Biography

Dr. Hudan Liu received her PhD in Rutgers, the State University of New Jersey and continued her postdoctoral training in the University of Pennsylvania, Perelman School of Medicine, where she started to focus her interest in hematology oncology. After serving as a principal investigator in Tongji Medical College, Huazhong University of Science and Technology for four years, she joined Medical Research Institute of Wuhan University in 2016. Dr Liu has been committed to the basic research on the molecular mechanisms and targeted therapy of acute leukemia. In particular, her research focuses on unraveling the intricate molecular pathways underlying the development and progression of T-cell acute lymphoblastic leukemia (T-ALL), with a particular emphasis on identifying potential therapeutic targets. Dr Liu has identified multiple potential drug targets and relevant biomarkers within the NOTCH1-MYC signaling network, providing scientific evidence for exploring new targeted therapeutic approaches in the treatment of T-cell leukemia. She has received ten research grants supported by National Science Foundation of China, and published over 40 research articles in internationally renowned academic journals such as Cancer Cell, Nature Communications, Science Advances, Haematologica, and Clinical Cancer Research. Her research achievements have been recognized as one of the Top Ten Advances in Hematology in China in 2020. Dr Liu is a recipient of the National Science Fund for Distinguished Young Scholars in China. She currently serves as the Deputy Chair of the Chinese Association of Blood Science; she is also a member of the Hematologic Oncology Committee of the Chinese Anti-Cancer Association, as well as the Experimental Hematology Committee of the Chinese Society of Pathophysiology.

Research

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and life-threatening hematologic malignancy currently lack of effective targeted therapeutics. Our research team is particularly interested in understanding the molecular pathogenesis of T-ALL with an attempt to identify potential therapeutic targets. We have been focusing the efforts on investigating the role of NOTCH1 and MYC, two major oncogenic drivers in T-ALL, in leukemogensis. Recent studies from our group have demonstrated that HSP90 and AURKB stabilize NOTCH1 and MYC proteins respectively, leading to robust amplification of the NOTCH1/MYC oncogenic programs (Clin Cancer Res 2017; Cancer Cell 2020). NOTCH1 and MYC, acting as transcriptional factors, in turn directly activate a series of downstream effectors that contribute to multiple aspects of leukemogenesis. We have identified SHQ1 as novel NOTCH1 direct transcriptional targets. To mediate the oncogenic role of NOTCH1, SHQ1 participates in regulation of RNA splicing (Nat Commun 2018). We have also demonstrated that MYC directly activates WEE1 transcription, and the MYC-WEE1 interaction amplifies aerobic glycolysis, thereby significantly contributing to metabolic reprogramming associated with leukemogenesis (Haematologica 2021). Recently, we have reported that the super elongation complex drives transcriptional addiction in MYCN-amplified tumors, suggesting disruption of the elongation complex as a promising therapeutic strategy (Science Advances 2023). In addition, by comparing gene expression between normal thymocytes and T-ALL cells, we revealed RNA binding proteins (RBPs) as crucial players in T cell transformation. The RNA helicase DHX15 promotes leukemia progression through RNA splicing-dependent and independent mechanisms (Haematologica 2023). Collectively, these studies identify multiple, essential regulators involved in T-cell leukemogenesis, opening a new avenue for developing potentially effective approaches for T-ALL therapy.

Representative  Publications

1. Jiang J#, Wang J#, Yue M#, Cai X, Wang T, Wu C, Su H, Wang Y, Han M, Zhang Y, Zhu X, Jiang P, Li P, Sun Y, Xiao W, Feng H, Qing G, Liu H*. Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T Cell Leukemogenesis. Cancer Cell. 2020, 37(2):200-215.

2. Su H, Hu J, Huang L, Yang Y, Thenoz M, Kuchmiy A, Hu Y, Li P, Feng H, Zhou Y, Taghon T, Van Vlierberghe P, Qing G, Chen Z*, Liu H*. SHQ1 regulation of pre-RNA splicing is required for T-lymphoblastic leukemia cell survival. Nature Communications. 2018,9(1):4281.

3. Wang D#, Yin Z#, Wang H#, Wang L, Li T, Xiao R, Xie T, Han R, Dong R, Liu H*, Liang K*, Qing G*. The Super Elongation Complex Drives Transcriptional Addiction in MYCN-amplified Neuroblastoma. Science Advances. 2023, 9(13): eadf0005.

4. Guo H#, Xu J#, Xing P#, Li Q, Wang D, Tang C, Palhais B, Roels J, Liu J, Pan S, Huang J, Liu Z, Zhu P, Taghon T, Qing G, Van Vlierberghe P*, Liu H*. RNA helicase DHX15 exemplifies a unique dependency in acute leukemia. Haematologica. 2023, 108(8):2029-2043.

5. Hu J#, Wang T#, Xu J, Wu S, Wang L, Su H, Jiang J, Yue M, Wang J, Wang D, Li P, Zhou F, Liu Y, Qing G, Liu H*. WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia. Haematologica. 2021, 106(7):1816-1827.

6. Wu C#, Xie T#, Guo Y, Wang D, Qiu M, Han R, Qing G, Liang K,Liu H*. CDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis. Oncogene. 2023, 42(16):1321-1330.

7. Wang J#, Jiang J#, Chen H, Wang L, Guo H, Yang L, Xiao D, Qing G*, Liu H*. FDA-approved drug screen identifies proteasome as a synthetic lethal target in MYC-driven neuroblastoma. Oncogene. 2019, 38(41):6737-6751.

8. Wang Z#, Hu Y#, Xiao D, Wang J, Liu C, Xu Y, Shi X, Jiang P, Huang L, Li P, Liu H*, Qing G*. Stabilization of Notch1 by the Hsp90 Chaperon is Crucial for T Cell Leukemogenesis. Clinical Cancer Research. 2017, 23(14):3834-3846.