Currents Projects<\/span><\/h1>\n
\nDNA-based cell typing, methylation cytometry<\/h3>\n
Stable epigenetic marks on our DNA called DNA methylation provide instructions to our genome, allowing our many different cell types to specialize their functions despite sharing the same genome. Our team has pioneered the development and application of novel DNA-based cell typing approaches and accompanying software that enable objective, standardized immune profiling using only measures of stable, cell-specific epigenetic modifications to DNA. Cytosine is either methylated or unmethylated and this measured binary signal is directly proportional to the number of cells generating the signal. Because DNA-based cell typing with methylation cytometry is fundamentally simple and measures a stable DNA modification, our technology can accurately quantify even low prevalence cell types in peripheral blood, tumor samples, and other specimen types. Methylation Cytometry provides a scalable, cost-effective approach for immune profiling and cell typing. Measures can be performed frequently using stable, easy-to-acquire samples (including in-home collection of blood), providing results that are comparable through time, and from patient to patient.<\/p>\n
Selected publications<\/a><\/p>\nCancer immunotherapy response<\/h3>\n
We have an ongoing clinical observational study of cancer immunotherapy response across tumor types and immunomodulatory treatment modalities at Dartmouth Cancer Center that has enrolled nearly 1,000 patients. We aim to identify and validate clinically valuable markers of patient response to therapy using both routinely collected patient data and clinical lab data, as well as detailed immune and epigenetic profiles in blood and tumors. By harnessing existing data and collecting new genome-scale data we aim to develop both practical and more immediately deployable biomarkers for shared clinical decision making, as well as immunologically informed strategies for \u00a0investigator-initiated clinical trial design at a time of growth in immunomodulatory therapy options. Major tumor types of focus include head and neck cancer, melanoma, lung cancer, and hematologic malignancies.<\/p>\n
Selected publications<\/a><\/p>\nPediatric central nervous system tumors<\/h3>\n
Pediatric central nervous system (CNS) tumors are a leading cause of childhood cancer deaths and we are using multi-omic genome-scale measures to better understand the biology of these diverse tumors and identify promising avenues for developing therapies. We've contributed single-cell transcriptomics and genome scale epigenetic DNA modification data to the research community and are currently pursuing expanded data collection to assess spatial transcriptomic profiles in tumors and non-tumor tissues.<\/p>\n
Selected publications<\/a><\/p>\nEarly risk factor related epigenetic alterations in breast carcinogenesis<\/h3>\n
Breast cancer is the most common non-keratinocyte cancer among women. Our proposal will characterize the relationships between risk factors for invasive breast cancer and epigenetic alterations in pre-cancerous and non-invasive breast tissues to extend our understanding of breast carcinogenesis and inform novel strategies for disease prevention.<\/p>\n
Cancer immunotherapy response<\/h3>\n
We have an ongoing clinical observational study of cancer immunotherapy response across tumor types and immunomodulatory treatment modalities at Dartmouth Cancer Center that has enrolled nearly 1,000 patients. We aim to identify and validate clinically valuable markers of patient response to therapy using both routinely collected patient data and clinical lab data, as well as detailed immune and epigenetic profiles in blood and tumors. By harnessing existing data and collecting new genome-scale data we aim to develop both practical and more immediately deployable biomarkers for shared clinical decision making, as well as immunologically informed strategies for \u00a0investigator-initiated clinical trial design at a time of growth in immunomodulatory therapy options. Major tumor types of focus include head and neck cancer, melanoma, lung cancer, and hematologic malignancies.<\/p>\n
Selected publications<\/a><\/p>\n Pediatric central nervous system (CNS) tumors are a leading cause of childhood cancer deaths and we are using multi-omic genome-scale measures to better understand the biology of these diverse tumors and identify promising avenues for developing therapies. We've contributed single-cell transcriptomics and genome scale epigenetic DNA modification data to the research community and are currently pursuing expanded data collection to assess spatial transcriptomic profiles in tumors and non-tumor tissues.<\/p>\n Selected publications<\/a><\/p>\n Breast cancer is the most common non-keratinocyte cancer among women. Our proposal will characterize the relationships between risk factors for invasive breast cancer and epigenetic alterations in pre-cancerous and non-invasive breast tissues to extend our understanding of breast carcinogenesis and inform novel strategies for disease prevention.<\/p>\nPediatric central nervous system tumors<\/h3>\n
Early risk factor related epigenetic alterations in breast carcinogenesis<\/h3>\n