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Xuebin Qin, MD, PhD

 

Associate Professor, Neuroscience

Phone: 215-707-5823

Email: xuebin.qin@temple.edu

 

Department of Neuroscience

 

Educational Background:

 

MD, Wannan Medical College, Wuhu, China, 1986

 

MS, Tongji Medical College, Wuhan, China, 1991

 

PhD, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China, 1996

 

Fellowship, Department of Physiology, Tufts University School of Medicine, Boston, MA, 1998

 

Research Associate, Department of Cell Biology, Labratory for Membrane Transport, Harvard Medical School, Boston, MA, 2002

 

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PROFESSIONAL AFFILIATIONS:

 

  • International Complement Society
  • American Heart Association
  • Americal Immunology Association
  • American Cancer Association

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Research Interests:

 

My research focuses on defining the role of the complement in the pathogenesis of human diseases such as cancer, virus infection, and cardiovascular diseases. I have a broad background in medicine, molecular and cellular biology, cancer biology, cardiovascular biology and immunology. I have generated following mouse models: 1) mouse CD59 knockout mice; and 2) human CD59 (hCD59) transgenic mice expressing hCD59 only in mouse erythrocytes or only in mouse endothelial and circulating cells. CD59 is a critical complement regulator for restricting complement membrane attack complex (MAC). My lab also developed a potent and specific hCD59 inhibitor, rll Yd4.


1) Development of therapeutic anti-hCD59 inhibitor for HIV and Ab-based cancer therapy


Recognizing that the up-regulation of CD59 in cancer cells or HIV-infected cells is one of major reasons for their escape from complement-dependent cytolysis (CDC), I focus on developing hCD59 inhibitor for cancer and HIV therapy. lntermedilysin (IL Y), a cytolytic pore-forming toxin secreted by Streptococcus intermedius, lyses only human cells due to its receptor specificity for hCD59. My lab used hCD59 transgenic mice to confirm the finding that IL Y binds only to hCD59 in vivo. Domain 4 of IL Y binds to AA42-58 region in hCD59, which also participate in the binding to C8 and C9. I demonstrated that the recombinant protein (114AA) derived from the IL Y domain 4 (rll Yd4) specifically block hCD59 function and potentiate antibody-mediated CDC effect on cancer cells and inhibit human xenograft tumor growth. In addition, rll Yd4 also potentiates endogenous anti-HIV antibody-mediated complement-dependent virolysis. Importantly, no overt toxicity was observed when rll Y4 was administered to mice, even when mice are expressing hCD59 on red cells. Objective of this project is to develop the anti-hCD59 inhibitor for cancer and viral therapy and define the role of complement in immune-cancer therapy and pathogenesis of HIV infection.


2) Role of complement system in the pathogenesis of atherosclerosis and aneurysm

 

Extensive evidence obtained from the histological studies of human atherosclerosis and aneurysm indicate that complement (C), a key mediator of inflammation and immune responses, may play a critical role in atherogenesis and aneurysm, immune and inflammatory diseases. By the utilization of the knockout and transgenic mice together with biochemical approaches, my lab has demonstrated the protective role of CD59 in atherosclerosis and aneurysm and established the critical role of MAC in the development of these diseases in vivo. We are working on defining the underlying molecular and cellular mechanisms by which MAC contributes to the pathogenesis of atherosclerosis and aneurysm and developing a novel approach for the treatment/prevention of atherosclerosis or even advanced atherosclerosis as well as aneurysm.


3) Development of a universal cell ablation model and studies of the pathogenesis of hemolysis-associated pulmonary hypertension


Conditional and targeted cell ablation is fast becoming a powerful approach for studying cellular functions and tissue regeneration in vivo. Taking advantage of the exclusive IL Y interaction with hCD59, I have developed a novel tool to investigate the role of specific cells in the pathogenesis of human diseases. IL Y administration to the transgenic mice expressing hCD59 in specific cells can be used to generate this cell ablation model, in which IL Y specifically damages hCD59-expressing cells in the mice. We can utilize this concept to develop a new cell ablation model to study the functions of different cell types under physiologic and patho-physiologic conditions including cell differentiation and tissue development in many species. I have established multiple collaborations with Scientists in USA to further utilize this approach for their research projects in many species.


Specifically, I have developed a unique hemolytic anemia model, in which IL Y exclusively lyses erythrocytes transgenically expressing hCD59 (ThCD59RBC mice). Using this model, I investigated the pathogenesis of hemolytic anemia-associated pulmonary hypertension and sudden death. I demonstrated that the lethality of acute intravascular hemolysis in the models results from a sudden increase in pulmonary pressure likely a consequence of the reduced bioavailability of nitric oxide (NO) and resulting pulmonary vasoconstriction and platelet activation. I am utilizing this unique hemolytic mouse model to define the pathogenesis of hemolysis-associated pulmonary hypertension and sudden death and to test novel therapeutics for the treatment/prevention of the hemolysisassociated complications in this unique hemolysis model.

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24979401. Qin XW, Hao CY, He SZ, Wu G, Tan LH, Xu F, Hu RS, Volatile Organic Compound Emissions from Different Stages of Cananga odorata Flower Development. Molecules 19:7(8965-80)2014 Jun 27

24817940. Wu G, Qin XQ, Guo JJ, Li TY, Chen JH, AKT/ERK activation is associated with gastric cancer cell resistance to paclitaxel. Int J Clin Exp Pathol 7:4(1449-58)2014

24760648. Sun Y, Wu G, Zhang B, Jiang Y, Han Y, He G, Zhuang Q, Qin X, [Clinical control study of laparoscopic versus open surgery for rectal cancer]. Zhonghua Wei Chang Wai Ke Za Zhi 17:4(369-72)2014 Apr

24685815. Liu F, Wu L, Wu G, Wang C, Zhang L, Tomlinson S, Qin X, Targeted mouse complement inhibitor CR2-Crry protects against the development of atherosclerosis in mice. Atherosclerosis 234:1(237-43)2014 May

24639397. Liu F, Dai S, Gordon J, Qin X, Complement and HIV-I infection/HIV-associated neurocognitive disorders. J Neurovirol 20:2(184-98)2014 Apr

24430557. Wang Y, Ma S, Wang Q, Hu W, Wang D, Li X, Su T, Qin X, Zhang X, Ma K, Chen J, Xiong L, Cao F, Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci China Life Sci 57:2(201-8)2014 Feb

22576768. Pang S, Shan J, Qiao Y, Ma L, Qin X, Wanyan H, Xing Q, Wu G, Yan B, Genetic and functional analysis of the NKX2-5 gene promoter in patients with ventricular septal defects. Pediatr Cardiol 33:8(1355-61)2012 Dec

22019898. Zhang J, Hu W, Xing W, You T, Xu J, Qin X, Peng Z, The protective role of CD59 and pathogenic role of complement in hepatic ischemia and reperfusion injury. Am J Pathol 179:6(2876-84)2011 Dec

21918174. Ge X, Wu L, Hu W, Fernandes S, Wang C, Li X, Brown JR, Qin X, rILYd4, a human CD59 inhibitor, enhances complement-dependent cytotoxicity of ofatumumab against rituximab-resistant B-cell lymphoma cells and chronic lymphocytic leukemia. Clin Cancer Res 17:21(6702-11)2011 Nov 1

21482449. Sun H, Teng M, Liu J, Jin D, Wu J, Yan D, Fan J, Qin X, Tang H, Peng Z, FOXM1 expression predicts the prognosis in hepatocellular carcinoma patients after orthotopic liver transplantation combined with the Milan criteria. Cancer Lett 306:2(214-22)2011 Jul 28

21431285. Sun HC, Li M, Lu JL, Yan DW, Zhou CZ, Fan JW, Qin XB, Tang HM, Peng ZH, Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma. Oncol Rep 25:6(1533-9)2011 Jun

21258360. You T, Hu W, Ge X, Shen J, Qin X, Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells. Cell Mol Immunol 8:2(157-63)2011 Mar

21252115. Hu W, Ge X, You T, Xu T, Zhang J, Wu G, Peng Z, Chorev M, Aktas BH, Halperin JA, Brown JR, Qin X, Human CD59 inhibitor sensitizes rituximab-resistant lymphoma cells to complement-mediated cytolysis. Cancer Res 71:6(2298-307)2011 Mar 15

20740546. Hong JL, Qin XY, Shu P, Wu G, Wang Q, Qin MJ, Analysis of catalpol derivatives by characteristic neutral losses using liquid chromatography combined with electrospray ionization multistage and time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 24:17(2680-6)2010 Sep 15

20511540. Hu W, Jin R, Zhang J, You T, Peng Z, Ge X, Bronson RT, Halperin JA, Loscalzo J, Qin X, The critical roles of platelet activation and reduced NO bioavailability in fatal pulmonary arterial hypertension in a murine hemolysis model. Blood 116:9(1613-22)2010 Sep 2

20212283. Wu G, Chen T, Shahsafaei A, Hu W, Bronson RT, Shi GP, Halperin JA, Aktas H, Qin X, Complement regulator CD59 protects against angiotensin II-induced abdominal aortic aneurysms in mice. Circulation 121:11(1338-46)2010 Mar 23

19955519. Hu W, Yu Q, Hu N, Byrd D, Amet T, Shikuma C, Shiramizu B, Halperin JA, Qin X, A high-affinity inhibitor of human CD59 enhances complement-mediated virolysis of HIV-1: implications for treatment of HIV-1/AIDS. J Immunol 184:1(359-68)2010 Jan 1

19229985. Qin X, Hu W, Song W, Blair P, Wu G, Hu X, Song Y, Bauer S, Feelisch M, Leopold JA, Loscalzo J, Halperin JA, Balancing role of nitric oxide in complement-mediated activation of platelets from mCd59a and mCd59b double-knockout mice. Am J Hematol 84:4(221-7)2009 Apr

19131645. Wu G, Hu W, Shahsafaei A, Song W, Dobarro M, Sukhova GK, Bronson RR, Shi GP, Rother RP, Halperin JA, Qin X, Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex. Circ Res 104:4(550-8)2009 Feb 27

19051264. Qin X, Hu W, Song W, Grubissich L, Hu X, Wu G, Ferris S, Dobarro M, Halperin JA, Generation and phenotyping of mCd59a and mCd59b double-knockout mice. Am J Hematol 84:2(65-70)2009 Feb

18779537. Zhou X, Hu W, Qin X, The role of complement in the mechanism of action of rituximab for B-cell lymphoma: implications for therapy. Oncologist 13:9(954-66)2008 Sep

18157141. Hu W, Ferris SP, Tweten RK, Wu G, Radaeva S, Gao B, Bronson RT, Halperin JA, Qin X, Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nat Med 14:1(98-103)2008 Jan

16541098. Qin X, Ferris S, Hu W, Guo F, Ziegeler G, Halperin JA, Analysis of the promoters and 5'-UTR of mouse Cd59 genes, and of their functional activity in erythrocytes. Genes Immun 7:4(287-97)2006 Jun

16272280. Qin X, Dobarro M, Bedford SJ, Ferris S, Miranda PV, Song W, Bronson RT, Visconti PE, Halperin JA, Further characterization of reproductive abnormalities in mCd59b knockout mice: a potential new function of mCd59 in male reproduction. J Immunol 175:10(6294-302)2005 Nov 15

15448097. Qin X, Goldfine A, Krumrei N, Grubissich L, Acosta J, Chorev M, Hays AP, Halperin JA, Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes. Diabetes 53:10(2653-61)2004 Oct

15059529. Wu GH, Qin XY, [Nutrition support in patients with gastric cancer]. Zhonghua Yi Xue Za Zhi 84:3(179-81)2004 Feb 2

12594949. Qin X, Krumrei N, Grubissich L, Dobarro M, Aktas H, Perez G, Halperin JA, Deficiency of the mouse complement regulatory protein mCd59b results in spontaneous hemolytic anemia with platelet activation and progressive male infertility. Immunity 18:2(217-27)2003 Feb

11471050. Qin X, Miwa T, Aktas H, Gao M, Lee C, Qian YM, Morton CC, Shahsafaei A, Song WC, Halperin JA, Genomic structure, functional comparison, and tissue distribution of mouse Cd59a and Cd59b. Mamm Genome 12:8(582-9)2001 Aug

10946279. Qian YM, Qin X, Miwa T, Sun X, Halperin JA, Song WC, Identification and functional characterization of a new gene encoding the mouse terminal complement inhibitor CD59. J Immunol 165:5(2528-34)2000 Sep 1

9388957. Qin X, Zhang J, Kong J, Shen Y, Wu G, [Construction of Chinese genomic cosmid library]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 18:5(333-7)1996 Oct

8844058. Huang T, Li LY, Shen Y, Qin XB, Pang ZL, Wu GY, Alternative splicing of the FMR1 gene in human fetal brain neurons. Am J Med Genet 64:2(252-5)1996 Aug 9

7877197. Peng ZH, Qin XF, Zhao YM, Multi-variate stepwise discriminant analysis research affecting portal hypertension's grade factors of liver function. J Tongji Med Univ 14:1(56-60)1994

7760438. Peng ZH, Qian JQ, Qin XF, Tang XZ, Morphometric measurement of collagen in liver tissue with posthepatitis liver cirrhosis portal hypertension. J Tongji Med Univ 14:4(242-4)1994

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