A5038592699- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Neurobiology and Insect Physiology Research
- Acute Myeloid Leukemia Research
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Genetic factors in colorectal cancer
- Genetic Syndromes and Imprinting
- Ocular Oncology and Treatments
- Cutaneous Melanoma Detection and Management
- Hematopoietic Stem Cell Transplantation
- Zebrafish Biomedical Research Applications
- ATP Synthase and ATPases Research
- Advanced biosensing and bioanalysis techniques
- Genomic variations and chromosomal abnormalities
- Bioinformatics and Genomic Networks
- Immunotherapy and Immune Responses
Princess Margaret Cancer Centre
2019-2024
University of Toronto
2020-2024
University Health Network
2018-2023
University of North Carolina at Chapel Hill
2011-2016
University of California, San Francisco
2009-2014
Harvard University
2002-2005
Massachusetts General Hospital
2001-2004
University of Chicago
1997
Kansas State University
1997
Selection of appropriate oviposition sites is essential for progeny survival and fitness in generalist insect species, such as Drosophila melanogaster, yet little known about the mechanisms regulating how environmental conditions innate adult preferences are evaluated balanced to yield final substrate choice egg-deposition. Female D. melanogaster attracted food containing acetic acid (AA) an substrate. However, our observations reveal that this egg-laying preference a complex process, it...
Prostatic acid phosphatase (PAP) and ecto-5′-nucleotidase (NT5E) hydrolyze extracellular AMP to adenosine in dorsal root ganglia (DRG) neurons the spinal cord. Previously, we found that production was reduced, but not eliminated, <i>Pap</i><sup>−/−</sup>/<i>Nt5e</i><sup>−/−</sup> double knock-out (dKO) mice, suggesting a third ectonucleotidase present these tissues. Here, tissue-nonspecific alkaline (TNAP, encoded by <i>Alpl</i> gene) is expressed functional DRG neurons. Using cell-based...
Purpose Anti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic can function as predictive biomarkers anti-PD1±anti-CTLA4 ICI in patients with advanced Methods performed a single-center retrospective cohort analysis of who received melanoma between 2012 and 2019. Primary type, BRAF...
Polycomb group (PcG) proteins are responsible for stable repression of homeotic gene expression during Drosophila melanogaster development. They thought to stabilize chromatin structure prevent transcription, though how they do this is unknown. We have established an in vitro system which the PcG complex PRC1 and a recombinant core (PCC) containing only able repress transcription by both RNA polymerase II T7 polymerase. find that assembly template into nucleosomes enhances PCC. The subunit...
In both mammalian and insect models of ethanol-induced behavior, low doses ethanol stimulate locomotion. However, the mechanisms stimulant effects on CNS are mostly unknown. We have identified tao , encoding a serine-threonine kinase Ste20 family, as gene necessary for locomotor hyperactivity in Drosophila . Mutations also affect behavioral responses to cocaine nicotine, making flies resistant drugs. show that function is required during development adult nervous system mutations cause...
5′-End fragments of two genes encoding plastid-localized acetyl-CoA carboxylase (ACCase; EC 6.4.1.2 ) wheat ( Triticum aestivum were cloned and sequenced. The sequences the genes, Acc-1,1 Acc-1,2 , are 89% identical. Their exon 98% amino acid sequence biotin domain encoded by is 93% identical with maize plastid ACCase but only 80–84% cytosolic ACCases from other plants wheat. Four overlapping cDNA covering entire coding region PCR ORF contains 2,311 acids a predicted molecular mass 255 kDa....
Polycomb group (PcG) genes propagate patterns of transcriptional repression throughout development.The products several such are part repressive complex 1 (PRC1), which inhibits chromatin remodeling and transcription in vitro.Genetic biochemical studies suggest the product Posterior sex combs (Psc) gene plays a central role both PcG-mediated vivo PRC1 activity vitro.To dissect relationship between vitro activities Psc, we identified lesions associated with 11 genetically characterized Psc...
Topoisomerase 1 (TOP1) inhibitors, including camptothecin and topotecan, covalently trap TOP1 on DNA, creating cleavage complexes (cc's) that must be resolved before gene transcription DNA replication can proceed. We previously found topotecan reduces the expression of long (>100 kb) genes unsilences paternal allele Ube3a in neurons. Here, we sought to evaluate overlap between TOP1cc-dependent -independent regulation To do this, utilized Top1 conditional knockout mice, knockdown, CRISPR-Cas9...
Repression and activation of the expression homeotic genes are maintained by proteins encoded Polycomb group (PcG) trithorax (trxG) genes. Complexes formed these targeted PcG or trxG response elements (PREs/TREs), which share binding sites for several same factors. GAGA factor Zeste bind specifically to PREs/TREs have been shown act as both activators repressors. We used purified complexes reconstituted from recombinant subunits characterize effects on function using a defined in vitro...
Abstract CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed literature-derived evidence characterizing the clinical utility cancer variants. As sequencing becomes more prevalent management, need for variant interpretation has grown beyond capability any single institution. contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally...
Neuronal signal transduction by the JNK MAP kinase pathway is altered a broad array of stimuli including exposure to widely abused drug ethanol, but behavioral relevance and regulation signaling unclear. Here we demonstrate that functions downstream Sterile20 family gene tao/Taok3 regulate effects acute ethanol in both fruit fly Drosophila mice. In flies tao required neurons promote sensitivity locomotor stimulant establish specific brain structures. Reduced expression key genes...
Abstract Leukemia stem cells (LSCs) are linked to relapse in acute myeloid leukemia (AML). The LSC17 gene expression score robustly captures LSC stemness properties AML and can be used predict survival outcomes response therapy, enabling risk-adapted, upfront treatment approaches. was developed validated a research setting. To enable widespread use of the clinical decision making, we established laboratory-developed test (LDT) for that deployed broadly molecular diagnostic laboratories. We...
3104 Background: Oncogenic non-V600E BRAF mts are present in many cancer types. Pre-clinical data indicate that some can be targeted with + MEK inhibitors. The BEAVER trial was designed to test the safety and efficacy of binimetinib encorafenib (B+E) patients (pts) mts. Safety were previously presented [ https://doi.org/10.1016/j.annonc.2021.08.1053 ]. Here, we final analysis exploratory objectives. Methods: Key eligibility criteria were: pts advanced solid tumors activating (Class 1 2) or...
Epidermal Growth Factor Receptor (EGFR) signaling has a conserved role in ethanol-induced behavior flies and mice, affecting sedation both species. However it is not known what other effects EGFR may have on behavior, or roles Tyrosine Kinase (RTK) pathways play ethanol induced behaviors. We examined the of Fibroblast (FGFR) RTK enhancement locomotion, distinct from that be associated with rewarding ethanol. find FGFR genes influence though their are opposite – suppresses this while promotes...
Drosophila tao, encoding a Ste20 family kinase, was identified as gene involved in ethanol, cocaine and nicotine sensitivity. The behavioral phenotypes appear to be caused by defects the development of adult brain. Specifically, tao functions promote axon guidance mushroom body (MB) neurons. MB is large structure central brain fly whose function have been well characterized. interacts genetically with mutations par-1 gene, also serine-threonine kinase. Since Par-1 has implicated regulation...
Drosophila tao, encoding a Ste20 family kinase, was identified as gene involved in ethanol, cocaine, and nicotine sensitivity. The behavioral phenotypes appear to be caused by defects the development of adult brain. Specifically, tao functions promote axon guidance mushroom body (MB) neurons. MB is large structure central brain fly whose function have been well characterized. interacts genetically with mutations par-1 gene, also serine-threonine kinase. Since Par-1 has implicated regulation...