A5000121808- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Medical Imaging and Pathology Studies
- Lung Cancer Treatments and Mutations
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Radiomics and Machine Learning in Medical Imaging
- Genetic factors in colorectal cancer
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Fungal and yeast genetics research
- Prostate Cancer Treatment and Research
- Mast cells and histamine
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Eosinophilic Disorders and Syndromes
- Eosinophilic Esophagitis
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Genomics and Chromatin Dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- Genetic Associations and Epidemiology
Foundation Medicine (United States)
2018-2025
Boston Foundation
2025
Veracyte (United States)
2025
Decipher Biosciences (Canada)
2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2011-2021
Computational Physics (United States)
2021
Navidea Biopharmaceuticals (United States)
2020
University of Ottawa
2018
Pfizer (United States)
2003-2011
Harvard University
1998-2000
The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 humans are unknown. We identified germline heterozygous subjects with severe dysregulation from four unrelated families. Whereas Ctla4 mice have no obvious phenotype, human haploinsufficiency caused FoxP3(+) regulatory (Treg) cells, hyperactivation effector and lymphocytic infiltration target organs. Patients also exhibited progressive loss circulating B...
Trafficking from bedside to bench Typically in translational research, a discovery cell or molecular biology is later exploited improve patient care. Occasionally, information flows the opposite direction. Lo et al. found that patients with an autoimmune disorder caused by deficiency of protein called LRBA responded dramatically drug abatacept (see Perspective Sansom). Abatacept contains segment potent inhibitory immune receptor, CTLA4. Experiments prompted this observation revealed...
As availability of precision therapies expands, a well-validated circulating cell-free DNA (cfDNA)-based comprehensive genomic profiling assay has the potential to provide considerable value as complement tissue-based testing ensure potentially life-extending are administered patients most likely benefit. Additional data supporting clinical validity cfDNA-based is necessary inform optimal use these assays in clinic. The FoundationOne®Liquid CDx pan-cancer that was recently approved by FDA....
Class IA phosphatidylinositol 3-kinases (PI3K), which generate PIP3 as a signal for cell growth and proliferation, exist an intracellular complex of catalytic subunit bound to regulatory subunit. We others have previously reported that heterozygous mutations in PIK3CD encoding the p110δ PI3K cause unique disorder termed p110δ-activating causing senescent T cells, lymphadenopathy, immunodeficiency (PASLI) disease. report four patients from three families with similar disease who harbor...
Genomic profiling of circulating tumor DNA derived from cell-free (cfDNA) in blood can provide a noninvasive method for detecting genomic biomarkers to guide clinical decision making cancer patients. We developed hybrid capture–based next-generation sequencing assay (FoundationACT). High-sequencing coverage and molecular barcode–based error detection enabled accurate alterations, including short variants (base substitutions, insertions/deletions) re-arrangements at low allele frequencies...
Abstract Purpose: Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect genomics, or it be a false that would clarified by tissue testing. method distinguishing between these scenarios could help clarify when follow-on testing valuable. Experimental Design: Here we evaluate circulating DNA (ctDNA) fraction (TF), quantification ctDNA in LBx samples, utility identifying true We assessed concordance and...
Protein interfaces are thought to be distinguishable from the rest of protein surface by their greater degree residue conservation. We test validity this approach on an expanded set 64 protein-protein using conservation scores derived two multiple sequence alignment types, one close homologs/orthologs and diverse homologs/paralogs. Overall, we find that interface is slightly more conserved than when either type, with alignments homologs showing marginally better discrimination. However, a...
Regulatory motifs can be found by local multiple alignment of upstream regions from coregulated sets genes, or regulons. We searched for regulatory using the program AlignACE together with a set filters that helped us choose most likely to biologically relevant in 17 complete microbial genomes. potentially genes grouped three methods: (1) make up functional pathways; (2) homologous regulons well-studied species ( Escherichia coli ); and (3) groups derived conserved operons. This last group...
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied child with life-threatening, recurrent respiratory tract infections, caused by viruses human rhinovirus (HRV), influenza virus, syncytial virus (RSV). identified in her homozygous missense mutation IFIH1 that encodes MDA5. Mutant was expressed but did not recognize the synthetic agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant failed to drive...
Nonimmunological connective tissue phenotypes in humans are common among some congenital and acquired allergic diseases. Several of these disorders have been associated with either increased TGF-β activity or impaired STAT3 activation, suggesting that pathways might intersect their disruption may contribute to atopy. In this study, we show negatively regulates signaling via ERBB2-interacting protein (ERBIN), a SMAD anchor for receptor activation SMAD2/3 binding protein. Individuals dominant-negative
Small interfering RNAs (siRNAs) are routinely used to reduce mRNA levels for a specific gene with the goal of studying its function. Several studies have demonstrated that siRNAs not always and can many off-target effects. The 3′ UTRs mRNAs often enriched in sequences complementary seed-region siRNA. We demonstrate siRNA off-targets be significantly reduced when cells treated dose is relatively low (e.g. 1 nM), but sufficient effectively silence intended target. reduction was both modified...
PFRED a software application for the design, analysis, and visualization of antisense oligonucleotides siRNA is described. The provides an intuitive user-interface scientists to design library or that target specific gene interest. Moreover, tool facilitates incorporation various criteria have been shown be important stability potency. has made available as open-source project so code can easily modified address future needs oligonucleotide research community. A compiled version downloading...
201 Background: VOPis an algorithm that predicts the cellular origin of variants, currently available on FoundationOneLiquid CDx (F1LCDx) for research use only. IMbassador250 (IM250, NCT03016312) is a completed phase III trial evaluated safety and efficacy atezolizumab in combination with enzalutamide men mCRPC who had prior progression abiraterone. Here, we prediction accuracy demonstrated clinical validity VOP IM250 samples. We hypothesized excluding predicted CH variants from maximum...
221 Background: CH results from fitness-enhancing mutations in hematopoietic stem cells that accumulate with age. Deep sequencing of LBx, a standard care for guiding therapy selection advanced PCa, can be confounded by sensitive detection variants (vars) arising both ctDNA and CH-derived DNA. Here we report the prevalence vars PCa other cancers describe an algorithmic method accurately distinguishing tumor signal, even at low variant allele frequencies (VAF). Methods: Plasma cell-free DNA...