Yubin Ge

Yubin Ge, Ph.D.
Associate Professor of Oncology
421 E. Canfield Street, Suite 3128
Detroit, MI 48201
313-578-4285
gey@karmanos.org

Mentoring: Daniel Luedtke  (Year 4)

Research Interests: 
Acute myeloid leukemia (AML) biology and leukemogenesis
Translational studies of AML, pancreatic cancer, diffuse intrinsic pontine glioma (DIPG), and neuroblastoma
 
Research Description:

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.

Selected Publications:

Liao Y, Xu L, Ou S, Edwards H, Ge Y, and Qin Z. Hydrogen peroxide/peroxynitrite-activated hydroxamic acid HDAC inhibitor prodrugs inhibit proliferation of acute myeloid leukemia cells. ACS Med Chem Lett. 2018;9:635-40.

Edwards H and Ge Y*. ONC201 shows promise in AML treatment. Cell Cycle. 2018;17:277.

Su Y, Li X, Ma J, Zhao J, Liu S, Wang G, Edwards H, Taub JW, Lin H, and Ge Y*. Targeting PI3K, mTOR, ERK, and Bcl-2 signaling network shows superior anti-leukemic activity against AML ex vivo. Biochem Pharmacol. 2018;148:13-26.

Pitre A, Ge Y, Lin W, Wang Y, Fukuda Yu, 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, and Schuetz JD. An unexpected protein interaction facilitates hematopoietic progenitor self-renewal and drug resistance. Nat Commun. 2017;8:1547.

Taub JW, Berman JN, Hitzler JH, 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, and Gamis AS. Improvement in treatment outcome and identification of a new prognostic parameter in myeloid leukemia of Down syndrome (ML-DS): results of the children's oncology group (COG) phase III AAML0431 trial. Blood. 2017;129(25):3304-13.

Luedtuke D, Niu X, Pan Y, Zhao J, Liu S, Edwards H, Wang G, Lin H, Taub JW, and Ge Y*. Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor Venetoclax in AML cells. Signal Transduction and Targeted Therapy. 2017;2:e17012.

Ma J, Li X, Su Y, Zhao J, Luedtke D, Epshteyn V, Edwards H, Wang G, Wang Z, Chu R, Taub JW, Lin H, Wang Y, and Ge Y*. Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells. Sci Rep. 2017;7:41950.

Liao Y, Niu X, Chen B, Edwards H, Xu L, Xie C, Polin L, Taub JW, Ge Y*, and Qin Z*. Synthesis and antileukemic activities of piperlongumine and HDAC inhibitor hybrids against acute myeloid leukemia cells. J Med Chem. 2016;59:7974-90.

Niu X, Zhao J, Ma J, Xie C, Edwards H, Wang G, Caldwell JT, Chu R, Wang Z, Lin H, Taub J, and Ge Y*. Binding of released Bim to Mcl-1 is a mechanism of intrinsic resistance to ABT-199 which can be overcome by combination with daunorubicin or cytarabine in acute myeloid leukemia cells. Clin Cancer Res. 2016;22:4440-51.

Shaham L, Vendarmini E,  Ge Y,  Goren Y, Tijssen M,  Birger Y, McNulty M, Geron I, Schwartzman O, Goldberg L, Chou ST, Pitman H, Weiss MJ, Michaeli S, Sredni B, Göttgens B, Crispino J, Taub JW, and Izraeli S. MiR-486-5p is an oncomiR in the myeloid leukemias of Down Syndrome. Blood. 2015;125:1292-301.

Xie C, Edwards, Caldwell JT, Wang G, Taub JW, and Ge Y*. Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage. Mol Oncol. 2015;9:409-21. 

Wang G, Niu X, Zhang W, Caldwell JT, Edwards H, Chen W, Taub JW, Zhao L, and Ge Y*. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015;356:656-68.

 

Education and Training
PhD (1998): Jilin University, Changchun, China

Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7240 Principles of Cancer Therapy
CB7300 Special Topics F31 Grant Writing Course

CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling
CB7700 Recent Developments in Cancer Biology (Course Co-Director)