A5058239570- Glycosylation and Glycoproteins Research
- Trace Elements in Health
- Ion channel regulation and function
- Drug Transport and Resistance Mechanisms
- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- MicroRNA in disease regulation
- RNA Research and Splicing
- Renal Diseases and Glomerulopathies
- Nanopore and Nanochannel Transport Studies
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Asymmetric Synthesis and Catalysis
- Genetic Associations and Epidemiology
- Chromosomal and Genetic Variations
- Organometallic Complex Synthesis and Catalysis
- Asymmetric Hydrogenation and Catalysis
- Genomics and Phylogenetic Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Various Chemistry Research Topics
- Signaling Pathways in Disease
- Galectins and Cancer Biology
- Heavy Metal Exposure and Toxicity
- Evolutionary Algorithms and Applications
- Bioinformatics and Genomic Networks
Icahn School of Medicine at Mount Sinai
2022-2025
Allen Institute for Brain Science
2022-2025
The Graduate Center, CUNY
2022-2024
Beth Israel Deaconess Medical Center
2019-2024
Harvard University
2019-2024
Massachusetts General Hospital
2019-2022
Queensland Government
2022
University of Southampton
2010-2013
Health and Human Development (2HD) Research Network
2013
Centre For Human Genetics
2013
Abstract Glycosylation is essential to brain development and function, but prior studies have often been limited a single analytical technique excluded region- sex-specific analyses. Here, using several methodologies, we analyze Asn-linked Ser/Thr/Tyr-linked protein glycosylation between regions sexes in mice. Brain N-glycans are less complex sequence variety compared other tissues, consisting predominantly of high-mannose fucosylated/bisected structures. Most O-glycans unbranched,...
Abstract Background We present the genome sequence of tammar wallaby, Macropus eugenii , which is a member kangaroo family and first representative iconic hopping mammals that symbolize Australia to be sequenced. The has many unusual biological characteristics, including longest period embryonic diapause any mammal, extremely synchronized seasonal breeding prolonged sophisticated lactation within well-defined pouch. Like other marsupials, it gives birth highly altricial young, small number...
A common missense variant in SLC39A8 is convincingly associated with schizophrenia and several additional phenotypes. Homozygous loss-of-function mutations result undetectable serum manganese (Mn) a Congenital Disorder of Glycosylation (CDG) due to the exquisite sensitivity glycosyltransferases Mn concentration. Here, we identified Mn-related changes human carriers allele. Analysis structural brain MRI scans showed dose-dependent change ratio T2w T1w signal regions. Comprehensive trace...
Potassium channels have become a focus in cancer biology as they play roles cell behaviours associated with progression, including proliferation, migration and apoptosis. Two-pore domain (K2P) potassium are background which enable the leak of ions from cells. As these open at rest profound effect on cellular membrane potential subsequently electrical activity behaviour cells expressed. The K2P family has 15 mammalian members already 4 this (K2P2.1, K2P3.1, K2P9.1, K2P5.1) been implicated...
Genome-wide association studies (GWASs) have identified hundreds of loci associated with psychiatric diseases, yet there is a lack understanding disease pathophysiology. Common risk variants can shed light on the underlying molecular mechanisms; however, identifying causal remains challenging. We map cis-regulatory elements in human neurons derived from pluripotent stem cells. This system allows us to determine enhancers that activate transcription neuronal activity-regulated gene programs,...
ABSTRACT Inverted formin-2 (INF2) gene mutations are among the most common causes of genetic focal segmental glomerulosclerosis (FSGS) with or without Charcot-Marie-Tooth (CMT) disease. Recent studies suggest that INF2, through its effects on actin and microtubule arrangement, can regulate processes including vesicle trafficking, cell adhesion, mitochondrial calcium uptake, fission, T-cell polarization. Despite roles for INF2 in multiple cellular processes, neither human pathogenic R218Q...
Two-pore domain potassium (K2P) channels play fundamental roles in cellular processes by enabling a constitutive leak of from cells which they are expressed, thus influencing membrane potential and activity. Hence, regulation these is critical importance to function. A key regulatory mechanism K2P the control their cell surface expression. Membrane protein delivery retrieval controlled passage through secretory endocytic pathways, post-translational modifications regulate progression...
The synthesis and characterization of several Cr(III) complexes the constrained macrocyclic ligand 1,4-C(2)-cyclam = 1,4,8,11-tetraazabicyclo[10.2.2]hexadecane is reported. appears to form only trans complexes, structure trans-[Cr(1,4-C(2)-cyclam)Cl(2)]PF(6) presented. constraint imposed by additional C(2) linkage distorts bond angles significantly away from ideal values 90 180 degrees. effect distortion enhance aquation rate trans-[Cr(1,4-C(2)-cyclam)Cl(2)](+) (k(obs) for...
Given the large number of genes significantly associated with risk for neuropsychiatric disorders, a critical unanswered question is extent to which diverse mutations --sometimes impacting same gene-- will require tailored therapeutic strategies. Here we consider this in context rare disorder-associated copy variants (2p16.3) resulting heterozygous deletions
Abstract A common missense variant in SLC39A8 is convincingly associated with schizophrenia and several additional phenotypes. Homozygous loss-of-function mutations result undetectable serum manganese (Mn) a Congenital Disorder of Glycosylation (CDG) due to the exquisite sensitivity glycosyltransferases Mn concentration. Here, we identified Mn-related changes human carriers allele. Analysis structural brain MRI scans showed dose-dependent change ratio T2w T1w signal regions. Comprehensive...
Acid-sensitive, two-pore domain potassium channels, K(2P)3.1 and K(2P)9.1, are implicated in cardiac nervous tissue responses to hormones, neurotransmitters drugs. K(2P)9.1 leak from the cell at rest directly impact membrane potential. Hence altering channel number on surface drives changes cellular electrical properties. The rate of delivery recovery plasma determines both cells. This study examines endocytosis K(2P)9.1. Plasma biotinylation was used follow fate internalized GFP-tagged rat...
Gene expression is orchestrated by a complex array of gene regulatory elements that govern transcription in cell-type-specific manner. Though previously studied, the ability to utilize identify disrupting variants remains largely elusive. To important factors within these regions, we generated enhancer–promoter interaction (EPI) networks and investigated presence disease-associated fall regions. Our study analyzed six neuronal cell types across neural differentiation, allowing us examine...
Summary Glycosylation is essential to brain development and function, though prior studies have often been limited a single analytical technique. Using several methodologies, we analyzed Asn-linked (N-glycans) Ser/Thr/Tyr-linked (O-glycans) protein glycosylation between regions sexes in mice. Brain N-glycans were surprisingly less complex sequence variety compared other tissues, consisting predominantly of high-mannose precursors fucosylated/bisected structures. Most O-glycans unbranched,...
Abstract A missense mutation (A391T) in the manganese transporter SLC39A8 is strongly associated with schizophrenia genomic studies, though molecular connection to brain remains hypothetical. Human carriers of A391T have reduced serum manganese, altered plasma glycosylation, and MRI changes consistent metal transport. Here, using a knock-in mouse model homozygous for A391T, we show that schizophrenia-associated variant protein glycosylation brain. N-linked was most significantly impaired,...