Assistant Professor, Pharmaceutical Sciences
- West Virginia University School of Pharmacy
- Pharmaceutical Sciences
Program 3: Alexander B. Osborn Hematopoietic Malignancy and Transplantation
- MD/PhD, Tohoku University, School of Medicine, Sendai Japan, 2007
Publication in 2017:
- Li Y, Amarachintha S, Wilson AF, Li X, Du W¥. (2017) Persistence response of Fanconi Anemia hematopoietic stem and progenitor cells to oxidative stress. ¥Corresponding author/Senior author. Cell Cycle. May 5.
- Sertorio M, Du W, Amarachintha S, Wilson A, Pang Q. (2017) In vivo RNAi-Screen Unveils PPARy as a regulator of Hematopoietic Stem Cell Homeostasis. Stem Cell Reports. 8(5):1242-1255.
- Zhang T, Du W, Wilson A, Namekawa S, Andreassen PR, Meetei RA, Pang Q. (2017) Fancd2 in vivo interaction network reveals a non-canonical role in mitochondrial function. Scientific Reports. 7:45626.
- Du W¥, Amarachintha S, Wilson AF, Pang Q. (2017) The immune receptors Trem1 cooperates with diminished DNA damage response to induce preleukemic stem cell expansion. ¥Corresponding author. Leukemia. 31(2):423-433.
Other recent publication:
- Du W¥, Amarachintha S, Erden O, Wilson A, Pang Q. (2016) The Faconi anemia pathway controls oncogenic response in hematopoietic stem and progenitor cells by regulating PRMT5-mediated p53 arginine methylation. ¥Corresponding author. Oncotarget. 7(37):60005-60020.
- Du W¥, Amarachintha S, Wilson AF, Pang Q. (2016) Hyper-active non-homologous end joining selects for synthetic lethality resistant and pathological hematopoietic stem cells. ¥Corresponding author. Scientific Report. 6:22167.
- Du W¥, Amarachintha S, Wilson AF, Pang Q. (2016) SCO2 mediates oxidative stress-induced glycolysis to OXPHOS switch in hematopoietic stem cells. ¥Corresponding author. Stem cells. 34(4):960-71.
- Du W¥, Amarachintha S, Erden O, Wilson AF, Meetei AR, Andreassen PR, Namekawa SH, Pang Q. (2015) Fancb deficiency impairs hematopoietic stem cell function. ¥Corresponding author. Scientific Report. 5: 18127.
- Du W, Erden O, Wilson A, Sipple J, Schick J, Mehta P, Myers KC, Davies SM, Steinbrecher K, Pang Q. (2014) Deletion of Fanca or Fancd2 dysregulates Treg in mice. Blood. 123(12):1938-1947.
- Li X, Erden O, Li L, Ye Q, Wilson A, Du W¥. (2014) Binding to WGR domain by Salidroside activates PARP1 and protects HSCs from oxidative stress. Antioxidants & Redox Signaling. 20(12):1853-65 ¥Corresponding/Senior author. Cover of the Journal.
- Li X, Sipple J, Pang Q, Du W¥. (2012) Salidroside stimulates DNA repair enzyme Parp-1 activity in HSC maintenance. Blood. 119(18): 4162-4173. ¥ Corresponding/Senior author.
- Du W, Rani R, Sipple J, Schick J, Myer KC, Mehta P, Davies SM, Pang Q. (2012) The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters. Blood. 119(18): 4142-4151.
- Du W¥, Li X, Sipple J, Pang Q. (2011) Overexpression of IL-3Ra on CD34+CD38- stem cells defines leukemia-initiating cells in FA AML. Blood. 117(16): 4243-4252. ¥ Corresponding author.
- Zhou Y*, Du W*, Koretsky T, Bagby GC, Pang Q. (2008) TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice. Blood. 112(6): 2474-2483. * Co-first author.
About Wei Du
Dr. Du is an Assistant Professor in the Department of Pharmaceutical Sciences, School of Pharmacy at WVU. She is also in Program 3: Alexander B. Osborn Hematopoietic Malignancy and Transplantation. She was originally trained as a physician in China. Then she was selected as an exchange student to study in Japan. After receiving her PhD in Pediatric Oncology from Tohoku University in Japan, she came to Cincinnati Children’s Hospital Medical Center for her postdoctoral training. Before joining WVU, she was a faculty member of University of Arkansas for Medical Sciences. Dr. Du’s research is focused on molecular analysis of abnormal hematopoiesis, primarily on the molecular pathogenesis of bone marrow failure and leukemia. Her laboratory takes a multi-disciplinary approach including the development of preclinical murine models, genetics, genomics, molecular immunology, and biochemistry. Her research has been published in over 30 peer-reviewed articles and has contributed to the understanding of the pathophysiology of cancer-prone diseases, including Fanconi anemia.
Alexander B. Osborn Hematopoietic Malignancy and Transplantation
Collaboration between DNA damage and immune responses in leukemic stem cell emergence and expansion
Acute Myeloid Leukemia (AML) has a 5-year survival rate of 25%. Thus, clinical evidence continues to support the need to identify novel targets and therapeutics for the treatment of this deadly disease. Experimental evidence has clearly shown that interaction of the leukemic cell with the tumor microenvironment (TME) contributes to de novo drug resistance and likely failure to eliminate minimal residual disease (MRD). It is currently less clear what the impact of TME-induced expansion of regulatory T cells (Tregs) in mediating MRD following standard of care treatment and bone marrow (BM) transplant. We will utilize a model of Fanconi anemia (FA), a cancer-prone disease with extremely high incidence of myelodysplastic syndrome (MDS) and AML, to determine the role of the TME in the expansion of the Treg population, relapse and progression of AML.
Hematopoietic stem cell polarity in bone marrow failure and leukemia
Stem cell and gene therapies through hematopoietic stem cell transplantation (HSCT) is the only definite treatment for various hematological malignancies, including FA. However, three major hurdles have been hampering scientific and clinical advance in the blood cancer HSCT field: 1) ineffective mobilization of patient stem cells; 2) hypersensitivity of recipient patients to pre-conditioning regimens; and 3) inefficient delivery of donor stem cells to the BM of cancer patients. Therefore, there is a great need to develop novel pre-conditioning agents that can optimize homing and entry of HSCs into recipient BM niche with minimal toxicity. The project will examine the mechanistic link between stem cell polarity, and HSC renewal and engraftment defects. Further, an innovative xenotransplant model will be employed to determine the potential of targeting stem-niche interaction in stem cell and gene therapies.
PARP-NHEJ interaction in cancer drug resistance
Compelling evidence suggested that the FA pathway promotes the error-free homologous recombination (HR) repair pathway while suppressing the error-prone non-homologous end-joining (NHEJ) pathway, likely through preventing inappropriate recruitment of NHEJ factors to sites of DNA damage. However, the exact mechanism by which the FA pathway counteracts the NHEJ pathway is largely unknown. PARP1 is a major DNA damage response protein primarily involved in the base excision repair (BER) pathway. It has been shown that PARP inhibitors could selectively target cancer cells with a defective HR repair of DSB, such as BRCA1-, BRCA2-, and ATM-deficient cells, by inducing genomic instability and eventual cell death due to the development of non-viable genetic errors generated by the error-prone NHEJ repair. We will investigate the mechanism by which FA leukemia develops resistance to synthetic lethality induced by PARP inhibition. Furthermore, FA AML xenotransplant model will be used to define the role of synthetic lethality resistance in leukemia relapse.
Grants and Research
Leukemia Research Foundation 2017-2018 (Du: PI)
WVU General International Grant 2017 (Du: PI)
West Virginia Clinical and Translational Science Institute Award 2016-2017(Du: PI)
West Virginia University Health Science Center Start-up package 2016-present (Du: PI)
West Virginia University School of Pharmacy Start-up package 2016-present (Du: PI)