Ling Li Lab
Research Overview
The Ling Li Lab investigates how abnormal myeloid hematopoiesis contributes to leukemia development and how leukemia stem cells survive therapeutic intervention. The laboratory focuses on acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with particular emphasis on leukemia initiation, stem cell maintenance, differentiation blockade, therapeutic resistance and anti-leukemia immunity.
To uncover disease mechanisms and identify novel therapeutic opportunities, the laboratory integrates molecular biology, functional genomics, metabolomics, genetic and epigenetic sequencing, advanced mouse models and single-cell technologies. Current research areas include targeting protein arginine methyltransferases, AMP biosynthesis and metabolic vulnerabilities, mitochondrial pathways and mechanisms of drug resistance in AML and MDS.
Research Highlights
Targeting PRMTs to Eliminate Leukemia Stem Cells and Overcome AML Resistance
Our research investigates how protein arginine methyltransferases (PRMTs) regulate leukemia stem cell (LSC) maintenance, therapeutic resistance and anti-leukemia immunity in acute myeloid leukemia (AML). We aim to identify PRMT-dependent vulnerabilities that can be therapeutically targeted to eradicate leukemia stem cells and improve treatment outcomes. Current projects focus on developing PRMT-targeted therapies for AML and defining PRMT9-mediated mechanisms of venetoclax resistance, with the goal of overcoming therapeutic resistance and achieving durable leukemia eradication.
Exploiting Metabolic Dependencies to Overcome Treatment Resistance in AML
Leukemia cells rely on distinct metabolic programs to sustain survival, stemness and resistance to therapy. Our research explores metabolic vulnerabilities in AML, with a particular emphasis on AMP biosynthesis and mitochondrial biology. We seek to identify metabolic dependencies that can be therapeutically exploited to overcome resistance to BH3 mimetics, including venetoclax-based therapies. Current studies also investigate how mitochondrial DNA activates anti-leukemia immune responses, linking cancer metabolism and mitochondrial function to AML-eradicating immunity.
Decoding MDS Stem Cells and Preventing Malignant Transformation
Myelodysplastic syndromes (MDS) arise from abnormal hematopoietic stem and progenitor cells and can progress to AML. Our research investigates the molecular and epigenetic mechanisms that sustain MDS stem and progenitor cells and drive malignant transformation. We focus on protein acetylation, TET2 function and epigenetic dysregulation to uncover vulnerabilities that distinguish abnormal from normal hematopoietic stem cells. These studies aim to identify therapeutic strategies that prevent MDS progression and transformation to AML.
Breaking the Differentiation Blockade to Eliminate Leukemia Stem Cells
A defining feature of AML is the inability of malignant cells to undergo normal differentiation. Our laboratory investigates the molecular mechanisms underlying differentiation blockade and how this state contributes to the persistence of leukemia stem cells. By identifying pathways that maintain differentiation arrest and stemness, we seek to develop therapeutic strategies that restore leukemia cell differentiation and selectively eliminate leukemia stem cells, providing new approaches for durable AML treatment.
Translating Molecular Vulnerabilities into New Leukemia Therapies
Our translational research program bridges mechanistic cancer biology and therapeutic development to identify actionable vulnerabilities in leukemia. We investigate a diverse range of disease-driving mechanisms, including aberrant protein synthesis, RNA and epigenetic regulation, metabolic dependencies and therapeutic resistance. By integrating molecular studies with preclinical models and therapeutic combination strategies, we aim to translate fundamental discoveries into new treatments for AML, MDS and other hematologic malignancies.
Dr. Li is a Professor in the Department of Hematological Malignancies Translational Science at City of Hope and a member of the Gehr Family Center for Leukemia Research and the Department of Hematology & Hematopoietic Cell Transplantation. His research focuses on elucidating the molecular and cellular mechanisms that drive leukemia initiation, leukemia stem cell maintenance, differentiation blockade, therapeutic resistance and malignant transformation in acute myeloid leukemia and myelodysplastic syndromes.
Lab Members
Interns
- Xiaoyi Yuan, 2026 Eugene and Ruth Roberts Summer Academy — currently in Arroyo Pacific Academy, Arcadia, California
- Elaine Sui, 2025 Eugene and Ruth Roberts Summer Academy — currently in Arcadia High School, Arcadia, California
- Milla Hu, 2025 Research Intern — currently at New York University, majoring in biochemistry
- Evan Chen, 2024 Eugene and Ruth Roberts Summer Academy — Third place at the Los Angeles County Science & Engineering fair; Currently at Washington University, majoring in biology (pre-medical track)
- Ada Zhong, 2019 Eugene and Ruth Roberts Summer Academy
- Johnny Wang, Research Intern
- Grace Huang, Research Intern
Lab Alumni
Former Postdoctoral Fellows
- 2022-2026, Umesh Yadav — currently at Loma Linda University, Loma Linda, California
- 2022-2023, Jie Xian — currently at University of California, San Diego, California
- 2016-2020, Yinghui Zhu — currently a principal investigator at the School of Life Sciences and Technology, Tongji University, China
- 2016-2017, Yimei Feng, MDS — currently a clinical fellow attending at the department of hematology, Xinqiao Hospital, China
Former Visiting Scholars
- 2023-2026, Yang Li — currently a clinical fellow at the Department of Hematology, Fujian Medical University Union Hospital, China
- 2023-2025, Jianai Sun — currently a clinical fellow at the Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, China
- 2018-2021, Hanying Wang — currently a clinical fellow at the Department of Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China
- 2019-2021, Yuhui Wu — currently a clinical fellow at the Department of Hematology, Sir Run Run Shaw Hospital
- 2019-2021, Zheng Li, — currently a clinical fellow at the Department of Hematology, the First Affiliated Hospital of Soochow University, China
- 2018-2020, Feiteng Huang — currently a clinical fellow at the Department of Hematology, Sir Run Run Shaw Hospital
- 2018-2019, Jinying Zou — currently an associate professor at School of Nursing, SuZhou Vocational Health College, China
- 2018-2019, Lei Zhu — currently a clinical fellow attending at the Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, China
Former Staff Scientist
- 2016-2021, Jie Sun — currently a principal investigator, Vice Director of Key Laboratory for Precision Medicine for Hematological Malignancies at the Department of Hematology, the First Affiliated Hospital of Zhejiang University School of Medicine
Our Publications
Li Y, He X, Zhang L, Dong H, Wang X, Che Y, Yadav UP, Liu M, Zhang L, Ge S, Wu G, Fu YH, Chen W, Kuo YH, Chen L, Marcucci G, Wang S, Li L.
He X, Zhang L, Li Y, Liu SB, Li Z, Dong H, Baker GE, Nguyen LXT, Chen W, Wang J, Jia Z, Lu X, Lin YC, Hu Z, Yadav UP, Liu M, Zhang L, Chen Z, Wu X, Chen J, Chen CW, Tiziani S, Hu W, Kuo YH, Xue SL, Zhang Y, Li M, Zhu Y, Marcucci G, Gu Z, Perry JJP, Luo YL, Li L.
Dong H, He X, Zhang L, Chen W, Lin YC, Liu SB, Wang H, Nguyen LXT, Li M, Zhu Y, Zhao D, Ghoda L, Serody J, Vincent B, Luznik L, Gojo I, Zeidner J, Su R, Chen J, Sharma R, Pirrotte P, Wu X, Hu W, Han W, Shen B, Kuo YH, Jin J, Salhotra A, Wang J, Marcucci G, Luo YL, Li L.
Wang H, He X, Zhang L, Dong H, Huang F, Xian J, Li M, Chen W, Lu X, Pathak KV, Huang W, Li Z, Zhang L, Nguyen LXT, Yang L, Feng L, Gordon DJ, Zhang J, Pirrotte P, Chen CW, Salhotra A, Kuo YH, Horne D, Marcucci G, Sykes DB, Tiziani S, Jin H, Wang X, Li L.
Sun J, He X, Zhu Y, Ding Z, Dong H, Feng Y, Du J, Wang H, Wu X, Zhang L, Yu X, Lin A, McDonald T, Zhao D, Wu H, Hua WK, Zhang B, Feng L, Tohyama K, Bhatia R, Oberdoerffer P, Chung YJ, Aplan PD, Boultwood J, Pellagatti A, Khaled S, Kortylewski M, Pichiorri F, Kuo YH, Carlesso N, Marcucci G, Jin H, Li L.
