svilar D, Brown AR, Sobol RW. Bioenergetic Metabolites Regulate Base Excision Repair-Dependent Cell Death in Response to DNA Damage. Mol Cancer Res. 8:67-79, 2010. PMID: 20068071.
4.       Bhatia S, Fei M, Yarlagadda M, Qi Z, Akira S, Saijo S, Iwakura Y, van Rooijen N, Gibson GA, St Croix CM, Ray A, Ray P.et al. 2011Rapid Host Defense against Aspergillusfumigatus Involves Alveolar Macrophages with a Predominance of Alternatively Activated Phenotype. PLoS ONE 6(1):e15943, 2011. PMID: 21246055.
5.       Thambiayya K, Wasserloos KJ, Huang Z, Kagan VE, St Croix CM, Pitt BR. LPS-induced decrease in intracellular labile zinc [Zni] contributes to apoptosis in cultured sheep pulmonary artery endothelial cells (SPAEC).Am J Physiol Lung Cell Mol Physiol. 300(4):L624-32, 2011. PMID: 21239534.
6.       Zhao J, O'Donnell VB, Balzar S, St Croix CM, Trudeau JB, Wenzel SE. 15-Lipoxygenase 1 interacts with phosphatidylethanolamine-binding protein to regulate MAPK signaling in human airway epithelial cells. Proc NatlAcadSci USA. 2011 Aug 23;108(34):14246-51, 2011. PMID: 21831839.
7.       Bernal PJ, Bauer EM, Cao R, Maniar S, Mosher M, Chen J, Wang QJ, Glorioso JC, Pitt BR, Watkins SC, St Croix CM. A Role for Zinc in Regulating Hypoxia-Induced Contractile Events in Pulmonary Endothelium.Am J Physiol Lung Cell Mol Physiol. 300(6):L874-886, 2011. PMID:21378023.
8.      Cioffi DL, Wu S, Chen H, Alexeyev M, St Croix CM, Pitt BR, Uhlig S, Stevens T. Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel. Circ Res. 2012 May 25;110(11):1435-44. Epub 2012 Apr 24. PubMed PMID: 22534489; PubMed Central PMCID: PMC3388001.
9.      Shvedova AA, Kapralov AA, Feng WH, Kisin ER, Murray AR,Mercer RR, St Croix CM, Lang MA,
Watkins SC, Konduru NV, Allen BL, Conroy J, Kotchey GP, Mohamed BM,  Meade AD, Volkov Y, Star A, Fadeel B, Kagan VE. Impaired clearance and enhanced pulmonary inflammatory/fibrotic response to carbon nanotubes in myeloperoxidase-deficient mice. PLoS One. 2012;7(3):e30923. Epub 2012 Mar 30. PubMed PMID: 22479306; PubMed Central PMCID: PMC3316527. 
10.    Watkins SC, Maniar S, Mosher M, Roman BL, Tsang M, St Croix CM. High resolution imaging of vascular function in zebrafish. PLoS One. 2012;7(8):e44018. Epub 2012 Aug 30. PubMed PMID: 22952858; PubMed Central PMCID: PMC3431338.
11.    Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC, Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD. NF-κB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest. 2012 Jul 2;122(7):2601-12. doi: 10.1172/JCI45785. Epub 2012 Jun 18. PubMed PMID: 22706308; PubMed Central PMCID: PMC3386805. 
12.   Al Ghouleh I, Frazziano G, Rodrigues AI, Csanyi G, Maniar S, St Croix CM, Kelley EE, Egana LA, Song GJ, Bisello A, Lee YJ, Pagano PJ. Aquaporin 1, Nox1 and Ask1 Mediate Oxidant-Induced Smooth Muscle Cell Hypertrophy. Cardiovasc Res. 2012 Sep 20. [Epub ahead of print] PubMed PMID: 22997161.
13.    Khoo NK, Cantu-Medellin N, Devlin JE, St Croix CM, Watkins SC, Fleming AM, Champion HC, Mason RP, Freeman BA, Kelley EE. Obesity-induced tissue free radical generation: an in vivo immuno-spin trapping study. Free RadicBiol Med. Jun  1-15;52(11-12):2312-9, 2012. PubMed PMID: 22564528.
14.   Svilar D, Dyavaiah M, Brown AR, Tang JB, Li J, McDonald PR, Shun TY, Braganza  A, Wang XH, Maniar S, St Croix CM, Lazo JS, Pollack IF, Begley TJ, Sobol RW. Alkylation sensitivity screens reveal a conserved cross-species functionome. Mol  Cancer Res. 2012 Oct 4. [Epub ahead of print] PubMed PMID: 23038810.
15.    Bonacci G, Baker PR, Salvatore SR, Shores D, Khoo NK, Koenitzer JR, Vitturi DA, Woodcock SR, Golin-Bisello F, Watkins S, St Croix C, Batthyany CI, Freeman BA, Schopfer FJ. Conjugated Linoleic Acid is a Preferential Substrate for Fatty Acid Nitration. J Biol Chem. 2012 287(53):44071-82. doi: 10.1074/jbc.M112.401356.
16.   Sayeed S, Nistico L, St Croix C, Di YP. Multifunctional role of human SPLUNC1  in Pseudomonas aeruginosa infection. Infect Immun. 2012 Nov 6. [Epub ahead of print] PubMed PMID: 23132494.
17.   Thambiayya K, Kaynar AM, St Croix CM, Pitt BR. Functional role of intracellular labile zinc
in pulmonary endothelium. Pulm Circ. 2012 Oct;2(4):443-51. doi:10.4103/2045-8932.105032. PubMed PMID: 23372928; PMCID: PMC3555414.
18.   Nasto LA, Robinson AR, Ngo K, Clauson CL, Dong Q, St Croix C, Sowa G, Pola E,  Robbins PD, Kang J, Niedernhofer LJ, Wipf P,Vo NV. Mitochondrial-derived reactive oxygen species (ROS) Play a causal role in aging-related intervertebral  disc degeneration. J Orthop Res. 2013 Feb 6. doi: 10.1002/jor.22320. [Epubahead  of print] PubMed PMID: 23389888. 
19.    Li HH, Li J, Wasserloos KJ, Wallace C, Sullivan MG, Bauer PM, Stolz DB, Lee JS, Watkins SC, St Croix CM, Pitt BR, Zhang LM. Caveolae-dependent and independent uptake of albumin in cultured rodent pulmonary endothelial cells. PLoS One. 2013 Nov 27;8(11):e81903. doi: 10.1371/journal.pone.0081903. PubMed PMID: 24312378; PubMed Central PMCID: PMC3842245.
20.    Coblentz J, St Croix C, Kiselyov K. TRPML1 loss promotes production of reactive oxygen species: is oxidative damage a factor in mucolipidosis type IV? Biochem J. 2013 Nov 6. [Epub ahead of print] PubMed PMID: 24192042.
21.    Pride CK, Mo L, Quesnelle K, Dagda RK, Murillo D, Geary L, Corey C, Portella R, Zharikov S, St Croix C, Maniar S, Chu CT, Khoo NK, Shiva S. Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion. Cardiovasc Res. 2013 Nov 5. [Epub ahead of print] PubMed PMID: 24081164.
22.   Fazzi F, Njah J, Di Giuseppe M, Winnica DE, Go K, Sala E, St Croix CM, Watkins SC, Tyurin VA, Phinney DG, Fattman CL, Leikauf GD, Kagan VE, Ortiz LA. TNFR1/Phox Interaction and TNFR1 Mitochondrial Translocation Thwart Silica-Induced Pulmonary Fibrosis. J Immunol. 2014 Apr 15;192(8):3837-46. doi: 10.4049/jimmunol.1103516. Epub 2014 Mar 12. PubMed PMID: 24623132; PubMed Central PMCID: PMC3977215.  
23.  Yao M, Rogers NM, Csányi G, Rodriguez AI, Ross MA, St Croix C, Knupp H, Novelli EM, Thomson AW, Pagano PJ, Isenberg JS. Thrombospondin-1 Activation of Signal-Regulatory Protein-α Stimulates Reactive Oxygen Species Production and Promotes Renal Ischemia Reperfusion Injury. J Am Soc Nephrol. 2014 Feb 7. [Epub ahead of print] PubMed PMID: 24511121.  
24.   Kelley EE, Baust J, Bonacci G, Golin-Bisello F, Devlin JE, St Croix CM, Watkins SC, Gor S, Cantu-Medellin N, Weidert ER, Frisbee JC, Gladwin MT, Champion HC, Freeman BA, Khoo NK. Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity. Cardiovasc Res. 2014 Mar 1;101(3):352-63. doi: 10.1093/cvr/cvt341. Epub 2014 Jan 2. PubMed PMID: 24385344; PubMed Central PMCID: PMC3928004.
25.    Sharifi-Sanjani M, Shoushtari AH, Quiroz M, Baust J, Sestito SF, Mosher M,Ross M, McTiernan CF, St Croix CM, Bilonick RA, Champion HC, Isenberg JS. Cardiac CD47 Drives Left Ventricular Heart Failure Through Ca2+-CaMKII-Regulated Induction of HDAC3. J Am Heart Assoc. 2014 Jun 10;3(3). pii: e000670. doi:10.1161/JAHA.113.000670. PubMed PMID: 24922625.26.    Kagan VE, Kapralov AA, St Croix CM, Watkins SC, Kisin ER, Kotchey GP,Balasubramanian K, Vlasova II, Yu J, Kim K, Seo W, Mallampalli RK, Star A,Shvedova AA. Lung Macrophages "Digest" Carbon Nanotubes Using a Superoxide/Peroxynitrite Oxidative Pathway. ACS Nano. 2014 Jun 4. [Epub ahead of print] PubMed PMID: 24871084.

Claudette Marie St. Croix
© 2017 by University of Pittsburgh Graduate School of Public Health

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