Weiguo Hu, MD & Ph.D

Education

• 2001-2004, PhD, Institute of Biochemistry, Chinese Academy of Sciences

• 1988-1997, MD, the Second Military Medical University

Work experience

• 2010-Present, PI/Professor, Fudan University

• 2005-2010, Postdoc/Senior Research Associate, Harvard Medical School

• 2004-2005, Postdoc, Yale Medical School

• 1997-2001, TA/Instructor, the Second Military Medical University

Contact

Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 Tel: +8621-34777590

Email: weiguohu@@fudan.edu.cn

Biography

Dr. Hu received his M.D. in 1997 at the Second Military Medical University, Shanghai, and had served there till 2001. He further earned his Ph.D. in 2004 at Institute of Biochemistry, Chinese Academy of Sciences, Shanghai. Afterwards, he finished his postdoctoral training in 2010 at Yale Cancer Center and Harvard Medical School. Currently, Dr. Hu is a Professor of Cancer Immunology at Institutes of Biomedical Sciences & Shanghai Cancer Center, Fudan University.

The complement system is an important component in the arsenal of innate immunity and bridges innate to adaptive immunity. The versatile complement functions basically as an intricate immune surveillance system to clear cellular debris, apoptotic cells, immune complexes and foreign intruders, and further involves in such diverse processes such as synapse maturation, angiogenesis, tissue regeneration and lipid metabolism. To prevent the deleterious damage on autologous cells, over ten complement regulatory proteins have been evolved to inhibit complement activation at diverse stages. Therefore, complement is finely tuned at a delicate balance between activation and regulation in normal condition. However, excessive or dysregulated complement activation can also turn its destructive capabilities against host cells, thus contributing to numerous diseases including cancer, immune, inflammatory, neurodegenerative, ischemic and age-related diseases. Using complement as a model system, the roles and mechanisms for complement in inflammation-induced malignant transformation, cancer therapy resistance, cancer metastasis, and cancer immunotherapy are investigated in Dr. Hu’s lab.

Research Area

Tumor Immunology

Research Interests

Focuses on defining the roles and mechanisms of complement system in tumor initiation, progression, metastasis, and therapy resistance accompanied by interests in development of complement agonist/antagonist for human diseases therapy.

Selected Publications

1. Ding P, Xu Y, Li L, Lv X, Li L, Chen J, Zhou D, Wang X, Wang Q, Zhang W, Liao T, Ji QH, Lei QY, Hu W*. Intracellular complement C5a/C5aR1 stabilizes β-catenin to promote colorectal tumorigenesis. Cell Reports. 2022 May 31;39(9):110851.

2. Song J, Zhao R, Yan C, Luo S, Xi J, Ding P, Li L, Hu W*, Zhao C*. A Targeted Complement Inhibitor CRIg/FH Protects Against Experimental Autoimmune Myasthenia Gravis in Rats via Immune Modulation. Frontiers in Immunology.2022 Jan 26;13:746068.

3. Zhang W, Zhang X, Huang S, Chen J, Ding P, Wang Q, Li L, Lv X, Li L, Zhang P, Zhou D, Wen W, Wang Y, Lei QY, Wu J, Hu W*. FOXM1D Potentiates PKM2-mediated tumor glycolysis and angiogenesis. Molecular Oncology. 2021 May;15(5):1466-1485.

4. Ding P, Li L, Li L, Lv X, Zhou D, Wang Q, Chen J, Yang C, Xu E, Dai W, Zhang X, Wang N, Wang Q, Zhang W, Zhang L, Zhou Y, Gu H, Lei Q, Zhou X, Hu W*. C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation. Theranostics. 2020 Jul 9;10(19):8619-8632.

5. Wang Q#, Zhang P#, Zhang W, Zhang X, Chen J, Ding P, Li L, Lv X, Li L, Hu W*. PI3K Activation Is Enhanced by FOXM1D Binding to p110 and p85 Subunits. Signal Transduction and Targeted Therapy. 2020 Jun 30;5(1):105. doi: 10.1038/s41392-020-00218-3.

6. Chen J, Ge X, Zhang W, Ding P, Du Y, Wang Q, Li L, Fang L, Sun Y, Zhang P, Zhou Y, Zhang L, Lv X, Li L, Zhang X, Zhang Q, Xue K, Gu H, Lei Q, Wong J, Hu W*. PI3K/AKT Inhibition Reverses R-CHOP Resistance by Destabilizing SOX2 in Diffuse Large B Cell Lymphoma. Theranostics. 2020 Feb 10;10(7):3151-3163.

7. Ge X, Chen J, Li L, Ding P, Wang Q, Zhang W, Li L, Lv X, Zhou D, Jiang Z, Zeng H, Xu Y, Hou Y*,Hu W*. Midostaurin potentiates rituximab antitumor activity in Burkitt's lymphoma by inducing apoptosis. Cell Death and Diseases. 2018; 10(1):8.

8. Hu C, Li L, Ding P, Li L, Ge X, Zheng L, Wang X, Wang J, Zhang W, Wang N, Gu H, Zhong F, Xu M, Rong R, Zhu T*,Hu W*.Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling. Journal of Immunology.2018; 201(12):3717-3730.

9. Zhou Y, Chu L, Wang Q, Dai W, Zhang X, Chen J, Li L, Ding P, Zhang L, Gu H, Li L, Lv X, Zhang W, Zhou D, Zhang P, Cai G, Zhao K*,Hu W*. CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair. Cell Death and Diseases. 2018; 9(9):887.

10. Zhang X, Zhang L, Du Y, Zheng H, Zhang P, Sun Y, Wang Y, Chen J, Ding P, Wang N, Yang C, Huang T, Yao X, Qiao Q, Gu H, Cai G, Cai S, Zhou X, Hu W*. A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. Oncogene. 2017; 36(6):807-819.

11. Chen J, Ding P, Li L, Gu H, Zhang X, Zhang L, Wang N, Gan L, Wang Q, Zhang W, Hu W*. CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance. Stem Cell Reports. 2017 January 10; 8(1): 140–151. Stem Cell Reports_ Best of 2016-2017

12. Yang C, Ding P, Wang Q, Zhang L, Zhang X, Zhao J, Xu E, Wang N, Chen J, Yang G,Hu W*, Zhou X*. Inhibition of Complement Retards Ankylosing Spondylitis Progression. Scientific Reports.2016 Oct 4;6:34643.

13. Qiao Q,Teng X,Wang N,Lu R,Guo L,Zhang X,Du Y,Wang W,Chen S,Wu Q,He G,Wang Y, Hu W*.A novel CRIg-targeted complement inhibitor protects cells from complement damage. FASEB J.2014, 28(11):4986-99.

14. Du Y,Teng X,Wang N,Zhang X,Chen J,Ding P,Qiao Q,Wang Q,Zhang L,Yang C,Yang Z,Chu Y,Du X,Zhou X*,Hu W*. NF-κB and enhancer-binding CREB protein scaffolded by CREB-binding protein (CBP)/p300 proteins regulate CD59 protein expression to protect cells from complement attack. Journal of Biological Chemistry. 2014; 289(5):2711-24.

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

16. Hu W#, Jin R#, Zhang J, You T, Bronson RT, Peng Z,Ge X, Loscalzo J, and Qin X*. The Mechanisms of Fatal Pulmonary Arterial Hypertension in a Unique Rapid Hemolysis Model. Blood.2010, 116(9):1613-22.

17. Hu W#, Yu Q #, Hu N, Byrd D, 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. Journal of Immunology. 2010,184(1):359-368.

18. Qin X #,Hu W#, Song W, Grubissich L, Song Y, Wu G, Hu X, Ferris S, Dobarro M, Bauer S, Feelisch M, Leopold JA, Loscalzo J, Halperin JA*. Balancing role of nitric oxide in complement-mediated platelet activation of mCd59a and mCd59b double knockout mice. American Journal of Hematology.2009, 84(4):221-7.

19. Hu W, Ferris S, Tweten RK, Wu G, Gao B, Bronson RT, Halperin JA and Qin X*. Conditional, rapid and targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nature Medicine. 2008; 14 (1): 98-103.

20. 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.2008; 13: 954-966.