Qun Sophia Zang, PhD
Associate Professor
Burn & Shock Trauma Research Institute
Department of Surgery
Bio
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Publications/Research Listings
Summaries
My research in the past decade has focused on cardiac failure in sepsis, a life- threatening condition of organ dysfunction caused by a deregulated host response to infection. Our goal is to understand the mechanisms underlying sepsis-induced, multi-organ failure, and to identify potential new drug targets for this devastating critical care condition. With continuous funding from NIH, we have been investigating the signaling cascade about how injured mitochondria and related production of mitochondria-derived, danger-associated molecular patterns (DAMPs) incite myocardial inflammation, oxidative stress, and cardiac dysfunction in sepsis using preclinical in vitro and in vivo models. Our lab is located within the Burn & Shock Trauma Research Institute in the Center for Translational Research and Education. Trainees are expected to obtain experience in applications of various pre-clinical disease models and to work with a multidisciplinary team with expertise in both basic science and clinical practice. Ongoing Research Projects: We have recently discovered the importance of a previously unidentified function of autophagy factor Beclin-1 in the regulation of mitochondrial quality control in the heart during sepsis. Next step studies are designed to decipher the signal transduction of Beclin-1 in the control of cardiac mitochondrial homeostasis via mitophagy and mitochondria-associated membranes in septic subjects using both genetic and pharmacological approaches. These investigations will not only advance the fundamental understanding of how cardiac mitochondria are regulated during sepsis pathogenesis, but also identify new therapies with promising potential to improve patient care quality and clinical outcomes for sepsis. In addition, we are interested in determining the regulatory mechanism of metabolic plasticity in the heart during sepsis. The myocardium utilizes free fatty acid as its primary energy source at rest state but aerobic glycolysis during sepsis. Our current investigation suggests that the shift of cardiac metabolic plasticity is dependent on autophagy, as well as a crosstalk between myocardium and immune cells. Therefore, we will determine whether and how myocardial metabolites are regulated and used to augment cardiac dysfunction in sepsis. We will pursue our investigation of sepsis-induced cardiac dysfunction in aged population and in neonates. Sepsis is more prevalent in the elderly population, with increased incidence and mortality occurring in patients age 65 or older. On the other hand, neonatal sepsis causes a substantial morbidity and mortality in pediatric patients. To further strengthen the clinical relevance of our research, we have established and validated the mouse models of neonatal sepsis and sepsis in older subjects. Using these tools, we are aiming to unveil the role of autophagy, mitophagy, and metabolic plasticity in cardiac dysfunction during sepsis in all age groups.
Publications
Lopez-Soler, RI; Nikouee, A; Kim, M; Khan, S; Sivaraman, L; Ding, X; Zang, QS Beclin-1 dependent autophagy improves renal outcomes following Unilateral Ureteral Obstruction (UUO) injury. Frontiers in immunology ; 14
Kim, M; Nikouee, A; Zou, R; Ren, D; He, Z; Li, J; Wang, L; Djukovic, D; Raftery, D; Purcell, H; Promislow, D; Sun, Y; Goodarzi, M; Zhang, QJ; Liu, ZP; Zang, QS Age-Independent Cardiac Protection by Pharmacological Activation of Beclin-1 During Endotoxemia and Its Association With Energy Metabolic Reprograming in Myocardium-A Targeted Metabolomics Study. Journal of the American Heart Association ; 11 14
Kim, M; Nikouee, A; Sun, Y; Zhang, QJ; Liu, ZP; Zang, QS Evaluation of Parkin in the Regulation of Myocardial Mitochondria-Associated Membranes and Cardiomyopathy During Endotoxemia. Frontiers in cell and developmental biology ; 10
Wei, Q; Lee, JH; Wu, CS; Zang, QS; Guo, S; Lu, HC; Sun, Y Metabolic and inflammatory functions of cannabinoid receptor type 1 are differentially modulated by adiponectin. World journal of diabetes ; 12 10
Zhang, QJ; He, Y; Li, Y; Shen, H; Lin, L; Zhu, M; Wang, Z; Luo, X; Hill, J; Cao, D; Luo, RL; Zou, R; McAnally, J; Liao, J; Bajona, P; Zang, Q; Yu, Y; Liu, ZP Matricellular Protein Cilp1 Promotes Myocardial Fibrosis in Response to Myocardial Infarction. Circulation research ;
Nikouee, A; Kim, M; Ding, X; Sun, Y; Zang, QS Beclin-1-Dependent Autophagy Improves Outcomes of Pneumonia-Induced Sepsis. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY ; 11
Sun, Y; Cai, Y; Qian, S; Chiou, H; Zang, QS Beclin-1 improves mitochondria-associated membranes in the heart during endotoxemia. FASEB bioAdvances ; 3 3
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Tsao; Tschan; Tse; Tsugawa; Tsvetkov; Tumbarello; Tumtas; Tuñón; Turcotte; Turk; Turner; Tuxworth; Tyler; Tyutereva; Uchiyama; Ugun-Klusek; Uhlig; Ulamek-Koziol; Ulasov; Umekawa; Ungermann; Unno; Urbe; Uribe-Carretero; Üstün; Uversky; Vaccari; Vaccaro; Vahsen; Vakifahmetoglu-Norberg; Valdor; Valente; Valko; Vallee; Valverde; Van den Berghe; van der Veen; Van Kaer; van Loosdregt; van Wijk; Vandenberghe; Vanhorebeek; Vannier-Santos; Vannini; Vanrell; Vantaggiato; Varano; Varela-Nieto; Varga; Vasconcelos; Vats; Vavvas; Vega-Naredo; Vega-Rubin-de-Celis; Velasco; Velázquez; Vellai; Vellenga; Velotti; Verdier; Verginis; Vergne; Verkade; Verma; Verstreken; Vervliet; Vervoorts; Vessoni; Victor; Vidal; Vidoni; Vieira; Vierstra; Viganó; Vihinen; Vijayan; Vila; Vilar; Villalba; Villalobo; Villarejo-Zori; Villarroya; Vincent; Vindis; Viret; Viscomi; Visnjic; Vitale; Vocadlo; Voitsekhovskaja; Volonté; Volta; Vomero; Von Haefen; Vooijs; Voos; Vucicevic; Wade-Martins; Waguri; Waite; Wakatsuki; Walker; Walter; Wandosell; Wang; Warnes; Warnsmann; Watada; Watanabe; Watchon; Wawrzynska; Weaver; Wegrzyn; Wehman; Wei; Weiergräber; Weihl; Weindl; Weiskirchen; Wells; Wen; Werner; Weykopf; Wheatley; Whitton; Whitworth; Wiktorska; Wildenberg; Wileman; Wilkinson; Willbold; Williams; Williamson; Wilson; Winner; Winsor; Witkin; Wodrich; Woehlbier; Wollert; Wong; Wu; Xavier; Xia; Xiang; Xiao; Xie; Xilouri; Xu; Xue; Yakhine-Diop; Yamaguchi; Yamamoto; Yamashina; Yan; Yanagi; Yang; Yao; Yasui; Yazdankhah; Yen; Yi; Yin; Ying; Yip; Yiu; Yoo; Yoshida; Yoshii; Yoshimori; Yousefi; Yu; Yuan; Yue; Yun; Yung; Zacks; Zaffagnini; Zambelli; Zanella; Zang; Zanivan; Zappavigna; Zaragoza; Zarbalis; Zarebkohan; Zarrouk; Zeitlin; Zeng; Žerovnik; Zhan; Zhang; Zhao; Zheng; Zhivotovsky; Zhong; Zhou; Zhu; Zhuang; Zientara-Rytter; Zimmermann; Ziviani; Zoladek; Zong; Zorov; Zorzano; Zou; Zuryn; Zwerschke; Brand-Saberi; Kenchappa; Oshima; Rong; Sluimer; Stallings Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy ;
Sun Y, Cai Y, Zang QS Cardiac Autophagy in Sepsis Cells ; 8 2 141
Lin L, Lee JH, Wang R, Wang R, Sheikh-Hamad D, Zang QS, Sun Y aP2-Cre Mediated Ablation of GHS-R Attenuates Adiposity and Improves Insulin Sensitivity during Aging International journal of molecular sciences ; 19 10
Sun Y, Yao X, Zhang QJ, Zhu M, Liu ZP, Ci B, Xie Y, Carlson D, Rothermel BA, Sun Y, Levine B, Hill JA, Wolf SE, Minei JP, Zang QS Beclin-1-Dependent Autophagy Protects the Heart During Sepsis Circulation ; 138 20 2247
Sehat A, Huebinger RM, Carlson DL, Zang QS, Wolf SE, Song J Burn Serum Stimulates Myoblast Cell Death Associated with IL-6-Induced Mitochondrial Fragmentation Shock ; 48 2 236-242
Yao X, Carlson D, Sun Y, Ma L, Wolf SE, Minei JP, Zang QS Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model PLoS ONE ; 10 10 e0139416
Barber RC, Maass DL, White J, Horton JW, Wolf SE, Minei JP, Zang QS. Deficiency in Heat Shock Factor 1 (HSF-1) Expression Exacerbates Sepsis-induced Inflammation and Cardiac Dysfunction SYMBIOSIS, SOJ SURGERY ; 1 1 10
Yao X, Wigginton JG, Maass DL, Ma L, Carlson D, Wolf SE, Minei JP, Zang QS Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs American Journal of Physiology - Heart & Circulatory Physiology ; 306 6 H882-94
Zang QS, Wolf SE, Minei JP Sepsis-induced Cardiac Mitochondrial Damage and Potential Therapeutic Interventions in the Elderly Aging and disease ; 5 2 137-49
Zang QS (corresponding author), Sadek H, Maass DL, Martinez B, Ma L, Kilgore JA, Williams NS, Frantz DE, Wigginton JG, Nwariaku FE, Wolf SE, Minei JP Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model American Journal of Physiology - Heart & Circulatory Physiology ; 302 9 H1847-59
Zang QS (corresponding author), Martinez B, Yao X, Maass DL, Ma L, Wolf SE, Minei JP Sepsis-induced cardiac mitochondrial dysfunction involves altered mitochondrial-localization of tyrosine kinase Src and tyrosine phosphatase SHP2 PLoS ONE ; 7 8 e43424
Wang Y, Zang QS (co-first author), Liu Z, Wu Q, Maass D, Dulan G, Shaul PW, Melito L, Frantz DE, Kilgore JA, Williams NS, Terada LS, Nwariaku FE Regulation of VEGF-induced endothelial cell migration by mitochondrial reactive oxygen species American Journal of Physiology - Cell Physiology ; 301 3 C695-704
Zang QS (corresponding author), Maass DL, Wigginton JG, Barber RC, Martinez B, Idris AH, Horton JW, Nwariaku FE Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes American journal of physiology. Heart and circulatory physiology ; 298 6 H1951-8
Zang Q, Maass DL, White J, Horton JW Cardiac mitochondrial damage and loss of ROS defense after burn injury: the beneficial effects of antioxidant therapy Journal of applied physiology (Bethesda, Md. : 1985) ; 102 1 103-12
Zang Q, Maass DL, Tsai SJ, Horton JW Cardiac mitochondrial damage and inflammation responses in sepsis Surgical Infections ; 8 1 41-54
Ferguson DA, Muenster MR, Zang Q, Spencer JA, Schageman JJ, Lian Y, Garner HR, Gaynor RB, Huff JW, Pertsemlidis A, Ashfaq R, Schorge J, Becerra C, Williams NS, Graff JM Selective identification of secreted and transmembrane breast cancer markers using Escherichia coli ampicillin secretion trap CANCER RESEARCH ; 65 18 8209-17
Schageman JJ, Ferguson DA, Zang Q, Spencer JA, Huff JW, Graff JM, Lian Y, Garner HR, Pertsemlidis A Reading the fine print of the human genome IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE ; 22 2 105-8
Lu C, Shimaoka M, Zang Q, Takagi J, Springer TA Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES ; 98 5 2393-8
Zang Q, Springer TA Amino acid residues in the PSI domain and cysteine-rich repeats of the integrin beta2 subunit that restrain activation of the integrin alpha(X)beta(2) JOURNAL OF BIOLOGICAL CHEMISTRY 2001-03-09 00:00:00.0; 276 10 6922-9
Huang C, Zang Q, Takagi J, Springer TA Structural and functional studies with antibodies to the integrin beta 2 subunit. A model for the I-like domain JOURNAL OF BIOLOGICAL CHEMISTRY 2000-07-14 00:00:00.0; 275 28 21514-24
Zang Q, Lu C, Huang C, Takagi J, Springer TA The top of the inserted-like domain of the integrin lymphocyte function-associated antigen-1 beta subunit contacts the alpha subunit beta -propeller domain near beta-sheet 3 JOURNAL OF BIOLOGICAL CHEMISTRY 2000-07-21 00:00:00.0; 275 29 22202-12
Zang Q, Lu Z, Curto M, Barile N, Shalloway D, Foster DA Association between v-Src and protein kinase C delta in v-Src-transformed fibroblasts JOURNAL OF BIOLOGICAL CHEMISTRY ; 272 20 13275-80
Lu Z, Hornia A, Jiang YW, Zang Q, Ohno S, Foster DA Tumor promotion by depleting cells of protein kinase C delta Molecular & Cellular Biology ; 17 6 3418-28