Biology subjects

Cohen, M. H.

Publications and source records attributed to Cohen, M. H..

3 recordsLinked to original sources

bioRxiv2026

A single-nucleus multiome analysis of transcriptome and chromatin accessibility reveals cell-type-specific immune modulation for chronic cannabis use among people with HIV infection

As cannabis use continues to rise among people with HIV (PWH), understanding its impact on immune function in this population is becoming increasingly important. To provide new insights on how cannabis modulates immune function, we analyzed single-nucleus multi-omic profiles of peripheral blood mononuclear cells (PBMCs) from PWH to characterize the changes in gene expression and chromatin accessibility associated with chronic cannabis exposure. We identified numerous differentially expressed genes (DEGs) between cannabis users and non-users in each cell type, approximately half of which were unique to individual cell types. Changes in pro- and anti-inflammatory gene expression associated with cannabis use are dependent on cell lineage and type. We identified hundreds of differential chromatin accessibility regions in each cell type, including cis-regulatory elements correlated with cell-type-dependent DEGs (e.g. NFKBIA in CD4+ T cells and CCL3L1 in classical monocytes). Multiple cannabis-associated transcription factors (e.g., NFKB1, FOS, and TCF7) emerge as regulators of the differentially expressed inflammatory genes. Furthermore, cannabis altered the communication between classical monocytes and lymphocytes. These findings indicate that cannabis-induced immunomodulatory effects are profound, dynamic and complex among cell types and that transcriptional changes are regulated at least in part by epigenetic mechanisms.

genomics↗

bioRxiv2023

Cell-type specific EWAS identifies genes involved in HIV pathogenesis andoncogenesis among people with chronic HIV infection

Epigenome-wide association studies (EWAS) of heterogenous blood cells have identified CpG sites associated with chronic HIV infection, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. Applying a computational deconvolution method validated by capture bisulfite DNA methylation sequencing, we conducted a cell type-based EWAS and identified differentially methylated CpG sites specific for chronic HIV infection among five immune cell types in blood: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes in two independent cohorts (Ntotal=1,134). Differentially methylated CpG sites for HIV-infection were highly concordant between the two cohorts. Cell-type level meta-EWAS revealed distinct patterns of HIV-associated differential CpG methylation, where 67% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of HIV-associated CpG sites (N=1,472) compared to any other cell type. Genes harboring statistically significant CpG sites are involved in immunity and HIV pathogenesis (e.g. CX3CR1 in CD4+ T-cells, CCR7 in B cells, IL12R in NK cells, LCK in monocytes). More importantly, HIV-associated CpG sites were overrepresented for hallmark genes involved in cancer pathology (FDR<0.05) (e.g. BCL family, PRDM16, PDCD1LGD, ESR1, DNMT3A, NOTCH2). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis such as Kras-signaling, interferon- and -{gamma}, TNF-, inflammatory, and apoptotic pathways. Our findings are novel, uncovering cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding pathogen-induced epigenetic oncogenicity, specifically on HIV and its comorbidity with cancers.

cancer biology↗

bioRxiv2021

A New Monocyte Epigenetic Clock Reveals Effects of Alcohol Consumption on Epigenetic Aging in Three Independent Cohorts

BackgroundExcessive alcohol consumption increases the risk of aging-related comorbidities and mortality. Assessing the impact of alcohol consumption on biological age is important for clinical decision-making and prevention. Evidence shows that alcohol alters monocyte function, and age is associated with DNA methylome and transcriptomic changes among monocytes. However, no monocyte-based epigenetic clock is currently available. In this study, we developed a new monocyte-based DNA methylation clock (MonoDNAmAge) by using elastic net regularization. The MonoDNAmAge was validated by benchmarking using epigenetic age acceleration (EAA) in HIV infection. Using MonoDNAmAge clock as well as four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on biological aging in three independent cohorts (N=2,242). ResultsMonoDNAmAge, comprised of 186 CpG sites, was highly correlated with chronological age (rtraining=0.96, p<2.20E-16; rtesting=0.86, p=1.55E-141). The MonoDNAmAge clock predicted an approximately 10-year age acceleration from HIV infection in two cohorts. Quadratic regression analysis showed a nonlinear relationship between MonoDNAmAge and alcohol consumption in the Yale Stress Center Community Study (YSCCS, pmodel=4.55E-08, px2 =7.80E-08) and in the Veteran Aging Cohort Study (VACS, pmodel=1.85E-02, px2 =3.46E-02). MonoDNAmAge and light alcohol consumption showed a negative linear relationship in the Womens Interagency HIV Study (WIHS, {beta}=-2.63, px=2.82E-06). Heavy consumption increased EAAMonoDNAmAge up to 1.60 years in the VACS while light consumption decreased EAAMonoDNAmAge to 2.66 years in the WIHS. These results were corroborated by the four established epigenetic clocks. ConclusionsWe observed a nonlinear effect of alcohol consumption on epigenetic age that is estimated by a novel monocyte-based "clock" in three distinct cohorts, highlighting the complex effects of alcohol consumption on biological age.

genomics↗