Richard A. Young
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View article: High‐throughput CRISPR screen of GWAS risk loci in human microglia reveals novel risk genes for Alzheimer's disease and multiple sclerosis
High‐throughput CRISPR screen of GWAS risk loci in human microglia reveals novel risk genes for Alzheimer's disease and multiple sclerosis Open
Background Alzheimer's (AD) and other neurological diseases (NDs) cause substantial health‐related and economic burdens, but progress toward preventative or ameliorative treatments has been limited. Genome‐wide association studies (GWAS) h…
View article: Functional genomic dissection of MS risk loci reveals convergence of cis and trans gene regulatory mechanisms in microglia
Functional genomic dissection of MS risk loci reveals convergence of cis and trans gene regulatory mechanisms in microglia Open
Summary Neurological diseases (NDs) are a major source of unmet medical need, and translational insights have been hampered by complex underlying pathophysiologies and limitations of experimental models. Noncoding single nucleotide polymor…
View article: CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs
CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs Open
Long noncoding RNAs (lncRNAs) are a significant yet largely uncharted component of the cancer transcriptome, with their isoform-specific functions remaining poorly understood. In this study, we employed RNA-targeting CRISPR-Cas13d to uncov…
View article: Epigenomics and single cell CRISPR screening to investigate the risk‐modifying role of microglia in Alzheimer’s disease and multiple sclerosis
Epigenomics and single cell CRISPR screening to investigate the risk‐modifying role of microglia in Alzheimer’s disease and multiple sclerosis Open
Background Alzheimer’s disease (AD) and other neurodegenerative diseases (NDs) cause substantial health‐related and economic burdens, but progress towards preventative or ameliorative treatments has been limited. Genome‐wide association st…
View article: Intellectual Disability (ID) and Chronic Conditions Burden among Adults : Insights from Harmonized Electronic Health Records
Intellectual Disability (ID) and Chronic Conditions Burden among Adults : Insights from Harmonized Electronic Health Records Open
CONTEXT: Adults with intellectual disabilities (ID) are susceptible to chronic conditions, disproportionately experience health disparities, and are less likely to receive optimal primary care management. Studies on adults with ID are scar…
View article: Intensity of medication review activities in private and public clinics
Intensity of medication review activities in private and public clinics Open
CONTEXT: Medication review is an essential part of most office visits. OBJECTIVE: We aimed to compare medication review activities between private and public clinics. STUDY DESIGN: Survey of medication review activities after primary care …
View article: RNA and condensates: Disease implications and therapeutic opportunities
RNA and condensates: Disease implications and therapeutic opportunities Open
Biomolecular condensates are dynamic membraneless organelles that compartmentalize proteins and RNA molecules to regulate key cellular processes. Diverse RNA species exert their effects on the cell by their roles in condensate formation an…
View article: Genetic predisposition to neuroblastoma results from a regulatory polymorphism that promotes the adrenergic cell state
Genetic predisposition to neuroblastoma results from a regulatory polymorphism that promotes the adrenergic cell state Open
Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like mesenchymal cell state and a more differentiated sympathetic adrenergic cell state. These cell states are governed by autoregulatory transcriptional …
View article: Regulatory architecture of housekeeping genes is driven by promoter assemblies
Regulatory architecture of housekeeping genes is driven by promoter assemblies Open
Genes that are key to cell identity are generally regulated by cell-type-specific enhancer elements bound by transcription factors, some of which facilitate looping to distant gene promoters. In contrast, genes that encode housekeeping fun…
View article: Oncogenic <i>CDK13</i> mutations impede nuclear RNA surveillance
Oncogenic <i>CDK13</i> mutations impede nuclear RNA surveillance Open
RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase 13 ( CDK13 ) is mutated in melanoma, and patient-mutated CDK1…
View article: Table S1 from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Table S1 from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma Open
Neuroblastoma Molecular subtypes and clinical information.
View article: Supplementary Data from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Supplementary Data from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma Open
Supplementary Experimental Procedures; Supplementary Figures S1-S10; Supplementary Table Legends S1-S9; Supplementary Tables S8-S9; Additional References
View article: Supplementary Figures 1-10 from Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression
Supplementary Figures 1-10 from Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression Open
Supplementary Figures 1-10 and corresponding legends
View article: Data from TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia
Data from TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia Open
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection–associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic …
View article: Data from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Data from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma Open
High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease…
View article: Table S1 from TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia
Table S1 from TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia Open
Table S1
View article: CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma
CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma Open
Therapeutic targeting of CDK7 has proven beneficial in pre-clinical studies, yet the off-target effects of currently available CDK7 inhibitors make it difficult to pinpoint the exact mechanisms behind MM cell death mediated by CDK7 inhibit…
View article: Genetic Predisposition to Neuroblastoma Results from a Regulatory Polymorphism that Promotes the Adrenergic Cell State
Genetic Predisposition to Neuroblastoma Results from a Regulatory Polymorphism that Promotes the Adrenergic Cell State Open
Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like “mesenchymal” cell state and a more differentiated sympathetic “adrenergic” cell state. These cell states are governed by autoregulatory transcriptio…
View article: Patient Provider Engagement in Family Medicine: A Qualitative Study from the PROMIS Learning Lab
Patient Provider Engagement in Family Medicine: A Qualitative Study from the PROMIS Learning Lab Open
CONTEXT: Patient engagement in family medicine clinics is critical for successful clinical experiences and patient outcomes. Improving patient engagement may lead to increased adherence to medications/treatments and shared decision-making.…
View article: Primary Care Interventions to Improve Medication Safety – A Qualitative Study
Primary Care Interventions to Improve Medication Safety – A Qualitative Study Open
CONTEXT: Many sources state that patients are frequently harmed by lapses in primary care medication safety. OBJECTIVE: We investigated beliefs and actions taken by primary care physicians (PCPs) and their teams to improve medication safet…
View article: Cellular Maturation of Oligodendrocytes is Governed by Transient Gene Melting
Cellular Maturation of Oligodendrocytes is Governed by Transient Gene Melting Open
SUMMARY Pluripotent stem cells (PSCs) provide an unlimited source for generating somatic cell types. However, generating fully mature cells constitutes a bottleneck for realizing their full potential in research and medicine. Here, we repo…
View article: Transcription factors interact with RNA to regulate genes
Transcription factors interact with RNA to regulate genes Open
Summary Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coac…
View article: A MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth
A MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth Open
Long noncoding RNAs (lncRNAs) can drive tumorigenesis and are susceptible to therapeutic intervention. Here, we used a large-scale CRISPR interference viability screen to interrogate cell-growth dependency to lncRNA genes in multiple myelo…