Faculty

Liling Wan, PhD

faculty photo
Assistant Professor of Cancer Biology
Department: Cancer Biology

Contact information
751 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: (215)-898-3116
Fax: (215)-573-6725
Lab: (215)-898-3698
Education:
B.S. (Biological Sciences and Biotechnology)
Tsinghua University, Beijing, China, 2008.
PhD (Molecular Biology)
Princeton University, Princeton, NJ, 2014.
Permanent link
 
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Description of Research Expertise

Research Interests:
The research interests in the Wan Lab lie in the intersection of cancer biology and epigenetics.

Keywords:
Cancer Biology, Epigenetics, Chromatin, Histone modifications, Gene regulation, Cell fate, Drug discovery, Leukemia, Kidney

Research Details:
Chromatin - the complex of DNA and histone proteins - is the physiological template of the eukaryotic genome through which transcription factors, signaling pathways, and other internal and external cues alter gene activity and cellular phenotypes. Cancer genome studies revealed that at least 40% of human cancers harbor mutations in genes encoding chromatin-associated factors, suggesting widespread roles of chromatin misregulation in cancer. We strive to understand chromatin function and its dysregulation in human cancer, with a focus on addressing how these mechanisms regulate cellular fate transition and plasticity that endow cancer cells with tumor-promoting potentials. We are also interested in leveraging our basic mechanistic discoveries for therapeutics development. We have multiple areas of ongoing research in the lab: (1) Elucidate how the epigenome is decoded by chromatin readers to influence cell fate decisions and tumorigenesis; (2) Investigate the structural and biochemical basis and functional consequence of cancer-associated mutations in chromatin regulators; (3) Investigate how epigenomic reprogramming influences transcriptional and cellular plasticity to impact cancer cell behaviors such as metastasis; and (4) Develop and/or characterize drugs that target newly identified epigenetic mechanisms in cancer.

Research techniques:
We use a host of different approaches including genome-wide sequencing, advanced imaging, functional genomics, biochemistry, structural biology, mouse models of disease, bioinformatics and more.

Rotation Projects:
Rotation projects are available in each area of interest in the lab. Please contact Dr. Wan for details.

Selected Publications

Wang X*, Fan D*, Liu Y*, Han Q*, Miao H, Wang X, Li Q, Chen D, Gore H, Himadewi P, Pfeifer G, Cierpicki T, Grembecka J, Su J#, Chong S#, Wan L#, Zhang X# (*co-first; #co-corresponding): Mutant NPM1 hijacks transcriptional hub to maintain pathogenic gene programs in acute myeloid leukemia. Cancer Discovery 2022.

Song L*, Yao X*, Li H, Peng B, Boka AP, Liu Y, Chen G, Liu Z, Mathias KM, Xia L, Li Q, Mir M, Li Y#, Li H#, Wan L# (*co-first; #co-corresponding): Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer. Molecular Cell 82(21): 4080-4098, November 2022.

Liu Y, Li H, Alikarami F, Barrett DR, Khan TA, Michino M, Hill C, Mahdavi L, Song L, Tang S, Yang L, Li Y, Pokharel SP, Li Q, Stamford AW, Liverton N, Renzetti LM, Taylor S, Watt GF, Ladduwahetty T, Kargman S, Meinke PT, Foley MA, Shi J, Li H, Chen CW, Gardini A, Huggins DJ, Bernt KM#, Wan L# (#co-corresponding): Small-molecule inhibition of the acyl-lysine reader ENL as a strategy against acute myeloid leukemia. Cancer Discovery 12(11): 2684-2709, November 2022.

Yan F, Li J, Milosevic J, Petroni R, Liu S, Shi Z, Yuan S, Reynaga JM, Qi Y, Rico J, Yu S, Liu Y, Rokudai S, Palmisiano N, Meyer SE, Sung PJ, Wan L, Lan F, Garcia BA, Stanger BZ, Sykes DB, Blanco MA: KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene Expression Programs. Cancer Discovery 12(3): 792-811, December 2021.

Shen M, Wei Y, Kim H, Wan L, Jiang, Y, Hang X, Raba M, Remiszewski S, Rowicki M, Wu C, Wu S, Zhang L, Lu X, Yuan M, Smith AS, Zheng A, Bertino J, Jin JF, Xing Y, Shao Z, Kang Y: Small-molecule Inhibitors that Disrupt the MTDH–SND1 Complex Suppress Breast Cancer Progression and Metastasis. Nature Cancer 3(1): 43-59, January 2022.

Shen M, Smith HA, Wei Y, Jiang Y, Zhao S, Wang N, Rowicki M, Tang Y, Hang X, Wu S, Wan L, Shao Z, Kang Y: Pharmacological Disruption of the MTDH–SND1 Complex Enhances Tumor Antigen Presentation and Synergizes with Anti-PD-1 Therapy in Metastatic Breast Cancer. Nature Cancer 3(1): 60-74, January 2022.

Wan L#, Chong S, Fan X, Liang A, Cui X, Gates L, Carroll TS, Li Y, Feng L, Chen G, Wang S, Ortiz MV, Daley S, Wang X, Xuan H, Kentsis A, Muir TW, Roeder RG, Li H, Li W, Tjian R, Wen H#, Allis CD# (#co-corresponding): Impaired Cell Fate through Gain-of-function Mutations in a Chromatin Reader. Nature 577(7788): 121-126, January 2020.

Wan L*, Wen H*, Li Y*, Lyu J, Xi Y, Hoshii T, Joseph JK, Wang X, Loh YE, Erb MA, Souza AL, Bradner JE, Shen L, Li W, Li H#, Allis CD#, Armstrong SA#, Shi X# (*co-first; #co-senior): ENL Links Histone Acetylation to Oncogenic Gene Expression in Acute Myeloid Leukemias. Nature 543(7644): 265-269, March 2017.

Wan L, Lu X, Yuan S, Wei Y, Guo F, Shen M, Yuan M, Chakrabarti R, Hua Y, Smith HA, Blanco MA, Chekmareva M, Wu H, Bronson RT, Haffty BG, Xing Y, Kang Y: MTDH-SND1 Interaction is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors. Cancer Cell 26(1): 92-105, July 2014.

Guo F*, Wan L*, Zheng A, Stanevich V, Wei Y, Satyshur KA, Shen M, Lee W, Kang Y#, Xing Y# (*co-first; #co-senior): Structural Insights into the Tumor-Promoting Function of the MTDH-SND1 Complex. Cell Reports 8(6): 1704-1713, September 2014.

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Last updated: 12/07/2022
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