Jeffrey Taub
Department
Pediatrics
Research Description
Dr. Taub's research has focused on studying the molecular epidemiology and pharmacology of childhood leukemia, the most common form of cancer in children and the leading cause of death from disease of American children. Using a unique source of blood samples collected at birth and used for genetic screening ("Guthrie cards"), his lab is screening for the presence of preleukemic clones (by PCR-based minimal residual disease assays) in the blood samples of children who subsequently developed leukemia. This would confirm a prenatal origin of leukemia and potential in utero exposures being linked to the development of leukemia. These studies are also examining factors including differences in folate metabolism which may account for the 2-3-fold higher incidence of acute lymphoblastic leukemia (ALL) in Caucasian compared to African American children in the United States. Another project in the laboratory is studying the biology of acute myeloid leukemia (AML) in children with Down syndrome. Children with Down syndrome have a 20-fold greater risk of developing leukemia compared to children without Down syndrome, and have the highest cure rate (80-100%) of any subgroup of AML patients. These studies use both primary clinical samples from patients diagnosed with AML, as well as clinically relevant leukemia cell lines, to examine the roles of both chromosome 21-localized and non-chromosome 21-localized genes in leukemogenesis and the metabolism of chemotherapy drugs. Findings from these studies are also being applied to developing new leukemia therapies in clinical trials for children without Down syndrome.
Selected publications
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 Biochem Pharmacol. 2018;148:13-26.
Ning C, Liang M, Wang G, Edwards H, Xia Y, Polin L, Dyson G, Taub JW, Mohammad RM, Azmi AS, Zhao L, Ge Y. Targeting ERK Enhances the Cytotoxic Effect of the Novel PI3K and mTOR Dual Inhibitor VS-5584 in Preclinical Models of Pancreatic Cancer. Oncotarget 2017;8:44295-311.
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, 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;129:3304-13.
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 Transduction and Targeted Therapy 2017;7;2:17012.
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, Ge Y Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells. Scientific Reports 2017;7:41950.
Zhao J, Xie C, Edwards H, Wang G, Taub JW, Ge Y. Histone deacetylases 1 and 2 cooperate in regulating BRCA1, CHK1, and RAD51 expression in acute myeloid leukemia cells. Oncotarget 2017;8:6319-29.
Edwards H, Rubenstein M, Dombkowski AA, Caldwell JT, Chu R, Xavier AC, Thummel R, Neely M, Matherly LH, Ge, Y Taub JW. Gene Signature of High White Blood Cell Count in B-precursor Acute Lymphoblastic Leukemia. PlosOne 2016;11:e0161539.
Liao Y, Niu X, Chen B, Edwards H, Xu L, Xie C, Lin H, Polin L, Taub JW, Ge Y, Qin Z. Piperlongumine Combined with Histone Deacetylase Inhibitor either in Combinatorial Treatment or Hybridized as Chimeric Molecules are Potent Antileukemic Agents against Acute Myeloid Leukemia Cells. Journal of Medicinal Chemistry 2016;59:7974-90.
Schwartz J, Niu X, Walton E, Hurley L, Lin H, Edwards H, Taub JW, Wang Z, Ge Y. Synergistic Anti-leukemic Interactions between ABT-199 and Panobinostat in Acute Myeloid Leukemia Ex Vivo. American Journal of Translational Research 2016;8:3893-902.
Zhao J, Niu X, Li X, Edwards H, Wang G, Wang Y, Taub JW, Lin H, Ge Y. Inhibition of CHK1 Enhances Cell Death Induced by the Bcl-2-selective Inhibitor ABT-199 in Acute Myeloid Leukemia Cells. Oncotarget 2016;8:6319-29.
Niu X, Zhao J, Ma J, Xie C, Edwards H, Wang G, Caldwell JT, Xiang S, Zhang X, Chu R, Wang J, Lin H, Taub JW, 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 AML cells. Clinical Cancer Research 2016;22:4440-51.
Qi W, Zhang W, Edwards H, Chu R, Madlambayan GJ, Taub JW, Wang Z, Wang Y, Li C, Lin H, Ge Y. Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo. Cancer Biology Therapy 2015;16:1784-93.
Shaham L, Vendrarmini E, Ge Y, Pitman H, Goren Y, Tijssen M, Birger Y, McNulty M, Geron I, Schwartzman O, Goldberg L, Chou ST, Weiss MJ, Israel LL, Lellouche E, Michaeli S, Lellouche JP, Sredni B, Göttgens B, Crispino J, Taub JW*, Izraeli S*. MicroRNA-486-5p in the myeloid leukemias of Down Syndrome. Blood 2015;125:1292-301. [*Co-corresponding authors]
Hanmod SS, Wang G, Edwards H, Buck SA, Ge Y, Taub JW, Wang Z. Targeting Histone Deacetylases (HDACs) and Wee1 for Treating High-risk Neuroblastoma. Pediatric Blood and Cancer 2015;62:52-9.
Xie C, Edwards H, Caldwell JT, Wang G, Taub JW, Ge Y. Obatoclax Potentiates the Cytotoxic Effect of Cytarabine on Acute Myeloid Leukemia Cells by Enhancing DNA Damage. Molecular Oncology 2015;9:409-21.
Education/Training
MD (1987): University of Western Ontario, London, Ontario, Canada
Transitional Internship (1987-1988): Victoria Hospital, London, Ontario, Canada
Pediatric Residency (1988-1991): Children's Hospital of Michigan, Detroit, Michigan
Fellowship in Pediatric Hematology/Oncology (1991-1994): Children's Hospital of Michigan, Detroit, Michigan
Courses Taught
CB7240 Principles of Cancer Therapy