Andrew Wilber

Andrew Wilber
Southern Illinois University School of Medicine | SIU School of Medicine · Department of Medical Microbiology, Immunology and Cell Biology

PhD

About

104
Publications
13,457
Reads
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3,142
Citations
Introduction
The Wilber laboratory has two main areas of research. The first approach is to combine complimentary state-of-the-art techniques to study primary human erythroid cell differentiation and globin gene regulation. The second approach utilizes mouse cancer models to understand the role of the tumor microenvironment in suppressing the natural cytotoxic activity of natural killer (NK) cells.
Additional affiliations
July 2017 - present
Southern Illinois University School of Medicine
Position
  • Managing Director
Description
  • We currently have two (2) research projects in the lab, 1) Mechanisms of fetal to adult hemoglobin switching and developmental erythropoiesis and 2) Role of soluble tumor-derived factors in NK-cell phenotype and function.
January 2008 - June 2017
Southern Illinois University School of Medicine
Position
  • Managing Director
June 2006 - December 2008
St. Jude Children's Research Hospital
Position
  • PostDoc Position
Description
  • Research Project titled, "Gene therapy for severe hemoglobin disorders achieved through production of fetal hemoglobin (HbF)."
Education
August 2002 - May 2006
University of Minnesota Twin Cities
Field of study
  • Molecular Genetics
August 1992 - May 1996
Millikin University
Field of study
  • Biology and Chemistry

Publications

Publications (104)
Article
Full-text available
Fetal hemoglobin (HbF) is a potent genetic modifier of the severity of beta-thalassemia and sickle cell anemia. We used an in vitro culture model of human erythropoiesis in which late-stage erythroblasts are derived directly from human CD34(+) hematopoietic cells to evaluate HbF production. This system recapitulates expression of globin genes accor...
Article
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β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α₂β₂;HbA). Increased levels of fetal hemoglobin (α₂γ₂;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro m...
Article
Full-text available
In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical m...
Article
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In multicellular organisms, cell growth and differentiation is controlled in part by programmed cell death or apoptosis. One major apoptotic pathway is triggered by Fas receptor (Fas)-Fas ligand (FasL) interaction. Neoplastic cells are frequently resistant to Fas-mediated apoptosis, evade Fas signals through down regulation of Fas and produce solub...
Article
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Sickle cell disease (SCD) and β-thalassemia are caused by structural abnormality or inadequate production of adult hemoglobin (HbA, α2β2), respectively. Individuals with either disorder are asymptomatic before birth because fetal hemoglobin (HbF, α2γ2) is unaffected. Thus, reversal of the switch from HbF to HbA could reduce or even prevent symptoms...
Article
Myeloid-lymphatic endothelial cell progenitors (M-LECP) are a subset of bone marrow (BM)-derived cells characterized by expression of M2-type macrophage markers. We previously showed significant contribution of M-LECP to tumor lymphatic formation and metastasis in human clinical breast tumors and corresponding mouse models. Since M2-type is induced...
Article
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Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 ( SLC22A5) gene that encodes a high-affinity sodium-ion–dependent organic cation transporter protein (OCTN2). Reduced carnitine transport results in diminished fatty acid oxidation in heart and skel...
Article
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Natural killer (NK) cells are classically associated with immune surveillance and destruction of tumor cells. Inconsistent with this function, NK cells are found in advanced human tumors including renal cell carcinoma (RCC). NK cells with non-classical phenotypes (CD56+CD16dim/neg; termed decidua NK (dNK) cells) accumulate at the maternal-fetal int...
Article
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Public health laboratories provide critical surveillance data to improve community health and environmental quality. Yet, the nation is facing a large shortfall in laboratory workers and leaders due to the number of those projected to retire and the increasing complexity of analyses and regulatory requirements. To help meet this demand, the Public...
Article
β-Hemoglobinopathies are among the most common single-gene disorders and are caused by different mutations in the β-globin gene. Recent curative therapeutic approaches for these disorders utilize lentiviral vectors (LVs) to introduce a functional copy of the β-globin gene into the patient's hematopoietic stem cells. Alternatively, fetal hemoglobin...
Article
Lymphatic metastasis is a high-impact prognostic factor for mortality of breast cancer (BC) patients, and it directly depends on tumor-associated lymphatic vessels. We previously reported that lipopolysaccharide-induced inflammatory lymphangiogenesis is strongly promoted by myeloid-derived lymphatic endothelial cell progenitors (M-LECPs) derived fr...
Article
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Various malignancies are reproducibly cured in mouse models, but most cancer immunotherapies show objective responses in a fraction of treated patients. One reason for this disconnect may be the use of young, lean mice lacking immune-altering comorbidities present in cancer patients. Although many cancer patients are overweight or obese, the effect...
Article
Full-text available
Background Myeloid-derived lymphatic endothelial cells (M-LECP) are induced by inflammation and play an important role in adult lymphangiogenesis. However, the mechanisms driving M-LECP differentiation are currently unclear. We previously showed that activation of Toll-like receptor-4 (TLR4) induces myeloid-lymphatic transition (MLT) of immortalize...
Data
Differentiated M-LECP acquire the capacity to perform endothelial-specific functions. Mouse CD11b+ isolated from BM were analyzed at three timepoints: ex vivo, after 6 days of treatment with CSF1 alone, and after four days with 50 ng/ml LPS for (A) the ability to uptake acetylated-LDL, (B) bind UEA-1 lectin, and (C) bind Tomato lectin. Representati...
Data
LPS-differentiated mouse M-LECP perform uptake of acetylated LDL and express endothelial-specific receptors for UEA-1 and Tomato lectins. Mouse CD11b+ cells were pretreated with CSF1 followed by 4 days exposure to LPS (50 ng/ml). Differentiated cells were incubated for 4 hours with FITC-tagged (A) 10μg/ml of AC-LDL, (B) 10μg/ml of UEA1 lectin or (C...
Data
Human CD14+ monocytes are positive for proliferative markers. Human CD14+ monocytes were isolated from whole blood and plated on slides. Slides were stained daily for evidence of proliferation with (A) acetylated histone H3 (Ac-histone) and (B) Ki-67 for 6 days. White arrowheads point to double nuclei. All images were acquired at 400X magnification...
Data
Sequences of human primers used for RT-qPCR. (PDF)
Data
TLR4-activated lymphatic reprogramming of bone marrow myeloid cells derived from C57BL/6 mice. (PDF)
Data
Sequences of mouse primers used for RT-qPCR. (PDF)
Data
Changes in expression in TLR4-activated human CD14+ monocytes undergoing lymphatic reprogramming. (PDF)
Data
TLR4-activated lymphatic reprogramming 0f bone marrow myeloid cells derived from CB-17/SCID mice. (PDF)
Article
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Background: Alterations in nuclear pore complex (NPC) genes have been previously associated with response to chemotherapy. Using agnostic exome sequencing, we envisioned that new alleles in NPC genes, predictive of sensitivity to platinum treatment, could be discovered. Methods: Twenty-two platinum-sensitive and six platinum-resistant ovarian ca...
Article
Background: By using exome sequencing, we envisioned that certain single nucleotide variants (SNVs), predictive of sensitivity to platinum treatment, could be discovered. Methods: Twenty-two Platinum-Sensitive (Pt-S) and 6 Platinum-Resistant (Pt-R) ovarian cancer patients were tested. Platinum sensitivity was defined as disease free survival greate...
Article
Inflammation triggers an immune cell-driven program committed to restoring homeostasis to injured tissue. Central to this process is vasculature restoration, which includes both blood and lymphatic networks. Generation of new vessels or remodeling of existing vessels are also important steps in metastasis-the major cause of death for cancer patient...
Article
Full-text available
Renal cell carcinoma (RCC) affects > 60,000 people in the United States annually, and ~ 30% of RCC patients have multiple metastases at the time of diagnosis. Metastatic RCC (mRCC) is incurable, with a median survival time of only 18 months. Immune-based interventions (e.g., interferon (IFN) and interleukin (IL)-2) induce durable responses in a fra...
Article
MP92-04 PROTUMOR CONVERSION OF NATURAL KILLER CELLS BY TRANSFORMING GROWTH FACTOR-b AND HYPOXIA IN RENAL CELL CARCINOMA Yue Guan, Christopher B. Chambers, Max Nutt*, Springfield, IL; Britnie James, Minneapolis, MN; Kathy Robinson, Shaheen Alanee, MD, MPH, MBA, Springfield, IL; Thomas Griffith, Minneapolis, MN; Donald Torry, Andrew Wilber, Springfi...
Article
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This paper describes data related to a research article titled, “Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death” [1]. Long noncoding RNAs (lncRNAs) are increasingly appreciated for their capacity to regulate every step of gene expression. While r...
Article
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Patients with severe sickle cell disease (SCD) are candidates for gene therapy using autologous hematopoietic stem cells (HSCs), but concomitant multi-organ disease may contraindicate pretransplant conditioning with full myeloablation. We tested whether nonmyeloablative conditioning, a regimen used successfully for allogeneic bone marrow transplant...
Article
Full-text available
Clinical observations of spontaneous disease regression in some renal cell carcinoma (RCC) patients implicate a role for tumor immunity in controlling this disease. Puzzling, however, are findings that high levels of tumor infiltrating lymphocytes (TIL) are common to RCC. Despite expression of activation markers by TILs, functional impairment of in...
Article
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Increasing popularity and improved technical feasibility of partial nephrectomy (PN) has encouraged urologists to treat larger renal masses with nephron-sparing surgery. We used a national database to characterize practice patterns for the surgical management of patients with T2 renal tumors and examined the effect of PN on cancer-specific survival...
Article
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Expression systems used to study the biological function of a gene of interest can have limited utility due to three major factors: i) weak or heterogeneous gene expression; ii) poorly controlled gene expression; and iii) low efficiencies of stable integration and persistent expression. We envisioned that the ideal system should be tightly controll...
Article
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Sickle-cell disease (SCD) is characterized by a single point mutation in the seventh codon of the beta-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells (HSCs) would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrat...
Article
Sickle cell disease (SCD) can be cured by allogeneic hematopoietic stem cell (HSC) transplant. However, this is only possible when a matched donor is available making the development of gene therapy using autologous HSCs a highly desired alternative. We used a culture model of human erythropoiesis to directly compare two insulated, self-inactivatin...
Article
There is a growing body of experience and research suggesting that telemedicine (video conferencing, smart phones and online patient portals) could be the solution to addressing gaps in the provision of specialised healthcare in rural areas. The proposed role of telemedicine in providing needed services in hard to reach areas is not new. The United...
Article
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Sickle cell disease (SCD) and b-thalassaemia result from inherited mutations that cause structural abnormality or deficient synthesis of adult haemoglobin. Palliative therapies improve the quality/duration of life for many, but side effects result from long-term use. Bone marrow transplantation can be curative, but is limited to individuals with a...
Article
Full-text available
Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumour cells in the b...
Article
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The basaloid triple-negative breast cancer (B-TNBC) is one of the most aggressive, therapy-resistant, and metastatic tumors. Current models do not recapitulate the basaloid phenotype of TNBC, thus limiting the understanding of its biology and designing new treatments. We identified HCC1806 as a line expressing typical B-TNBC markers, engineered a s...
Article
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AKR1B10 (aldo-keto reductase 1B10) is overexpressed in liver and lung cancer, and plays a critical role in tumour development and progression through promoting lipogenesis and eliminating cytotoxic carbonyls. AKR1B10 is a secretory protein and potential tumour marker; however, little is known about the regulatory mechanism of AKR1B10 expression. Th...
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Metastatic disease is the major cause of cancer deaths, and recurrent tumors at distant organs are a critical issue. However, how metastatic tumor cells become dormant and how and why tumors recur in target organs are not well understood. In this study, we demonstrate that BMP7 (bone morphogenetic protein 7) secreted from bone stromal cells induces...
Article
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The molecular mechanisms that operate within the organ microenvironment to support metastatic progression remain unclear. Here, we report that upregulation of hyaluronan synthase 2 (HAS2) occurs in highly metastatic breast cancer stem-like cells (CSC) defined by CD44(+)/CD24(-)/ESA(+) phenotype, where it plays a critical role in the generation of a...
Article
Preeclampsia is associated with reduced trophoblast placenta growth factor (PGF) expression, elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased bioactivity of nitric oxide (NO). Elevated sFlt-1 reduces bio-availability of PGF and vascular endothelial growth factor (VEGF) leading to maternal endothelial dysfunction. Although NO can r...
Article
Elevated level of lipogenic enzymes and overall lipogenesis have been reported in a wide variety of cancers, and blocking the lipogenic pathway by chemical inhibitors or RNA interference causes tumor cell death by apoptosis. In this study, we investigated the role of lipogenesis in cancer stem-like cells (CSCs) in ductal carcinoma in situ (DCIS) wh...
Article
Background: Inflammatory breast cancer (IBC) is a highly lethal form of breast cancer which is characterized by skin redness, irritation, swelling, pain, as well as extensive lymph nodes (LN) and hematogenous metastasis. Animal models of IBC are highly desirable for studying its pathology and for designing effective therapies. In this study, we est...
Article
Background: Triple-negative breast cancers are highly aggressive and resistant to chemotherapy. In this study, we established a new model of triple-negative breast cancer and used it to test the novel combination of nab-paclitaxel with anti-VEGF antibody bevacizumab, which has been effective in treating other metastatic cancer types. Methods: The t...
Data
Description of HSV-2 MS-GFP and HSV-2 MS-luciferase. (A) Schematic of CMV-GFP and CMV-luciferase expression cassettes introduced into the non-essential LAT gene of HSV-2 MS-GFP and MS-luciferase, respectively. These gene expression cassettes replaced bases 119,359–119,530 of the LAT promoter. (B) Southern blot analysis of NotI-digested plasmid DNA...
Data
Spread of HSV-2 MS-GFP infection between Days 1 and 7 after challenge of naïve versus HSV-2 0ΔNLS-immunized mice. Progression of the spread of GFP expression across the faces of naïve and 0ΔNLS-immunized mice challenged with 100,000 pfu per eye of HSV-2 MS-GFP, as visualized on Days 1, 3, 5, and 7 post-challenge. These experiments were performed on...
Article
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Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection...
Article
Background: Angiopoietin-2 (Ang-2) is an angiogenic factor whose overexpression is associated with increased tumor vascularity, metastasis, and decreased patient survival. The pro-angiogenic effect of Ang-2 is mediated through activation of the Tie-2 receptor that leads to vessel destabilization and dismantling. The latter is an essential step for...
Article
Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Inflammatory breast cancer (IBC) is a one of the most lethal forms of breast cancer with a 5-year survival of 40%. The hallmarks of IBC include skin redness, irritation, swelling, pain, as well as extensive lymph nodes (LN) and hematogenous metastasis. Animal...
Article
Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction: Elevation of VEGFR-3, the primary mediator of lymphangiogenesis (i.e., new lymphatic vessel formation), is associated with chronically inflamed tumors and correlates with increased metastasis. However, the mechanisms regulating inflammation-induced expressi...
Article
Background: Tumors that lack estrogen, progesterone, and Her2/nu (triple-negative) are one of the most aggressive, therapy-resistant and highly metastatic subtypes of breast cancer (BC). Most currently available models do not recapitulate expression profile of triple-negative BC, thus making it difficult to devise new treatments that target this tu...