BS, Nankai University, Tianjing, China
MS, Nankai University, Tianjing, China
PhD, University of Medicine and Dentistry of New Jersey (UMDNJ), Piscataway, NJ
Post-Doc, University of Pennsylvania, Philadelphia, PA
Cancer cell stress response with three
main focuses: 1) Proteotoxicity (the cytotoxic effect of misfolded
proteins) and redox homeostasis; 2) Oncogenic signaling in protein
turnover and cell metabolism; 3 Unfolded protein response (ER stress) in
oncogenesis. We use mostly biochemical, molecular biological, and cell
biological techniques, as well as genetically engineered mouse models
and clinical samples.
1. Proteotoxic stress and signaling
Many cell types including cancer cells are often under the stress of misfolded proteins that leads to many molecular consequences such as increased reactive oxygen species (ROS), unfolded protein response signaling, and cell death. Inhibition of protein degradation is an emerging anti-cancer strategy. A major line of research in the lab is to understand the mechanisms underlying these molecular events. Ongoing projects involve the regulation of redox homeostasis by the ubiquitin E3 ligase TRIM21, and the regulation of cell death via p62-mediated caspase-8 aggregation.
2. Oncogenic regulation of protein and bioenergetics homeostasis
We study how phosphatidylinositol 3-kinases (PI3Ks) regulate autophagy and endocytosis, and how these functions are involved in oncogenesis. Another line of research in the lab is to understand how PI3-kinases and c-Myc oncogenes regulate cancer cell metabolism.
3. Squamous cell carcinoma antigen (SCCA) in tumorigenesis
Squamous cell carcinoma antigens (SCCAs) are members of the Serpin family of endogenous serine and cysteine protease inhibitors. Elevated expression of SCCA has been found to associate with poorly differentiated and advanced squamous cell carcinomas of the uterine cervix, lung, head and neck, esophagus, liver, and breast. However, despite its relevance with human cancer, the biological function of SCCA remains largely unclear. We are currently studying how SCCA functions to promote tumorigenesis and can be targeted for therapy.
Pan JA, Sun Y, Jiang YP, Bott AJ, Jaber N, Dou Z, Yang B, Chen JS, Catanzaro JM, Du C, Ding WX, Diaz-Meco MT, Moscat J, Ozato K, Lin RZ, and Zong WX. 2016. TRIM21 ubiquitylates SQSTM1/p62 and suppresses protein sequestration to regulate redox homeostasis. Mol Cell 61: 720-733. “Featured Article”. PMID: 26942676
Zong WX, Rabinowitz JD, and White E. 2016. Mitochondria and cancer. Mol Cell 61: 667-676. PMID: 26942671
Bott AJ, Peng IC (co-first author), Fan Y, Faubert B, Zhao L, Li J, Neidler S, Sun Y, Jaber N, Krokud D, Lu W, Rabinowitz J, Hatzoglou M, Powers S, Murphy DJ, Jones R, Wu S, Girnun G, and Zong WX. 2015. Myc induces expression of glutamine synthetase through thymine DNA glycosylase-mediated promoter demethylation. Cell Metab 22:1068-1077. PMID: 26603296
Sheshadri N, Catanzaro JM (co-first author), Bott A, Sun Y, Ullman E, Wu S, Pan JA, Chen E, Crawford HC, Zhang J, and Zong WX. 2014. Squamous cell carcinoma antigen 1 (SCCA1)/SerpinB3 promotes tumorigenesis through induction of unfolded protein response and IL-6 signaling. Cancer Res 74:6318-6329. PMID: 25213322
Catanzaro JM, Sheshadri N (co-first author), Pan JA, Shi C, Li J, Powers RS, Crawford HC, and Zong WX. 2014. Oncogenic Ras induces cytokine production by up-regulating squamous cell carcinoma antigens SerpinB3/B4. Nat Commun. 5:3729. PMID: 24759783
Dou Z, Pan JA, Dbouk HA, Ballou LM, DeLeon JL, Fan YJ, Chen JS, Liang Z, Li G, Backer JM, Lin RZ, and Zong WX. 2013. Class IA PI3-kinase p110β subunit promotes autophagy through Rab5 small GTPase in response to trophic factor limitation. Mol Cell 50:29-42. PMID: 23434372
Pan JA. Fan Y. Gandhirajan RK, Madesh M. and Zong WX. 2013. Hyperactivation of the mammalian degenerin MDEG promotes caspase-8 activation and apoptosis. J Biol Chem 288:2952-2963. “Paper-of-the-week”. PMID: 23239879
Jaber N, Dou Z, Chen JS, Catanzaro JM, Jiang YP, Ballou LM, Selinger E, Ouyang X, Lin RZ, Zhang J, and Zong WX. 2012. Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Nat Acad Sci, USA109:2003-2008. PMID: 22308354
Ullman E, Pan JA, and Zong WX. 2011. Squamous cell carcinoma antigen 1 (SCCA1) promotes caspase-8-mediated apoptosis in response to endoplasmic reticulum stress while inhibits necrosis induced by lysosomal injury. Mol Cell Biol 31:2902-2919. PMID: 21576355
Pan JA, Ullman E, Dou Z, and Zong WX. 2011. Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranes. Mol Cell Biol 31:3158-3170. PMID: 21628531
Guerriero JL, Ditsworth D, Catanzaro JM, Sabino G, Furie MB, Kew R, and Zong WX. 2011. DNA alkylating therapy induces an HMGB1-dependent activation of innate immunity and tumor clearance. J Immunol 186:3517-3626. “Featured Article”. PMID: 21300822
Catanzaro JM, Guerriero JL (co-first author), Liu J, Ullman E, Sheshadri N, Chen JJ, and Zong WX. 2011. Elevated expression of squamous cell carcinoma antigen (SCCA) is associated with human breast carcinoma. PLoS One 6: e19096. PMID: 21526154
Dou Z, Chattopadhyay M, Pan JA, Guerriero JL, Jiang YP, Ballou LM, Yue Z, Lin RZ, and Zong WX. 2010. The Class IA phosphatidylinositol 3-kinase p110β subunit is a positive regulator of autophagy. J Cell Biol 191:827-843. PMID: 21059846
Fan Y, Dickman K, and Zong WX. 2010. Akt and c-Myc differentially activate cellular metabolic programs and prime cells to bioenergetic inhibition. J Biol Chem 285: 7324-7333. PMID: 20018866
Guerriero JL, Ditsworth D, Fan Y, Zhao F, Crawford HC, Zong WX. 2008. Chemotherapy induces tumor clearance independent of apoptosis. Cancer Res 68: 9595-9600. PMID: 19047135
Ullman E, Fan Y (co-first author), Stawowczyk M, Chen HM, Yue Z, and Zong WX. 2008. Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress. Cell Death Diff 16:422-425. PMID: 17917679