Stefano Monti

Stefano Monti
Boston University | BU · Department of Medicine

Ph.D.

About

232
Publications
33,798
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21,760
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Introduction
My laboratory integrates systems biology, machine learning, and bioinformatics approaches to investigate the molecular drivers of human disease, with the goals of advancing prevention and care. This multidisciplinary effort relies on the development of computational methodologies, and on the design of experiments based on generation and integrative analysis of high-throughput 'omics' data, with the goal of identifying novel therapeutic targets and to develop diagnostic and prognostic biomarkers.
Additional affiliations
January 2012 - present
Boston University
January 2004 - December 2010
Dana-Farber Cancer Institute
January 2003 - December 2012

Publications

Publications (232)
Article
OBJECTIVE To identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD. RESEARCH DESIGN AND METHODS We conducted a global serum metabolomics analys...
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Full-text available
Changes of cell type composition across samples can carry biological significance and provide insight into disease and other conditions. Single cell transcriptomics has made it possible to study cell type composition at a fine resolution. Most single cell studies investigate compositional changes between samples for each cell type independently, no...
Article
Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells but undergo plasticity to a basal-like state upon transformation. Identifying cellular mechanisms underlying this luminal-basal plasticity will allow an improved understanding of the pathogenesis...
Article
Lysine-specific demethylase 1 (LSD1) is a histone demethylase that contributes to the etiology of oral squamous cell carcinoma (OSCC) in part by promoting cancer stem cell phenotypes. The molecular signals regulated by LSD1, or acting with LSD1, are poorly understood, particularly in the development of OSSC. In this study, we show that conditional...
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Full-text available
Mosaic chromosomal alterations (mCAs) are structural alterations that include deletions, duplications, or copy-neutral loss of heterozygosity. mCAs are reported to be associated with survival, age, cancer, and cardiovascular disease. Previous studies of mCAs in large population-based cohorts (UK Biobank, MGBB, BioBank Japan, and FinnGen) have demon...
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Full-text available
Age-related disability and diseases are known to be delayed in people living to 100 years or more. Changes in the immune system with age are known, including in cell type composition and gene expression differences. To further explore changes in extreme longevity subjects, we investigated peripheral blood immune system cell subpopulations across ag...
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Full-text available
As high-throughput genomics assays become more efficient and cost effective, their utilization has become standard in large-scale biomedical projects. These studies are often explorative, in that relationships between samples are not explicitly defined a priori, but rather emerge from data-driven discovery and annotation of molecular subtypes, ther...
Article
Full-text available
Proper lung function relies on the precise balance of specialized epithelial cells that coordinate to maintain homeostasis. Herein, we describe essential roles for the transcriptional regulators YAP/TAZ in maintaining lung epithelial homeostasis, reporting that conditional deletion of Yap and Wwtr1/Taz in the lung epithelium of adult mice results i...
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Full-text available
Background: Chemicals in disparate structural classes activate specific subsets of the transcriptional programs of peroxisome proliferator-activated receptor-γ (PPARγ) to generate adipocytes with distinct phenotypes. Objectives: Our objectives were to a) establish a novel classification method to predict PPARγ ligands and modifying chemicals; an...
Preprint
Full-text available
Network analysis offers a powerful technique to model the relationships between genes within biological regulatory networks. Inference of biological network structures is often performed on high-dimensional data, yet is hindered by the limited sample size of high throughput "omics" data typically available. To overcome this challenge, we exploit kn...
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Full-text available
Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial...
Article
We conducted a genome-wide association study of 1320 centenarians from the New England Centenarian Study (median age = 104 years) and 2899 unrelated controls using >9 M genetic variants imputed to the HRC panel of ~65,000 haplotypes. The genetic variants with the most significant associations were correlated to 4131 proteins that were profiled in t...
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Full-text available
Background Microbial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visua...
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Full-text available
A tool for conducting Genome-Wide Association Study (GWAS) in a systematic, automated and reproducible manner is overdue. We developed an automated GWAS pipeline by combining multiple analysis tools - including bcftools, vcftools, the R packages SNPRelate/GENESIS/GMMAT and ANNOVAR - through Nextflow, which is a portable, flexible, and reproducible...
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Full-text available
Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age‐matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR <...
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Full-text available
G Protein Suppressor 2 (GPS2) is a multifunctional protein that exerts important roles in inflammation and metabolism in adipose, liver, and immune cells. GPS2 has recently been identified as a significantly mutated gene in breast cancer and other malignancies and proposed to work as a putative tumor suppressor. However, molecular mechanisms by whi...
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Full-text available
For decades, the aryl hydrocarbon receptor (AHR) was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had a “normal” physiological function. However, the ongoing accumulation of data from an ever-expand...
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Full-text available
We conducted a genome-wide association study of 1317 centenarians from the New England Centenarian Study and 2885 controls using >9M genetic variants. The most significantly associated variants were correlated to 4131 serum proteins in 224 study participants. The genetic and protein associations were replicated in a genome-wide association study of...
Preprint
Full-text available
As high-throughput genomics assays become more efficient and cost effective, their utilization has become standard in large-scale biomedical projects. These studies are often explorative, in that relationships between samples are not explicitly defined a priori , but rather emerge from data-driven discovery and annotation of molecular subtypes, the...
Article
Full-text available
Protein-protein interaction (PPI) databases are an important bioinformatics resource, yet existing literature-curated databases usually represent cell-type-agnostic interactions, which is at variance with our understanding that protein dynamics are context specific and highly dependent on their environment. Here, we provide a resource derived throu...
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Full-text available
s> Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11 and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the ad...
Conference Paper
Single-cell RNA-seq (scRNA-seq) is an emerging platform for high-throughput profiling of individual cells in a sample and is routinely employed to investigate the transcriptional landscapes of the cellular constituents of tumors. To this end, many scRNA-seq specific clustering algorithms have emerged to analytically partition cells into modules of...
Conference Paper
Head and neck squamous cell carcinoma (HNSCC) is associated with high morbidity, poor survival rates, and limited treatment options. We previously reported that aberrant activation of nuclear β-catenin/cAMP-responsive element binding (CREB)-binding protein (CBP) signaling in primary HNSCC tumors was associated with progression to advanced disease a...
Conference Paper
Head and neck squamous cell carcinoma (HNSCC) is a pernicious malignancy that arises from populations of cancer stem cells (CSCs). We and others have shown that the Wnt/β-catenin signaling pathway drives CSC gene expression mediated, in part, by epigenetic alterations directed by interactions between nuclear β-catenin and the cAMP-responsive elemen...
Conference Paper
Aberrant activation of the DPAGT1 gene, encoding an essential enzyme in the metabolic pathway of protein N-glycosylation, has been shown to be associated with head and neck squamous cell carcinoma (HNSCC). We have shown that DPAGT1 inhibits intercellular adhesion and functions in a positive feedback loop with Wnt/β-catenin signaling, and that the n...
Conference Paper
Head and neck squamous cell carcinoma (HSCC) is the sixth most common malignancy in the world with oral squamous cell carcinomas (OSCC) accounting for the majority of HSCC cases. A major driver of OSCC is the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK) with 12 -glycosylation sites. Fucosylated -linked glycans on EGFR a...
Preprint
Full-text available
Background Microbial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visua...
Preprint
Full-text available
Background: Microbial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visu...
Preprint
Full-text available
Background: Microbial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visu...
Article
Epidermal growth factor receptor (EGFR) is a major driver of head and neck cancer, a devastating malignancy with a major sub-site in the oral cavity manifesting as oral squamous cell carcinoma (OSCC). EGFR is a glycoprotein receptor tyrosine kinase (RTK) whose activity is upregulated in >80 % OSCC. Current anti-EGFR therapy relies on the use of cet...
Conference Paper
The PI3K/AKT signaling pathway is a known oncogenic pathway in breast cancer, involved in essential cellular processes necessary for cancer development and progression, including altered proliferation, metabolism, and cell survival. Mutations in this pathway occur in 20% of all TNBC cases, making it the most deregulated pathway in the only subclass...
Article
Full-text available
A major challenge for cancer immunotherapy is sustaining T-cell activation and recruitment in immunosuppressive solid tumors. Here, we report that the levels of the Hippo pathway effector Yes-associated protein (Yap) are sharply induced upon the activation of cluster of differentiation 4 (CD4)-positive and cluster of differentiation 8 (CD8)-positiv...
Article
Full-text available
The emergence of large-scale multi-omics data warrants method development for data integration. Genomic studies from cancer patients have identified epigenetic and genetic regulators – such as methylation marks, somatic mutations, and somatic copy number alterations (SCNAs), among others – as predictive features of cancer outcome. However, identifi...
Article
Full-text available
The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 2...
Article
Full-text available
Mosaicism, the presence of two or more genotypically or karyotypically distinct populations of cells in a single individual, plays an important role in human disease. Mosaicism can result in mutations and/or chromosomal alterations such as loss, gain, or copy-number neutral loss of heterozygosity. Clonal mosaicism and its relationship to aging and...
Article
Geneset enrichment is a popular method for annotating high-throughput sequencing data. Existing tools fall short in providing the flexibility to tackle the varied challenges researchers face in such analyses, particularly when analyzing many signatures across multiple experiments. We present a comprehensive R package for geneset enrichment workflow...
Article
Motivation: Over the last decade, more diverse populations have been included in genome-wide association studies. If a genetic variant has a varying effect on a phenotype in different populations, genome-wide association studies applied to a dataset as a whole may not pinpoint such differences. It is especially important to be able to identify pop...
Article
Full-text available
B-cell receptor (BCR) signaling pathway components represent promising treatment targets in multiple B-cell malignancies including diffuse large B-cell lymphoma (DLBCL). In in vitro and in vivo model systems, a subset of DLBCLs depend upon BCR survival signals and respond to proximal BCR/phosphoinositide 3 kinase (PI3K) blockade. However, single-ag...
Article
Full-text available
The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late‐onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an exte...
Conference Paper
Head and neck cancer is a debilitating malignancy, with the majority of cases arising in the oral cavity as oral squamous cell carcinoma (OSCC). A major driver of OSCC is the epidermal growth factor receptor (EGFR), whose activity is aberrantly upregulated in >80% of tumors. EGFR is highly modified with -linked glycans; fucosylation of -glycans int...
Conference Paper
Head and neck cancer is a debilitating malignancy, with the majority of cases arising in the oral cavity as oral squamous cell carcinoma (OSCC). A major driver of OSCC is the epidermal growth factor receptor (EGFR), whose activity is aberrantly upregulated in >80% of tumors. EGFR is highly modified with -linked glycans; fucosylation of -glycans int...
Article
Full-text available
The advent of high-throughput sequencing technologies has led to the need for flexible and user-friendly data preprocessing platforms. The Pipeliner framework provides an out-of-the-box solution for processing various types of sequencing data. It combines the Nextflow scripting language and Anaconda package manager to generate modular computational...
Preprint
Geneset enrichment is a popular method for annotating high-throughput sequencing data. Existing tools fall short in providing the flexibility to tackle the varied challenges researchers face in such analyses, particularly when analyzing many signatures across multiple experiments. We present a comprehensive R package for geneset enrichment workflow...
Preprint
Full-text available
A major challenge for cancer immunotherapy is sustaining T cell activation and recruitment in immunosuppressive solid tumors. Here we report that Yap levels are sharply induced upon CD4+ and CD8+ T cell activation and that Yap functions as an immunosuppressive factor and inhibitor of effector differentiation. Loss of Yap results in enhanced T cell...
Article
Full-text available
Background: Most chemicals in commerce have not been evaluated for their carcinogenic potential. The de facto gold-standard approach to carcinogen testing adopts the 2-y rodent bioassay, a time-consuming and costly procedure. High-throughput in vitro assays are a promising alternative for addressing the limitations in carcinogen screening. Object...
Preprint
Full-text available
The emergence of large-scale multi-omics data warrants method development for data integration. Genomic studies from cancer patients have identified epigenetic and genetic regulators – such as methylation marks, somatic mutations, and somatic copy number alterations (SCNAs), among others – as predictive features of cancer outcome. However, identifi...
Article
Full-text available
The need to reduce per sample cost of RNA-seq profiling for scalable data generation has led to the emergence of highly multiplexed RNA-seq. These technologies utilize barcoding of cDNA sequences in order to combine multiple samples into a single sequencing lane to be separated during data processing. In this study, we report the performance of one...
Article
Full-text available
The identification of genetic alteration combinations as drivers of a given phenotypic outcome, such as drug sensitivity, gene or protein expression, and pathway activity, is a challenging task that is essential to gaining new biological insights and to discovering therapeutic targets. Existing methods designed to predict complementary drivers of s...
Preprint
Full-text available
Background: Growing evidence suggests that chemicals in disparate structural classes activate specific subsets of PPARγ's transcriptional programs to generate adipocytes with distinct phenotypes. Objectives: Our objectives were to 1) establish a novel classification method to predict PPARγ interacting and modifying chemicals, and 2) create a taxono...
Preprint
Full-text available
The advent of high-throughput sequencing technologies has led to the need for flexible and user-friendly data pre-processing platforms. The Pipeliner framework provides an out-of-the-box solution for processing various types of sequencing data. It combines the Nextflow scripting language and Anaconda package manager to generate modular computationa...
Article
Full-text available
We used a high-throughput Somascan platform to quantify 4785 proteins in serum of 224 centenarians, offspring, and controls (mean ages: 105, 80, 79) from the New England Centenarian Study, and conducted various analyses to identify protein sets that change with extreme old age. We identified almost 1300 proteins that differed between centenarians,...
Preprint
Full-text available
The need to reduce per sample cost of RNA-seq profiling for scalable data generation has led to the emergence of highly multiplexed RNA-seq. These technologies utilize barcoding of cDNA sequences in order to combine samples into single sequencing lane to be separated during data processing. In this study, we report the performance of one such techn...
Article
Full-text available
Tributyltin (TBT), a peroxisome proliferator-activated receptor γ (PPARγ)/retinoid X receptor (RXR) ligand and founding member of the environmental obesogen chemical class, induces adipocyte differentiation and suppresses bone formation. A growing number of environmental PPARγ ligands are being identified. However, the potential for environmental P...
Article
Full-text available
In the version of this article originally published, some text above the “Tri–nucleotide sequence motifs” label in Fig. 2a appeared incorrectly. The text was garbled and should have appeared as nucleotide codes. Additionally, the labels on the bars in Fig. 2c were not italicized in the original publication. These are gene symbols, and they should h...
Article
Full-text available
In the version of this article originally published, an asterisk was omitted from Fig. 1a. The asterisk has been added to the figure. Additionally, a "NOTCH2" label was erroneously included in Fig. 4a. The label has been removed. The errors have been corrected in the PDF and HTML versions of this article.
Article
Full-text available
Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of thi...
Article
Background: Lung squamous cell carcinoma (SqCC) arises in the epithelial layer of the bronchial airway and is often preceded by the development of premalignant lesions. However, not all premalignant lesions progress to lung SqCC and many will regress spontaneously. Understanding the somatic alterations and molecular subtypes associated with progres...
Article
Head and neck cancer is a debilitating malignancy, with the majority of cases arising in the oral cavity as oral squamous cell carcinoma (OSCC). A major driver of OSCC is the epidermal growth factor receptor (EGFR), whose activity is aberrantly upregulated in >90% of tumors. EGFR is highly modified with N-linked glycans; fucosylation of N-linked gl...