Ph.D., Principal Investigator
Laboratory of Hematological Malignancies
Research Interests or Current Research Focus
Dr. Wang’s research focuses on understanding the pathogenesis of hematological malignancies and stem cell studies. In particular, Dr. Wang is interested in identifying the genes that are disrupted in these disorders, and developing the new therapeutic strategies for patients with these diseases. Blood cells are generated by hematopoietic stem cells, which are proposed to be the cell of origin in leukemia and we are studying how their behavior goes awry when the cells become transformed. Cancer stem cells show loss of normal growth control mechanisms, leading to abnormal cell division, survival and expansion. The development of hematological malignancies is commonly associated with aberrant transcriptional regulation, where genes are inappropriately turned on or off. In most cases, correcting these abnormalities would block the development or progression of hematological malignancies in patients.
Major Research Achievement
Dr. Wang began studying the targeted therapy of hematological malignancies in 2002. Dr. Wang investigated the effects of Eriocalyxin B (EriB) on t(8;21) leukemia. Dr. Wang’s study showed that EriB could cause a caspase-3 dependent degradation of AML1-ETO, and significantly prolong life span in the murine model of AML. Dr. Wang also discovered that Realgar-Indigo naturalis formula, with tetraarsenictetrasulfide, indirubin and tanshinone IIA, yields synergy in the treatment of a murine acute promyelocyte leukemia (APL) model and in the induction of cell differentiation through promoting AQP9-mediated transportation of arsenic into cells and intensifingubiquitination/degradation of PML-RARα.
At Memorial Sloan-Kettering Cancer Center, Dr. Wang’s study suggests that AML1-ETO directly interacts with histone acetyltransferase p300, and that p300 can acetylate two lysine residues in AML1-ETO and AML1-ETO9a in human and mouse leukemia cells. The post-translational acetylation, adding an acetyl group to a specific amino acid in AML1-ETO, is the key to the ability of AML1-ETO to promote self-renewal of hematopoietic stem/progenitor cells. Further, inhibition of this acetylation reduces the growth of cancer cells. The information generated by this study may be useful for developing targeted therapeutics for human leukemia.
Dr. Wang is also interested in using murine leukemia models to identify therapeutic targets for leukemia stem cells. AML1-ETO and p300 coopreatively activate the transcription of Id1, and the upregulation of Id1 may promote the development of hematological malignancies. Using genetically modifiedmice, we identified the crucialrole of Id1 in t(8;21)leukemogenesis throughregulating AKT signaling.Id1 inhibitor has a significanttherapeutic effect in themouse model of t(8;21)leukemia. We also found thatloss of Id1 delaysleukemogenesis in fetal MLLAF9leukemia model, butaccelerates leukemogenesisin postnatal MLL-AF9leukemia model.Deletion of p21rescues the loss of Id1 in bothMLL-AF9 mouse models.Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9–driven leukemia.
1998-2002: Fudan University, Bachelor
2002-2007: Institute of Health Sciences, Shanghai Institute of Life Science, Chinese Academy of Science, Ph.D.
Major Academic Appointments
2008-2010: Research Fellow, Memorial Sloan - Kettering Cancer Center
2010-2012: Research Associate, Memorial Sloan - Kettering Cancer Center
2013-2015: Assistant Professor, Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami
2015-Present: Principle Investigator, Institute of Health Sciences, SIBS, CAS / SJTUSM
Honors, Certificates, and Academic Society
2005: Excellent Student, Chinese Academy of Sciences.
2005-2006: "Chen Zhu and Chen Saijuan" Award for Out standing Graduate Student, Shanghai Iinstitute of Hematology.
2009: Leukemia Lymphoma Society Fellowship
2010: American Society of Hematology meeting travel award
2010: Faculty of 1000 Post-publication peer review Associate faculty member
2011: Empire State Stem Cell Scholars Fellow to Faculty award
2013：Member of Sylvester Comprehensive Cancer Center
2014-2015: Gabrielle's Angel Foundation for Cancer Research award
2014-2015: The Woman's Cancer Association of the University of Miami award
2014-2015: Leukemia Research Foundation New Investigator award
2015: Stanley J. Glaser Foundation Award
2015: Recipient of the Recruitment Program of Global Experts (Young Program)
2015: Editor of Frontiers in Biosciences
2016: China National Funds for Excellent Young Scientists
2016: The Excellent Overseas Returnees Award by Ministry of Human Resources and Social Security
- Na Man, Sun XJ, Tan Y, Cao M, Liu F, Cheng G, Hatlen M, Xu H, Shah R, Huang G, Zhou Y, Sheng M, Yang F, Benezra R, Nimer SD, Wang L. Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin. Blood. 2016 May 12; 127(19):2322-6.
- Liu F, Wang L, Perna F, Nimer SD. Beyond transcription factors: how oncogenic signaling reshapes the epigenetic landscape. Nature Reviews Cancer. 2016 June; 16(6):359-72.
- Shirakawa K, Wang L, Man N, Maksimoska J, Sorum AW, Lim HW, Lee IS, Shimazu T, Newman JC, Schroder S, Ott M, Marmorstein R, Meier J, Nimer S, Verdin E. Salycylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity. Elife. 2016 May 31;5.
- Megan A. Hatlen, Arora K, Vacic V, Grabowska E, Liao W, Riley-Gillis B, Oschwald D, Wang L, Joergens J, Shih A, Rapaport F, Gu S, Voza F, Asai T, Neel B, Kharas M, Gonen M, Levine R, Nimer SD. Integrative analysis of the mutational landscape of mouse and human AML identifies functionally relevant leukemia disease alleles. J Exp Med. 2016 Jan 11; 213(1):25-34
- Wang L, Hamard PJ, Nimer SD. PARP inhibitors: a treatment option for AML? Nature Medicine 2015 Dec 8;21(12):1393-4.
- Wang L*, Man N, Sun XJ, Tan Y, Cao MG, Liu F, Hatlen M, Xu H, Huang G, Mattlin M, Mehta A, Rampersaud E, Benezra R, Nimer SD. Regulation of AKT signaling by Id1 controls t(8;21) leukemia initiation and progression. Blood. 2015 Jul 30;126(5):640-50. (* corresponding author)
- Liu F, Cheng G, Hamard PJ, Greenblatt S, Wang L, Man N, Perna F, Xu H, Tadi M, Luciani L, Nimer SD. Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. J Clin Invest. 2015 Sep;125(9):3532-44.
- Sun XJ, Man N, Tan Y, Nimer SD, Wang L. The role of histone acetyltransferase in normal and malignant hematopoiesis. Front Oncol. 2015 May 26;5:108.
- Vu L, Perna F, Wang L, Voza F, et al. PRMT4 Blocks Myeloid Differentiation by Assembling a Methyl-RUNX1-Dependent Repressor Complex. Cell Reports. 2013 Dec 26;5(6):1625-38.
- Sun X-J, Wang Z, Wang L, Jiang Y, et al. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature. 2013 Aug 1; 500(7460):93-7.
- Hatlen MA, Wang L, Nimer SD. AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches. Front Med. 2012 Sep;6(3):248-62.
- Huang G, Zhao X, Wang L, Elf S, et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011 Dec 15;118(25):6544-52.
- Wang L, Gural A, Sun X-J, et al. The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science. 2011 Aug 5;333(6043):765-9.
- Liu F, Zhao X, Perna F, Wang L, Koppikar P, et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell. 2011 Feb 15;19(2):283-94.
- Perna F, Gurvich N, Hoya-Arias R, Abdel-Wahab O, Levine RL, Asai T, Voza F, Menendez S. Wang L, et al. Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q- polycythemia vera. Blood. 2010 Oct 14;116(15):2812-21.
- Zhang YW, Jiang XX, Chen QS, Shi WY, Wang L, et al. Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular signaling pathways. Experimental Hematology. 2010 Mar;38(3):191-201.
- Wang L, Huang G, et al. Post-translational modifications of Runx1 regulate its activity in the cell. Blood Cells Mol Dis. 2009 Jul-Aug; 43(1):30-4.
- Wang L, Zhou GB, et al. Dissection of mechanism of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci U S A. 2008; 105(12):4826-31.
- Zhao WL, Wang L (co-first author), Liu YH, et al. Histone deacetylase inhibitor promotes rituximab-induced apoptosis in non-Hodgkin’s B-lymphoma cells by NF-kB-mediated Bcl-2/Bcl-XL downregulation and c-Myc degradation. Experimental Hematology. 2007; 35(12):1801-11.
- Zhou GB, Kang H, Wang L(co-first author), Gao L, et al. Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo. Blood. 2007; 109(8):3441-50.
- Wang L, Zhao WL, et al. Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death and Differentiation. 2007;14,306-317.
- Wang L, Chen SJ. Monoclonal antibodies treat hematopoietic malignancies. Shanghai: Shanghai Science and Technology Press, 2006 pp.309-322.
- Sun XJ, Wei J, Wu XY, Hu M, Wang L, et al. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005; 280: 5261-71.