Chih-Chi Andrew Hu

Chih-Chi Andrew Hu, PhD

Professor of Oncology, Academic Institute
Full Member, Research Institute
Houston Methodist


Hu Lab


Biography

Chih-Chi Andrew Hu, PhD, earned his Bachelor’s degree from China Medical University and Master’s degree from National Sun Yat-Sen University in Taiwan. During his military service as a second lieutenant, he taught histology and performed research at the National Defense Medical Center. Dr. Hu pursued his doctoral training at the New York University School of Medicine (2001-2006) to study membrane protein assembly on the surface of the urinary bladder. Dr. Hu pursued his postdoctoral training with Dr. Hidde L. Ploegh, at the Whitehead Institute/Massachusetts Institute of Technology (2006-2010) to study the functions of the endoplasmic reticulum in normal B cells. He became an Assistant Professor at the Moffitt Cancer Center/University of South Florida (2010-2014) and was later recruited to the Wistar Institute/University of Pennsylvania as an Associate Professor (2014-2019). He was promoted to Full Professor at the same institute in 2020 and recruited to the Houston Methodist Research Institute in December 2020.

Description of Research

My laboratory investigates the biology of the endoplasmic reticulum (ER) in normal and malignant B cells. The work from my laboratory establishes that inhibiting the IRE-1/XBP-1s pathway of the ER stress response and activating IRE-1’s interacting protein, STING, are effective therapeutic strategies for B cell cancer and graft-versus-host disease. We also develop novel small molecules to target these pathways. We continue to identify and characterize ER-resident proteins that can be targeted for therapy of human diseases.

Publications

Targeting the IRE1a/XBP1s pathway suppresses CARM1-expressing ovarian cancer
Lin, J, Liu, H, Fukumoto, T, Zundell, J, Yan, Q, Tang, CHA, Wu, S, Zhou, W, Guo, D, Karakashev, S, Hu, CCA, Sarma, K, Kossenkov, AV & Zhang, R 2021, , Nature Communications, vol. 12, no. 1, 5321. https://doi.org/10.1038/s41467-021-25684-3

Targeting the IRE1a/XBP1 Endoplasmic Reticulum Stress Response Pathway in ARID1A-Mutant Ovarian Cancers
Zundell, JA, Fukumoto, T, Lin, J, Fatkhudinov, N, Nacarelli, T, Kossenkov, AV, Liu, Q, Cassel, J, Hu, C-CA, Wu, S & Zhang, R 2021, , Cancer research, vol. 81, no. 20, pp. 5325-5335. https://doi.org/10.1158/0008-5472.CAN-21-1545

Targeting the IRE1a/XBP1 Endoplasmic Reticulum Stress Response Pathway in ARID1A-Mutant Ovarian Cancers
Zundell, JA, Fukumoto, T, Lin, J, Fatkhudinov, N, Nacarelli, T, Kossenkov, AV, Liu, Q, Cassel, J, Hu, CCA, Wu, S & Zhang, R 2021, , Cancer research, vol. 81, no. 20, pp. OF1-OF11. https://doi.org/10.1158/0008-5472.CAN-21-1545

XBP-1s Promotes B Cell Pathogenicity in Chronic GVHD by Restraining the Activity of Regulated IRE-1a-Dependent Decay
Choi, H-J, Tang, C-HA, Tian, L, Wu, Y, Sofi, MH, Ticer, T, Schutt, SD, Hu, C-CA & Yu, X-Z 2021, , Frontiers in immunology, vol. 12, pp. 705484. https://doi.org/10.3389/fimmu.2021.705484

XBP-1s Promotes B Cell Pathogenicity in Chronic GVHD by Restraining the Activity of Regulated IRE-1a-Dependent Decay
Choi, HJ, Tang, CHA, Tian, L, Wu, Y, Sofi, MH, Ticer, T, Schutt, SD, Hu, CCA & Yu, XZ 2021, , Frontiers in immunology, vol. 12, 705484. https://doi.org/10.3389/fimmu.2021.705484

Deletion of mFICD AMPylase alters cytokine secretion and affects visual short-term learning in vivo
McCaul, N, Porter, CM, Becker, A, Tang, CHA, Wijne, C, Chatterjee, B, Bousbaine, D, Bilate, A, Hu, CCA, Ploegh, H & Truttmann, MC 2021, , Journal of Biological Chemistry, vol. 297, no. 3, 100991. https://doi.org/10.1016/j.jbc.2021.100991

Distinct mechanisms govern populations of myeloid-derived suppressor cells in chronic viral infection and cancer
Tcyganov, EN, Hanabuchi, S, Hashimoto, A, Campbell, D, Kar, G, Slidel, TWF, Cayatte, C, Landry, A, Pilataxi, F, Hayes, S, Dougherty, B, Hicks, KC, Mulgrew, K, Tang, CHA, Hu, CCA, Guo, W, Grivennikov, S, Ali, MAA, Beltra, JC, Wherry, EJ, Nefedova, Y & Gabrilovich, DI 2021, , Journal of Clinical Investigation, vol. 131, no. 16, e145971. https://doi.org/10.1172/JCI145971

Endoplasmic reticulum-associated degradation is required for nephrin maturation and kidney glomerular filtration function
Yoshida, S, Wei, X, Zhang, G, OConnor, CL, Torres, M, Zhou, Z, Lin, L, Menon, R, Xu, X, Zheng, W, Xiong, Y, Otto, E, Tang, CHA, Hua, R, Verma, R, Mori, H, Zhang, Y, Hu, CCA, Liu, M, Garg, P, Hodgin, JB, Sun, S, Bitzer, M & Qi, L 2021, , Journal of Clinical Investigation, vol. 131, no. 7, e143988. https://doi.org/10.1172/JCI143988

STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function
Wu, Y, Tang, CHA, Mealer, C, Bastian, D, Hanief Sofi, M, Tian, L, Schutt, S, Choi, HJ, Ticer, T, Zhang, M, Sui, X, Huang, L, Mellor, AL, Hu, CCA & Yu, XZ 2021, , Cellular and Molecular Immunology, vol. 18, no. 3, pp. 632-643. https://doi.org/10.1038/s41423-020-00611-6

Molecular Evaluation of Endoplasmic Reticulum Homeostasis Meets Humoral Immunity
van Anken, E, Bakunts, A, Hu, CCA, Janssens, S & Sitia, R 2021, , Trends in Cell Biology, vol. 31, no. 7, pp. 529-541. https://doi.org/10.1016/j.tcb.2021.02.004

An interdomain helix in IRE1a mediates the conformational change required for the sensor's activation
Ricci, D, Tutton, S, Marrocco, I, Ying, M, Blumenthal, D, Eletto, D, Vargas, J, Boyle, S, Fazelinia, H, Qian, L, Suresh, K, Taylor, D, Paton, JC, Paton, AW, Tang, CHA, Hu, CCA, Radhakrishnan, R, Gidalevitz, T & Argon, Y 2021, , Journal of Biological Chemistry, vol. 296, 100781. https://doi.org/10.1016/J.JBC.2021.100781

Development of tumor-targeting ire-1 inhibitors for b-cell cancer therapy
Shao, A, Xu, Q, Spalek, WT, Cain, CF, Kang, CW, Tang, CHA, Del Valle, JR & Hu, CCA 2020, , Molecular Cancer Therapeutics, vol. 19, no. 12, pp. 2432-2444. https://doi.org/10.1158/1535-7163.MCT-20-0127

Clarifying the translational potential of B-I09
Del Valle, JR, Betts, BC, Yu, XZ, Janssens, S, Lambrecht, BN, Simon, MC & Hu, CCA 2020, , Nature Chemical Biology, vol. 16, no. 11, pp. 1152. https://doi.org/10.1038/s41589-020-00654-w

Sel1L-Hrd1 ER-associated degradation maintains ß cell identity via TGF-ß signaling
Shrestha, N, Liu, T, Ji, Y, Reinert, RB, Torres, M, Li, X, Zhang, M, Tang, CHA, Hu, CCA, Liu, C, Naji, A, Liu, M, Lin, JD, Kersten, S, Arvan, P & Qi, L 2020, , Journal of Clinical Investigation, vol. 130, no. 7, pp. 3499-3510. https://doi.org/10.1172/JCI134874

STING regulates BCR signaling in normal and malignant B cells
Tang, CHA, Lee, AC, Chang, S, Xu, Q, Shao, A, Lo, Y, Spalek, WT, Pinilla-Ibarz, JA, Del Valle, JR & Hu, CCA 2021, , Cellular and Molecular Immunology, vol. 18, no. 4, pp. 1016-1031. https://doi.org/10.1038/s41423-020-00552-0

Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
Liao, Y, Tham, DKL, Liang, FX, Chang, J, Wei, Y, Sudhir, PR, Sall, J, Ren, SJ, Chicote, JU, Arnold, LL, Hu, CCA, Romih, R, Andrade, LR, Rindler, MJ, Cohen, SM, DeSalle, R, Garcia-España, A, Ding, M, Wu, XR & Sun, TT 2019, , Molecular Biology of the Cell, vol. 30, no. 24, pp. 2969-2984. https://doi.org/10.1091/mbc.E19-05-0284

Structural Tailoring of a Novel Fluorescent IRE-1 RNase Inhibitor to Precisely Control Its Activity
Shao, A, Kang, CW, Tang, CHA, Cain, CF, Xu, Q, Phoumyvong, CM, Del Valle, JR & Hu, CCA 2019, , Journal of Medicinal Chemistry, vol. 62, no. 11, pp. 5404-5413. https://doi.org/10.1021/acs.jmedchem.9b00269

Inhibition of Human Dendritic Cell ER Stress Response Reduces T Cell Alloreactivity Yet Spares Donor Anti-tumor Immunity
Betts, BC, Locke, FL, Sagatys, EM, Pidala, J, Walton, K, Menges, M, Reff, J, Saha, A, Djeu, JY, Kiluk, JV, Lee, MC, Kim, J, Kang, CW, Tang, CHA, Frieling, J, Lynch, CC, List, A, Rodriguez, PC, Blazar, BR, Conejo-Garcia, JR, Del Valle, JR, Hu, CCA & Anasetti, C 2018, , Frontiers in immunology, vol. 9, 2887. https://doi.org/10.3389/fimmu.2018.02887

CD19 alterations emerging after CD19-directed immunotherapy cause retention of the misfolded protein in the endoplasmic reticulum
Bagashev, A, Sotillo, E, Tang, CHA, Black, KL, Perazzelli, J, Seeholzer, SH, Argon, Y, Barrett, DM, Grupp, SA, Hu, CCA & Thomas-Tikhonenkoa, A 2018, , Molecular and Cellular Biology, vol. 38, no. 21, e0038318. https://doi.org/10.1128/MCB.00383-18

Secretory IgM exacerbates tumor progression by inducing accumulations of MDSCs in mice
Tang, CHA, Chang, S, Hashimoto, A, Chen, YJ, Kang, CW, Mato, AR, Del Valle, JR, Gabrilovich, DI & Hu, CCA 2018, , Cancer immunology research, vol. 6, no. 6, pp. 696-710. https://doi.org/10.1158/2326-6066.CIR-17-0582