Yunqing Li, PhD

Assistant Professor of Neurology

Dr. Li’s lab focuses on uncovering the genetic and epigenetic mechanisms of brain tumor growth and standard-of-care resistance. The ultimate goal is to develop novel anti-tumor therapeutic strategies to treat brain tumor malignancy. The following projects are ongoing in the lab:

Project 1: Grade II-III astrocytomas(IDH1R132H/p53mut/ATRXloss )most commonly occur in young adults and have a high probability to progress to higher-grade tumors including glioblastoma (i.e., secondary GBM) despite aggressive surgical resection, ionizing radiation (IR) and/or chemotherapy (temozolomide, TMZ). Interactions between astrocytoma cells and immune cells within the tumor microenvironment (TME) play a critical role in tumor growth, progression, and anti-tumor immune responses. This project aims to identify the epigenetic mechanisms underlying the immunosuppressive interactions between astrocytoma cells and immune cells within TME and their augmentation by IR and establish novel combination strategies to sensitize astrocytoma to emerging immunotherapeutics.

Project 2: GBM is heterogeneous at the cellular level and contains small populations of tumor-propagating stem-like cells (e.g., glioma stem-like cells, GSCs) that have a high capacity to propagate tumor growth and drive therapeutic resistance and tumor recurrence. GSCs are associated with the repression of anti-tumor cytotoxic T-cell responses and limiting anticancer immunity. This project aims to understand and then target GSC epigenetic transcriptional determinants that are associated with the GSCs’ immunosuppressive phenotype and tumor-immune microenvironment (TME) leading to GSC and bulk tumor immune evasion.

Project 3: Immunotherapy holds promise in other cancers but has been ineffective in GBM. Tumor cell heterogeneity and an immunosuppressive tumor microenvironment underlie GBM immunotherapy failure and therapeutic resistance and GBM recurrence. Current experimental models lack GBM heterogeneity and realistic GBM TME, therefore, cannot model the dynamic GBM: immune cell crosstalk. The broad goal of this project is to establish a platform for more faithfully recapitulating GBM characteristics such as cell-type heterogeneity and immune microenvironment at the level of an individual GBM patient and use this platform to study the interactions between GBM and immune cells within a CNS context and identify novel immune determinant that enhance GBM checkpoint inhibitor immunotherapy.

https://www.ncbi.nlm.nih.gov/myncbi/yunqing.li.1/bibliography/public/

• Li Y*, Angela Li, Martin Glas, Bachchu Lal, Mingyao Ying, Yingying Sang, Shuli Xia, Daniel Trageser, Hugo Guerrero-Cázares, Charles G. Eberhart, Alfredo Quiñones-Hinojosa, Bjorn Scheffler, and John Laterra1. C-Met Signaling Induces a Reprogramming Network and Supports the Glioblastoma Stem-Like Phenotype. Proc Natl Acad Sci USA. 2011 Jun 14; 108(24):9951-6. PMID: 21628563. Response author

• Li Y, Guessous F, Zhang Y, DiPierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, Lopes B, Schiff D, Purow B and Abounader R. MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes. Cancer Research 69, 7569, September 22, 2009

• Chengchen Hu, Kimberly Wang, Ceylan Damon, Yi Fu, Tengjiao Ma, Lisa Kratz, Bachchu Lal, Mingyao Ying, Shuli Xia, Daniel P. Cahill, Christopher M. Jackson, Michael Lim, John Laterra and Yunqing Li*. ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma. Neuro Oncol. 2022, Jun 1, 24(6):888-900. PMID: 34951647

• Lopez-Bertoni H, Lal B, Li A, Caplan M, Guerrero-Cázares H, Eberhart CG, Quiñones-Hinojosa A, Glas M, Scheffler B, Laterra J, Li Y. DNMT-dependent suppression of microRNA regulates the induction of GBM tumor-propagating phenotype by Oct4 and Sox2. Oncogene, 2015. 34(30):3994-4004. PMID: 25328136

• Tengjiao Ma, Chengchen Hu, Bachchu Lal, Weiqiang Zhou, Yongxin Ma, Mingyao Ying , Panagiotis Prinos , Alfredo Quiñones-Hinojosa, Michael Lim , John Laterra, Yunqing Li* Reprogramming Transcription Factors Oct4 and Sox2 Induce a BRD-Dependent Immunosuppressive Transcriptome in GBM-Propagating Cells. Cancer Res. 2021 May 81(9): 2457-2469.PMID: 33574085