造血干细胞恶性转化是血液肿瘤研究的关键问题，但是其机理尚不甚清楚。申请人研究专长为结合动物模型和生化机制分析造血干细胞恶性转化的分子机制。发表Science 等国际期刊论文20 篇，获中国专利3项，另1项美国专利被受理，专著章节1篇，获中组部“青年千人计划”支持。目前主要研究成果包括：1）发现p300乙酰化致病融合蛋白AML1-ETO，控制白血病干细胞自我更新；2）发现Caspase-3诱导AML1-ETO降解, 并揭示可有效激活Caspase-3的二萜类化合物对白血病治疗有效；3）发现中药复方有效成分硫化砷，靛玉红和丹参酮调控水通道蛋白AQP9的表达，并揭示AQP9可作为砷泵控制白血病细胞内砷浓度；4）建立独立课题组后，发现特异敲除DNA结合抑制蛋白Id1能够阻断白血病干细胞的自我更新以及Id1在婴儿和成人白血病形成中有截然相反作用。长期目标为建设国际一流的血液肿瘤研究团队。

The transformation from hematopoietic stem cell to leukemia initiating cell is the key question in the hematological malignancies research area, while the underlying molecular mechanisms remain largely unknown. The applicant has research expertise both in animal models and biochemistry and aims at studying the driving forces of the transformation from hematopoietic stem cell to leukemia initiating cell with multidisciplinary approaches. The applicant has published 20 papers in international reputable journals such as Science, Nature and Cancer cell, 3 China Patents, 1 U.S. patent in application, and 2 book chapters. She was awarded by the “1000 Young Talent Plan”. The main scientific contributions by the applicant include: 1) 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. 2) Dr. Wang investigated the effects of Eriocalyxin B (EriB) on the t(8;21)-leukemia. EriB induced programmed cell death of leukemia cells through damage of mitochondria functions, down-regulation of Bcl-2, and activation of caspase-3. Dr. Wang’s study showed that EriB could cause a caspase-3 dependent degradation of AML1-ETO, and the aspartic acid residue at position 188 of AML1-ETO was the cleavage site. Interestingly, EriB significantly prolonged life span in the murine model of AML. 3) Dr. Wang also discovered that Realgar-Indigo naturalis formula, with tetraarsenic tetrasulfide, 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 intensifing ubiquitination/degradation of PML-RARα. 4) 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. Loss of Id1 abrogates the leukemia progression in mouse models. Therefore, the drugs developed to inhibit Id1 levels may provide new therapies for these The long-term goal is to develop her research team into an internationally leading laboratory in the field of hematological malignancies.