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.
Li X, Su Y, Hege K, Madlambayan G, Edwards H, Knight T, Polin L, Kushner J, Dzinic SH, White K, Yang J, Miller R, Wang G, Zhao L, Wang Y, Lin H, Taub JW, 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. 2020 Mar 12. pii: haematol.2019.233445. doi: 10.3324/haematol.2019.233445. [Epub ahead of print]
Luedtke DA, Su Y, Ma J, Li X, Buck SA, Edwards H, Polin L, Kushner J, Dzinic SH, White K, Lin H, Taub JW, 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.
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, Ge Y. Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia. Clin Cancer Res. 2019;25:6815-26.
Shatara M, Xavier AC, Dombkowski A, Cukovic D, Poulik JM, Altinok D, Ge Y, Taub JW. Monozygotic twins with neuroblastoma MS have a similar molecular profile: a case of twin-to-twin metastasis. Br J Cancer. 2019;121:890-3.
Li X, Su Y, Madlambayan G, Edwards H, Polin L, Kushner J, Dzinic SH, White K, Ma J, Knight T, Wang G, Wang Y, Yang J, Taub JW, Lin H, Ge Y. Antileukemic activity and mechanism of action of the novel PI3K and histone deacetylase dual inhibitor CUDC-907 in acute myeloid leukemia. Haematologica. 2019;104:2225-40.
Wang T, Shatara M, Liu F, Knight T, Edwards H, Wang G, Lin H, Wang Y, Taub JW, Ge Y. Simultaneous cotargeting of ATR and RNA Polymerase I transcription demonstrates synergistic antileukemic effects on acute myeloid leukemia. Signal Transduct Target Ther. 2019;4:44.
Liu F, Knight T, Su Y, Edwards H, Wang G, Wang Y, Taub JW, Lin H, Sun L, Ge Y. Venetoclax Synergistically Enhances the Anti-leukemic Activity of Vosaroxin Against Acute Myeloid Leukemia Cells Ex Vivo. Target Oncol. 2019;14:351-64.
Knight T, Edwards H, Taub JW, Ge Y. Evaluating venetoclax and its potential in treatment-naïve acute myeloid leukemia. Cancer Manag Res. 2019;11:3197-213.
Knight T, Luedtke D, Edwards H, Taub JW, Ge Y. A delicate balance - The BCL-2 family and its role in apoptosis, oncogenesis, and cancer therapeutics. Biochem Pharmacol. 2019;162:250-61.
Luedtke DA, Su Y, Liu S, Edwards H, Wang Y, Lin H, Taub JW, Ge Y. Inhibition of XPO1 enhances cell death induced by ABT-199 in acute myeloid leukaemia via Mcl-1. J Cell Mol Med. 2018;22:6099-111.
Volk A, Liang K, Suraneni P, Li X, Zhao J, Bulic M, Marshall S, Pulakanti K, Malinge S, Taub J, Ge Y, Rao S, Bartom E, Shilatifard A, Crispino JD. A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia Pathogenesis. Cancer Cell. 2018;34:707-723.e7.
Su Y, Li X, Ma J, Zhao J, Liu S, Wang G, Edwards H, Taub JW, Lin H, Ge Y. Targeting PI3K, mTOR, ERK, and Bcl-2 signaling network shows superior antileukemic activity against AML ex vivo. Biochem Pharmacol. 2018;148:13-26.
Pitre A, Ge Y, Lin W, Wang Y, Fukuda Y, Temirov J, Phillips AH, Peters JL, Fan Y, Ma J, Nourse A, Sinha C, Lin H, Kriwacki R, Downing JR, Gruber TA, Centonze VE, Naren AP, Chen T, Schuetz JD. An unexpected protein interaction promotes drug resistance in leukemia. Nat Commun. 2017;8:1547.
Taub JW, Berman JN, Hitzler JK, Sorrell AD, Lacayo NJ, Mast K, Head D, Raimondi S, Hirsch B, Ge Y, Gerbing RB, Wang YC, Alonzo TA, Campana D, Coustan-Smith E, Mathew P, Gamis AS. Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children's Oncology Group AAML0431 trial. Blood. 2017;129:3304-13.
Luedtke DA, Niu X, Pan Y, Zhao J, Liu S, Edwards H, Chen K, Lin H, Taub JW, Ge Y. Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells. Signal Transduct Target Ther. 2017;2:17012.
Ma J, Li X, Su Y, Zhao J, Luedtke DA, Epshteyn V, Edwards H, Wang G, Wang Z, Chu R, Taub JW, Lin H, Wang Y, Ge Y. Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells. Sci Rep. 2017;7:41950.
PhD (1998): Jilin University, Changchun, China
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