A5058945634- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Trace Elements in Health
- CAR-T cell therapy research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Kruppel-like factors research
- Zebrafish Biomedical Research Applications
- Monoclonal and Polyclonal Antibodies Research
- Pregnancy and preeclampsia studies
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- Chronic Myeloid Leukemia Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Erythropoietin and Anemia Treatment
- CRISPR and Genetic Engineering
- Eosinophilic Disorders and Syndromes
- Advanced Breast Cancer Therapies
- RNA Interference and Gene Delivery
- Porphyrin Metabolism and Disorders
- Cancer Immunotherapy and Biomarkers
- Sirtuins and Resveratrol in Medicine
- Autoimmune Neurological Disorders and Treatments
- GDF15 and Related Biomarkers
- Magnesium in Health and Disease
AstraZeneca (United States)
2022-2024
Sanofi (United States)
2017-2021
Sanofi (France)
2021
Beth Israel Deaconess Medical Center
2011-2020
Harvard University
2009-2020
Cancer Research Institute
2016-2020
Ukrainian Medical Stomatological Academy
2018-2019
Palmetto Hematology Oncology
2017
Dana-Farber Cancer Institute
2005-2008
Howard Hughes Medical Institute
2005-2008
Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage release, is potential drug target for patients with overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP6) interleukin-6 (IL-6) by effects on mothers against decapentaplegic homolog (Smad)4 or signal transducer activator (Stat)3, respectively. We conducted small-scale chemical screen...
The anemia of chronic disease is an old concept, but contemporary research in the role proinflammatory cytokines and iron biology has shed new light on pathophysiology condition. Recent epidemiologic studies have connected with critical illness, obesity, aging, kidney failure, as well well-established associations cancer, infection, autoimmune disease. Functional deficiency, mediated principally by interaction interleukin-6, regulatory hormone hepcidin, exporter ferroportin, a major...
Missense mutations in ferroportin1 (fpn1), an intestinal and macrophage iron exporter, have been identified between transmembrane helices 3 4 the zebrafish anemia mutant weissherbst (weh(Tp85c-/-)) patients with type hemochromatosis. To explore effects of fpn1 mutation on blood development homeostasis adult zebrafish, weh(Tp85c-/-) were rescued by injection dextran studied comparison injected uninjected WT heterozygotes. Although deposition was observed all iron-injected fish, only exhibited...
PurposeThe current standard-of-care for front-line therapy acute myeloid leukaemia (AML) is a combination of an anthracycline with cytarabine resulting in significant short-term and long-term toxicity, but still approximately 40% children relapse. Therefore, there major need to accelerate the introduction innovative medicines into therapy, yet drug development continues be adult-focused. Furthermore, are differences, including differing profiles genetic abnormalities, making clinical adult...
A greenish mutant of the normally blue-green cyanobacterium Synechocystis sp.PCC 6803, designated UVGp, has been isolated and characterized.UV6p possesses functional photosystems I I1 (PSI PSII) but lacks normal light harvesting phycobilisomes because allophycocyanin is absent core-specific linker proteins are almost entirely absent.The mutation responsible for UV6p phenotype identified; it a base substitution which results in creation termination codon within coding region apcA...
Iron is a crucial metal for normal development, being required the production of heme, which incorporated into cytochromes and hemoglobin. The zebrafish chianti (cia) mutant manifests hypochromic,microcytic anemia after onset embryonic circulation, indicative perturbation in red blood cell hemoglobin production. We show that cia encodes tfr1a, specifically expressed developing requisite only iron uptake erythroid precursors. In process isolating tfr1, we discovered two tfr1-like genes (tfr1a...
Background Melanin-concentrating hormone (MCH), an evolutionarily conserved appetite-regulating neuropeptide, has been recently implicated in the pathogenesis of inflammatory bowel disease (IBD). Expression MCH is upregulated inflamed intestinal mucosa humans with colitis and MCH-deficient mice treated trinitrobenzene-sulfonic acid (TNBS) develop attenuated form compared to wild type animals. Zebrafish have emerged as a new animal model IBD, although majority reported studies concern...
Abstract Background: MEDI1191 is an IT-administered lipid nanoparticle-formulated mRNA encoding IL-12. This phase 1, open-label study (NCT03946800) showed that in sequential (seq) or concurrent (conc) combination with IV D (anti-PD-L1) was safe and had preliminary antitumor activity pts advanced/metastatic solid tumors who progressed on SoC. Here we present updated analyses, including the first report of deep-seated lesions. Methods: In Part 1A (subcutaneous/cutaneous [SC/C] lesions),...
Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription iron regulatory hormone hepcidin by activating bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers Hjv's function. Using zebrafish model, we evaluated effects hjv its interacting proteins on expression during embryonic development. We found that is strongly expressed notochord somites embryo...
Hepcidin, a peptide hormone produced in the liver, decreases intestinal iron absorption and macrophage release via effects on ferroportin. Bone morphogenic protein Stat3 signaling regulate Hepcidin's transcription. Hepcidin is potential drug target for patients with overload syndromes because its levels are inappropriately low these individuals. To generate tool identifying small molecules that modulate expression, we stably transfected human hepatocytes (HepG2) cells reporter construct...
Previous studies have shown that administration of ferristatin II to rats is associated with decreased serum iron, reduced transferrin saturation, and increased hepatic hepcidin expression. BMP IL-6 signaling act via Smad Stat3 transcription factors, respectively, increase expression hepcidin, the master regulator iron metabolism. In this study, we aimed explore underlying mechanism action on production. We found greatly both in vivo vitro. rat liver, treatment downstream targets Smad7 Id1...
Interleukin-2 is an effective agent against renal cell carcinoma and melanoma, but it has been associated with autoimmune sequelae such as hypothyroidism vitiligo. A 64-year-old man non-insulin-dependent diabetes metastatic developed insulin-dependent after his first cycle of therapy high-dose (HD) interleukin-2. After additional interleukin-2, the patient generalized myasthenia gravis (MG) polymyositis, both which responded to treatment corticosteroids plasmapheresis. To investigate role...
Abstract Transferrin‐bound iron (TBI), the physiological circulating form, is acquired by cells through transferrin receptor (TfR1) endocytosis. In erythroid cells, most of incorporated into heme in mitochondria. Cellular trafficking indispensable for erythropoiesis and many other essential biological processes. Comprehensive elucidation molecular pathways governing regulating cellular acquisition required to better understand pathological processes affecting erythropoiesis. Here, we report...
Abstract Folate receptor alpha (FRα) is a cell surface GPI-anchored protein overexpressed in several solid tumors with highest prevalence ovarian cancer and lung adenocarcinoma but restricted expression normal tissues. An antibody drug conjugate (ADC) microtubule inhibitor (MTI) payload recently received accelerated approval from the FDA for FRα-expressing platinum-resistant cancer. We describe first time preclinical activity of AZD5335, an FRα-targeting conjugated to AZ’s proprietary...
Novel therapies are needed for effective treatment of AML. In the relapsed setting, prognosis is very poor despite salvage with chemotherapy. Evidence suggests that leukemic stem cells (LSCs) cause relapse. The cell surface receptor CD123 highly expressed in blast and LSCs from AML patients a potential therapeutic target. cross-over dual-variable domain T-cell engager (CD123-CODV-TCE) bispecific antibody an innovative format. One arm targets CD3εδ subunit co-receptors on T cells, while other...
Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2, MPL, and CALR genes; however, 10%-15% of cases triple negative (TN). A previous study showed lower rate JAK2 V617F primary myelofibrosis patients exposed to low doses ionizing radiation (IR) from Chernobyl accident. To examine distinct mutations, we enrolled 281 Ukrainian IR-exposed unexposed MPN patients. Genomic DNA was obtained peripheral blood leukocytes. V617F, MPL W515, types 1- 2-like were identified by...
<h3>Background</h3> MEDI1191 is an investigational therapy composed of mRNA encoding bioactive interleukin-12 (IL-12p70) in a lipid nanoparticle optimized for intratumoral injection. We hypothesized that injection will reprogram the immunosuppressed tumor microenvironment (TME) and increase cytotoxic T-cell recruitment, proliferation activation. <h3>Methods</h3> In ongoing phase 1 dose escalation study (NCT03946800), patients with C/SC lesions received 0.1-12µg sequentially (Part 1A) or...
Iron overload causes the generation of reactive oxygen species that can lead to lasting damage liver and other organs. The goal this study was identify genes modify toxicity iron overload. We studied effect on hepatic transcriptional metabolomic profile in mouse models using a dietary model genetic model, hemojuvelin knockout mouse. then evaluated correlation nicotinamide N-methyltransferase (NNMT) expression with body stores human patients NNMT knockdown gene viability primary hepatocytes....