A5065778793- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Cellular Mechanics and Interactions
- Cell Image Analysis Techniques
- Pancreatic function and diabetes
- Cellular transport and secretion
- Chronic Kidney Disease and Diabetes
- Renal Diseases and Glomerulopathies
- Microbial Metabolic Engineering and Bioproduction
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Diabetes Treatment and Management
- Pharmacogenetics and Drug Metabolism
- Phosphodiesterase function and regulation
- Neuropeptides and Animal Physiology
- Genetics, Bioinformatics, and Biomedical Research
- 3D Printing in Biomedical Research
- Biomedical Text Mining and Ontologies
- Renal and related cancers
- Adenosine and Purinergic Signaling
Icahn School of Medicine at Mount Sinai
2016-2025
Institute for Systems Biology
2023
Mount Sinai Medical Center
1989-2022
RELX Group (United States)
2005-2021
Landscape Research Group
2021
RELX Group (Netherlands)
2021
Mount Sinai Hospital
1992-2019
Center for Systems Biology
2012-2018
University of Michigan
2018
Pharmac
2018
Many distinct signaling pathways allow the cell to receive, process, and respond information. Often, components of different interact, resulting in networks. Biochemical networks were constructed with experimentally obtained constants analyzed by computational methods understand their role complex biological processes. These exhibit emergent properties such as integration signals across multiple time scales, generation outputs depending on input strength duration, self-sustaining feedback...
Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein C (PKC) system is one such network that regulates many machines, including the cell cycle machinery autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis experiments in mouse NIH-3T3 fibroblasts understand design principles this controller network. find growth factor-stimulated containing MAPK 1,...
Biological signaling pathways interact with one another to form complex networks. Complexity arises from the large number of components, many isoforms that have partially overlapping functions; connections among components; and spatial relationship between components. The origins behavior networks analytical approaches deal emergent complexity are discussed here.
MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise using extracellular miRNAs to diagnose disease is the notion that abundance reflects their abnormal cells causing disease. As result, search such has focused on abundant origin. Here we report released do not necessarily reflect miRNA cell We find release from into blood, milk ductal selective selection may correlate with malignancy. In particular, bulk...
Long-term potentiation (LTP) at the Schaffer collateral–CA1 synapse involves interacting signaling components, including calcium (Ca 2+ )/calmodulin–dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhibitor phosphatase–1 (PP1), substituted for cAMP pathway activation in LTP. Stimulation that induced LTP triggered cAMP-dependent phosphorylation endogenous decrease PP1...
Both the α and βγ subunits of heterotrimeric guanine nucleotide–binding proteins (G proteins) communicate signals from receptors to effectors. Gβγ can regulate a diverse array effectors, including ion channels enzymes. Gα bound diphosphate (Gα-GDP) inhibit signal transduction through subunits, suggesting common interface on for binding effector interaction. The molecular basis interaction with effectors was characterized by mutational analysis Gβ residues that make contact Gα-GDP. Analysis...
Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell single-nucleus assays (>400,000 nuclei or cells) spatial imaging technologies to a broad spectrum healthy reference kidneys (45 donors) diseased (48 patients). This has provided high-resolution cellular atlas 51 main types, which include rare previously undescribed...
We developed a model of 545 components (nodes) and 1259 interactions representing signaling pathways cellular machines in the hippocampal CA1 neuron. Using graph theory methods, we analyzed ligand-induced signal flow through system. Specification input output nodes allowed us to identify functional modules. Networking resulted emergence regulatory motifs, such as positive negative feedback feedforward loops, that process information. Key regulators plasticity were highly connected required...
The COVID-19 pandemic has affected millions of individuals and caused hundreds thousands deaths worldwide. Predicting mortality among patients with who present a spectrum complications is very difficult, hindering the prognostication management disease. We aimed to develop an accurate prediction model using unbiased computational methods, identify clinical features most predictive this outcome.
Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map cells, pathways, genes using unaffected regions nephrectomy tissues undiseased biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics proteomics, near-single-cell 3D CODEX imaging, spatial metabolomics to...
Methods were developed to adequately extract, separate and, without the use of NaF as stabilizing agent, purify better than 90% purity human erythrocyte N, and Ni, stimulatory inhibitory guanine nucleotide-and Mg-binding regulatory components adenylyl cyclases, well a protein containing M, = 35,000 subunits.On basis functional assay for N,, it was purified about 5,000-fold from starting washed membranes with yield 10%.A typical purification yields 60 units outdated blood, between 500 1,000 p...