A5066734701- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Bioinformatics and Genomic Networks
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- HIV/AIDS drug development and treatment
- Virology and Viral Diseases
- Renal cell carcinoma treatment
- Immune Cell Function and Interaction
- Immune cells in cancer
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Protein Degradation and Inhibitors
- Machine Learning in Materials Science
- Virus-based gene therapy research
- Evolution and Genetic Dynamics
- Microtubule and mitosis dynamics
- Glycosylation and Glycoproteins Research
- Mathematical Biology Tumor Growth
- Single-cell and spatial transcriptomics
- Lung Cancer Treatments and Mutations
- Acute Myeloid Leukemia Research
Harvard University
2016-2021
Evolutionary Genomics (United States)
2016-2019
Harvard University Press
2019
Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, among treatment-naïve metastases has not been comprehensively assessed. We analyzed sequencing data 76 untreated from 20 patients and inferred cancer phylogenies breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, prostate cancers. found that individual patients, a large driver gene mutations common to all metastases. Further...
Significance The HIV-1 latent reservoir cannot be eradicated by antiretroviral therapy (ART). is a major barrier to cure. To characterize the mechanisms that contribute persistence of reservoir, we examined clonally expanded cell populations carrying replication-competent and followed them longitudinally. Expanded clones harboring were identified in all study participants, but these emerge wane on time scale years. A similar pattern was viruses sampled from residual viremia. findings suggest...
Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data enabled modern phylogenomic methods to accurately dissect subclones phylogenies from noisy impure bulk tumour samples at unprecedented depth. However, existing are not designed infer metastatic seeding patterns. Here we develop a tool, called Treeomics, reconstruct phylogeny map anatomic locations. Treeomics...
SIV-infected rhesus macaques on antiretroviral therapy experienced a reduction in the SIV reservoir after treatment with TLR7 agonists.
The vast majority of mutations in the exome cancer cells are passengers, which do not affect reproductive rate cell. Passengers can provide important information about evolutionary history an individual cancer, and serve as a molecular clock. also become targets for immunotherapy or confer resistance to treatment. We study stochastic expansion population describing growth primary tumors metastatic lesions. first analyze process by looking forward time calculate fixation probabilities...
Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities management recurrent cancer, we performed whole-exome or targeted sequencing 10 resected primary cancers matched intrapancreatic recurrences distant metastases. We identified that disease adjuvant first-line platinum therapy corresponds to an increased mutational burden. Recurrent enriched genetic...
Abstract HIV infection can be treated but not cured with antiretroviral therapy, motivating the development of new therapies that instead target host immune responses. Three such immunotherapies were recently tested in non-human primates – a TLR7-agonist, therapeutic vaccine, and broadly-neutralizing antibody subset animals by preventing or controlling viral rebound after antiretrovirals stopped. However, their mechanism action remains unknown; for example, whether they reduced pool...
Abstract Surgery is the only curative option for Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities management recurrent cancer we performed whole exome or targeted sequencing 10 resected primary cancers matched intrapancreatic recurrences distant metastases. We identified that adjuvant first-line platinum therapy corresponds to an increased mutational burden Recurrent disease enriched mutations activate...
Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications 1–3 . Genome-wide sequencing data enabled modern phylogenomic methods to accurately dissect subclones phylogenies from noisy impure bulk tumor samples at unprecedented depth 4–7 However, existing are not designed infer metastatic seeding patterns. We have developed a tool, called Treeomics, that utilizes Bayesian inference Integer Linear...
Abstract The evolution of metastases is responsible for 90% cancer-related deaths. Genome wide sequencing and phylogenomic methods enable the reconstruction evolutionary history a patient's cancer at unprecedented depth. However, due to lack samples from multiple spatially-distinct untreated patients tools applicable noisy impure samples, rules governing metastatic spread have remained poorly understood. We performed whole-genome (coverage: median 51x) as well deep targeted 347x) on 21...
<p>Figures S1-S3</p>
<p>Supplemental Tables</p>
<div>Abstract<p>Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities management recurrent cancer, we performed whole-exome or targeted sequencing 10 resected primary cancers matched intrapancreatic recurrences distant metastases. We identified that disease adjuvant first-line platinum therapy corresponds to an increased mutational...
<p>Supplemental Tables</p>
<p>Figures S1-S3</p>
<div>Abstract<p>Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities management recurrent cancer, we performed whole-exome or targeted sequencing 10 resected primary cancers matched intrapancreatic recurrences distant metastases. We identified that disease adjuvant first-line platinum therapy corresponds to an increased mutational...