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 Immunology in Medicine, Academic Institute
Full Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Immunomonitoring Core


Biography

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

Publications

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 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer
Sun, K, Xu, Y, Zhang, L, Niravath, P, Darcourt, J, Patel, T, Teh, BS, Farach, AM, Guerrero, C, Mathur, S, Sultenfuss, MA, Gupta, N, Schwartz, MR, Haley, SL, Nair, S, Li, X, Nguyen, TTA, Butner, JD, Ensor, J, Mejia, JA, Mei, Z, Butler, EB, Chen, SH, Bernicker, EH & Chang, JC 2022, , Clinical cancer research : an official journal of the American Association for Cancer Research, vol. 28, no. 20, pp. 4392-4401. https://doi.org/10.1158/1078-0432.CCR-22-0622

Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
GBD 2019 Hepatitis B Collaborators 2022, , The Lancet Gastroenterology and Hepatology, vol. 7, no. 9, pp. 796-829. https://doi.org/10.1016/S2468-1253(22)00124-8

A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: The RAD VACCINE MIBC trial
Satkunasivam, R, Lim, K, Teh, BS, Guzman, J, Zhang, J, Farach, A, Chen, SH, Wallis, CJD, Efstathiou, E, Esnaola, NF & Sonpavde, GP 2022, , Future Oncology, vol. 18, no. 25, pp. 2771-2781. https://doi.org/10.2217/fon-2022-0380

Chemotherapy Coupled to Macrophage Inhibition Induces T-cell and B-cell Infiltration and Durable Regression in Triple-Negative Breast Cancer
Singh, S, Lee, N, Pedroza, DA, Bado, IL, Hamor, C, Zhang, L, Aguirre, S, Hu, J, Shen, Y, Xu, Y, Gao, Y, Zhao, N, Chen, SH, Wan, YW, Liu, Z, Chang, JT, Hollern, D, Perou, CM, Zhang, XHF & Rosen, JM 2022, , Cancer research, vol. 82, no. 12, pp. 2281-2297. https://doi.org/10.1158/0008-5472.CAN-21-3714

Antibody-Mediated LILRB2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells to Kill Mycobacterium tuberculosis
Singh, VK, Khan, A, Xu, Y, Mai, S, Zhang, L, Mishra, A, Restrepo, BI, Pan, PY, Chen, SH & Jagannath, C 2022, , Frontiers in immunology, vol. 13, 865503. https://doi.org/10.3389/fimmu.2022.865503

Dedifferentiation-mediated stem cell niche maintenance in early-stage ductal carcinoma in situ progression: insights from a multiscale modeling study
Butner, JD, Dogra, P, Chung, C, Ruiz-Ramírez, J, Nizzero, S, Plodinec, M, Li, X, Pan, P-Y, Chen, S-H, Cristini, V, Ozpolat, B, Calin, GA & Wang, Z 2022, , Cell death & disease, vol. 13, no. 5, pp. 485. https://doi.org/10.1038/s41419-022-04939-x

Dedifferentiation-mediated stem cell niche maintenance in early-stage ductal carcinoma in situ progression: insights from a multiscale modeling study
Butner, JD, Dogra, P, Chung, C, Ruiz-Ramírez, J, Nizzero, S, Plodinec, M, Li, X, Pan, PY, Chen, SH, Cristini, V, Ozpolat, B, Calin, GA & Wang, Z 2022, , Cell Death and Disease, vol. 13, no. 5, 485. https://doi.org/10.1038/s41419-022-04939-x

Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome
Jewell, BE, Xu, A, Zhu, D, Huang, MF, Lu, L, Liu, M, Underwood, EL, Park, JH, Fan, H, Gingold, JA, Zhou, R, Tu, J, Huo, Z, Liu, Y, Jin, W, Chen, YH, Xu, Y, Chen, SH, Rainusso, N, Berg, NK, Bazer, DA, Vellano, C, Jones, P, Eltzschig, HK, Zhao, Z, Kaipparettu, BA, Zhao, R, Wang, LL & Lee, DF 2021, , PLoS Genetics, vol. 17, no. 12, e1009971. https://doi.org/10.1371/journal.pgen.1009971

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. https://doi.org/10.1126/scitranslmed.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, PY, Chen, SH & Shen, H 2021, , Journal of Immunology, vol. 207, no. 12, pp. 3131-3140. https://doi.org/10.4049/jimmunol.2100719

A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells
Welte, T, Mai, J, Zhang, Z, Tian, S, Zhang, G, Xu, Y, Zhang, L, Chen, SS, Wang, T & Shen, H 2021, , iScience, vol. 24, no. 11, 103349. https://doi.org/10.1016/j.isci.2021.103349

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). https://doi.org/10.4049/jimmunol.2100719

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. https://doi.org/10.7554/eLife.70130

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. https://doi.org/10.7554/eLife.70130

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. https://doi.org/10.1016/j.cellimm.2021.104300

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. https://doi.org/10.1002/bies.202000339

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. https://doi.org/10.3389/fimmu.2020.645213

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. https://doi.org/10.1007/s00262-021-02927-2

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. https://doi.org/10.1002/adtp.202100144