A5046499318- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Erythropoietin and Anemia Treatment
- Prenatal Screening and Diagnostics
- Trace Elements in Health
- Blood groups and transfusion
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Blood properties and coagulation
- RNA and protein synthesis mechanisms
- Folate and B Vitamins Research
- RNA Research and Splicing
- MicroRNA in disease regulation
- Lysosomal Storage Disorders Research
- Neonatal Health and Biochemistry
- Cytokine Signaling Pathways and Interactions
- Kruppel-like factors research
- Parvovirus B19 Infection Studies
- Genomics and Chromatin Dynamics
- Neurogenetic and Muscular Disorders Research
University of Pennsylvania
2016-2025
California Institute for Regenerative Medicine
2022-2025
Children's Hospital of Philadelphia
2016-2025
Hospital of the University of Pennsylvania
2024-2025
Penn Center for AIDS Research
2019-2025
California University of Pennsylvania
2024
Institute for Learning Innovation
2024
Philadelphia University
2016-2023
Cornell University
2010-2020
Pediatrics and Genetics
2013-2020
β-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both characterized by low levels hepcidin (HAMP), hormone that regulates iron absorption. As a consequence, patients affected these exhibit overload, which is main cause morbidity mortality. HAMP expression controlled activation SMAD1,5,8/SMAD4 complex. TMPRSS6 serine protease reduces SMAD blocks expression. We identified second generation antisense oligonucleotides (ASOs) targeting...
Hereditary hemolytic anemias are a group of disorders with variety causes, including red cell membrane defects, blood enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged cells passing through the pulp spleen removed by splenic macrophages, splenectomy is one possible therapeutic approach to management severely affected patients. However, except for hereditary spherocytosis which effectiveness has been well documented, efficacy in...
Red blood cells detect and bind cell-free nucleic acids, contributing to anemia immune cell activation during acute inflammation.
Hematopoietic stem cells (HSCs) are the source of all blood over an individual's lifetime. Diseased HSCs can be replaced with gene-engineered or healthy through HSC transplantation (HSCT). However, current protocols carry major side effects and have limited access. We developed CD117/LNP-messenger RNA (mRNA), a lipid nanoparticle (LNP) that encapsulates mRNA is targeted to cell factor receptor (CD117) on HSCs. Delivery anti-human CD117/LNP-based editing system yielded near-complete...
The mesencephalic dopaminergic (mDA) cell system is composed of two major groups projecting cells in the substantia nigra (SN) (A9 neurons) and ventral tegmental area (VTA) (A10 cells). A9 neurons form nigrostriatal pathway are involved regulating voluntary movements postural reflexes. Their selective degeneration leads to Parkinson's disease. Here, we report that gene expression analysis (DA) identifies transcripts for α- β-chains hemoglobin (Hb). Globin immunoreactivity decorates majority...
Excessive iron absorption is one of the main features β-thalassemia and can lead to severe morbidity mortality. Serial analyses β-thalassemic mice indicate that while hemoglobin levels decrease over time, concentration in liver, spleen, kidneys markedly increases. Iron overload associated with low hepcidin, a peptide regulates metabolism by triggering degradation ferroportin, an iron-transport protein localized on absorptive enterocytes as well hepatocytes macrophages. Patients also have...
ABSTRACT Retroviruses are highly susceptible to transcriptional silencing and position effects imparted by chromosomal sequences at their integration site. These phenomena hamper the use of recombinant retroviruses as stable gene delivery vectors. As insulators able block promoter-enhancer interactions reduce in some transgenic animals, we examined effect an insulator on expression structure randomly integrated retroviruses. We used cHS4 element, from chicken β-like globin cluster, which has...
Abstract Many of the gene mutations found in genetic disorders, including cancer, result premature termination codons (PTC) and rapid degradation their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket SMG7 protein, key component NMD mechanism, to identify compounds that disrupt SMG7–UPF1 complex inhibit NMD. Several these upregulated NMD-targeted at nanomolar concentrations, with minimal toxicity cell-based assays. As expected, pharmacologic...
Abnormal blood cell production is associated with chronic kidney disease (CKD) and cardiovascular (CVD). Bone-derived FGF-23 (fibroblast growth factor-23) regulates phosphate homeostasis bone mineralization. Genetic deletion of Fgf-23 in mice (Fgf-23(-/-)) results hypervitaminosis D, abnormal mineral metabolism, reduced lymphatic organ size. Elevated levels are linked to CKD greater risk CVD, left ventricular hypertrophy, mortality dialysis patients. However, whether involved the regulation...