Brooks A. Benard
A5045236493- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
- Multiple Myeloma Research and Treatments
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Cancer-related Molecular Pathways
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Peptidase Inhibition and Analysis
- Hematological disorders and diagnostics
- Hematopoietic Stem Cell Transplantation
- Advanced Biosensing Techniques and Applications
- Immunotherapy and Immune Responses
- Restraint-Related Deaths
Stanford University
2017-2025
Translational Genomics Research Institute
2014-2024
California Institute for Regenerative Medicine
2019-2020
Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Myeloma Research Foundation's Relating Clinical Outcomes in Personal Assessment Genetic Profile study ( NCT01454297 ) longitudinal, observational clinical newly diagnosed patients with multiple (n = 1,143) where samples using whole-genome sequencing, whole-exome sequencing...
Acute myeloid leukemia inhibits normal erythroid differentiation through paracrine effects of IL-6.
Abstract The impact of clonal heterogeneity on disease behavior or drug response in acute myeloid leukemia remains poorly understood. Using a cohort 2,829 patients, we identify features clonality associated with clinical and sensitivities. High variant allele frequency for 7 mutations (including NRAS TET2 ) associate dismal prognosis; elevated GATA2 correlates better outcomes. Clinical such as white blood cell count blast percentage correlate the subclonal abundance TP53 IDH1 . Furthermore,...
Abstract Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The MMRF CoMMpass study longitudinal, observational clinical newly diagnosed multiple patients where samples using whole genome, exome, RNA sequencing at diagnosis progression, data collected every three months. Analyses the baseline cohort identified genes that target...
Abstract The interaction of germline variation and somatic cancer driver mutations is under-investigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) show that rare variants affecting nuclear- mitochondrially-encoded complex I genes near-mutual exclusivity with isocitrate dehydrogenase 1 ( IDH1 ), but not IDH2 suggesting a unique epistatic relationship. Whereas AML cells or all display attenuated respiration, heightened sensitivity to...
Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels a constant yet puzzling feature, as this lacks tyrosine kinase activity. Here, we show the heterodimeric IL3Rα/βc assembles into hexamers dodecamers through unique interface 3D...
Abstract Acute myeloid leukemia (AML) has a poor prognosis and heterogeneous mutation landscape. Although common mutations are well-studied, little research characterized how the sequence of relates to clinical features. Using published, single-cell DNA sequencing data from three institutions, we compared clonal evolution patterns in AML patient characteristics, disease phenotype, outcomes. Mutation trees, which represent order select mutations, were created for 207 patients targeted panel...
Abstract TP53 , the most frequently mutated gene in human cancer, encodes a transcriptional activator that induces myriad downstream target genes. Despite importance of p53 tumor suppression, specific genes important for suppression remain unclear. Recent studies have identified p53-inducible Zmat3 as critical effector but many questions regarding its p53-dependence, activity across contexts, and mechanism alone cooperation with other To address these questions, we used Tuba-seq Ultra...
<p>Key interactions between distinct residues in the IL-3R ternary complex crystal structure.</p>
<p>Key interactions between distinct residues in the IL-3R ternary complex crystal structure.</p>
<p>IL3Rα P248 at the IL-3R assembly interface is critical for cell differentiation.</p>
<p>The IL-3R dodecamer activates STAT1 to induce cell differentiation.</p>
<p>The IL-3R dodecamer activates STAT1 to induce cell differentiation.</p>
<p>Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.</p>
<p>Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.</p>
<p>Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.</p>
<p>Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.</p>
<p>Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in vivo engraftments.</p>
<p>IL3Rα/βc transcript and protein expression ratio in AML patient samples.</p>