Avi Ma'ayan

Avi Ma'ayan
Icahn School of Medicine at Mount Sinai | MSSM · Department of Pharmacological Sciences

PhD

About

434
Publications
68,586
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
28,705
Citations
Additional affiliations
July 2015 - present
Icahn School of Medicine at Mount Sinai
Position
  • Professor (Full)
January 2013 - July 2015
Icahn School of Medicine at Mount Sinai
Position
  • Professor (Associate)
October 2007 - December 2012
Icahn School of Medicine at Mount Sinai
Position
  • Professor (Assistant)
Education
May 2002 - March 2006
Icahn School of Medicine at Mount Sinai
Field of study
  • Biological Sciences

Publications

Publications (434)
Article
Millions of transcriptome samples were generated by the Library of Integrated Network-based Cellular Signatures (LINCS) program. When these data are processed into searchable signatures along with signatures extracted from Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO), connections between drugs, genes, pathways and diseases ca...
Article
Pluripotent stem-cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease, but they are functionally and structurally immature. Here, we induce efficient human PSC-CM (hPSC-CM) maturation through metabolic-pathway modulations. Specifically, we find that peroxisome-proliferator-associate...
Article
Motivation Many biological and biomedical researchers commonly search for information about genes and drugs to gather knowledge from these resources. For the most part, such information is served as landing pages in disparate data repositories and web portals. Results The Gene and Drug Landing Page Aggregator (GDLPA) provides users with access to...
Article
Full-text available
Background PubMed contains millions of abstracts that co-mention terms that describe drugs with other biomedical terms such as genes or diseases. Unique opportunities exist for leveraging these co-mentions by integrating them with other drug-drug similarity resources such as the Library of Integrated Network-based Cellular Signatures (LINCS) L1000...
Article
Motivation The identification of pathways and biological processes from differential gene expression is central for interpretation of data collected by transcriptomics assays. Gene-Set Enrichment Analysis (GSEA) is the most common used algorithm to calculate the significance of the relevancy of an annotated gene set with a differential expression s...
Article
The Illuminating the Druggable Genome (IDG) consortium is a National Institutes of Health (NIH) Common Fund program designed to enhance our knowledge of under-studied proteins, more specifically, proteins unannotated within the three most commonly drug-targeted protein families: G-protein coupled receptors, ion channels, and protein kinases. Since...
Preprint
The Common Fund Data Ecosystem has created a flexible system of data federation that enables users to discover datasets from across the Common Fund without requiring the data owners to move, reformat, or rehost those data. The CFDEs federation system is centered on a metadata catalog that ingests metadata from individual Common Fund Program Data Co...
Preprint
The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive phosphoproteomics and proteomics data for tumor and tumoradjacent normal tissue across multiple cancer types. This dataset provides an unprecedented opportunity to systematically characterize pan-cancer kinase activities, whic...
Article
Full-text available
Loss of fatty acid β-oxidation (FAO) in the proximal tubule is a critical mediator of acute kidney injury and eventual fibrosis. However, transcriptional mediators of FAO in proximal tubule injury remain understudied. Krüppel-like factor 15 (KLF15), a highly enriched zinc-finger transcription factor in the proximal tubule , was significantly reduce...
Article
Chronic wounds present a major disease burden in people with recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering skin disorder caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils at the dermal‐epidermal junction. Treatment of RDEB wounds is mostly symptomatic and there is conside...
Preprint
Full-text available
The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understand...
Article
Full-text available
Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms fol...
Preprint
Full-text available
Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease. A major caveat however is that they remain functionally and structurally immature in culture, limiting their potential for disease modeling and regenerative approaches. Here, we address the question of how differ...
Article
Altered cellular metabolism in kidney proximal tubule (PT) cells plays a critical role in acute kidney injury (AKI). The transcription factor Krüppel-like factor 6 (KLF6) is rapidly and robustly induced early in the PT after AKI. We found that PT-specific Klf6 knockdown ( Klf6 PTKD ) is protective against AKI and kidney fibrosis in mice. Combined R...
Article
Full-text available
Phosphoproteomics and proteomics experiments capture a global snapshot of the cellular signaling network, but these methods do not directly measure kinase state. Kinase Enrichment Analysis 3 (KEA3) is a webserver application that infers overrepresentation of upstream kinases whose putative substrates are in a user-inputted list of proteins. KEA3 ca...
Article
Full-text available
Fibrosis occurs when collagen deposition and fibroblast proliferation replace healthy tissue. Red light (RL) may improve skin fibrosis via photobiomodulation, the process by which photosensitive chromophores in cells absorb visible or near-infrared light and undergo photophysical reactions. Our previous research demonstrated that high fluence RL re...
Article
Full-text available
Understanding the underlying molecular and structural similarities between seemingly heterogeneous sets of drugs can aid in identifying drug repurposing opportunities and assist in the discovery of novel properties of preclinical small molecules. A wealth of information about drug and small molecule structure, targets, indications and side effects;...
Article
Full-text available
Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory “dimensions” coordinate cell fate decisions are currently poorly un...
Article
Full-text available
Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection...
Article
Full-text available
Jupyter Notebooks have transformed the communication of data analysis pipelines by facilitating a modular structure that brings together code, markdown text, and interactive visualizations. Here, we extended Jupyter Notebooks to broaden their accessibility with Appyters. Appyters turn Jupyter Notebooks into fully functional standalone web-based bio...
Article
Profiling samples from patients, tissues, and cells with genomics, transcriptomics, epigenomics, proteomics, and metabolomics ultimately produces lists of genes and proteins that need to be further analyzed and integrated in the context of known biology. Enrichr (Chen et al., 2013; Kuleshov et al., 2016) is a gene set search engine that enables the...
Article
While hundreds of genes have been associated with pain, much of the molecular mechanisms of pain remain unknown. As a result, current analgesics are limited to few clinically validated targets. Here, we trained a machine learning (ML) ensemble model to predict new targets for 17 categories of pain. The model utilizes features from transcriptomics,...
Preprint
Full-text available
Gene co-expression correlations from mRNA-sequencing (RNAseq) can be used to predict gene function based on the covariance structure that exists within such data. In the past, we showed that RNA-seq co-expression data is highly predictive of gene function and protein-protein interactions. We demonstrated that the performance of such predictions is...
Article
Full-text available
The choreography of complex immune responses, including the priming, differentiation, and modulation of specific effector T cell populations generated in the immediate wake of an acute pathogen challenge, is in part controlled by chemokines, a large family of mostly secreted molecules involved in chemotaxis and other patho/physiological processes....
Article
Full-text available
Pathogen-specific memory T cells (TM) contribute to enhanced immune protection under conditions of reinfection, and their effective recruitment into a recall response relies, in part, on cues imparted by chemokines that coordinate their spatiotemporal positioning. An integrated perspective, however, needs to consider TM as a potentially relevant ch...
Conference Paper
The tumor microenvironment and genomic landscape of intermediate and high-risk primary localized prostate cancers are clinically heterogeneous and result in variable treatment response in individuals. Cancer-specific alterations at DNA and RNA level is a critical driver of intra-tumoral heterogeneity that significantly impacts the molecular process...
Preprint
Full-text available
In an effort to interfere with the biology of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, we focused on restoring the transcriptional response induced by infection. Utilizing expression patterns of SARS-CoV-2-infected cells, we identified a region in gene expression space that was unique to virus infection and inversely proportiona...
Article
Glioblastoma (GBM) is the most aggressive primary brain tumor. In addition to being genetically heterogeneous, GBMs are also immunologically heterogeneous. However, whether the differences in immune microenvironment are driven by genetic driver mutation is unexplored. By leveraging the versatile RCAS/tv‐a somatic gene transfer system, we establish...
Article
Full-text available
In a short period, many research publications that report sets of experimentally validated drugs as potential COVID-19 therapies have emerged. To organize this accumulating knowledge, we developed the COVID-19 Drug and Gene Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of drug and gene sets related to COVID-19 research from multip...
Article
Full-text available
Advancements in regenerative medicine have brought to the fore the need for increased standardization and sharing of stem cell product characterization to help drive these innovative interventions toward public availability. Although numerous attempts have been made to store this data, there is still a lack of a platform that incorporates heterogen...
Article
Full-text available
Rapid progress in proteomics and large-scale profiling of biological systems at the protein level necessitates the continued development of efficient computational tools for the analysis and interpretation of proteomics data. Here, we present the piNET server that facilitates integrated annotation, analysis and visualization of quantitative proteom...
Preprint
Full-text available
The coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 (COVID-19) pandemic has received rapid response by the research community to offer suggestions for repurposing of approved drugs as well as to improve our understanding of the COVID-19 viral life cycle molecular mechanisms. In a short period, tens of thousands of research preprint...
Article
Motivation: Micro-blogging with Twitter to communicate new results, discuss ideas, and share techniques is becoming central. While most Twitter users are real people, the Twitter API provides the opportunity to develop Twitter bots and to analyze global trends in tweets. Results: EnrichrBot is a bot that tracks and tweets information about human...
Article
Full-text available
Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs and how this information is encoded is unclear. To better understand how this information is stored, we performed RNA sequencing on HSC populations differing only in their divi...
Article
Full-text available
Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This appro...
Article
RNA-Sequencing (RNA-Seq) is currently the leading technology for genome-wide transcript quantification. Mapping the raw reads to transcript and gene level counts can be achieved by different aligners. Here we report an in-depth comparison of transcript quantification methods. Our goal is the specific use of cost-efficient RNA-Seq analysis for deplo...
Preprint
Full-text available
The choreography of complex immune responses, including the priming, differentiation, and modulation of specific effector T cell populations generated in the immediate wake of an acute pathogen challenge, is in part controlled by chemokines, a large family of mostly secreted molecules involved in chemotaxis and other patho/physiological processes....
Article
Tissue homeostasis requires the balance of growth by cell production and regression through cell loss. In the hair cycle during follicle regression, the niche traverses the skin through an unknown mechanism to reach the stem cell reservoir and trigger new growth. Here we identify the dermal sheath that lines the follicle as the key driver of tissue...
Presentation
Hematopoietic stem cells (HSCs) are maintained by bone marrow (BM) niches in vivo, but the ability of niche cells to maintain HSCs ex vivo is markedly diminished. Expression of niche factors (Scf, Cxcl12, Vcam1 and Angpt1) by Nestin-GFP+ mesenchymal-derived stem cells (MSCs) is downregulated upon culture and lose its effect of maintaining HSC in vi...
Article
Full-text available
The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program with the goal of generating a large-scale and comprehensive catalogue of perturbation-response signatures by utilizing a diverse collection of perturbations across many model systems and assay types. The LINCS Data Portal (LDP) has been the primary acc...
Preprint
Full-text available
iLINCS (http://ilincs.org) is an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The portal facilitates analysis of user-submitted omics signatures of diseases and cellular perturbations in the context of a large compendium of pre-computed signatures (>200,000), as well as mining and re-analysis o...
Article
Full-text available
Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell pr...
Article
Full-text available
Diabetes is far more prevalent in smokers than non-smokers, but the underlying mechanisms of vulnerability are unknown. Here we show that the diabetes-associated gene Tcf7l2 is densely expressed in the medial habenula (mHb) region of the rodent brain, where it regulates the function of nicotinic acetylcholine receptors. Inhibition of TCF7L2 signall...
Article
As more digital resources are produced by the research community, it is becoming increasingly important to harmonize and organize them for synergistic utilization. The findable, accessible, interoperable, and reusable (FAIR) guiding principles have prompted many stakeholders to consider strategies for tackling this challenge. The FAIRshake toolkit...
Preprint
Full-text available
Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. Yet the specific immune dysregulations within the atherosclerotic lesions that lead to clinical cerebro- and cardiovascular complications (i.e. ischemic stroke and myocardial infarction) are poorly understood. Here, using...
Presentation
Hematopoietic stem cells (HSCs) are maintained by bone marrow (BM) niches in vivo, but the ability of niche cells to maintain HSCs ex vivo is markedly diminished. Expression of niche factors by Nestin-GFP+ mesenchymal-derived stem cells (MSCs) is downregulated upon culture, suggesting that transcriptional rewiring may contribute to this reduced HSC...
Article
Connectivity mapping resources consist of signatures representing changes in cellular state following systematic small-molecule, disease, gene, or other form of perturbations. Such resources enable the characterization of signatures from novel perturbations based on similarity; provide a global view of the space of many themed perturbations; and al...
Article
Evidence that some high-impact biomedical results cannot be repeated has stimulated interest in practices that generate findable, accessible, interoperable, and reusable (FAIR) data. Multiple papers have identified specific examples of irreproducibility, but practical ways to make data more reproducible have not been widely studied. Here, five rese...
Preprint
Full-text available
Protein Kinase Membrane Associated Tyrosine/Threonine 1 (PKMYT1) is an understudied member of the serine/threonine protein kinase family. PKMYT1 is listed as a dark kinase according to the Illuminating the Druggable Genome (IDG) target development level classification. Using a combination of bioinformatics tools that we developed, we predict that t...
Preprint
Full-text available
As more datasets, tools, workflows, APIs, and other digital resources are produced by the research community, it is becoming increasingly difficult to harmonize and organize these efforts for maximal synergistic integrated utilization. The Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles have prompted many stakeholders to...
Article
Full-text available
Identifying the transcription factors (TFs) responsible for observed changes in gene expression is an important step in understanding gene regulatory networks. ChIP-X Enrichment Analysis 3 (ChEA3) is a transcription factor enrichment analysis tool that ranks TFs associated with user-submitted gene sets. The ChEA3 background database contains a coll...
Article
Full-text available
The frequency by which genes are studied correlates with the prior knowledge accumulated about them. This leads to an imbalance in research attention where some genes are highly investigated while others are ignored. Geneshot is a search engine developed to illuminate this gap and to promote attention to the under-studied genome. Through a simple w...
Article
High-throughput experiments produce increasingly large datasets that are difficult to analyze and integrate. While most data integration approaches focus on aligning metadata, data integration can be achieved by abstracting experimental results into gene sets. Such gene sets can be made available for reuse through gene set enrichment analysis tools...
Article
Full-text available
Haematopoietic stem cells (HSCs) are maintained by bone marrow niches in vivo1,2, but the ability of niche cells to maintain HSCs ex vivo is markedly diminished. Expression of niche factors by Nestin-GFP⁺ mesenchymal-derived stromal cells (MSCs) is downregulated upon culture, suggesting that transcriptional rewiring may contribute to this reduced H...
Preprint
Full-text available
Large proteomics data, including those generated by mass spectrometry, are being generated to characterize biological systems at the protein level. Computational methods and tools to identify and quantify peptides, proteins and post-translational modifications (PTMs) that are captured in modern mass spectrometers have matured over the years. On the...
Article
Although tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy in advanced lung adenocarcinoma (LUAD) patients with pathogenic alterations in EGFR, most patients develop acquired resistance to these agents via mechanisms enabling the sustained activation of the PI3K and MAPK oncogenic pathways downstream of EGFR. The tumor suppre...
Article
Full-text available
Background The opioid epidemic in the United States is averaging over 100 deaths per day due to overdose. The effectiveness of opioids as pain treatments, and the drug-seeking behavior of opioid addicts, leads physicians in the United States to issue over 200 million opioid prescriptions every year. To better understand the biomedical profile of op...