Shu-Hsia Chen

Shu-Hsia Chen, PhD

Emily Herrmann Chair in Immunology Research, Dr. Mary and Ron Neal Cancer Center
Director, Center for Immunotherapy Research
Professor of Oncology, Academic Institute
Full Member, Research Institute
Houston Methodist
Weill Cornell Medical College

Immunomonitoring Core


Shu-Hsia Chen, PhD, is the Emily Herrmann endowed Professor in cancer immunotherapy, director of Cancer Immunotherapy Research Center and Immune Assessment Core at the Methodist Research Institute. Prior to joining Houston Methodist, she was a tenured Professor in the Department of Oncological Sciences and Surgery in the Icahn School of Medicine at Mount Sinai in New York. She obtained her PhD from National Yang-Ming Medical University in Taiwan in 1993 and finished her fellowship training at the Howard Hughes Medical Institute. In 1996, she assumed the role of Assistant Professor in the Department of Cell Biology at Baylor College of Medicine in Houston. She has made significant contributions to the fields of gene therapy and cancer immunotherapy. Dr. Chen invented adenoviral gene delivery of suicide and immune modulatory genes for use in cancer immune therapies. Subsequently, she identified myeloid derived suppressor cell (MDSC) populations and has played an integral role in demonstrating MDSC-mediated suppression of antitumor T cell immune responses, identifying the tumor factors involved in MDSC expansion/accumulation, and discovering MDSC-mediated regulatory T cell activation in the tumor microenvironment. Furthermore, Dr. Chen identified the novel immune checkpoint receptors on MDSC population and was able to reprogram the myeloid cell differentiation, thereby modulating the tumor microenvironment. Her current research focuses on overcoming immune suppression in the tumor microenvironment, controlling MDSC/tumor associated macrophage differentiation, and developing effective immune therapeutic strategies for clinical use in cancer and autoimmune diseases. Dr. Chen is a world-class researcher and has done pioneering work in the field of gene therapy and immunotherapy, as demonstrated by her several inventions. She has also served on national and international grant review committees and as a reviewer/consultant for multiple international journals, institutes, and cancer centers. Her laboratory has published high-impact research articles in the field and her research has been continuously supported by multiple NIH grants, DOD grants, and pharmaceutical companies.

Description of Research

Over the past years, my laboratory has focused on gene therapies and cancer immunotherapies. My laboratory has also, to a large extent, focused on elucidating the mechanisms underlying the establishment of immune suppressive tumor microenvironments, a major impediment to the success of immune-based cancer therapies and overcoming cancer cells’ resistance to chemo-radiation therapies. Specifically, we have been examining the mechanisms of immune suppression that are mediated by myeloid derived suppressor cells, macrophages, B cells, and T regulatory cells. In addition, we have been studying the biology of cancer initiating cells, the control of differentiation of myeloid cells and tumor associated macrophages, and modulation of the tumor microenvironment, all of which will influence our ability to control malignant disease.

Our laboratory is working to further define the activation of cancer initiating cells, as well as the immunological changes inside the distinct tumor microenvironment, after administration of radiation therapy, chemotherapy, targeted therapeutics, T cell therapy, and antibody-based novel immune checkpoint therapies. This will help researchers and clinicians integrate conventional therapies with the ideal immunotherapies, thereby achieving the maximal therapeutic efficacy in patients. We are also investigating whether and how targeting therapeutics can overcome the stress-/inflammation-induced immune suppression that subsequently interferes with the success of immunotherapy and chemo/radiation therapy.

One of the primary aims of my lab is to examine how novel immune checkpoint pathways influence tumor growth, receptor/ligand interaction, and the tumor microenvironment. We also aim to develop novel therapeutic agents that effectively target tumors or tumor stromal cells, causing an increase local antigen priming and T cell activation/infiltration for subsequent immunotherapy. This is a key component of achieving long-term tumor remission and lasting immune memory. Using our newly developed immune checkpoints, nanotechnology, and T cell therapy, we can improve tumor targeting and reduce toxicity in patients. Collaborating with colleagues, we have been continually successful in obtaining support from NIH, DOD, and pharmaceutical companies, with the aim of developing novel therapeutic strategies through preclinical and clinical trials.

Program 1.  Modulate tumor microenvironment to facilitate cancer immune therapy.

Program 2. Identify novel immune checkpoints, reprogram of myeloid cell/macrophage function and stress signaling to develop novel immune therapy strategies.

Program 3. Tumor inflammation on the regulation of tumor progression and metastases.

Program 4. The MDSC and macrophage mediated immune regulation in human health

Program 5. Synergist effect of innate and adaptive immune response for immune therapy


Biophysical modeling of cancer in-silico
Dogra, P, Jeffrey Brinker, C, Chen, S-H, Chung, C, Fleming, JB, Lowengrub, J & Cristini, V 2022, . Springer.

A phase 1/2 clinical trial of the nitric oxide synthase inhibitor L-NMMA and taxane for treating chemoresistant triple-negative breast cancer
Chung, AW, Anand, K, Anselme, AC, Chan, AA, Gupta, N, Venta, LA, Schwartz, MR, Qian, W, Xu, Y, Zhang, L, Kuhn, J, Patel, T, Rodriguez, AA, Belcheva, A, Darcourt, J, Ensor, J, Bernicker, E, Pan, PY, Chen, SH, Lee, DJ, Niravath, PA & Chang, JC 2021, , Science translational medicine, vol. 13, no. 624, abj5070.

The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells
Hinkle, L, Liu, Y, Meng, C, Chen, Z, Mai, J, Zhang, L, Xu, Y, Pan, P-Y, Chen, S-H & Shen, H 2021, , Journal of immunology (Baltimore, Md. : 1950).

Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling
Butner, JD, Martin, GV, Wang, Z, Corradetti, B, Ferrari, M, Esnaola, N, Chung, C, Hong, DS, Welsh, JW, Hasegawa, N, Mittendorf, EA, Curley, SA, Chen, S-H, Pan, P-Y, Libutti, SK, Ganesan, S, Sidman, RL, Pasqualini, R, Arap, W, Koay, EJ & Cristini, V 2021, , eLife, vol. 10.

Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling
Butner, JD, Martin, GV, Wang, Z, Corradetti, B, Ferrari, M, Esnaola, N, Chung, C, Hong, DS, Welsh, JW, Hasegawa, N, Mittendorf, EA, Curley, SA, Chen, SH, Pan, PY, Libutti, SK, Ganesan, S, Sidman, RL, Pasqualini, R, Arap, W, Koay, EJ & Cristini, V 2021, , eLife, vol. 10, e70130.

Myeloid-derived suppressor cells as cellular immunotherapy in transplantation and autoimmune diseases
Zhang, J, Hodges, A, Chen, SH & Pan, PY 2021, , Cellular Immunology, vol. 362, 104300.

Amphibian regeneration and mammalian cancer: Similarities and contrasts from an evolutionary biology perspective: Comparing the regenerative potential of mammalian embryos and urodeles to develop effective strategies against human cancer
Corradetti, B, Dogra, P, Pisano, S, Wang, Z, Ferrari, M, Chen, S-H, Sidman, RL, Pasqualini, R, Arap, W & Cristini, V 2021, , BioEssays, vol. 43, no. 7, pp. e2000339.

Corrigendum: Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment (Frontiers in Immunology, (2020), 11, (1842), 10.3389/fimmu.2020.01842)
Davidov, V, Jensen, G, Mai, S, Chen, SH & Pan, PY 2021, , Frontiers in immunology, vol. 11, 645213.

Nutrient supplements from selected botanicals mediated immune modulation of the tumor microenvironment and antitumor mechanism
Chen, HM, Sun, L, Pan, PY, Wang, LH & Chen, SH 2021, , Cancer Immunology, Immunotherapy, vol. 70, no. 12, pp. 3435-3449.

Virus-Mimic mRNA Vaccine for Cancer Treatment
Meng, C, Chen, Z, Mai, J, Shi, Q, Tian, S, Hinkle, L, Li, J, Zhang, Z, Ramirez, M, Zhang, L, Xu, Y, Zhang, J, Pan, PY, Chen, SH, Li, H & Shen, H 2021, , advanced therapeutics, vol. 4, no. 11, 2100144.

Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection
Liu, X, Wang, YL, Wu, J, Qi, J, Zeng, Z, Wan, Q, Chen, Z, Manandhar, P, Cavener, VS, Boyle, NR, Fu, X, Salazar, E, Kuchipudi, SV, Kapur, V, Zhang, X, Umetani, M, Sen, M, Willson, RC, Chen, SH & Zu, Y 2021, , Angewandte Chemie - International Edition, vol. 60, no. 18, pp. 10273-10278.

Analyzing One Cell at a TIME: Analysis of Myeloid Cell Contributions in the Tumor Immune Microenvironment
Davidov, V, Jensen, G, Mai, S, Chen, SH & Pan, PY 2020, , Frontiers in immunology, vol. 11, 1842.

Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy
Butner, JD, Elganainy, D, Wang, CX, Wang, Z, Chen, SH, Esnaola, NF, Pasqualini, R, Arap, W, Hong, DS, Welsh, J, Koay, EJ & Cristini, V 2020, , Science advances, vol. 6, no. 18, eaay6298.

Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1
Liu, HC, Viswanath, DI, Pesaresi, F, Xu, Y, Zhang, L, Di Trani, N, Paez-Mayorga, J, Hernandez, N, Wang, Y, Erm, DR, Ho, J, Susnjar, A, Liu, X, Demaria, S, Chen, SH, Teh, BS, Butler, EB, Xuan Chua, CY & Grattoni, A 2021, , International Journal of Radiation Oncology Biology Physics, vol. 110, no. 2, pp. 492-506.

The mechanistic study behind suppression of GVHD while retaining GVL activities by myeloid-derived suppressor cells
Zhang, J, Chen, HM, Ma, G, Zhou, Z, Raulet, D, Rivera, AL, Chen, SH & Pan, PY 2019, , Leukemia, vol. 33, no. 8, pp. 2078-2089.

Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity
Chen, H-M, van der Touw, W, Wang, YS, Kang, K, Mai, S, Zhang, J, Alsina-Beauchamp, D, Duty, JA, Mungamuri, SK, Zhang, B, Moran, T, Flavell, R, Aaronson, S, Hu, H-M, Arase, H, Ramanathan, S, Flores, R, Pan, P-Y & Chen, S-H 2018, , The Journal of clinical investigation, vol. 128, no. 12, pp. 5647-5662.

Glatiramer acetate enhances myeloid-derived suppressor cell function via recognition of paired Ig-like receptor B
Van Der Touw, W, Kang, K, Luan, Y, Ma, G, Mai, S, Qin, L, Bian, G, Zhang, R, Mungamuri, SK, Hu, HM, Zhang, CC, Aaronson, SA, Feldmann, M, Yang, WC, Chen, SH & Pan, PY 2018, , Journal of Immunology, vol. 201, no. 6, pp. 1727-1734.

LILRB receptor-mediated regulation of myeloid cell maturation and function
van der Touw, W, Chen, HM, Pan, PY & Chen, SH 2017, , Cancer Immunology, Immunotherapy, vol. 66, no. 8, pp. 1079-1087.

Leukocyte immunoglobulin-like receptors in human diseases: An overview of their distribution, function, and potential application for immunotherapies
Zhang, J, Mai, S, Chen, H-M, Kang, K, Li, XC, Chen, SH & Pan, PY 2017, , Journal of Leukocyte Biology, vol. 102, no. 2, pp. 351-360.

Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards
Bronte, V, Brandau, S, Chen, SH, Colombo, MP, Frey, AB, Greten, TF, Mandruzzato, S, Murray, PJ, Ochoa, A, Ostrand-Rosenberg, S, Rodriguez, PC, Sica, A, Umansky, V, Vonderheide, RH & Gabrilovich, DI 2016, , Nature Communications, vol. 7, 12150.