About

Professor Christopher Glass leads the Glass Laboratory at UCSD, where the research focuses on understanding the transcriptional mechanisms that regulate the development and function of macrophages. Macrophages are critical cells involved in immunity and inflammatory diseases. The laboratory's current efforts aim to elucidate the biochemical and biological roles of sequence-specific transcription factors and their associated co-regulators at both gene-specific and genome-wide levels. To achieve this, the lab employs a combination of biochemical, cellular, and genetic model systems, including macrophage-specific knockouts, microarray technologies, massively parallel sequencing, and bioinformatics approaches. These methodologies are used to unravel how specific factors contribute to the development of specialized macrophage functions in immunity and the pathogenesis of inflammatory diseases. The research interests of the Glass Laboratory include investigating enhancer selection and function, particularly how macrophage lineage-determining factors such as PU.1 prime enhancers for subsequent actions of signal-dependent transcription factors like NFkB and members of the nuclear receptor superfamily. The lab also uses genome-wide approaches to define how developmental origin and tissue environment influence macrophage functions in both mouse and human models in health and disease contexts. Additionally, the lab exploits natural genetic variation from different inbred mouse strains as a mutagenesis strategy to define transcription factor networks in macrophages, extending these approaches to understand the effects of natural genetic variation on human disease phenotypes. Furthermore, the laboratory is developing novel machine learning formulations to capture models from multi-omic data related to immune system cells, particularly macrophages. These machine learning models are applied for structure discovery of transcription factor compositions and networks, in silico mutagenesis, and understanding cell fate and signal-driven enhancer selection and function.

Research topics

• Biology
• Genetics
• Cell biology
• Medicine
• Pathology
• Neuroscience
• Computer Science
• Immunology
• Sociology
• Cancer research
• Psychology
• Internal medicine
• Evolutionary biology
• Cognitive science
• Cardiology
• Philosophy
• Epistemology
• Computational biology

Selected publications

• Pathogenic myeloid phenotypes drive disease pathology in a novel human neurohistiocytosis model

  Blood · 2026-03-31

  article

  Innate immunity is increasingly recognized as a driver of neurodegeneration, though pathogenic mechanisms are incompletely understood. Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplastic disorder caused by activating somatic mutations in mitogen-activated protein kinase (MAPK) pathway genes, most commonly BRAFV600E, in myeloid precursors. A subset of LCH patients develop progressive neurodegeneration (LCH-ND). We generated a human induced pluripotent stem cell (iPSC) model from patients with somatic hematologic mosaicism for BRAFV600E. Brain macrophages/microglia from LCH iPSCs exhibit unique disease specific pathogenic features. Stepwise differentiation identified hematopoietic progenitors as hyperproliferative, whereas brain macrophages were apoptosis resistant. Through application of cerebral organoids and a humanized murine xenotransplantation model we identify marked heterogeneity of differentiation potential within clonal BRAFV600E lines in vivo. This model phenocopied human specific phenotypes including dense basal ganglia foci of abnormal macrophages, marked neurodegeneration with astrogliosis, and progressive ataxia. This approach will allow for preclinical testing of therapeutics for LCH-ND.

  PublisherDOI

• Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression

  Immunity · 2025-03-20 · 19 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Genetic variation in the activity of a TREM2–p53 signaling axis determines oxygen-induced lung injury

  Nature Immunology · 2025-07-25 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Macrophage sensing of the acidic milieu: BRD4 condensates in focus

  Life Metabolism · 2025-09-13

  articleOpen accessSenior author
  PublisherDOI

• ChIPseq libraries preparation v1

  2025-04-07 · 1 citations

  preprintOpen access

  ChIP-seq was performed to analyze H3K27ac and H3K27me3 in CTRL and EZH2KO UN-KC6141 cells. Cells were crosslinked, lysed, and sonicated. Chromatin was immunoprecipitated using specific antibodies and Protein G Dynabeads. Libraries were prepared on beads using the NEBNext Ultra II kit, PCR-amplified, size-selected (200–500 bp), and sequenced on HiSeq 4000 or NextSeq 500.

  PublisherOA PDFDOI

• Self-amplifying NRF2–EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer

  Nature Cancer · 2025-06-30 · 7 citations

  articleOpen access
  PublisherOA PDFDOI

• Machine-guided cell-fate engineering

  Cell Reports · 2025-05-17 · 2 citations

  articleOpen access

  The creation of induced pluripotent stem cells (iPSCs) has enabled scientists to explore the function, mechanisms, and differentiation processes of many types of cells. One of the fastest and most efficient approaches is transcription factor (TF) over-expression. However, finding the right combination of TFs to over-express to differentiate iPSCs directly into other cell types is a difficult task. Here, we describe a machine-learning (ML) pipeline, called CellCartographer, that uses chromatin accessibility and transcriptomics data to design multiplex TF pooled-screening experiments for cell-type conversions that then may be iteratively refined. We validate this method by differentiating iPSCs into twelve cell types at low efficiency in preliminary screens and iteratively refine our TF combinations to achieve high-efficiency differentiation for six of these cell types in <6 days. Finally, we functionally characterize iPSC-derived cytotoxic T cells (iCytoTs), regulatory T cells (iTregs), type II astrocytes (iAstIIs), and hepatocytes (iHeps) to validate functionally accurate differentiation.

  PublisherOA PDFDOI

• Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease

  Nature Immunology · 2025-10-22 · 10 citations

  articleOpen access

  MEF2C encodes a transcription factor that is critical in nervous system development. Here, to examine disease-associated functions of MEF2C in human microglia, we profiled microglia differentiated from isogenic MEF2C-haploinsufficient and MEF2C-knockout induced pluripotent stem cell lines. Complementary transcriptomic and functional analyses revealed that loss of MEF2C led to a hyperinflammatory phenotype with broad phagocytic impairment, lipid accumulation, lysosomal dysfunction and elevated basal inflammatory cytokine secretion. Genome-wide profiling of MEF2C-bound sites coupled with the active regulatory landscape enabled inference of its transcriptional functions and potential mechanisms for MEF2C-associated cellular functions. Transcriptomic and epigenetic approaches identified substantial overlap with idiopathic autism datasets, suggesting a broader role of human microglial MEF2C dysregulation in idiopathic autism. In a mouse xenotransplantation model, loss of MEF2C led to morphological, lysosomal and lipid abnormalities in human microglia in vivo. Together, these studies reveal mechanisms by which reduced microglial MEF2C could contribute to the development of neurological diseases.

  PublisherOA PDFDOI

• CCL26 and CXCL12 preserve insulin-sensitizing macrophages in subcutaneous adipose tissue in obesity

  Cell Reports · 2025-10-01 · 1 citations

  articleOpen access

  Unlike visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) can protect against insulin resistance and metabolic dysfunction in obesity. Here, we show that, in obesity, subcutaneous adipose tissue macrophages (ATMs) release small extracellular vesicles (sEVs) that can improve insulin sensitivity, opposite to the effect of visceral ATM sEVs. This functional difference is associated with an increase in the proportion of insulin-sensitizing, resident ATMs in SAT. In vivo and in vitro measurements of ATM growth and trafficking combined with single-cell RNA sequencing revealed that higher resident ATM survival and lower blood monocyte immigration along with decreased transition to pro-inflammatory ATMs collectively lead to the relative abundance of resident ATMs in SAT in obesity. These changes are mediated by CCL26 derived from subcutaneous adipocytes and adipocyte progenitors and CXCL12 secreted from resident ATMs. Our results elucidate previously unknown mechanisms for how SAT retains protective functions against metabolic dysfunction in obesity.

  PublisherOA PDFDOI

• Global human myeloid replacement with peripheral progenitors induces interferonopathy and neurodegeneration

  Research Square · 2025-10-03 · 1 citations

  preprintOpen access
  PublisherOA PDFDOI

Recent grants

• Mechanisms controlling human microglia gene expression

  NIH · $4.3M · 2016–2026

• NIH Grant U19DK062434

  NIH · $51.6M · 2012

• Gene Networks controlling macrophage-adipocyte interactions in insulin

  NIH · $33.0M · 2007–2018

• NIH Grant R01CA052599

  NIH · $6.7M · 2011

• NIH Grant P50HL014197

  NIH · $22.0M · 1997

Frequent coauthors

• Michael G. Rosenfeld

  University of California, San Diego

  244 shared

• David W. Rose

  The University of Texas at Tyler

  73 shared

• Mitchell A. Lazar

  University of Pennsylvania

  59 shared

• Johannes C. M. Schlachetzki

  University of California, San Diego

  56 shared

• Frank J. Gonzalez

  Colciencias

  55 shared

• Liliane Michalik

  University of Lausanne

  53 shared

• Johan Auwerx

  École Polytechnique Fédérale de Lausanne

  52 shared

• Christopher Benner

  University of California, San Diego

  52 shared

Education

• Ph.D., Molecular Biology

  University of California, San Diego

  1990

• B.S., Biology

  University of California, San Diego

  1985