Entity

Time filter

Source Type

New York City, NY, United States

Erlich Y.,Columbia University | Erlich Y.,New York Genome Center
Genome Research | Year: 2015

Genomics has recently celebrated reaching the $1000 genome milestone, making affordable DNA sequencing a reality. With this goal successfully completed, the next goal of the sequencing revolution can be sequencing sensors-miniaturized sequencing devices that are manufactured for real-time applications and deployed in large quantities at low costs. The first part of this manuscript envisions applications that will benefit from moving the sequencers to the samples in a range of domains. In the second part, the manuscript outlines the critical barriers that need to be addressed in order to reach the goal of ubiquitous sequencing sensors. © 2015 Erlich. Source


Cox L.M.,NYU Langone Medical Center | Yamanishi S.,NYU Langone Medical Center | Sohn J.,NYU Langone Medical Center | Alekseyenko A.V.,NYU Langone Medical Center | And 12 more authors.
Cell | Year: 2014

Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. PaperClip © 2014 Elsevier Inc. Source


Berisa T.,New York Genome Center
Nature Genetics | Year: 2016

We performed a scan for genetic variants associated with multiple phenotypes by comparing large genome-wide association studies (GWAS) of 42 traits or diseases. We identified 341 loci (at a false discovery rate of 10%) associated with multiple traits. Several loci are associated with multiple phenotypes; for example, a nonsynonymous variant in the zinc transporter SLC39A8 influences seven of the traits, including risk of schizophrenia (rs13107325: log-transformed odds ratio (log OR) = 0.15, P = 2 × 10-12) and Parkinson disease (log OR = −0.15, P = 1.6 × 10-7), among others. Second, we used these loci to identify traits that have multiple genetic causes in common. For example, variants associated with increased risk of schizophrenia also tended to be associated with increased risk of inflammatory bowel disease. Finally, we developed a method to identify pairs of traits that show evidence of a causal relationship. For example, we show evidence that increased body mass index causally increases triglyceride levels. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source


Luo C.T.,Sloan Kettering Cancer Center | Liao W.,New York Genome Center | Dadi S.,Sloan Kettering Cancer Center | Toure A.,Sloan Kettering Cancer Center | Li M.O.,Sloan Kettering Cancer Center
Nature | Year: 2016

Regulatory T (Treg) cells expressing the transcription factor Foxp3 have a pivotal role in maintaining immunological self-tolerance; yet, excessive Treg cell activities suppress anti-tumour immune responses. Compared to the resting Treg (rTreg) cell phenotype in secondary lymphoid organs, Treg cells in non-lymphoid tissues exhibit an activated Treg (aTreg) cell phenotype. However, the function of aTreg cells and whether their generation can be manipulated are largely unexplored. Here we show that the transcription factor Foxo1, previously demonstrated to promote Treg cell suppression of lymphoproliferative diseases, has an unexpected function in inhibiting aTreg-cell-mediated immune tolerance in mice. We find that aTreg cells turned over at a slower rate than rTreg cells, but were not locally maintained in tissues. aTreg cell differentiation was associated with repression of Foxo1-dependent gene transcription, concomitant with reduced Foxo1 expression, cytoplasmic localization and enhanced phosphorylation at the Akt sites. Treg-cell-specific expression of an Akt-insensitive Foxo1 mutant prevented downregulation of lymphoid organ homing molecules, and impeded Treg cell homing to non-lymphoid organs, causing CD8+ T-cell-mediated autoimmune diseases. Compared to Treg cells from healthy tissues, tumour-infiltrating Treg cells downregulated Foxo1 target genes more substantially. Expression of the Foxo1 mutant at a lower dose was sufficient to deplete tumour-associated Treg cells, activate effector CD8+ T cells, and inhibit tumour growth without inflicting autoimmunity. Thus, Foxo1 inactivation is essential for the migration of aTreg cells that have a crucial function in suppressing CD8+ T-cell responses; and the Foxo signalling pathway in Treg cells can be titrated to break tumour immune tolerance preferentially. © 2016 Macmillan Publishers Limited. All rights reserved. Source


Lappalainen T.,New York Genome Center | Lappalainen T.,Columbia University
Genome Research | Year: 2015

Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field. © 2015 Lappalainen. Source

Discover hidden collaborations