A5102886761- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Iron Metabolism and Disorders
- Blood groups and transfusion
- RNA modifications and cancer
- Alcohol Consumption and Health Effects
- Immunodeficiency and Autoimmune Disorders
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Pancreatic function and diabetes
- Kruppel-like factors research
- Immune Response and Inflammation
- Epigenetics and DNA Methylation
- Folate and B Vitamins Research
- Hemoglobin structure and function
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS drug development and treatment
- Metabolomics and Mass Spectrometry Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Cells and Metastasis
- Metabolism and Genetic Disorders
- T-cell and B-cell Immunology
- Apelin-related biomedical research
- Nitric Oxide and Endothelin Effects
- Cannabis and Cannabinoid Research
Augusta University
2005-2018
Kumamoto Orthopedic Surgery Hospital
2015
Augusta University Health
2011
Boston University
1997-2004
Center for Human Genetics
2001-2004
University of Milan
2001
Wayne State University
1998
University of California, San Francisco
1993-1998
Howard Hughes Medical Institute
1991-1998
University of Oklahoma Health Sciences Center
1998
Fetal-globin (γ-globin) chains inhibit the polymerization of hemoglobin S (sickle hemoglobin) and can functionally substitute for β-globin that are defective or absent in patients with β-thalassemias. Identifying safe mechanisms to stimulate fetal-hemoglobin production is therefore great interest. Previous studies have shown administering butyrate selectively stimulates promoter human fetal-globin gene leads increases γ-globin-gene expression developing fetus, cultured cells, animal models.
The X-chromosome-linked glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP+ oxidoreductase, EC 1.1.1.49) of humans and other mammals consists a subunit with molecular weight about 58,000. enzyme plays key role in the generation NADPH, particularly matured erythrocytes, genetic deficiency is associated chronic drug- or food-induced hemolytic anemia humans. was purified to homogeneity from human erythrocytes. complete amino acid sequence subunit, consisting 531 residues, determined...
Despite considerable concerns with pharmacological stimulation of fetal hemoglobin (Hb F) as a therapeutic option for the β-globin disorders, molecular basis action Hb F-inducing agents remains unclear. Here we show that an intracellular pathway including soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG) plays role in induced expression γ-globin gene. sGC, obligate heterodimer α- β-subunits, participates variety physiological processes by converting GTP to cGMP....
We have investigated in vivo protein-DNA interactions the beta-globin gene locus by dimethyl sulfate (DMS) footprinting K562 cells, which express epsilon- and gamma-globin but not beta-globin. In control region, hypersensitive site 2 (HS-2) exhibited footprints several putative protein binding motifs. HS-3 was footprinted. The beta promoter also footprinted, while extensive were observed of active gene. No seen A gamma 3' enhancers. With motifs, additional alterations patterns occurred with...
Class I human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) consists of several homo- and heterodimers alpha, beta, gamma subunits that are governed by the ADH1, ADH2, ADH3 loci. We previously cloned a full length cDNA for beta subunit, complete sequence 374 amino acid residues was established. cDNAs alpha were characterized. A liver library, constructed in phage lambda gt11, screened using synthetic oligonucleotide probe matched to but not sequence. Clone pUCADH 21...
We have cloned a full-length cDNA coding for human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) from liver library constructed in phage lambda gt11. The was screened by using rabbit antibody against ADH as first probe, the modified method of Young and Davis [Young, R. A. & Davis, W. (1983) Proc. Natl. Acad. Sci. USA 80, 1194-1198]. Mixed 14-mer synthetic oligonucleotides encoding Asp-Asp-His-Val-Val Gln-Cys-Gly-Lys-Cys were used second probe. These amino acid...
Much attention has been directed to the physiological effects of nitric oxide (NO)-cGMP signaling, but virtually nothing is known about its hematologic effects. We reported for first time that cGMP signaling induces human γ-globin gene expression. Aiming at developing novel therapeutics anemia, we examined here NO-cGMP in vivo and vitro. treated wild-type mice with NO activate soluble guanylate cyclase (sGC), a key enzyme signaling. Compared untreated mice, NO-treated had higher red blood...
Summary The present study found that the cyclic adenosine monophosphate (cAMP)‐dependent pathway efficiently induced γ‐globin expression in adult erythroblasts, and this plays a role gene ( HBG ) β‐thalassaemia. Expression of mRNA increased to about 46% non‐HBA erythroblasts treated with forskolin, while guanosine (cGMP) analogue levels <20% mRNA. In patients β‐thalassaemia intermedia, cAMP were elevated both red blood cells nucleated but no consistent elevation was cGMP levels....
Adhesion molecules play a critical role in the adhesive interactions of multiple cell types sickle disease (SCD). We previously showed that anti-P-selectin aptamer efficiently inhibits adhesion to endothelial cells (ECs) and permits SCD mice survive hypoxic stress. In an effort discover new mechanisms with which inhibit P-selectin, we examined glycosylation. P-selectin is 90 kDa protein but was found migrate as 140 bands on gel electrophoresis. When isolated from ECs digested peptide...
Summary KLF1/EKLF and related Krueppel‐like factors (KLFs) are variably implicated in the regulation of HBB ‐like globin genes. Prompted by observation that four KLF sites distributed human α‐globin gene ( HBA ) promoter, we investigated if KLFs could also act to modulate expression Among tested, only KLF4/GKLF bound specifically three out sites. The occupancy same KLF4 vivo was confirmed chromatin immunoprecipitation assays with KLF4‐specific antibodies. In luciferase reporter MEL cells,...