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Stanley L. Hazen, M.D., Ph.D.StaffDept. of Cell Biology |
Mechanisms of atherosclerosis; leukocyte peroxidases; nitric oxide and reactive oxygen species; oxidant injury in asthma and other inflammatory diseases; cardiovascular genetics
A long term goal of my laboratory is to understand the mechanisms through which inflammation and oxidative damage contributes to diseases such as atherosclerosis and asthma. A parallel objective is to investigate genetic and biochemical determinants cardiovascular disease. Several major research programs are currently under investigation. The first focuses on the role of myeloperoxidase, a heme protein present in neutrophils, monocytes and certain tissue macrophages, in promoting oxidant stress in vivo, and its potential participation in cardiovascular diseases. The second area focuses on HDL structure/function, and mechanisms for rendering HDL dysfunctional within human atheroma. A third area of research interest is to identify the pathways responsible for development of vulnerable plaque and sudden cardiac death. A fourth area of investigation is to identify genetic determinants of cardiovascular disease initiation and propagation. Finally, the fifth area focuses on the role of eosinophils in mediating oxidative tissue injury in asthma. All research projects rely on multidisciplinary approaches and span from bench to bedside, including biochemical biophysical mechanistic studies, genetic, cellular and animal model studies assessing biochemical and functional roles of specific pathways, and performance of human clinical studies aimed at elaborating the contributions of specific inflammatory pathways to disease pathogenesis.
Wu Z, Wagner MA, Zheng L, Parks JS, Shy JM 3rd, Smith JD, Gogonea V, Hazen SL. The refined structure of nascent HDL reveals a key functional domain for particle maturation and dysfunction. Nat. Struct. Mol. Biol. (2007) 14(9): 861-8.
Podrez EA, Byzova1 TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M, Poliakov E, Sun M, Finton PJ, Curtis BR, Chen J, Zhang R, Silverstein RL, Hazen SL. Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nature Medicine. (2007) 13(9): 1086-1095.
Wang Z, Nicholls SJ, Rodriguez ER, Kummu O, Hörkkö S, Barnard J, Topol EJ, Hazen SL. Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nature Medicine. (2007) 13(10): 1176-84.
Sehayek E, Hazen SL. Cholesterol absorption from the intestine is a major determinant of reverse cholesterol transport from peripheral tissue macrophages. Arterioscler Thromb Vasc Biol. (2008) 28(7):1296-7.PMID: 18420997
Brovkovych V, Gao XP, Ong E, Brovkovych S, Brennan ML, Su X, Hazen SL, Malik AB, Skidgel RA. Augmented inducible nitric oxide synthase expression and increased NO production reduce sepsis-induced lung injury and mortality in myeloperoxidase-null mice. Am J Physiol Lung Cell Mol Physiol. (2008) 295(1):L96-103. PMID: 18424617
Vaccarino V, Brennan ML, Miller AH, Bremner JD, Ritchie JC, Lindau F, Veledar E, Su S, Murrah NV, Jones L, Jawed F, Dai J, Goldberg J, Hazen SL. Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study. Biol Psychiatry. (2008) 64(6):476-83. PMID: 18514165
El-Bejjani D, Hazen SL, Mackay W, Glass NE, Hulgan T, Tungsiripat M, McComsey GA. Higher plasma myeloperoxidase levels are not associated with an increased risk for cardiovascular events in HIV-infected adults. HIV Clin Trials. (2008) 9(3):207-11. PMID: 18547908
Shishehbor MH, Oliveira LP, Lauer MS, Sprecher DL, Wolski K, Cho L, Hoogwerf BJ, Hazen SL. Emerging cardiovascular risk factors that account for a significant portion of attributable mortality risk in chronic kidney disease. Am J Cardiol. (2008) 101(12):1741-6. PMID: 18549850
Lara A, Khatri SB, Wang Z, Comhair SA, Xu W, Dweik RA, Bodine M, Levison BS, Hammel J, Bleecker E, Busse W, Calhoun WJ, Castro M, Chung KF, Curran-Everett D, Gaston B, Israel E, Jarjour N, Moore W, Peters SP, Teague WG, Wenzel S, Hazen SL, Erzurum SC; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Alterations of the arginine metabolome in asthma. Am J Respir Crit Care Med. (2008) 178(7):673-81. PMID: 18635886
Jin G, Zhou X, Wang H, Zhao H, Cui K, Zhang XS, Chen L, Hazen SL, Li K, Wong ST. The knowledge-integrated network biomarkers discovery for major adverse cardiac events. J Proteome Res. (2008) 7(9):4013-21.PMID: 18665624
Wilson Tang WH, Tong W, Shrestha K, Wang Z, Levison BS, Delfraino B, Hu B, Troughton RW, Klein AL, Hazen SL. Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure. Eur Heart J. (2008) 29(20):2506-13. PMID: 18687662
Peng DQ, Brubaker G, Wu Z, Zheng L, Willard B, Kinter M, Hazen SL, Smith JD. Apolipoprotein A-I tryptophan substitution leads to resistance to myeloperoxidase-mediated loss of function. Arterioscler Thromb Vasc Biol. (2008) 28(11):2063-70. PMID: 18688016
Pham TD, Wang H, Zhou X, Beck D, Brandl M, Hoehn G, Azok J, Brennan ML, Hazen SL, Li K, Wong ST. Computational prediction models for early detection of risk of cardiovascular events using mass spectrometry data. IEEE Trans Inf Technol Biomed. (2008) 12(5):636-43. PMID: 18779078
Diab DL, Yerian L, Schauer P, Kashyap SR, Lopez R, Hazen SL, Feldstein AE. Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients. Clin Gastroenterol Hepatol. (2008) 6(11):1249-54. PMID: 18995215
Nicholls SJ, Hazen SL. Myeloperoxidase, modified lipoproteins and atherogenesis. J Lipid Res. (2008) 50 Suppl:S346-51.
Wedes S, Khatri S, Zhang, R, Wu W, Comhair S, Wenzel S, Teague W, Israel E, Erurum S, Hazen SL. Noninvasive markers of airway inflammation in asthma. Clinical and Translational Science. (2009) 2:112-117.
Shishehbor MH, Hazen SL. Jupiter to earth: a statin helps people with normal LDL-C and high hs-CRP, but what does it mean? Cleve Clin J Med. (2009) 76:37-44.
Tang WH, Katz R, Phil D, Brennan ML, Aviles RJ, Tracy RP, Psaty BM, Hazen SL. Usefulness of myeloperoxidase levels in healthy elderly subjects to predict risk of developing heart failure. American J of Cardiology. (2009) 103: 1269-74.
Tang WH, Wang Z, Cho L, Brennan D, Hazen SL. Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk. J American Col. Cardiology. (2009) 53: 2061-7.
Zhou X, Wang H, Wang J, Wang Y, Hoehn G, Azok J, Brennan ML, Hazen SL, Li K, Chang SF, Wong ST. Identification of biomarkers for risk stratification of cardiovascular events using genetic algorithm with recursive local floating search. Proteomics. (2009) 9:2286-94.
Kato GJ, Wang Z, Machado RF, Blackwelder WC, Taylor JG 6th, Hazen SL. Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol. (2009) 145:506-13.
Kashyap SR, Diab DL, Baker AR, Yerian L, Bajaj H, Gray-McGuire C, Schauer PR, Gupta M, Feldstein AE, Hazen SL, Stein CM. Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring). (2009) In Press.
Wang Z, Tang WH, Cho L, Brennan DM, Hazen SL. Targeted metabolomic evaluation of arginine methylation and cardiovascular risks. Potential Mechanisms Beyond Nitric Oxide Synthase Inhibition. Arterioscler Thromb Vasc Biol. (2009) In Press.