A5044776929- Immune Cell Function and Interaction
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Evolution and Genetic Dynamics
- Extracellular vesicles in disease
- Angiogenesis and VEGF in Cancer
- Lipoproteins and Cardiovascular Health
- Diabetes and associated disorders
- Lipid metabolism and disorders
- Erythropoietin and Anemia Treatment
- Pleistocene-Era Hominins and Archaeology
Boston Biomedical Research Institute
2022
Novartis (United States)
2020-2022
New York University
2005-2021
Novartis (Switzerland)
2021
Cornell University
2005-2016
Courant Institute of Mathematical Sciences
2009-2012
Background Current technologies have lead to the availability of multiple genomic data types in sufficient quantity and quality serve as a basis for automatic global network inference. Accordingly, there are currently large variety inference methods that learn regulatory networks varying degrees detail. These different strengths weaknesses thus can be complementary. However, combining mutually reinforcing manner remains challenge. Methodology We investigate how three scalable combined into...
<h3>Importance</h3> Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk atherosclerotic cardiovascular disease, and mouse experiments suggest that CHIP related to<i>Tet2</i>loss function in myeloid cells accelerates atherosclerosis via augmented interleukin (IL) 1β signaling. <h3>Objective</h3> To assess whether individuals have greater event reduction response to IL-1β neutralization the Canankinumab Anti-inflammatory Thrombosis Outcomes Trial (CANTOS)....
Chimeric antigen receptor-T (CAR-T) cell therapies can eliminate relapsed and refractory tumors, but the durability of antitumor activity requires in vivo persistence. Differential signaling through CAR costimulatory domain alter T metabolism, memory differentiation, influence long-term CAR-T cells costimulated with 4-1BB or ICOS persist xenograft models those constructed CD28 exhibit rapid clearance. Here, we show that a single amino acid residue drove exhaustion hindered persistence...
Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS). We present tailored analytical methods and software that facilitate X-wide (XWAS), which we further applied reanalyze data from 16 GWAS different autoimmune related (AID). associated several X-linked genes with risk, among (1) ARHGEF6 is Crohn's replicated study...
Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The assay for transposase-accessible chromatin (ATAC)–seq, coupled with TF motif analysis, provides indirect evidence of binding hundreds TFs genome-wide. Here, we propose methods TRN inference in a mammalian setting, using ATAC-seq data to improve expression modeling. We test our the context T Helper Cell Type 17 (Th17)...
Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRβ) is expressed by V-SVZ NSCs olfactory bulb interneurons Selective deletion of PDGFRβ leads their release from quiescence, uncovering gliogenic domains for different glial cell types. These are also recruited upon injury. We identify an intraventricular oligodendrocyte...
Background Many current works aiming to learn regulatory networks from systems biology data must balance model complexity with respect availability and quality. Methods that associations based on unit-less metrics, such as Mutual Information, are attractive in they scale well reduce the number of free parameters (model complexity) per interaction a minimum. In contrast, methods for learning explicit dynamical models more complex less gracefully, but may allow direct prediction...
Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result drug resistance and disease recurrence. Therefore, simultaneous of multiple pathways could principle be an effective approach to treating Here we provide proof-of-concept that a small-molecule inhibitor nuclear β-catenin activity (called C3) inhibit both β-catenin–signaling are often misregulated Treatment with C3 ablated cancer cell growth by disruption...
Current methods for reconstructing biological networks often learn either the topology of large or kinetic parameters smaller with a well-characterized topology. We have recently described network reconstruction algorithm, Inferelator 1.0, that given set genome-wide measurements as input, simultaneously learns both and kinetic-parameters. Specifically, it system ordinary differential equations (ODEs) describe rate change in transcription each gene gene-cluster, function environmental...
The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, Sox2. Wnt/β-catenin pathway promotes alleviating T factor TCF3-mediated repression the PTN. However, it has remained unclear how β-catenin’s function as activator with TCF1 influences mESC fate. Here, we show that TCF1-mediated transcription up-regulated in differentiating...
Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one the most important components TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter enhancer regions alter target expression patterns. Advances genomic technologies as well advances computational biology have led multiple large network models (directed networks) each with corpus supporting data gene-annotation. There possible biological motivations for...
ABSTRACT Many complex human diseases are highly sexually dimorphic, suggesting a potential contribution of the X chromosome to disease risk. However, has been neglected or incorrectly analyzed in most genome-wide association studies (GWAS). We present tailored analytical methods and software that facilitate X-wide (XWAS), which we further applied reanalyze data from 16 GWAS different autoimmune related (AID). associated several X-linked genes with risk, among (1) ARHGEF6 is Crohn’s...
Abstract Transcriptional regulatory networks (TRNs) provide insight into cellular behavior by describing interactions between transcription factors (TFs) and their gene targets. The Assay for Transposase Accessible Chromatin (ATAC)-seq, coupled with transcription-factor motif analysis, provides indirect evidence of chromatin binding hundreds TFs genome-wide. Here, we propose methods TRN inference in a mammalian setting, using ATAC-seq data to influence expression modeling. We rigorously test...
Abstract Genetic risk for common autoimmune diseases is influenced by hundreds of small effect, mostly non-coding variants, enriched in regulatory regions active adaptive-immune cell types. DNaseI hypersensitivity sites (DHSs) are a genomic mark DNA. Here, we generated single DHSs annotation from fifteen deeply sequenced DNase-seq experiments as well non-immune Using this quantified accessibility across types matrix format amenable to statistical analysis, deduced the subset unique types,...