Gabriella C. Reeder
A5073087569- COVID-19 Clinical Research Studies
- Immune cells in cancer
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Immune responses and vaccinations
- Sex and Gender in Healthcare
- Interdisciplinary Research and Collaboration
- Cancer Genomics and Diagnostics
- COVID-19 Impact on Reproduction
- Pregnancy and preeclampsia studies
- Immunotherapy and Immune Responses
- Gut microbiota and health
- Virus-based gene therapy research
- Career Development and Diversity
- Inflammation biomarkers and pathways
- CRISPR and Genetic Engineering
- Reproductive System and Pregnancy
- Respiratory Support and Mechanisms
- Sepsis Diagnosis and Treatment
- Birth, Development, and Health
- Pneumonia and Respiratory Infections
University of California, San Francisco
2020-2025
Gladstone Institutes
2023
Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between mild phenotypes pathology disease 2019 (COVID-19) its origins, we performed whole-blood-preserving single-cell analysis protocol integrate contributions from all major immune cell types blood-including neutrophils, monocytes,...
Precise targeting of large transgenes to T cells using homology-directed repair has been transformative for adoptive cell therapies and biology. Delivery DNA templates via adeno-associated virus (AAV) greatly improved knockin efficiencies, but the tropism current AAV serotypes restricts their use human employed in immunodeficient mouse models. To enable targeted knockins murine cells, we evolved Ark313, a synthetic that exhibits high transduction efficiency cells. We performed genome-wide...
Abstract The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results comparative lower tract transcriptional profiling tracheal aspirate 52 critically ill patients with COVID-19 or etiologies, as well controls without ARDS. In contrast to a “cytokine storm,” observe reduced proinflammatory gene expression in when compared due causes. is characterized by...
The autoimmune regulator (Aire), a well-defined transcriptional in the thymus, is also found extrathymic Aire-expressing cells (eTACs) secondary lymphoid organs. eTACs are hematopoietic antigen-presenting and inducers of immune tolerance, but their precise identity has remained unclear. Here, we use single-cell multiomics, transgenic murine models, functional approaches to define at transcriptional, genomic, proteomic level. We find that consist two similar cell types: CCR7+ migratory...
Gender inequities persist in science, with women encountering significant barriers at various career stages, particularly fields such as Immunology. This article highlights the work of Immunologists for Equity (IgEquity), a trainee-led organization within ImmunoX Program University California, San Francisco (UCSF), which is committed to addressing these disparities. Through initiatives focused on community building, mentorship, outreach and advocacy, IgEquity seeks advance gender equity...
Abstract Dexamethasone is the standard of care for critically ill patients with COVID-19, but mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk single-cell RNA sequencing samples from lower respiratory tract blood, assess plasma cytokine profiling to study dexamethasone on both systemic pulmonary immune cell compartments. In blood samples, associated decreased expression genes T activation, including TNFSFR4...
Intratumoral T cells that might otherwise control tumors are often identified in an "exhausted" state, defined by specific epigenetic modifications and upregulation of genes such as CD38, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PD1). Although the term imply inactivity, there has been little study this state at phenotypic level to understand extent their incapacitation. Starting with observation move more quickly through mouse longer they reside progress...
Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway blood cells from patients with acute lung injury SARS-CoV-2 or other causes across 7 cohorts. This was associated greater clinical severity predicted future mechanical ventilation death.
Abstract While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction COVID-19 pathology, its origins. performed wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes contents serum. Patients with mild disease display coordinated pattern interferonstimulated...
SUMMARY Cancers display significant heterogeneity with respect to tissue of origin, driver mutations and other features the surrounding tissue. It is likely that persistent tumors differentially engage inherent patterns–here ‘Archetypes’–of immune system, both benefit from a tumor microenvironment (TIME) disengage tumor-targeting. To discover dominant system archetypes, Immunoprofiler Initiative (IPI) processed 364 individual across 12 cancer types using standardized protocols. Computational...
Abstract Protein-coding genes in the human genome evolved via modular rearrangement of domains from ancestral 1 . Here, we develop a scalable, evolutionarily guided method to assemble novel protein-coding constituent within protein family, termed DESynR (Domain Engineered Synthesis and Recombination) genes. Using primary chimeric antigen receptor T cells as model system, find that expression Activator Protein-1 (AP-1) transcription factors (TFs) significantly outperforms overexpression...
Abstract The placenta, the first organ to functionally mature, undergoes disordered development in many pregnancy complications. Molecular investigations have been hampered by extreme cellular heterogeneity of and this complexity is further exaggerated at maternal-fetal interface where maternal fetal cells co-mingle. We generated paired single nucleus epigenomes transcriptome for each ∼200,000 human from early term. These data identified cell-type-specific transcriptional regulatory programs...
Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for COVID-19, we comparatively assess longitudinal airway microbiome dynamics and the pulmonary transcriptome patients who developed 2°BP versus controls did not. We find that significantly both mortality corticosteroid treatment. The in characterized by increased RNA mass...
Abstract Intratumoral T cells that might otherwise control tumors are often identified in an ‘exhausted’ state, defined by specific epigenetic modifications as well upregulation of genes such CD38, CTLA-4 and PD-1. While the term imply inactivity, there has been little study this state at phenotypic level to understand extent their incapacitation. Starting with observation move more quickly through mouse residence time increases they progress towards exhaustion, we elaborated a...
Cancers display significant heterogeneity with respect to tissue of origin, driver mutations and other features the surrounding tissue. It is likely that persistent tumors differentially engage inherent patterns–here ‘Archetypes’–of immune system, both benefit from a tumor microenvironment (TIME) disengage tumor-targeting. To discover dominant system archetypes, Immunoprofiler Initiative (IPI) processed 364 individual across 12 cancer types using standardized protocols. Computational...
Abstract While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction COVID-19 pathology, its origins. performed whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes contents serum. Patients with mild disease display coordinated pattern interferon-stimulated...
Abstract The Autoimmune Regulator ( Aire ) gene, well defined for its role in medullary thymic epithelial cells (mTECs) and immune self-tolerance, is also expressed extrathymic -expressing (eTACs) the secondary lymphoid organs. eTACs have been shown to be hematopoietic antigen presenting (APCs) potent inducers of tolerance (1–3). However, precise identity function these remain unclear. Here, we use high-dimensional single-cell multiomics functional approaches define at transcriptional,...