- West Virginia University School of Pharmacy
- Pharmaceutical Sciences
Co-Leader Alexander B. Osborn Hematopoietic Malignancy and Transplantation
- West Virginia University WVU Cancer Institute
- WVU Cancer Institute Research Laboratories
- MD/PhD, Tohoku University, School of Medicine, Sendai Japan, 2007
Top 10 papers:
Reduced Cell Division Control Protein 42 Activity Compromises Hematopoiesis-Supportive Function of Fanconi Anemia Mesenchymal Stromal Cells.
Xu J, Li X, Cole A, Sherman Z, Du W.
Stem Cells. 2018 May;36(5):785-795. doi: 10.1002/stem.2789. Epub 2018 Feb 9.
Icariin improves Fanconi anemia hematopoietic stem cell function through SIRT6-mediated NF-kappa B inhibition.
Li Y, Li X, Cole A, McLaughlin S, Du W.
Cell Cycle. 2018;17(3):367-376. doi: 10.1080/15384101.2018.1426413. Epub 2018 Feb 8.
Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation.
Li X, Wilson AF, Du W, Pang Q.
Stem Cell Reports. 2018 Feb 13;10(2):339-346. doi: 10.1016/j.stemcr.2017.12.006. Epub 2018 Jan 4.
Immune-DDR crosstalk in pre-leukemia stem cells.
Wu L, Cole A, Du W.
Oncotarget. 2017 Sep 19;8(47):81731-81732. doi: 10.18632/oncotarget.21047. eCollection 2017 Oct 10. No abstract available.
Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.
Li Y, Amarachintha S, Wilson AF, Li X, Du W.
Cell Cycle. 2017 Jun 18;16(12):1201-1209. doi: 10.1080/15384101.2017.1320627. Epub 2017 May 5.
In Vivo RNAi Screen Unveils PPARγ as a Regulator of Hematopoietic Stem Cell Homeostasis.
Sertorio M, Du W, Amarachintha S, Wilson A, Pang Q.
Stem Cell Reports. 2017 May 9;8(5):1242-1255. doi: 10.1016/j.stemcr.2017.03.008. Epub 2017 Apr 13.
Fancd2 in vivo interaction network reveals a non-canonical role in mitochondrial function.
Zhang T, Du W, Wilson AF, Namekawa SH, Andreassen PR, Meetei AR, Pang Q.
Sci Rep. 2017 Apr 5;7:45626. doi: 10.1038/srep45626.
The immune receptor Trem1 cooperates with diminished DNA damage response to induce preleukemic stem cell expansion.
Du W, Amarachintha S, Wilson A, Pang Q.
Leukemia. 2017 Feb;31(2):423-433. doi: 10.1038/leu.2016.242. Epub 2016 Aug 29.
Deletion of Fanca or Fancd2 dysregulates Treg in mice.
Du W, Erden O, Wilson A, Sipple JM, Schick J, Mehta P, Myers KC, Steinbrecher KA, Davies SM, Pang Q.
Blood. 2014 Mar 20;123(12):1938-47. doi: 10.1182/blood-2013-09-528018. Epub 2014 Feb 5.
Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance.
Li X, Sipple J, Pang Q, Du W.
Blood. 2012 May 3;119(18):4162-73. doi: 10.1182/blood-2011-10-387332. Epub 2012 Mar 16.
- On Dec 11, 2017, Wei Du gave an oral presentation on “FANCD2 and HES1 Synergistically Regulate the Immunometabolism of Hematopoietic Stem Cells through Transcriptional Suppression of Pparg-mediated Fatty Acid Oxidation and Oxidative Phosphorylation” at 59th Annual American Society of Hematology (ASH) meeting, the world largest hematology society meeting, in Atalanta, GA.
- On Jan 1, 2018, Wei Du received American Cancer Society Pilot grant.
- On Jan 1, 2018, Wei Du was appointed as Co-leader of Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program at West Virginia University Cancer Institute.
- On Jan 9, 2108, our paper entitled “Cell cycle-specific function of p53 in Fanconi anemia hematopoietic stem and progenitor cell proliferation checkpoint” was reported by Hematopoiesis News.
- On Jan 23, 2108, our paper entitled “Icariin improves Fanconi anemia hematopoietic stem cell function through SIRT6-mediated NF-kappa B inhibition” was reported by Hematopoiesis News.
- On Jan 30, 2108, our paper entitled “Reduced Cdc42 Activity Compromises Hematopoiesis-Supportive Function of Fanconi Anemia Mesenchymal Stromal Cells” was reported by Mesenchymal Cell News.
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
American Cancer Society Pilot Grant 2017-2018 (Du: PI)
Leukemia Research Foundation 2017-2018 (Du: PI)
WVU General International Grant 2017 (Du: PI)
NIH/NIGMS (U54GM104942) 2016-2017
West Virginia University Health Science Center Start-up Fund 2016-present (Du: PI)
West Virginia University School of Pharmacy Start-up Fund 2016-present (Du: PI)