Colin Farrell

Colin Farrell
UCLA · Department of Human Genetics

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40
Publications
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749
Citations

Publications

Publications (40)
Article
Full-text available
Epigenetic clocks, DNA methylation-based predictive models of chronological age, are often utilized to study aging associated biology. Despite their widespread use, these methods do not account for other factors that also contribute to the variability of DNA methylation data. For example, many CpG sites show strong sex-specific or cell-type-specifi...
Article
Background and Aims Extracellular vesicles (EVs) secreted by cardiosphere-derived cells exert immunomodulatory effects through the transmission of small non-coding RNAs. Methods The mechanism and role of yREX3, a small Y RNA abundant in EVs in myocardial injury, was investigated. Results yREX3 attenuates cardiac ischaemic injury by selective DNA...
Article
Full-text available
Epigenetic clocks are DNA methylation-based chronological age prediction models that are commonly employed to study age-related biology. The difference between the predicted and observed age is often interpreted as a form of biological age acceleration, and many studies have measured the impact of environmental and disease-associated factors on epi...
Preprint
Full-text available
Epigenetic clocks, DNA methylation based predictive models of chronological age, are often utilized to study aging associated biology. Despite their widespread use, these methods do not account for other factors that also contribute to the variability of DNA methylation data. For example, many CpG sites show strong sex-specific or cell type specifi...
Article
Full-text available
Ecophysiologists have reported a range of relationships, including intrinsic trade‐offs across and within species between plant relative growth rate in high resource conditions (RGR) vs adaptation to tolerate cold or arid climates, arising from trait‐based mechanisms. Few studies have considered ecotypes within a species, in which the lack of a tra...
Article
Full-text available
Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF...
Article
Unlike genomes, which are static throughout the lifespan of an organism, DNA methylomes are dynamic. To study these dynamics, we developed quantitative models that measure the effect of multiple factors on DNA methylomes including, age, sex, weight, and genetics. We conducted our study in canids, which prove to be an ideal species to assess epigene...
Article
Full-text available
In eucaryotic cells, intron lariats produced by the spliceosome contain a 2'5' phosphodiester linkage. The RNA lariat debranching enzyme, Dbr1, is the only enzyme known to hydrolyze this bond. Dbr1 is a member of the metallophosphoesterase (MPE) family of enzymes, and recent X-ray crystal structures and biochemistry data demonstrate that Dbr1 from...
Article
Full-text available
Species that hibernate generally live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor–arousal cycles occur multiple times during hibernation, and it has been suggested that process...
Article
Full-text available
Immune cell-type composition changes with age, potentially weakening the response to infectious diseases. Profiling epigenetics marks of immune cells can help us understand the relationship with disease severity. We therefore leveraged a targeted DNA methylation method to study the differences in a cohort of pneumonia patients (both COVID-19 positi...
Article
Full-text available
DNA methylation modulates telomere function. In Arabidopsis thaliana, telomeric regions have a bimodal chromatin organization with unmethylated telomeres and methylated subtelomeres. To gain insight into this organization we have generated TAIR10-Tel, a modified version of the Arabidopsis reference genome with additional sequences at most chromosom...
Article
Full-text available
The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow with age. In this study, we use pseudotime analysis to determine the functional form of these trajectories. Unlike epigenetic clocks that constrain the functional form of met...
Article
Introduction: Breast tissue age, measured with DNA methylation-based estimates, is accelerated in healthy women compared with matched peripheral blood samples. While we have shown that the degree of acceleration in breast epigenetic age is related to hormonal factors including elevated body mass index and earlier age at menarche, no prior work has...
Article
Full-text available
Effective conservation and management of threatened wildlife populations require an accurate assessment of age structure to estimate demographic trends and population viability. Epigenetic aging models are promising developments because they estimate individual age with high accuracy, accurately predict age in related species, and do not require in...
Preprint
Full-text available
The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow. In this study, we use pseudotime analysis to determine these trajectories. Unlike epigenetic clocks that constrain the functional form of methylation changes with time, pseu...
Article
Full-text available
The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that g...
Preprint
Full-text available
Epigenetic clocks, DNA methylation based chronological age prediction models, are commonly employed to study age related biology. The error between the predicted and observed age is often interpreted as a form of biological age acceleration and many studies have measured the impact of environmental and other factors on epigenetic age. Epigenetic cl...
Article
Full-text available
γδ T cells constitute a major portion of lymphocytes in the blood of both ruminants and swine. Subpopulations of swine γδ T cells have been distinguished by CD2 and CD8α expression. However, it was not clear if they have distinct expression profiles of their T-cell receptor (TCR) or WC1 genes. Identifying receptor expression will contribute to unde...
Preprint
Full-text available
Species that hibernate live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor-arousal cycles occur multiple times during hibernation, and it has been suggested that processes control...
Article
Full-text available
Background Bisulfite sequencing is commonly used to measure DNA methylation. Processing bisulfite sequencing data is often challenging owing to the computational demands of mapping a low-complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis-ready methylation matrix from read alignments. To address thes...
Preprint
Full-text available
Five of the seven extant wild species of the genus Equus are species of significant conservation concern. Effective conservation and management of such threatened wildlife populations depends on the ability to estimate demographic trends and population viability and therefore requires accurate assessment of age structure. However, reliably aging wi...
Preprint
Full-text available
Species that hibernate live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor-arousal cycles occur multiple times during hibernation, and it has been suggested that processes control...
Article
Full-text available
Extra-pulmonary manifestations of COVID-19 are associated with a much higher mortality rate. Yet, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2 induced severe systemic toxicity and multi-organ involvement by expressing the human ACE2 transgene in multiple tissues via viral...
Article
Full-text available
Cardiac fibrosis is a pathophysiologic hallmark of the aging heart, but little is known about how fibroblast proliferation and transcriptional programs change throughout the life span of the organism. Using EdU pulse labeling, we demonstrated that more than 50% of cardiac fibroblasts were actively proliferating in the first day of postnatal life. H...
Article
Full-text available
Robust biomarkers of aging have been developed from DNA methylation in humans and more recently, in mice. This study aimed to generate a novel epigenetic clock in rats—a model with unique physical, physiological, and biochemical advantages—by incorporating behavioral data, unsupervised machine learning, and network analysis to identify epigenetic s...
Preprint
Full-text available
Background Bisulfite sequencing is commonly employed to measure DNA methylation. Processing bisulfite sequencing data is often challenging due to the computational demands of mapping a low complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis ready methylation matrix from read alignments. To address th...
Conference Paper
Background: ACT of TCR transgenic T cells recognizing shared tumor antigens is associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated most frequently using a murine stem cell virus (MSCV) gamma retroviral vector....
Article
Transgenic T-cell receptor (TCR) adoptive cell therapies recognizing tumor antigens are associated with robust initial response rates, but frequent disease relapse. This usually occurs in the setting of poor long-term persistence of cells expressing the transgenic TCR, generated using murine stem cell virus (MSCV) γ-retroviral vectors. Analysis of...
Article
Epigenetic rates of change, much as evolutionary mutation rate along a lineage, vary during lifetime. Accurate estimation of the epigenetic state has vast medical and biological implications. To account for these nonlinear epigenetic changes with age, we recently developed a formalism inspired by the Pacemaker model of evolution that accounts for v...
Preprint
Full-text available
Aging has been shown to be a strong driver of DNA methylation changes, leading to the development of robust biomarkers in humans and more recently, in mice. This study aimed to generate a novel epigenetic clock in rats; a model with unique physical, physiological, and biochemical advantages for studying mammalian aging. Additionally, we incorporate...
Article
Full-text available
Human leukocyte antigen (HLA)-independent, T cell–mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR–Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while rem...
Article
Epigenetic changes during aging have been characterized by multiple epigenetic clocks, that allow the prediction of chronological age based on methylation status. Despite their accuracy and utility, epigenetic age biomarkers leave many questions about epigenetic aging unanswered. Specifically, they do not permit the unbiased characterization of non...
Article
Most epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabol...
Preprint
Full-text available
Most epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabol...
Article
In an iron deficient child, oral iron repeatedly failed to improve the condition. Whole exome sequencing identified one previously reported plus two novel mutation in the TMPRSS6 gene, with no mutations in other iron-associated genes. We propose that these mutations result in a novel variety of iron-refractory iron deficiency anemia.
Article
Full-text available
Both familial and sporadic porphyria cutanea tarda (PCT) are iron dependent diseases. Symptoms of PCT resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y, c.843G>A, rs1800562) that enhances iron aborption by reducing hepcidin expression is a risk factor for PCT. Recently, a polymorphic variant (D519G, c.1556A>G...
Article
Symptoms of porphyria cutanea tarda (PCT) resolve when iron stores are depleted by phlebotomy, and a sequence variant of HFE (C282Y) that increases iron absorption by reducing hepcidin expression is a risk factor for PCT. These observations suggest that PCT is an iron dependent disease and that factors that affect iron homeostasis influence the ris...

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