A5003767361- Immune responses and vaccinations
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Immune Response and Inflammation
- Diabetes and associated disorders
- Epigenetics and DNA Methylation
- Sepsis Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Neonatal Respiratory Health Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Mesenchymal stem cell research
- COVID-19 Impact on Reproduction
- Glycogen Storage Diseases and Myoclonus
- Phagocytosis and Immune Regulation
- Advanced biosensing and bioanalysis techniques
- Streptococcal Infections and Treatments
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Milk Quality and Mastitis in Dairy Cows
- Cytomegalovirus and herpesvirus research
- Retinoids in leukemia and cellular processes
- Biomedical Research and Pathophysiology
- Hydrogen's biological and therapeutic effects
Cincinnati Children's Hospital Medical Center
2023-2024
Baylor College of Medicine
2019-2024
Texas Children's Hospital
2021-2023
University of Missouri
2014-2017
Abstract Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing transcriptomes and epitopes sequencing (CITE-seq) enables coupled surface protein transcriptome profiling, thereby revealing genomic programs underlying states. To perform CITE-seq systematically on primary bone marrow cells, we used titrations with 266 antibodies (antibody-derived tags) machine learning to optimize a panel 132 antibodies....
New therapeutic strategies to reduce sepsis-related mortality are urgently needed, as sepsis accounts for one in five deaths worldwide. Since hematopoietic stem and progenitor cells (HSPCs) responsible producing blood immune cells, including response immunological stress, we explored their potential treating sepsis. In a mouse model of Group A Streptococcus (GAS)-induced sepsis, severe stress was associated with significant depletion bone marrow HSPCs within approximately 5–7 days. We...
Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called "trained immunity." However, the specificity cell types responsible for this response remain poorly defined. We established model of trained immunity in mice Mycobacterium avium infection. scRNA-seq analysis revealed HSPCs activate interferon gamma-response genes heterogeneously primary while rare populations...
Basic leucine zipper ATF-like transcription factor 2 (BATF2), an interferon-activated immune response regulator, is a key responsible for myeloid differentiation and depletion of HSC during chronic infection. To delineate the mechanism BATF2 function in HSCs, we assessed Batf2 KO mice infection found that they produced less pro-inflammatory cytokines, cell recruitment to spleen, impaired with better preservation capacity compared WT. Co-IP analysis revealed forms complex JUN amplify...
The enzyme phosphoglucomutase 1 (PGM1) plays a central role in glucose homeostasis. Clinical studies have identified mutations human PGM1 as the cause of deficiency, an inherited metabolic disease. One residue, Asp263, has two known variants associated with disease: D263G and D263Y. Biochemical shown that these mutants are soluble well folded, but significant catalytic impairment. To better understand this defect, we determined crystal structures missense variants, both which reveal similar...
Acute myeloid leukemia (AML) is a multi-clonal disease, existing as milieu of clones with unique but related genotypes initiating acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the evolution that occurs patients undergo therapy. To interrogate evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32