A5042842689- Histone Deacetylase Inhibitors Research
- Multiple Myeloma Research and Treatments
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- Gene expression and cancer classification
- Protease and Inhibitor Mechanisms
- Computational Drug Discovery Methods
- Genomics and Rare Diseases
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Fungal and yeast genetics research
- Peptidase Inhibition and Analysis
- Genomics and Phylogenetic Studies
- Cutaneous Melanoma Detection and Management
- Click Chemistry and Applications
- Acute Myeloid Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Advanced Proteomics Techniques and Applications
National Human Genome Research Institute
2010-2023
Cornell University
2012-2021
Weill Cornell Medicine
2018-2021
National Institutes of Health
2009-2013
Cancer Genetics (United States)
2010-2013
Carnegie Institution for Science
2013
Carnegie Department of Plant Biology
2013
Howard Hughes Medical Institute
2010
National Institute of Dental and Craniofacial Research
2010
National Cancer Institute
2010
The Hippo pathway plays a key role in organ size control by regulating cell proliferation and apoptosis Drosophila . Although recent genetic studies have shown that the is regulated NF2 Fat tumor suppressors, physiological regulations of this are unknown. Here we show mammalian cells, transcription coactivator YAP (Yes-associated protein), inhibited density via pathway. Phosphorylation Lats suppressor kinase leads to cytoplasmic translocation inactivation oncoprotein. Furthermore,...
Plant environmental responses involve dynamic changes in growth and signaling, yet little is understood as to how progress through these events regulated. Here, we explored the phenotypic transcriptional involved acclimation of Arabidopsis thaliana seedling root a rapid change salinity. Using live-imaging analysis, show that dynamically regulated with period quiescence followed by recovery then homeostasis. Through use new high-resolution spatio-temporal map, identify key hormone signaling...
Identifying Important Identifiers Each of us has millions sequence variations in our genomes. Signatures purifying or negative selection should help identify which those is functionally important. Khurana et al. ( 1235587 ) used polymorphisms from 1092 humans across 14 populations to patterns selection, especially noncoding regulatory regions. Noncoding regions under very strong included binding sites some chromatin and general transcription factors (TFs) core motifs important TF families....
Synonymous mutations, which do not alter the protein sequence, have been shown to affect function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683–691]. However, synonymous mutations are rarely investigated in cancer genomics field. We used whole-genome and -exome sequencing identify somatic 29 melanoma samples. Validation of one mutation BCL2L12 285 samples identified 12 cases that harbored recurrent F17F mutation. This led increased mRNA levels because differential targeting WT...
Summary Microphthalmia‐associated transcription factor (MITF) is involved in melanocyte cell development, pigmentation and neoplasia. To determine whether MITF somatically mutated melanoma, we compared the sequence of from primary metastatic lesions to patient‐matched normal DNA. In 50 melanoma tumor lines analysed, discovered four samples that had genomic amplifications mutations regions encoding transactivation, DNA binding or basic, helix‐loop‐helix domains. Sequence analysis for SOX10 ,...
Given the frequent and largely incurable occurrence of multiple myeloma, identification germline genetic mutations that predispose cells to myeloma may provide insight into disease etiology developmental mechanisms its cell origin, plasma (PC). Here, we identified familial early-onset kindreds with truncating in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor primarily demethylates histone H3 on lysine 4 regulates hematopoietic stem self-renewal. In...
Abstract Each human genome carries tens of thousands coding variants. The extent to which this variation is functional and the mechanisms by they exert their influence remains largely unexplored. To address gap, we leverage ExAC database 60,706 exomes investigate experimentally impact 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions, generating interaction profiles for 4797 SNV-interaction pairs, 421 SNVs segregate at > 1% allele frequency in...
Understanding the functional relevance of DNA variants is essential for all exome and genome sequencing projects. However, current mutagenesis cloning protocols require Sanger sequencing, thus are prohibitively costly labor-intensive. We describe a massively-parallel site-directed approach, "Clone-seq", leveraging next-generation to rapidly cost-effectively generate large number mutant alleles. Using Clone-seq, we further develop comparative interactome-scanning pipeline integrating...
To standardize DPYD allele nomenclature and to conform with international human gene guidelines, an alternative the current arbitrary system is described. Based on recommendations for genome nomenclature, we propose that each distinct be designed by followed asterisk Arabic numeral. The number specifies key mutation and, where appropriate, a letter following indicates additional mutant allele. Criteria classification as are also presented.
The fission yeast Schizosaccharomyces pombe has more metazoan-like features than the budding Saccharomyces cerevisiae, yet it similarly facile genetics. We present a large-scale verified binary protein-protein interactome network, "StressNet," based on high-throughput two-hybrid screens of interacting proteins classified as part stress response and signal transduction pathways in S. pombe. performed systematic, cross-species mapping using StressNet protein network orthologous cerevisiae....
The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due challenges of genetic heterogeneity and inheritance models. We describe a HRP that addresses intra-familial heterogeneity, identifies inherited segments important for mapping regulatory risk. apply this new Shared Genomic Segment (SGS) method 11 extended, Utah, multiple myeloma (MM) HRPs,...
The disintegrin-metalloproteinases with thrombospondin domains (ADAMTS) genes have been suggested to function as tumor suppressors several found be epigenetically silenced in various cancers. We performed a mutational analysis of the ADAMTS gene family human melanoma and identified large fraction melanomas harbor somatic mutations. To evaluate functional consequences most commonly mutated gene, ADAMTS18, six its mutations were biologically examined. ADAMTS18 had little effect on cell growth...
We performed a mutational analysis of the 19 disintegrin-metalloproteinases (ADAMs) genes in human cutaneous metastatic melanoma and identified eight to be somatically mutated 79 samples, affecting 34% tumors analyzed. Functional two frequently ADAM genes, ADAM29 ADAM7 demonstrated that mutations affect adhesion cells specific extracellular matrix proteins some cases increase their migration ability. This suggests could play role progression. © 2011 Wiley-Liss, Inc.