Dr. Wilber is an Assistant Professor in the Department of Medical Microbiology, Immunology and Cell Biology, Director of the Public Health Laboratory Sciences graduate program, and Chairman of the Infection Control and Safety committee. He is a member of the American Society for Hematology and American Society of Gene and Cell Therapy for which he serves as on the New Investigator Committee (2011-2013). He is an academic editor for PLoS One and a reviewer for Blood, BMC Biology, Stem Cells and PLoS journals.
Training:
1996 B.S. Millikin University, Decatur, IL
Biology/Chemistry
2006 Ph.D. University of Minnesota, Minneapolis, MN
Molecular Genetics
Graduate Advisor: Dr. R. Scott McIvor
2008 Postdoctoral Research Fellow
Department of Hematology
St. Jude Children’s Research Hospital, Memphis, TN
Mentor: Dr. Arthur Nienhuis
Research Interests:
developmental erythropoiesis, hemoglobin gene regulation, gene delivery using viral (lentivirus) and non-viral (transposons) integrating vectors, stem cells, anti-tumor immunity
Techniques:
culture models of human erythropoiesis, hemoglobin analysis, coding and non-coding gene expression, lentivirus, Sleeping Beauty transposon, NK cell phenotype and function, mouse models
Research Description:
Gene Therapy for Severe Hemoglobin Disorders
The goal of this research is to utilize lentivirus-based gene delivery in adult human CD34+ hematopoietic progenitor cells to enhance expression of the g-globin gene and production of fetal hemoglobin (HbF) as a curative therapy for patients with b-thalassemia and Sickle Cell Disease (SCD). To this end, we utilize an in vitro culture model of human erythropoiesis to monitor production of HbF following lentivirus-mediated delivery of (i) an exogenous g-globin gene, (ii) a trans-acting factor GG1-VP64 designed to induce transcription of the endogenous g-globin genes and (iii) shRNAs targeting the g-globin gene repressor protein BCL11A.
Factors and Mechanisms Influencing Expression of Fetal Hemoglobin
The goal of this research is to uncover novel factors and mechanisms that influence the expression of HbF in human erythroid cells. We developed an in vitro erythroid culture system utilizing primary human CD34+ hematopoietic cells as a seed population which can be differentiated into late stage erythroblasts over a 20 day period. We found that fetal liver CD34+ cells give rise to late stage erythroblasts which exclusively express HbF, while erythroblasts derived from adult CD34+ cells express HbA. Using these two cell populations, a series of comparative studies are being performed to identify differences in the protein-DNA interactions at the β-globin locus and differences in the mRNA, microRNA (miRNA) and long non-coding RNA (lncRNA) transcriptomes.
Anti-tumor Immunity
The goal of this research is to understand the role of tumor-mediated production of soluble factors in suppressing the cytotoxic activity of natural killer (NK) cells. Our studies are based on the notion that soluble factors produced by tumor cells fuels tumor progression through direct recruitment or trans-differentiation of NK cells with angiogenic properties. Initial studies being performed using a novel syngeneic mouse model of renal cell cancer (RCC) and patient-derived renal tumor tissue. These efforts could paradigm shift the generalized role of NK cells in tumor biology, whereby, prevention of these processes may be an interesting goal of future tumor therapy.
Selected Publications:
- Wilber A., Ulloa Montoya F., Hammer L., Moriarity B.S., Geurts A.M., Largaespada D.A., Verfaillie C.M., McIvor R.S. & Lakshmipathy U. (2011) Efficient non-viral integration and stable gene expression in multipotent adult progenitor cells. Stem Cells International. 717069. PMID: 21977042.
- Wilber A., Nienhuis A.W. & Persons D.A. (2011) Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities. Blood, 117(15):3945-3953. PMID: 21321359
- Wilber A., Hargrove P.W., Kim Y.S., Riberdy J.M., Sankaran V.G., Papanikolaou E., Georgomanoli M., Anagnou N.P., Orkin S.H., Nienhuis A.W. & Persons D.A. (2011) Therapeutic Levels of fetal hemoglobin in erythroid progeny of b-thalassemic CD34+ cells following lentiviral vector-mediated gene transfer. Blood, 117(10):2817-2826. PMID: 21156846
- Rajput S. & Wilber A. Roles of inflammation in cancer initiation, progression, and metastasis. (2010) Frontiers in Bioscience (Scholar Edition), 2:176-183. PMID: 20036938
- Wilber A., Tschulena U., Hargrove P.W., Kim Y.S., Persons D.A., Barbas C.F. & Nienhuis, A.W. (2010) A zinc-finger transcriptional activator designed to interact with the g-globin gene promoters enhances fetal hemoglobin production in primary human adult erythroblasts. Blood, 115(15):3033-3041. PMID: 20190190
- Wilber A., Linehan J.L., Tian X., Woll P.S., Morris J.K., Belur L.R., McIvor R.S. & Kaufman D.S. (2007) Efficient and stable transgene expression in human embryonic stem cells using transposon-mediated gene transfer. Stem Cells, 25(11):2919-2927. PMID: 17673526
- Wilber A., Wangensteen K.J., Chen Y., Zhou L., Frandsen J.L., Bell J., Chen Z.J., Ekker S.C., McIvor R.S. & Wang X. (2007) Messenger RNA as a source of transposase for Sleeping Beauty transposon-mediated correction of Hereditary Tyrosinemia type I. Molecular Therapy, 15(7):625-630. PMID: 17440442
- Wilber A., Frandsen J.L., Geurts J.L., Largaespada D.A., Hackett P.B. & McIvor R.S. (2006) RNA as a source of transposase for Sleeping Beauty-mediated gene insertion and expression in somatic cells and tissues. Molecular Therapy, 13(3):625-630. PMID: 16368272
- Huang X., Wilber A., Bao L., Tuong D., Tolar J., Orchard P.J., Levine B.L., June C.H., McIvor R.S., Blazar, B.R. & Zhou X. (2006) Stable gene transfer and expression in human primary T-cells by the Sleeping Beauty transposon. Blood, 107(2):483-491. PMID: 16189271
- Wilber A., Frandsen J.L., Wangensteen K.J., Ekker S.C., Wang X. & McIvor R.S. (2005) Dynamic gene expression following systemic delivery of plasmid DNA as determined by in vivo bioluminescent imaging. Human Gene Therapy, 16(11):1325-1332. PMID: 16259566
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