Research
Dr. Chen’s laboratory studies the molecular and biological processes governing the development and progression of primary (e.g., glioblastoma) and metastatic (e.g., brain metastatic breast cancer) brain cancers. The research in his laboratory focuses on understanding the molecular mechanisms underlying the symbiotic interactions between cancer cells/cancer stem cells and immune cells, as well as how such heterotypic signaling enables a tumor-promoting ecosystem and informs therapeutic strategies intercepting these co-dependencies in brain cancers. Based on these mechanistic studies, his laboratory aims to develop novel and effective therapeutic approaches against these symbiotic interactions combining with or without immunotherapy, anti-angiogenic therapy, and/or conventional therapy for glioblastoma and brain metastatic breast cancer.
Biography
Peiwen Chen, PhD, is an Associate Staff in the Department of Cancer Biology at Cleveland Clinic Lerner Research Institute. In 2009, Dr. Chen was accepted by Tsinghua University (China) to pursue his PhD studies focusing on how tumor-associated macrophages (TAMs) promote angiogenesis in melanoma. With the support from the Italian Cariparo Foundation, Dr. Chen continued his PhD studies at the University of Padova, where he revealed the role of extracellular matrix protein collagen VI in the nervous system, macrophage biology, and hair follicle growth. After receiving his PhD in 2015, Dr. Chen joined UT Southwestern Medical Center as a postdoctoral researcher, where he identified lactate-Gpr132 axis as a ligand-receptor pair that drives breast cancer metastasis via stimulation of tumor-macrophage interplay. In July 2016, he joined MD Anderson Cancer Center as a postdoc fellow to study the biology of myeloid cells, including macrophages and microglia, in glioblastoma. Dr. Chen moved to Cleveland Clinic in July 2024 from Northwestern University Feinberg School of Medicine, where he was a tenure-track Assistant Professor since October 2020 in the Department of Neurological Surgery. Dr. Chen’s lab focuses on studying tumor-immune symbiotic interactions and developing novel immunotherapies in primary (e.g., glioblastoma) and metastatic (e.g., brain metastatic breast cancer) brain cancers.
Education & Professional Highlights
Education & Fellowships
Postdoctoral Fellowship – MD Anderson Cancer Center, Cancer Biology, Houston, TX, USA 2020
Graduate – University of Padova, Molecular Medicine, Padova, Italy 2015
Awards & Honors
Tony Hunter Award in Cancer Research (2024)
American Cancer Society Institutional Research Grant Award (2022)
Department of Defense Career Development Award-Scholar Option (2021-2024)
Cancer Research Foundation Young Investigator Award (2021-2023)
Lynn Sage Breast Cancer Foundation Lynn Sage Scholar Award (2021-2023)
SPORE Career Enhancement Award (2020 and 2022)
NCI K99/R00: Pathway to Independence Award (2020-2023)
MD Anderson Cancer Center (MDACC) Harter Prize (declined, 2020)
MDACC Harold C. and Mary L. Daily Endowment Fellowship (2019 and 2020)
Cancer Research Institute Postdoctoral Fellowship Award (2018-2020)
AACR-American Brain Tumor Association Scholar-in-Training Award (2018)
MDACC Caroline Ross Endowed Fellowship in Brain Cancer Research (2018 and 2019)
MDACC One-time Trainee Cash Award (2017 and 2018)
Chinese Award for Outstanding Self-financed Students Abroad (2013)
Italian Cariparo Foundation PhD Fellowship Award (2012-2014)
Research
The Chen laboratory studies the molecular and biological processes governing the development of brain malignancies, including primary (e.g., glioblastoma) and metastatic (tumors originating from other locations in the body, such as breast cancer) brain cancers. Specifically, the laboratory focuses on characterizing the molecular mechanisms governing the symbiotic interactions between cancer cells/cancer stem cells and immune cells (including macrophages, microglia, myeloid-derived suppressor cells and T cells) in brain malignancies, and how such heterotypic signaling enables a tumor-promoting ecosystem and informs therapeutic strategies intercepting these co-dependencies.
The laboratory takes an integrated strategy combining gain- and loss-of-function approaches, in vitro and in vivo systems, as well as proteomic and transcriptomic analyses to:
(1) study how specific tumor context, such as genetic alternations (e.g., tumor suppressor gene mutation/deletion and oncogene amplification/mutation), epigenetic modifications, circadian dysregulation, and metabolic changes of cancer cells and cancer stem cells can shape an immunosuppressive tumor microenvironment by regulating the infiltration and polarization of myeloid cells (e.g., macrophages, microglia, and myeloid-derived suppressor cells).
(2) elucidate the mechanisms for how these infiltrated and polarized myeloid cells affect tumor growth, brain metastasis, and T cell-mediated anti-tumor immunity.
(3) understand how this tumor-immune cell symbiosis affects the effectiveness of cancer therapies (e.g., immunotherapy, anti-angiogenic therapy, and conventional therapies), thus developing novel and effective combination therapies. Our mission is to uncover novel mechanisms governing the development and progression of brain malignancies (including primary and metastatic brain cancers) and offer new therapeutic strategies for patients with these diseases.
Our Team
Selected Publications
View publications for Peiwen Chen, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
Selected Research Articles
Liu Y, Wu J, Najem H, Lin Y, Pang L, Khan F, Zhou F, Ali H, Heimberger AB and Chen P# (2024) Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma. Journal of Clinical Investigation 10.1172/JCI178628.
Khan F, Lin Y, Ali H, Pang L, Dunterman M, Hsu WH, Frenis K, Rowe RG, Wainwright DA, McCortney K, Horbinski C, Lesniak MS and Chen P# (2024) LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression. Nature Communications 15(1):1987. doi: 10.1038/s41467-024-46193-z.
Pang L*, Dunterman M*, Guo S, Khan F, Liu Y, Taefi E, Bahrami A, Geula C, Hsu WH, Horbinski C, James CD and Chen P# (2023) Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma. Nature Immunology 24(10):1654-1670. (Cover article).
Pang L*, Guo S*, Khan F*, Dunterman M, Ali H, Liu Y, Huang Y and Chen P# (2023) Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma. Cell Reports Medicine 4(11):101238. doi: 10.1016/j.xcrm.2023.101238.
Pang L*, Dunterman M*, Xuan W, Gonzalez A, Lin Y, Hsu WH, Khan F, Hagan RS, Muller WA, Heimberger AB and Chen P# (2023) Circadian Regulator CLOCK Promotes Tumor Angiogenesis in Glioblastoma. Cell Reports 42 (2), 112127.
Xuan W, Hsu WH, Khan F, Dunterman M, Pang L, Wainwright DA, Ahmed AU, Heimberger AB, Lesniak MS and Chen P# (2022) Circadian Regulator CLOCK Drives Immunosuppression in GBM. Cancer Immunology Research 10(6):770-784.
Chen P, Hsu WH, Chang A, Tan Z, Lan Z, Zhou A, Spring DJ, Lang FF, Wang YA and DePinho RA (2020) Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment. Cancer Discovery 10(3):371-381. (Cover article)
Chen P, Zhao D, Li J, Liang X, Li J, Chang A, Henry VK, Lan Z, Spring DJ, Rao G, Wang YA and DePinho RA (2019) Symbiotic macrophage-glioma cell interactions reveal synthetic lethality in PTEN null glioma. Cancer Cell 35(6):868-884. (Selected as the Wall of Science at MD Anderson)
Selected Review Articles
Pang L*, Zhou F*, Liu Y, Ali H, Khan F, Heimberger AB and Chen P# (2024) Epigenetic regulation of tumor immunity. Journal of Clinical Investigation 134(12):e178540.
Liu Y*, Ali H*, Khan F, Pang L and Chen P# (2024) Epigenetic regulation of tumor-immune symbiosis in glioma. Trends in Molecular Medicine 30(5):429-442. (Cover article).
Liu Y*, Zhou F*, Ali H, Lathia JD and Chen P# (2024) Immunotherapy for glioblastoma: Current state, challenges, and future perspectives. Cellular & Molecular Immunology doi: 10.1038/s41423-024-01226-x.
Khan F*, Pang L*, Dunterman M, Lesniak MS, Heimberger AB and Chen P# (2023) Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy. Journal of Clinical Investigation 133(1):e163446.
Pang L, Khan F, Heimberger AB and Chen P# (2022) Mechanism and Therapeutic Potential of Tumor-Immune Symbiosis in Glioblastoma. Trends in Cancer 8(10):839-854. (Cover article).
Pang L, Khan F, Dunterman M and Chen P# (2022) Pharmacological Targeting of the Tumor-Immune Symbiosis in Glioblastoma. Trends in Pharmacological Sciences 43(8): 686–700.
Xuan W*, Khan F*, James CD, Heimberger AB, Lesniak MJ and Chen P# (2021) Circadian Regulation of Cancer Cell and Tumor Microenvironment Crosstalk. Trends in Cell Biology 31(11): 940–950. (Cover article)
Xuan W, Lesniak MJ, James CD, Heimberger AB and Chen P# (2021) Context-Dependent Glioblastoma-Macrophage/microglia Symbiosis and Associated Mechanisms. Trends in Immunology 42(4):280–292. (Cover article)