A5038541716- Iron Metabolism and Disorders
- Trace Elements in Health
- Heavy Metal Exposure and Toxicity
- Hemoglobinopathies and Related Disorders
- Epigenetics and DNA Methylation
- RNA regulation and disease
- RNA Research and Splicing
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Child Nutrition and Water Access
- Infant Nutrition and Health
- Cytokine Signaling Pathways and Interactions
- Folate and B Vitamins Research
- Selenium in Biological Systems
- Erythrocyte Function and Pathophysiology
- Autophagy in Disease and Therapy
- Neurological diseases and metabolism
- Phagocytosis and Immune Regulation
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Diet and metabolism studies
- Whipple's Disease and Interleukins
- Crystallization and Solubility Studies
- Nuclear Receptors and Signaling
University of Michigan–Ann Arbor
2017-2024
Harvard University
2013-2016
Pennsylvania State University
2009-2015
Applied Research Laboratory at Penn State
2012
Park University
2012
Shipping iron around in small packages Iron plays a crucial role wide variety of biological functions, which turn rely on the proteins that transport metal and out cells. Grillo et al. used simple lipophilic molecule binds ions to restore animal models with deficiencies transporters. This cyclic ketol, hinokitiol, was first tested yeast then shown promote gut absorption rats mice, as well hemoglobin production zebrafish. Science , this issue p. 608
SLC39A8 encodes ZIP8, a divalent metal ion transporter. Mutations in the gene are associated with congenital disorder of glycosylation type II and Leigh syndrome. Notably, affected patients both disorders exhibited severe manganese (Mn) deficiency. The cellular function human (hSLC39A8) mechanisms by which mutations this protein lead to diseases unclear. Herein, we show that hSLC39A8 mediates 54Mn uptake cells, its expression is regulated Mn. While wild-type increased activity,...
We examined the physiologic role of ferroportin (Fpn) in manganese (Mn) export using flatiron (ffe/+) mice, a genetic model Fpn deficiency. Blood (0.0123 vs. 0.0107 mg/kg; P = 0.0003), hepatic (1.06 0.96 0.0125), and bile Mn levels (79 38 0.0204) were reduced ffe/+ mice compared to +/+ controls. Erythrocyte Mn-superoxide dismutase was also at 6 (0.154 0.096, 0.0101), 9 (0.131 0.089, 0.0162), 16 weeks age (0.170 0.090 units/mg protein/min; < 0.0001). 54Mn uptake after intragastric gavage...
Diet plays a significant role in the pathogenesis of inflammatory bowel disease (IBD). A recent epidemiological study has shown an inverse relationship between nutritional manganese (Mn) status and IBD patients. Mn is essential micronutrient required for normal cell function physiological processes. To date, roles intestinal homeostasis remain unknown contribution to yet be explored. Here, we provide evidence that critical maintenance barrier deficiency exacerbates dextran sulfate sodium...
Iron has long been established as a critical mediator of T cell development and proliferation. However, the mechanisms by which iron controls CD4 activation expansion remain poorly understood. In this study, we show that stimulation cells from C57BL/6 mice not only decreases total labile levels but also leads to changes in expression homeostatic machinery. Additionally, restraining availability vitro severely inhibited proliferation cycle progression. Although modulating cellular increased...
Abstract Histone H3 lysine 4 methylation (H3K4me) is extensively regulated by numerous writer and eraser enzymes in mammals. Nine H3K4me are associated with neurodevelopmental disorders to date, indicating their important roles the brain. However, interplay among during brain development remains largely unknown. Here, we show functional interactions of a writer-eraser duo, KMT2A KDM5C , which responsible for Wiedemann-Steiner Syndrome (WDSTS), mental retardation X-linked syndromic...
Abstract The metal ion transporter SLC39A8 is associated with physiological traits and diseases, including blood manganese (Mn) levels inflammatory bowel diseases (IBD). mechanisms by which controls Mn homeostasis epithelial integrity remain elusive. Here, we generate Slc39a8 intestinal cell-specific-knockout ( Slc39a8- IEC KO) mice, display markedly decreased in most organs. Radiotracer studies reveal impaired absorption of dietary KO mice. localized to the apical membrane mediates 54...
Female reproductive tissues such as mammary glands, ovaries, uterus, and placenta are phenotypically dynamic, requiring tight integration of bioenergetic apoptotic mechanisms. Mitochondrial zinc (Zn) pools have emerged a central player in regulating bioenergetics apoptosis. Zn must first be imported into mitochondria to modulate mitochondrion-specific functions; however, mitochondrial import mechanisms not been identified. Here we documented that the transporter ZnT2 is associated with inner...
Mammary gland involution is the most dramatic example of physiological cell death. It occurs through an initial phase lysosomal-mediated death (LCD) followed by mitochondrial-mediated apoptosis. Zinc (Zn) activates both LCD and apoptosis in vitro. The Zn transporter ZnT2 imports into vesicles mitochondria ZnT2-overexpression mammary epithelial cells (MECs). We tested hypothesis that ZnT2-mediated transport critical for mice. Following weaning, abundance increased lysosomes mitochondria,...
The zinc transporter ZnT2 ( SLC30A2) plays an important role in secretion into milk during lactation. physiological process of mammary gland is regulated through complex integration multiple lactogenic hormones. Prolactin a primary this regulation the activation various signaling cascades including Jak2/STAT5, mitogen-activated protein kinase (MAPK), p38, and phosphatidylinositol 3-kinase (PI3K). precise mechanisms that regulate transfer specific nutrients such as are not well understood....
Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by the abnormal progressive degeneration nervous system. One recently identified subtypes NBIA β-propeller protein-associated neurodegeneration (BPAN). BPAN caused de novo mutations in WDR45/WIPI4 (WD repeat domain 45) gene. WDR45 one four mammalian homologs yeast Atg18, regulator autophagy. deficiency patients animal models may result defects...
In response to an immune challenge, naive T cells undergo a transition from quiescent activated state acquiring the effector function. Concurrently, these reprogram cellular metabolism, which is regulated by iron. We and others have shown that iron homeostasis controls proliferation mitochondrial function, but underlying mechanisms are poorly understood. Given derived heme makes up large portion of pool, we investigated in using mice with cell-specific deletion exporter, FLVCR1 [referred as...
Zinc transporter 2 (ZnT2) plays a major role in zinc (Zn) export from the mammary gland. Recently, we determined that ZnT2 is associated with secretory vesicles reflecting its Zn secretion during lactation. Herein, identified two distinct single nucleotide polymorphisms (SNPs) SLC30A2, which encodes ZnT2. SNP1 (rs35235055) results leucine-to-proline substitution (Leu(23)Pro), while SNP2 (rs35623192) an arginine-to-cysteine (Arg(340)Cys). We examined localization and function of each SNP...
Flatiron (ffe) mice display features of "ferroportin disease" or Type IV hereditary hemochromatosis. While it is known that both Fe and Mn metabolism are impaired in flatiron mice, the effects ferroportin (Fpn) deficiency on physiological distribution these other biometals unknown. We hypothesized Fe, Mn, Zn and/or Cu would be altered ffe/+ compared to wild-type (+/+) mice. ICP-MS analysis showed levels were significantly reduced femurs from Bone deposits reflect metal accumulation,...
Hemochromatosis is a frequent genetic disorder, characterized by the accumulation of excess iron across tissues. Mutations in FPN1 gene, encoding cell surface exporter [ferroportin (Fpn)], are responsible for hemochromatosis type 4, also known as ferroportin disease. Recently, Fpn has been implicated regulation manganese (Mn), another essential nutrient required numerous cellular enzymes. However, roles Mn remain ill-defined, and impact disease mutations on levels unknown. Here, we provide...
Deficiencies of the transmembrane iron-transporting protein ferroportin (FPN1) cause iron misdistribution that underlies disease, anemia inflammation, and several other human diseases conditions. A small molecule natural product, hinokitiol, was recently shown to serve as a surrogate transporter can restore hemoglobinization in zebrafish deficient transporting proteins increase gut absorption FPN1-deficient flatiron mice. However, whether hinokitiol normal physiology animals or primary cells...
Divalent metal transporter-1 (DMT1) mediates dietary iron uptake across the intestinal mucosa and facilitates peripheral delivery of released by transferrin in endosome. Here, we report that classical cannabinoids (Δ9-tetrahydrocannabinol, Δ9-THC), nonclassical (CP 55,940), aminoalkylindoles (WIN 55,212-2) endocannabinoids (anandamide) reduce 55Fe 54Mn HEK293T(DMT1) cells stably expressing transporter. siRNA knockdown cannabinoid receptor type 2 (CB2) abrogated inhibition. CB2 is a G-protein...