A5011817383- Immune cells in cancer
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Liver Disease Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Nuclear Receptors and Signaling
- Phagocytosis and Immune Regulation
- Adipose Tissue and Metabolism
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Genetics, Aging, and Longevity in Model Organisms
- Liver physiology and pathology
- DNA Repair Mechanisms
- Bioinformatics and Genomic Networks
- S100 Proteins and Annexins
- Heat shock proteins research
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Cancer-related gene regulation
- Liver Diseases and Immunity
- Neurogenesis and neuroplasticity mechanisms
- Chemokine receptors and signaling
University of California, San Diego
2014-2024
University of California, Los Angeles
2013
Ann Arbor Center for Independent Living
2005
University of California, Berkeley
2002
Fred Hutch Cancer Center
2001
Of mice and men's microglia Microglia are immune system cells that function in protecting maintaining the brain. Gosselin et al. examined epigenetics RNA transcripts from single microglial observed consistent profiles among samples despite differences age, sex, diagnosis. Mouse human demonstrated similar microglia-specific gene expression profiles, as well a shared environmental response collected either immediately after surgery (ex vivo) or culturing (in vitro). Interestingly, those genes...
Noncoding genetic variation is a major driver of phenotypic diversity, but functional interpretation challenging. To better understand common associated with brain diseases, we defined noncoding regulatory regions for cell types the human brain. Whereas psychiatric disorders were primarily variants in transcriptional enhancers and promoters neurons, sporadic Alzheimer's disease (AD) largely confined to microglia enhancers. Interactome maps connecting disease-risk cell-type-specific revealed...
In clinical and experimental NASH, the origin of scar-forming myofibroblast is HSC. We used foz/foz mice on a Western diet to characterize in detail phenotypic changes HSCs NASH model.We examined single-cell expression profiles (scRNA sequencing) purified from normal livers chow diet, with fibrosis during regression after switching back diet. Selected genes were analyzed using immunohistochemistry, quantitative real-time PCR, short hairpin RNA knockdown primary mouse HSCs. Our analysis liver...
Abstract Spalt-like transcription factor 1 (SALL1) is a critical regulator of organogenesis and microglia identity. Here we demonstrate that disruption conserved microglia-specific super-enhancer interacting with the Sall1 promoter results in complete specific loss expression microglia. By determining genomic binding sites SALL1 leveraging enhancer knockout mice, provide evidence for functional interactions between SMAD4 required gene expression. binds directly to expression, consistent an...
Microglia phenotypes are highly regulated by the brain environment, but transcriptional networks that specify maturation of human microglia poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes fetal postnatal acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, cerebral organoids, following engraftment into humanized mice. Parallel development computational approaches considered transcription factor (TF)...
The genes encoding Hoxa9 and Meis1 are transcriptionally coactivated in a subset of acute myeloid leukemia (AML) mice. In marrow reconstitution experiments, coexpression both produces rapid AML, while neither gene alone generates overt leukemia. Although can bind DNA as heterodimers, also heterodimerize with Pbx proteins. Thus, their coactivation may result from the necessity to promoters it altering independent biochemical pathways that cooperate generate either monomers or heterodimers...
Homeobox transcription factors Meis1 and Hoxa9 promote hematopoietic progenitor self-renewal cooperate to cause acute myeloid leukemia (AML). While alone blocks the differentiation of nonleukemogenic cell-committed progenitors, coexpression with is required for production AML-initiating which also transcribe a group stem cell genes, including Cd34 Flt3 (defined as Meis1-related leukemic signature genes). Here, we use dominant trans-activating (Vp16 fusion) or trans-repressing (engrailed...
Hoxa9 and Meis1a are homeodomain transcription factors that heterodimerize on DNA down-regulated during normal myeloid differentiation. cooperate to induce acute leukemia (AML) in mice, coexpressed human AML. Despite their cooperativity leukemogenesis, we demonstrated previously retroviral expression of alone—in the absence Meis1 or endogenous Meis genes—blocks neutrophil macrophage differentiation primary progenitors cultured granulocyte–macrophage colony-stimulating factor (GM-CSF)....
Sotos syndrome is a human developmental and cognitive disorder caused by happloinsufficiency of transcription factor NSD1. Similar phenotypes arise from NSD1 gene deletion or point mutations in 9 13 domains, including all 6 PHD indicating that each domain performs an essential role. To gain insight into the biochemical basis syndrome, we tested ability to bind histone H3 when methylated at regulatory sites Lys4, Lys9, Lys27, Lys36, Lys79, H4 Lys20, determined whether disrupted methylation...
Senescence is a prominent solid tumor response to therapy in which cells avoid apoptosis and instead enter into prolonged cell cycle arrest. We applied quantitative proteomics screen identify signals that lead therapy-induced senescence discovered Bcl2-associated athanogene 3 (Bag3) up-regulated after adriamycin treatment MCF7 cells. Bag3 member of the BAG family co-chaperones interacts with Hsp70. also regulates major cell-signaling pathways. Mass spectrometry analysis Complex revealed...
Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, newborns. However, mild can be protective against later, more severe exposure via "hypoxic preconditioning," phenomenon that not yet fully understood. Accordingly, we have established optimized an embryonic zebrafish model to study hypoxic preconditioning. Using functional genomic approach, used this identify validate five novel hypoxia-protective genes, including irs2, crtc3, camk2g2, which been...
Abstract Noncoding genetic variation drives phenotypic diversity, but underlying mechanisms and affected cell types are incompletely understood. Here, investigation of effects natural on the epigenomes transcriptomes Kupffer cells derived from inbred mouse strains identified strain-specific environmental factors influencing phenotypes, including leptin signaling in a steatohepatitis-resistant strain. Cell-autonomous non-cell-autonomous were resolved by analysis F1 hybrid mice engrafted into...
Abstract The structure of the human neocortex underlies species-specific features and is a reflection intricate developmental programs. Here we analyzed neocortical cellular lineages through comprehensive assessment brain somatic mosaicism—which acts as neutral recorder lineage history. We employed deep whole genome variant sequencing in single postmortem neurotypical across 25 anatomic regions three distinct modalities: bulk geographies, sorted cell types, nuclei. identified 259 mosaic...