John Greally

John Greally
Albert Einstein College of Medicine | AECOM · Department of Genetics

Doctor of Medicine

About

373
Publications
29,174
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Publications

Publications (373)
Preprint
Environmental obesogens are being studied for their potential role in the increasing prevalence of obesity globally. A major focus in this field of research has been on the mechanism by which these agents act. In this study we focused on the obesogenic organotin tributyltin (TBT), which is believed to act by binding to the PPAR𝛾 nuclear receptor in...
Article
Full-text available
Vitamin D, a fat-soluble vitamin, plays a critical role in calcium homeostasis, the immune system, and normal development. Many epidemiological cohort studies globally have found high prevalence rates of vitamin D deficiency and insufficiency, recognized as an important health issue that needs to be solved. In particular, reproductive age and pregn...
Article
Full-text available
Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger,...
Article
Background and Aims Individuals of African (AFR) ancestry have a higher incidence of colorectal cancer (CRC) than those of European (EUR) ancestry and exhibit significant health disparities. Previous studies have noted differences in the tumor microenvironment between AFR and EUR patients with CRC. However, the molecular regulatory processes that u...
Article
Full-text available
Background Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized mate...
Article
Full-text available
Background: While the current national prevalence rate of vitamin A deficiency (VAD) is estimated to be less than 1%, it is suggested that it varies between different ethnic groups and races within the U.S. We assessed the prevalence of VAD in pregnant women of different ethnic groups and tested these prevalence rates for associations with the vita...
Article
Full-text available
The Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) is becoming popular in the neuroscience field where chromatin regulation is thought to be involved in neurodevelopment, activity-dependent gene regulation, hormonal and environmental responses, and pathophysiology of neuropsychiatric disorders. The advantages of using ATAC-seq...
Article
Full-text available
Background In genomics, we often assume that continuous data, such as gene expression, follow a specific kind of distribution. However we rarely stop to question the validity of this assumption, or consider how broadly applicable it may be to all genes that are in the transcriptome. Our study investigated the prevalence of a range of gene expressio...
Preprint
Full-text available
Detection of DNA cytosine modifications such as 5-methylcytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) is essential for understanding the epigenetic changes that guide development, cellular lineage specification, and disease. The wide variety of approaches available to interrogate these modifications has created a need for harmonized materials,...
Article
Hematological malignancies are an aggregate of diverse populations of cells that arise following a complex process of clonal evolution and selection. Recent approaches have facilitated the study of clonal populations and their evolution over time across multiple phenotypic cell populations. In this review, we present current concepts on the role of...
Article
Full-text available
Background: Endometrial cancer (EC) is the most common gynecologic cancer in women, and the incidence of EC has increased by about 1% per year in the U. S over the last 10 years. Although 5-year survival rates for early-stage EC are around 80%, certain subtypes of EC that lose nuclear hormone receptor (NHR) expression are associated with poor surv...
Article
Dynamic histone changes occur as a central part of chromatin regulation. Deposition of histone variants and post-translational modifications of histones are strongly associated with properties of chromatin status. Characterizing the kinetics of histone variants allows important insights into transcription regulation, chromatin maintenance and other...
Preprint
Full-text available
Vitamin A is an essential micronutrient that plays critical roles in many biological functions of the body. Limited access to vitamin A-rich food or supplements severely affects tissue and blood levels of vitamin A. Therefore, low serum vitamin A and poverty levels are strongly associated in vitamin A deficiency (VAD) studies that have focused main...
Preprint
Full-text available
Vitamin A is an essential micronutrient that plays critical roles in many biological functions of the body. Limited access to vitamin A-rich food or supplements severely affects tissue and blood levels of vitamin A. Therefore, low serum vitamin A and poverty levels are strongly associated in vitamin A deficiency (VAD) studies that have focused main...
Preprint
Full-text available
Background Vitamin A is an essential micronutrient that plays critical roles in many biological functions of the body. The current national prevalence rate of vitamin A deficiency (VAD) in the United States is reported to be very low (<1%). However, our recent study in an urban city of the U. S. (the Bronx study) revealed that pregnant women in the...
Preprint
Full-text available
The Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) is becoming increasingly popular in the neuroscience field where chromatin regulation is thought to be involved in neurodevelopment, activity-dependent gene regulation, hormonal and environmental responses, and the pathophysiology of neuropsychiatric disorders. The advantages o...
Article
The CRISPR-Cas9 system can be modified to perform "epigenetic editing" by utilizing the catalytically inactive (dead) Cas9 (dCas9) to recruit regulatory proteins to specific genomic locations. In prior studies, epigenetic editing with multimers of the transactivator VP16 and guide RNAs (gRNAs) was found to cause adverse cellular responses. These si...
Article
Rationale: Obesity-related asthma disproportionately affects minority children, and is associated with non-atopic T helper (Th) 1 polarized inflammation that correlates with pulmonary function deficits. Its underlying mechanisms are poorly understood. Objectives: Utilize functional genomics to identify cellular mechanisms associated with non-ato...
Article
Full-text available
High-Throughput Sequencing can enhance the analysis of aptamer libraries generated by the Systematic Evolution of Ligands by EXponential enrichment (HTS-SELEX). Robust analysis of the resulting sequenced rounds is best implemented by determining a ranked consensus of reads following the processing by multiple aptamer detection algorithms. Whilst se...
Preprint
Full-text available
The CRISPR/Cas9 system can be modified to perform 'epigenetic editing' by utilizing the catalytically-inactive (dead) Cas9 (dCas9) to recruit regulatory proteins to specific genomic locations. In prior studies, epigenetic editing with multimers of the transactivator VP16 and guide RNAs (gRNAs) was found to cause adverse cellular responses. These si...
Article
Full-text available
Profound global loss of DNA methylation is a hallmark of many cancers. One potential consequence of this is the reactivation of transposable elements (TEs) which could stimulate the immune system via cell-intrinsic antiviral responses. Here, we develop REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing...
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
Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with ov...
Article
Full-text available
While human lymphoblastoid cell lines represent a valuable resource for population genetic studies, they have usually been regarded as difficult for CRISPR-mediated genomic editing because of very inefficient DNA transfection and retroviral or lentiviral transduction in these cells, which becomes a substantial problem when multiple constructs need...
Article
Full-text available
Functional variants in the genome are usually identified by their association with local gene expression, DNA methylation or chromatin states. DNA sequence motif analysis and chromatin immunoprecipitation studies have provided indirect support for the hypothesis that functional variants alter transcription factor binding to exert their effects. In...
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
The MLL3 gene has been shown to be recurrently mutated in many malignancies including in families with acute myeloid leukemia. We demonstrate that many MLL3 variant calls made by exome sequencing are false positives due to misalignment to homologous regions, including a region on chr21, and can only be validated by long-range PCR. Numerous other re...
Article
Full-text available
Male and female brains differ significantly in both health and disease, and yet the female brain has been understudied. Sex-hormone fluctuations make the female brain particularly dynamic and are likely to confer female-specific risks for neuropsychiatric disorders. The molecular mechanisms underlying the dynamic nature of the female brain structur...
Article
Full-text available
Background Numerical chromosomal variation is a hallmark of populations of malignant cells. Identifying the factors that promote numerical chromosomal variation is important for understanding mechanisms of carcinogenesis. However, the ability to quantify and visualize differences in chromosome number between experimentally-defined groups (e.g. cont...
Article
Full-text available
The heritability of chromatin states through cell division is a potential contributor to the epigenetic maintenance of cellular memory of prior states. The macroH2A histone variant has properties of a regulator of epigenetic cell memory, including roles controlling gene silencing and cell differentiation. Its mechanisms of regional genomic targetin...
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...
Article
Full-text available
Cell subtype proportion variability between samples contributes significantly to the variation of functional genomic properties such as gene expression or DNA methylation. Although the impact of the variation of cell subtype composition on measured genomic quantities is recognized, and some innovative tools have been developed for the analysis of h...
Data
A correlation heatmap of the principal components (PCs). The PC of variation in cell subtype proportions (y axis) are correlated with the PCs for gene expression (x axis) in a study of asthma. In particular, the first and second PCs of cell subtype proportions are significantly associated with the PCs of gene expression. The PCs selected for adjust...
Data
Deconvolution of cell subtype proportions from gene expression profiles of SLE patients and healthy control. (a) The estimated cell subtype proportions using gene expression status. A boxplot showed that proportions of T-cells regulatory and monocytes were significantly increased and NK-cells resting was decreased in SLE patient. The significance w...
Data
A list of differentially expressed genes without cell subtype proportion adjustment (Healthy-Severe Asthma). (XLSX)
Data
Contributions of each cell type for top 5 principal components obtained by PCA on variation of the expression profiles (PC-ex). (XLSX)
Data
A list of differentially expressed genes with cell subtype proportion (actual cell proportion) adjustment (Healthy-Severe Asthma). (XLSX)
Data
Lists of cell subtype proportion adjustment eliminated genes and newly identified genes. (XLSX)
Data
A list of differentially expressed genes with PCs (PC1-PC5 and PC9) of cell subtype proportion adjustment (Healthy-Severe Asthma). (XLSX)
Data
A list of cell type-specific gene from PBMC scRNA-seq data. (XLSX)
Data
A list of known reference gene expression profile of each cluster and the cell type estimate. (XLSX)
Data
Lists of differentially genes in LUPUS patients before and after the cell subtype proportion adjustment (PC-ces). (XLSX)
Data
A list of cell type specific genes in e14.5 mouse kidney. (XLSX)
Data
Surrogate variable analysis. (PDF)
Data
Lists of differentially methylated CpG site in LUPUS patients before and after the cell subtype proportion adjustment (PC-ces). (XLSX)
Data
Quality checks, preprocessing and estimating cells subtype proportions. (PDF)
Data
Generating an e14.5 mouse kidney signature profile from single cell RNA-seq results. (PDF)
Preprint
Full-text available
In genomics, we often impose the assumption that gene expression data follows a specific distribution. However, rarely do we stop to question this assumption or consider its applicability to all genes in the transcriptome. Our study investigated the prevalence of genes with expression distributions that are non-Normal in three different tumor types...
Article
Full-text available
Background: Oncogenes promote the development of therapeutic targets against subsets of cancers. Only several hundred oncogenes have been identified, primarily via mutation-based approaches, in the human genome. Transcriptional overexpression is a less-explored mechanism through which oncogenes can arise. Methods: Here, a new statistical approac...
Article
Although ccRCC has been shown to have widespread aberrant cytosine methylation and loss of hydroxymethylation (5hmC), the prognostic impact and therapeutic targeting of this epigenetic aberrancy has not been fully explored. Analysis of 576 primary ccRCC samples demonstrated that loss of 5hmC was significantly associated with aggressive clinicopatho...
Preprint
Motivation Aberrations in chromosomal copy number are one of the most common molecular features observed in cancer. Quantifying the degree of numerical chromosomal variation in single cells across a population of cells is of interest to researchers studying whole chromosomal instability (W-CIN). W-CIN, a state of high numerical chromosomal variatio...
Preprint
Full-text available
High-Throughput Sequencing can enhance the analysis of aptamer libraries generated by the Systematic Evolution of Ligands by EXponential enrichment (HTS-SELEX). Robust analysis of the resulting sequenced rounds is best implemented by determining a ranked consensus of reads following the processing by multiple aptamer detection algorithms. Whilst se...
Article
Key Points We have generated allele-specific base resolution methylomes of primary basophilic erythroblasts. DNA demethylation during differentiation of HSPC into BasoE occurs mostly in inactive regions causing formation of PMD in 74% of methylome.
Article
Full-text available
DNA methylation patterns in the genome both reflect and help to mediate transcriptional regulatory processes. The digital nature of DNA methylation, present or absent on each allele, makes this assay capable of quantifying events in subpopulations of cells, whereas genome-wide chromatin studies lack the same quantitative capacity. Testing DNA methy...
Preprint
Profound loss of DNA methylation is a well-recognized hallmark of cancer. Given its role in silencing transposable elements (TEs), we hypothesized that extensive TE expression occurs in tumors with highly demethylated DNA. We developed REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The C...
Preprint
Full-text available
While lymphoblastoid cell lines (LCLs) represent a valuable resource for population genetic studies, they are usually regarded as difficult for CRISPR-mediated genomic editing. It would be valuable to be able to take the results of their functional variant studies and test them in the same LCLs. We describe a protocol using a single-stranded donor...
Article
Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexp...
Article
Epigenetic changes in cancer are thought to contribute to the regulation of invasion and metastasis. To study this at a genome-wide level in melanoma, we analyzed the methylome of 44 cases of malignant melanoma. We saw widespread demethylation occurring preferentially outside of CpG islands. Comparison of primary and metastatic lesions showed demet...
Preprint
Full-text available
The heritability of chromatin states through cell division is a potential contributor to the epigenetic maintenance of cellular memory of prior states. The macroH2A histone variant has properties of a regulator of epigenetic cell memory, including roles controlling gene silencing and cell differentiation. Its mechanisms of regional genomic targetin...
Chapter
Here we describe a method for genome wide investigation of methylation and hydroxymethylation status of cytosines. This protocol is an improvement of the HELP-tagging protocol previously described by Suzuki et al. It involves the glucosylation of 5-hydroxymethylcytosines (5-hmC) with β-glucosyl transferase (β-GT), thus rendering them resistant to d...
Article
Full-text available
Current approaches to detect and characterize mosaic chromosomal aneuploidy are limited by sensitivity, efficiency, cost or the need to culture cells. We describe the mosaic aneuploidy detection by massively-parallel sequencing (MAD-seq) capture assay and the MADSEQ analytical approach that allow low (<10%) levels of mosaicism for chromosomal aneup...
Article
Full-text available
Background: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the...