A5082013900- Porphyrin Metabolism and Disorders
- Iron Metabolism and Disorders
- Folate and B Vitamins Research
- RNA modifications and cancer
- Heme Oxygenase-1 and Carbon Monoxide
- Hemoglobinopathies and Related Disorders
- Genetic Associations and Epidemiology
- Bacteriophages and microbial interactions
- Aortic aneurysm repair treatments
- Influenza Virus Research Studies
- Lymphoma Diagnosis and Treatment
- Aortic Disease and Treatment Approaches
- Connective tissue disorders research
- Trace Elements in Health
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Metalloenzymes and iron-sulfur proteins
- Chronic Lymphocytic Leukemia Research
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Erythrocyte Function and Pathophysiology
- Animal Virus Infections Studies
- Neonatal Health and Biochemistry
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA regulation and disease
University of Wisconsin–Madison
2022-2025
VA Boston Healthcare System
2021-2024
Boston Children's Hospital
2012-2024
University of Wisconsin Carbone Cancer Center
2022-2024
Harvard University
2012-2021
Booz Allen Hamilton (United States)
2021
Boston Children's Museum
2014-2019
Boston University
2018
Montana State University
2008-2013
During terminal differentiation, the global protein complement is remodeled, as epitomized by erythrocytes, whose cytosol ~98% globin. The erythroid proteome undergoes a rapid transition at reticulocyte stage; however, mechanisms driving programmed elimination of preexisting cytosolic proteins are unclear. We found that mutation in murine
Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of from mouse forebrain at embryonic days E8.5 vs. E10.5 (before after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated E10.5. This was matched by decreases ribosome biogenesis and synthesis, together with age-related proteomic content adjacent fluids. Notably,...
Abstract The current understanding of the genetic determinants thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies rare, Mendelian forms disease. Here, we conducted a genome-wide association study (GWAS) TAAD, testing ~25 million DNA sequence variants in 8,626 participants with 453,043 without TAAD Million Veteran Program, replication an independent sample 4,459 individuals 512,463 from six cohorts. We identified 21 risk loci, 17 which have not...
The daily production of 200 billion erythrocytes requires 20 mg iron, accounting for nearly 80% the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism uptake which loaded transferrin (Tf) binds to receptor (TfR) at cell surface. Tf:TfR complex then enters endosome via receptor-mediated endocytosis. Upon endosomal acidification, is released from Tf, reduced Fe 2+ by Steap3, and transported across membrane divalent metal transporter 1. major ferrireductase...
Sulfolobus turreted icosahedral virus (STIV) was isolated in acidic hot springs where it infects the archeon solfataricus . We determined STIV structure using near-atomic resolution electron microscopy and X-ray crystallography allowing tracing of structural polypeptide chains visualization transmembrane proteins embedded viral membrane. propose that vertex complexes orchestrate virion assembly by coordinating interactions membrane various protein components involved. shares same coat...
X‐linked sideroblastic anemia (XLSA) is the most common form of congenital anemia. In affected males, it uniformly associated with partial loss‐of‐function missense mutations in erythroid‐specific heme biosynthesis protein 5‐aminolevulinate synthase 2 (ALAS2). Here, we report five families XLSA owing to a GATA transcription factor binding site located transcriptional enhancer element intron 1 ALAS2 gene. As such, this study defines new class that should be evaluated patients undergoing...
Abstract Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, primary clinical manifestations of myopathic exercise intolerance a macrocytic anemia. One cause MLASA recessive mutations in PUS1 , which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe mouse model due to . As expected, certain Ψ modifications were missing cytoplasmic mitochondrial tRNAs from Pus1 −/− animals. mice born at the expected Mendelian...
Steap4 is a cell surface metalloreductase linked to obesity-associated insulin resistance. Initial characterization of its activity has been reported, but thorough biochemical this lacking. Here, we report detailed kinetic analysis the activities. shows physiologically relevant Km values for both Fe(3+) and Cu(2+) retains at acidic pH, suggesting it may also function within intracellular organelles reduce these metals. Flavin-dependent NADPH oxidase that was much greater than equivalent...
The congenital sideroblastic anemias (CSAs) can be caused by primary defects in mitochondrial iron-sulfur (Fe-S) cluster biogenesis. HSCB (heat shock cognate B), which encodes a cochaperone, also known as HSC20 protein 20), is the partner of heat A9 (HSPA9). Together with glutaredoxin 5 (GLRX5), and HSPA9 facilitate transfer nascent 2-iron, 2-sulfur clusters to recipient proteins. Mutations both GLRX5 have previously been associated CSA. Therefore, we hypothesized that mutations could cause...
Although indolent T-lymphoblastic proliferations (iT-LBP) are rare, this diagnosis should be excluded in any patient with an extrathymic proliferation of immature TdT+T cells. Unlike leukemia/lymphoma, patients iT-LBP do not require chemotherapy. We report a case disseminated multinodal involvement otherwise healthy 49-year-old woman. Multiple lymph node biopsies were performed over the course several months demonstrating persistent and anatomically diffuse involvement. Over 18 months,...
Abstract Lung cancer remains the leading cause of mortality, despite declines in smoking rates. Previous lung genome-wide association studies (GWAS) have identified numerous loci, but separating genetic risks and behavioral susceptibility challenging. We performed multi-ancestry GWAS meta-analyses using Million Veteran Program (MVP) cohort a previous study European-ancestry individuals, comprising 42,102 cases 181,270 controls, followed by replication an independent 19,404 17,378 controls....
Taken together, these genetic and functional data strongly support the conclusion that mutations in an enhancer element ALAS2 intron 1 contains a GATA-binding site result clinical phenotype similar to patients with XLSA owing coding sequence itself.In our own survey of >125 probands CSA (Ref. 2 not shown), constitute _3% all _5% cases XLSA.For this reason, we suggest GATAbinding variants can be excluded males hypochromic, microcytic, nonsyndromic sideroblastic anemias lacking or biallelic...
Abstract Current understanding of the genetic contribution to thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies focusing on rare, Mendelian forms disease. In current analysis we performed largest genome-wide association study (GWAS) TAAD date, testing ~25 million DNA sequence variants in 8,626 participants with (7,050 European, 1,266 African, 310 Hispanic ancestry individuals) 453,043 without Million Veteran Program. The results were replicated an...
The creatinine value in Table 1 Definition of Myeloma these three articles should read "0.173 mmol/L" instead "1.73 mmol/L".The conventional units given parenthesis is correct.We apologize for any confusion this error might have caused.