Address421 E. Canfield Street, Suite 3128 Detroit, MI 48201
421 E. Canfield Street, Suite 3128
Detroit, MI 48201
Acute myeloid leukemia (AML) biology and leukemogenesis
Translational studies of AML, pancreatic cancer, diffuse intrinsic pontine glioma (DIPG), and neuroblastoma
Research in the Ge laboratory spans the basic biology and development of acute myeloid leukemia (AML) in children and adults, to combinational therapies and translational studies with primary patient specimens, cell line- and patient-derived xenograft models. Leukemia is the most common form of childhood cancer and cancer is the leading cause of death from disease of American children. Hence, improving leukemia therapy is of utmost importance in pediatric health. This is particularly relevant to AML in which progress has lagged significantly in comparison to childhood acute lymphoblastic leukemia. AML is even more challenging to treat in the elderly due to decreased tolerability to intensive therapy and increased therapy-related mortality. Resistance to cytarabine- and anthracycline-based chemotherapy is a major cause of treatment failure in this disease. Therefore, new therapies for patients with AML are urgently needed to overcome drug resistance, decrease relapse rates, and reduce short- and long-term adverse effects of treatment. The Ge laboratory studies are currently focusing on the antileukemic activity and molecular basis for novel targeted agents, including histone deacetylase (HDAC) inhibitors (HDACIs), Bcl-2 inhibitors, FLT3 inhibitors, and cell cycle checkpoint inhibitors, either alone or in combination, in preclinical models of AML. Dr. Ge's laboratory identified molecular mechanisms of resistance to the Bcl-2-selective inhibitor, Venetoclax (ABT-199), in AML, and is identifying therapeutic targets for combination therapies with ABT-199 to overcome intrinsic resistance. In addition to AML, the Ge laboratory is also developing novel combinational therapies in preclinical models of pancreatic cancer, diffuse intrinsic pontine glioma (DIPG), and neuroblastoma.
Wu S, Edwards H, Wang D, Liu S, Qiao X, Carter J, Wang Y, Taub JW, Wang G, and Ge Y. Inhibition of Mcl-1 Synergistically Enhances the Antileukemic Activity of Gilteritinib and MRX-2843 in Preclinical Models of FLT3-mutated Acute Myeloid Leukemia. Cells. 2022;11:2752.
Liu S, Qiao X, Wu S, Gai Y, Su Y, Edwards H, Wang Y, Lin H, Taub JW, Wang G, and Ge Y. c-Myc plays a critical role in the antileukemic activity of the Mcl-1 selective inhibitor AZD5991 in acute myeloid leukemia. Apoptosis. 2022. doi: 10.1007/s10495-022-01756-7. Online ahead of print.
Knight T, Pitman H, Taub JW, and Ge Y. MAP4K1 expression is a novel resistance mechanism and independent prognostic marker in AML – But can be overcome via targeted inhibition. EBioMedicine. 2021;70:103488.
Qiao X, Ma J, Knight T, Su Y, Edwards H, Polin L, Li J, Kushner J, Dzinic SH, White K, Wang J, Lin H, Wang Y, Wang L, Wang G, Taub JW, and Ge Y. The Combination of CUDC-907 and Gilteritinib Shows Promising in vitro and in vivo Anti-Leukemic Activity Against FLT3-ITD AML. Blood Cancer J. 2021;11:111.
Niu X, Rothe K, Chen M, Grasedieck S, Li R, Nam SE, Zhang X, Novakovskiy G, Ahn YH, Maksakova IA, Lai S, Zhang H, Yan J, Liu H, Zhao Y, Wu D, Ge Y, Wasserman W, Rouhi A, Kuchenbauer FC, Yip CK, Zhang Z, Jiang X. Inhibition of AXL Kinase Uniquely Sensitizes Therapy-Insensitive Cancer Stem and Progenitor Cells to Venetoclax Treatment in Acute Myeloid Leukemia. Blood. 2021;137:3641-55.
Li X, Su Y, Hege K, Madlambayan G, Edwards H, Knight T, Polin L, Kushner J, Dzinic SH, White K, Miller R, Wang G, Zhao L, Wang Y, Lin H, Taub JW, and Ge Y. The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia. Haematologica. 2021;106:1262-77.
Carter JL, Hege K, Kalpage HA, Edwards H, Hüttemann M, Taub JW, Ge Y. Targeting Mitochondrial Respiration for the Treatment of Acute Myeloid Leukemia. Biochem Pharmacol. 2020;182:114253.
Carter JL, Hege K, Yang J, Kalpage HA, Su Y, Edwards H, Hüttemann M, Taub JW, and Ge Y. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy. Signal Transduct Target Ther. 2020;5:288.
Liu F, Kalpage H, Wang D, Edwards H, Huttemann M, Ma J, Su Y, Carter J, Li X, Polin L, Kushner J, Dzinic SH, White K, Wang G, Taub JW, and Ge Y. Cotargeting of Mitochondrial Complex I and Bcl-2 Shows Antileukemic Activity against Acute Myeloid Leukemia Cells Reliant on Oxidative Phosphorylation. Cancers (Basel). 2020;12:2400.
Hu C, Xia H, Bai S, Zhao J, Edwards H, Li X, Lyu J, Yang Y, Dong Y, and Ge Y. CUDC-907, a novel dual PI3K and HDAC inhibitor, in prostate cancer: antitumor activity and molecular mechanism of action. J Cell Mol Med. 2020; 24:7239-53.
Luedtke DA, Su Y, Ma J, Li X, Buck SA, Edwards H, Polin L, Kushner J, Dzinic SH, White K, Lin H, Taub JW, and Ge Y. Inhibition of CDK9 by Voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia. Signal Transduct Target Ther. 2020;5:17.
Wang T, Shatara M, Liu F, Edwards H, Wang G, Lin H, Wang Y, Taub JW, and Ge Y. Simultaneous co-targeting of ATR and RNA Pol I transcription shows synergistic antileukemic effects on acute myeloid leukemia. Signal Transduct Target Ther. 2019; 4:44.
Shatara M, Xavier AC, Dombkowski A, Cukovic D, Poulik JM, Altinok D, Ge Y, and Taub JW. Monozygotic Twins with Neuroblastoma MS have similar molecular profile: a case of twin-to-twin metastasis. Br J Cancer. 2019; 121:890-3.
Ma J, Zhao S, Qiao X, Knight T, Edwards H, Polin L, Kushner J, Dzinic SH, White K, Wang G, Zhao L, Lin H, Wang Y, Taub JW, and Ge Y*. Inhibition of Bcl-2 synergistically enhances antileukemic activity of midostaurin and gilteritinib in preclinical models of FLT3-mutated acute myeloid leukemia. Clin Cancer Res. 2019; 25:6815-26. [CCR Translations commentary: Perl AE. Improving Response to FLT3 Inhibitors–BCL2 the Rescue? Clin Cancer Res. 2019;25:6567-9.]
Li X, Su Y, Madlambayan G, Edwards H, Polin L, Kushner J, Dzinic S, White K, Ma J, Knight T, Wang G, Wang Y, Yang J, Taub JW, Lin H, and Ge Y. Antileukemic activity and mechanism of action of the novel PI3K and HDAC dual inhibitor CUDC-907 in acute myeloid leukemia. Haematologica. 2019;104:2225-40.
Liu F, Knight T, Su Y, Edwards H, Wang G, Wang Y, Taub JW, Lin H, Sun L, and Ge Y. Venetoclax synergistically enhances the antileukemic activity of vosaroxin against acute myeloid leukemia ex vivo. Targeted Oncology. 2019; 2019;14:351-64.
Knight T, Luedtke D, Edwards H, Taub JW, and Ge Y. A delicate balance - the Bcl-2 family and its role in apoptosis, oncogenesis, and cancer therapeutics. Biochem Pharmacol. 2019;162:250-61.
Volk A, Liang K, Suraneni P, Li X, Zhao J, Bulic M, Marshall S, Pulakanti K, Malinge S, Taub JW, Ge Y, Rao S, Bartom E, Shilatifard A, and Crispino JD. A CHAF1B-dependent molecular switch in hematopoiesis and leukemia pathogenesis. Cancer Cell. 2018;34:707-723.e7.
PhD (1998): Jilin University, Changchun, China