A5101975763- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Aquatic Invertebrate Ecology and Behavior
- Genomics and Phylogenetic Studies
- Mitochondrial Function and Pathology
- Gene expression and cancer classification
- Genetic Syndromes and Imprinting
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Genetic diversity and population structure
- Gene Regulatory Network Analysis
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Genomics and Rare Diseases
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Ecology and biodiversity studies
- Cancer-related molecular mechanisms research
Albert Einstein College of Medicine
2013-2024
Yeshiva University
2020
Zhejiang University
2020
University of California, Los Angeles
1996-1998
University of Toronto
1998
Hospital for Sick Children
1998
SickKids Foundation
1998
Hôpital de la Timone
1998
Fondazione Stella Maris
1998
University of Pisa
1998
Abstract We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11‐13 deletions (class I), uniparental disomy II), methylation imprinting abnormalities III), and mutation in the UBE3A gene IV). Twenty patients were prospectively selected based on clinical cytogenetic molecular diagnosis AS. All had 6 to 72 hours closed‐circuit television videotaping digitized electroencephalographic (EEG) telemetry. Patients from all genotypic classes characteristic...
The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) the processed into two smaller fragments unequal size. breakpoints are located rRNA divergent region 6 excise fragment 263 nt. excised unique does not show homology other genomic regions. Because this hidden break site could alter ribosome...
Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed pipeline for obtaining species-specific ortholog sequences, profiled gene expression RNA-seq small molecules metabolite profiling, identified genes metabolites correlating longevity. Cells longer lived...
Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation mutation rate of 518 GM-associated genes in naked mole rat (NMR), mouse, human genomes. GM appeared to be strongly conserved, with only four genes. Interestingly, found NMR have a higher CEBPG, regulator DNA repair, TINF2, protector telomere integrity. NMR, well human, was also lower germline nucleotide...
Enhancers, as specialized genomic cis-regulatory elements, activate transcription of their target genes and play an important role in pathogenesis many human complex diseases. Despite recent systematic identification them the genome, currently there is urgent need for comprehensive annotation databases enhancers with a focus on disease connections. In response, we built Human Enhancer Disease Database (HEDD) to facilitate studies potential roles HEDD provides information ∼2.8 million...
Schizophrenia is a severe mental disorder with large genetic component. Recent genome-wide association studies (GWAS) have identified many schizophrenia-associated common variants. For most of the reported associations, however, underlying biological mechanisms are not clear. The critical first step for their elucidation to identify likely disease genes as source signals. Here, we describe general computational framework post-GWAS analysis complex gene prioritization. We 132 putative...
Malignant breast cancer with complex molecular mechanisms of progression and metastasis remains a leading cause death in women. To improve diagnosis drug development, it is critical to identify panels genes pathways involved tumor malignant transition. Using the PyMT mouse, genetically engineered mouse model that has been widely used study human cancer, we profiled analyzed gene expression from four distinct stages (hyperplasia, adenoma/MIN, early carcinoma late carcinoma) during which...
Long-lived rodents have become an attractive model for the studies on aging. To understand evolutionary paths to long life, we prepare chromosome-level genome assemblies of two longest-lived rodents, Canadian beaver (Castor canadensis) and naked mole rat (NMR, Heterocephalus glaber), which were scaffolded with in vitro proximity ligation chromosome conformation capture data complemented long-read sequencing. Our comparative genomic analyses reveal that amino acid substitutions at...
Abstract Alzheimer’s disease (AD) is a genetically complex, multifactorial neurodegenerative disease. It affects more than 45 million people worldwide and currently remains untreatable. Although genome-wide association studies (GWAS) have identified many AD-associated common variants, only about 25 genes are known to affect the risk of developing AD, despite its highly polygenic nature. Moreover, variants underlying GWAS AD-association signals remain unknown. Here, we describe deep post-GWAS...
Abstract Juvenile myoclonic epilepsy is a common type of idiopathic generalized characterized by myoclonic, tonic‐clonic, and in 30% patients, absence seizures. We studied three‐generation pedigree 33 members, 10 whom were clinically affected with juvenile or presented subclinical electroencephalographic (EEG) 3.5‐ to 6.0‐Hz diffuse polyspike‐wave spike‐wave complexes. the EEG trait segregated as an autosomal dominant 70% penetrance. Linkage analysis using this model showed significant...
Abstract Gene variants associated with longevity are also protection against cognitive decline, dementia and Alzheimer's disease, suggesting that common physiologic pathways act at the interface of function. To test hypothesis in genes implicated function may promote exceptional longevity, we performed a comprehensive 3‐stage study to identify functional longevity‐associated ~700 candidate up 450 centenarians 500 controls by target capture sequencing analysis. We found an enrichment nPKC...
Abstract Immunosenescence is a hallmark of aging and manifests as increased susceptibility to infection, autoimmunity, cancer in the elderly. One component immunosenescence thymic involution, age‐associated shrinkage thymus, observed all vertebrates studied date. The naked mole rat ( Heterocephalus glaber ) has become an attractive animal model research due its extreme longevity resistance disease. Here, we show that rats display no involution up 11 years age. Furthermore, found large...
Abstract Summary: The extraction of targeted subnetworks is a powerful way to identify functional modules and pathways within complex networks. Here, we present SubNet, Java-based stand-alone program for extracting subnetworks, given basal network set selected nodes. Designed with graphical user-friendly interface, SubNet combines four different methods, which offer the possibility interrogate biological according question investigated. Of note, developed method based on highly successful...
MicroRNAs (miRNAs) are small non-coding RNA molecules of about 22 nucleotides which function to silence the expression their target genes. Numerous studies have shown that miRNAs not only key regulators in important cellular processes but also drivers development many diseases, especially cancer. Estrogen receptor positive luminal B is second most common least studied subtype breast Only a few examined profiles cancer, and regulatory roles cancer progression yet be investigated.In this...
While mitochondria have been linked to many human diseases through genetic association and functional studies, the precise role of in specific pathologies, such as cardiovascular, neurodegenerative, metabolic diseases, is often unclear. Here, we take advantage catalog genome-wide associations, whole-genome tissue expression quantitative trait loci datasets, annotated mitochondrial proteome databases examine common variation mitonuclear genes disease. Through pathway-based analysis identified...
The North American beaver is an exceptionally long-lived and cancer-resistant rodent species. Here, we report the evolutionary changes in its gene coding sequences, copy numbers, expression. We identify that likely increase ability to detoxify aldehydes, enhance tumor suppression DNA repair, alter lipid metabolism, potentially contributing longevity cancer resistance. Hpgd, a suppressor gene, uniquely duplicated beavers among rodents, several genes associated with are under positive...
Abstract Malignant breast cancer remains a major health threat to women of all ages worldwide and epigenetic variations on DNA methylation have been widely reported in cancers different types. We profiled with ERRBS (Enhanced Reduced Representation Bisulfite Sequencing) across four main stages tumor progression the MMTV-PyMT mouse model (hyperplasia, adenoma/mammary intraepithelial neoplasia, early carcinoma late carcinoma), during which malignant transition occurs. identified large number...
Rare variants of major effect play an important role in human complex diseases and can be discovered by sequencing-based genome-wide association studies. Here, we introduce integrated approach that combines the rare variant test with gene network phenotype information to identify risk genes implicated for diseases. Our data integration method follows a 'discovery-driven' strategy without relying on prior knowledge about disease thus maintains unbiased character Simulations reveal our...
Abstract Summary Although the genome-wide association study (GWAS) is a powerful method to identify disease-associated variants, it does not directly address biological mechanisms underlying such genetic signals. Here, we present PGA, Perl- and Java-based program for post-GWAS analysis that predicts likely disease genes given list of GWAS-reported variants. Designed with command line interface, PGA incorporates genomic eQTL data in identifying gene candidates uses network ontology score them...
The highly polygenic nature of human longevity renders pleiotropy an indispensable feature its genetic architecture. Leveraging the correlation between aging-related traits (ARTs), we aimed to model additive variance in lifespan as a function cumulative liability from pleiotropic segregating variants. We tracked allele frequency changes viability across different age bins and prioritized 34 variants with immediate implication on lipid metabolism, body mass index (BMI), cognitive performance,...