Levi A. Garraway
A5055048393- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Prostate Cancer Treatment and Research
- Genetic factors in colorectal cancer
- Advanced Breast Cancer Therapies
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Colorectal Cancer Treatments and Studies
- Synthesis and biological activity
- PI3K/AKT/mTOR signaling in cancer
- Cancer Treatment and Pharmacology
- Cutaneous Melanoma Detection and Management
- Epigenetics and DNA Methylation
- Breast Cancer Treatment Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Gene expression and cancer classification
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- Genetics, Bioinformatics, and Biomedical Research
Dana-Farber Cancer Institute
2015-2025
Broad Institute
2015-2025
Center for Neuro-Oncology
2023-2025
Weatherford College
2025
Harvard University
2012-2023
La Roche College
2021-2023
Howard Hughes Medical Institute
2014-2022
Brigham and Women's Hospital
2011-2022
Eli Lilly (United States)
2017-2020
Beth Israel Deaconess Medical Center
2016-2020
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, endothelial cells. Malignant within same tumor displayed transcriptional heterogeneity associated with cell cycle, spatial context, a drug-resistance program. In particular, all tumors harbored malignant two states, such that characterized by high levels MITF transcription factor also...
High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown be more significantly associated with response PD-1 PD-L1 blockade immunotherapy than or expression, as measured by immunohistochemistry (IHC). The distribution TMB the subset patients high not well characterized in majority cancer types. In this study, we compare a targeted comprehensive genomic profiling (CGP) assay exome sequencing simulate expected variance when...
The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire neoantigens created by genetic mutations within cells. Like corresponding mutations, these show intratumoral heterogeneity. Some are present all cells (clonal), and others only a fraction (subclonal). In study lung cancer melanoma, McGranahan et al. found that high burden clonal correlated with improved patient survival, an increased presence tumor-infiltrating lymphocytes, durable...
<h2>Summary</h2> Papillary thyroid carcinoma (PTC) is the most common type of cancer. Here, we describe genomic landscape 496 PTCs. We observed a low frequency somatic alterations (relative to other carcinomas) and extended set known PTC driver include <i>EIF1AX</i>, <i>PPM1D</i>, <i>CHEK2</i> diverse gene fusions. These discoveries reduced fraction cases with unknown oncogenic from 25% 3.5%. Combined analyses variants, expression, methylation demonstrated that different groups lead...
Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but predictors of response to these therapies remain incompletely characterized. To investigate the roles tumor-specific neoantigens and alterations in tumor microenvironment we analyzed whole exomes from pretreatment biopsies matching germline tissue samples 110...
Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited profile consistent with tobacco exposure; human papillomavirus was detectable by DNA infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, HRAS), our analysis revealed many not implicated in this At least 30% of cases...
Promoter Mutations and Cancer genome sequencing projects have highlighted the pathogenic role of recurrent mutations within protein-coding regions genes. Now, two studies suggest that scope in human tumors extends to gene regulatory regions. In a study 70 melanomas, Huang et al. (p. 957 , published online 24 January) found 71% harbored one specific promoter region TERT coding for catalytic subunit telomerase, enzyme caps chromosome ends. Independently, Horn 959 identified disease-segregating...
Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence germline among men localized cancer who unselected for family predisposition is insufficient to warrant routine testing, frequency patients metastatic has not been established.
Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis poorly understood. Here we report the massively parallel sequencing 38 tumour genomes their comparison to matched normal DNAs. Several new unexpected oncogenic mechanisms were suggested by pattern somatic mutation across data set. These include genes involved in protein translation (seen nearly half patients), histone methylation, blood coagulation. In addition, a broader than anticipated role NF-κB signalling...