A5070443632- Veterinary Oncology Research
- Virus-based gene therapy research
- Sarcoma Diagnosis and Treatment
- Vascular Tumors and Angiosarcomas
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Infectious Diseases and Mycology
- Tumors and Oncological Cases
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Microbial infections and disease research
- Cancer-related Molecular Pathways
- Amyotrophic Lateral Sclerosis Research
- Angiogenesis and VEGF in Cancer
- Hedgehog Signaling Pathway Studies
- Ear and Head Tumors
- Neurogenetic and Muscular Disorders Research
- Bioinformatics and Genomic Networks
- Genomic variations and chromosomal abnormalities
- Animal Behavior and Welfare Studies
- Neurological diseases and metabolism
- Salivary Gland Tumors Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Genetic and phenotypic traits in livestock
- Cancer-related gene regulation
Broad Institute
2015-2024
Science for Life Laboratory
2015-2021
Uppsala University
2015-2021
Harvard University
2019
Massachusetts Institute of Technology
2016
Behavioral genetics in dogs has focused on modern breeds, which are isolated subgroups with distinctive physical and, purportedly, behavioral characteristics. We interrogated breed stereotypes by surveying owners of 18,385 purebred and mixed-breed genotyping 2155 dogs. Most traits heritable [heritability ( h 2 ) > 25%], admixture patterns reveal propensities. Breed explains just 9% variation individuals. Genome-wide association analyses identify 11 loci that significantly associated...
Abstract Angiosarcoma is a highly aggressive cancer of blood vessel–forming cells with few effective treatment options and high patient mortality. It both rare heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from similar cancer, called hemangiosarcoma, breeds like the golden retriever carrying heritable genetic factors that put them at risk. If clinical similarity canine hemangiosarcoma human angiosarcoma reflects shared etiology, dogs could...
Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma both malignancies the hematologic system that clinically histologically similar to non-Hodgkin angiosarcoma, respectively. Golden retrievers in US show significantly elevated lifetime risk for (6%) (20%). We conducted genome-wide association studies lymphoma, identifying two shared predisposing loci. The associated loci located on...
Abstract Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay evolution—and progression—require a deep understanding of underlying molecular processes. Herein we discuss suite concepts tools from theory that can inform biology in new meaningful ways. We also highlight current challenges...
Abstract Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes suppressors, compared them...
Significance Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM promising model for ALS, because genome-wide association identified mutation superoxide dismutase 1 gene ( SOD1 ), known ALS gene. This found many dog breeds increases the risk of DM, and pathological findings clinical progression two diseases are similar. In this study, we identify modifier gene, SP110 nuclear body protein ) , which...
Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly complex diseases like cancer. Comprehensive genomic annotation regulatory elements active in healthy canine tissues is crucial both identifying candidate causal variants designing functional studies needed to translate genetic associations into disease insight. Currently, geneticists rely primarily on annotations human or mouse genome that have been remapped dog, approach misses...
Abstract Although cancer is widely regarded as a major contributor to canine morbidity and mortality, its frequency in companion dogs has only infrequently been characterised. We analysed cross‐sectional data from the baseline survey of owners 27 541 living enrolled Dog Aging Project 31 December 2020 estimate lifetime prevalence malignant benign tumours several potentially‐associated characteristics. Survey questions elicited information on history ‘cancer or tumors’ including organ site...
Abstract Despite a considerable expenditure of time and resources significant advances in experimental models disease, cancer research continues to suffer from extremely low success rates translating preclinical discoveries into clinical practice. The continued failure drug development, particularly late the course human testing, not only impacts patient outcomes, but also drives up cost for those therapies that do succeed. It is clear paradigm shift necessary if improvements this process...
Abstract Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types cancers, but their existence remain unclear sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human 76 spontaneous canine hemangiosarcomas to identify associated with malignancies. Ten novel...
Abstract Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape HSA may aid in developing therapeutic strategies for dogs and also inform therapies rare human angiosarcoma. The objectives this study were to build a framework leveraging real‐world clinical data that could provide foundation precision medicine veterinary oncology, determine relationships between features canine splenic HSA. One hundred nine...
Dogs represent a unique spontaneous cancer model. Osteosarcoma (OSA) is the most common primary bone tumor in dogs (OMIA 001441-9615), and strongly resembles human forms of OSA. Several large- to giant-sized dog breeds, including Leonberger, have greatly increased risk developing We performed genome-wide association analysis with high-density imputed SNP genotype data from 273 Leonberger cases median age 8.1 [3.1-13.5] years 365 controls older than eight years. This revealed significant...
The characterization of immortalized canine osteosarcoma (OS) cell lines used for research has historically been based on phenotypic features such as cellular morphology and expression bone specific markers. With the increasing use these to investigate novel therapeutic approaches prior in vivo translation, a much more detailed understanding regarding genomic landscape is required ensure accurate interpretation findings. Here we report first whole genome eight OS lines, including single...
Abstract Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with high fatality and few effective treatment options. It both rare heterogenous, making large, well powered genomic studies nearly impossible. In dogs, angiosarcoma common, breeds like the golden retriever carrying heritable genetic factors that put them at very risk. If clinical similarity canine human reflects shared etiology, dogs could be critically needed model for advancing research. We assessed...
Abstract Sporadic angiosarcomas (ASs) are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types cancers, but their existence remain unclear sporadic ASs. In this study, we leveraged RNA sequencing data from thirteen human ASs 76 spontaneous canine hemangiosarcomas (HSAs) to identify associated with...
Abstract Naturally occurring canine cancers have remarkable similarities to their human counterparts. In order determine whether these occur at the molecular level, we investigated hotspot mutations in a variety of spontaneously arising and found high concordance oncogenic drivers between both species. These findings suggest that canines may present powerful complementary model for preclinical investigations targeted cancer therapeutics. Through analysis 708 client-owned dogs from 96 breeds...
ABSTRACT While liquid biopsy has potential to transform cancer diagnostics through minimally-invasive detection and monitoring of tumors, the impact preanalytical factors such as timing anatomical location blood draw is not well understood. To address this gap, we leveraged pet dogs with spontaneous a model system, their compressed disease timeline facilitates rapid diagnostic benchmarking. Key metrics from were consistent existing reports human patients. The tumor content samples was higher...
Abstract Angiosarcoma is an aggressive, albeit rare cancer in humans. The cause of the vast majority sporadic angiosarcomas unknown, mortality high, and no therapeutic targets have been identified to improve outcomes. Hemangiosarcoma (HSA) a common dogs, it shares histopathologic features with human angiosarcoma. In our previous work, canine HSAs were classified into angiogenic, inflammatory, adipogenic subtypes based on transcriptional profiles. However, genetic molecular events that...
<div>Abstract<p>Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types cancers, but their existence remain unclear sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human 76 spontaneous canine hemangiosarcomas to identify associated with...
<div>Abstract<p>Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types cancers, but their existence remain unclear sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human 76 spontaneous canine hemangiosarcomas to identify associated with...
<div>Abstract<p>Angiosarcoma is a highly aggressive cancer of blood vessel–forming cells with few effective treatment options and high patient mortality. It both rare heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from similar cancer, called hemangiosarcoma, breeds like the golden retriever carrying heritable genetic factors that put them at risk. If clinical similarity canine hemangiosarcoma human angiosarcoma reflects shared...
<p>S1. Representative putative inter-chromosomal fusion transcripts in human AS and canine HSA. SCLT1-NIPBL angiosarcoma. S2. Fusion genes their association with tumor content sequencing depth HSA tissues. S3. A, Primers designed for amplification of identified B, gene by quantitative RT-PCR. Expression value represents 2(-â^†Ct)(Fusion gene/GAPDH). C, four hemangiosarcomas. D, was confirmed tumors E, Electrophoresis (1% agarose gel) DNA product RTPCR done. S4. Genetic alterations...
<div>Abstract<p>Angiosarcoma is a highly aggressive cancer of blood vessel–forming cells with few effective treatment options and high patient mortality. It both rare heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from similar cancer, called hemangiosarcoma, breeds like the golden retriever carrying heritable genetic factors that put them at risk. If clinical similarity canine hemangiosarcoma human angiosarcoma reflects shared...