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Research at Mass General
Our main research focus is on changes in melanoma tumors during treatment with current systemic therapies, such as targeted therapy and immunotherapy.
Genevieve M. Boland, MD, PhD, is Principal Investigator (PI) on the Melanoma Tumor Repository protocol and works closely with Medical Oncology and Pathology to collect serial blood and tumor specimens from which correlative studies can be done.
The group is specifically focused on changes in the tumor and tumor microenvironment that can be detected through analysis of circulating microvesicles, exosomes.
Learn more about the Boland Lab.
Dr. Boland is an Assistant in Surgery in the Division of Surgical Oncology at the Massachusetts General Hospital and Assistant Professor at Harvard Medical School. Her primary clinical focus is on melanoma and cutaneous oncology. She undertook combined MD/PhD training, completing a PhD in Cell and Tissue Engineering at the National Institutes of Health focusing on signaling pathways in adult, human mesenchymal stem cells. Her PhD mentor was Dr. Rocky Tuan.
She completed research fellowship at the University of Texas MD Anderson Cancer Center in the lab of Lynda Chin studying melanoma genomics. She was a member of The Cancer Genome Atlas (TCGA) project. She joined the Mass General Division of Surgical Oncology in 2014 and is currently the PI of the Melanoma Tumor Repository and an active clinical surgeon.
She works closely with Medical Oncology, Pathology, and Dermatology to focus on correlative studies using human patient samples. Dr. Boland’s laboratory is currently focusing on molecular profiling of melanoma and identification of circulating biomarkers of cancer.
Dr. Boland has received several awards and grants for her current studies including the Department of Surgery Faculty Development Award, The Association for Women Surgeons/Ethicon Inc Fellowship, the KL2 CMeRIT Research Investigator Award through the Harvard Catalyst Program, and the American Surgical Association Foundation Fellowship.
William (Bill) Michaud is a research scientist in the Boland Lab. He obtained a PhD in Biology from the University of Maryland in 2001.
He worked in the Rocco Lab from 2001 – 2014 studying molecular changes in head and neck tumors, focusing on predictors of responsiveness to therapy. He joined the Boland Lab in 2014 and has optimized techniques for exosome extraction from cell culture and human sera, RNA preparation and analysis.
In additional to his technical expertise, Bill is a talented chef, brewmaster, biker and fisherman.
Recent breakthroughs in the treatment of melanoma have shown promising clinical success, with response rates of up to 50% observed in the setting of immune checkpoint blockade.
Response rates with targeted therapy against oncogenic BRAF are higher (up to 80%), though durability of response remains an issue with a median time to progression of ~6 months for BRAF monotherapy and 10 months with combined BRAF + MEK inhibition.
Mechanisms of resistance to targeted therapy are multiple and involve genomic mutations as well as potential immune mechanisms of resistance. Genomic and transcriptomic profiling in tumor tissues has proven fruitful in patients on targeted therapy, and has informed on evolving vulnerabilities of cancer cells – offering a better definition of therapeutic windows.
Resistance mechanisms to immune checkpoint blockage inhibitors, albeit less understood, may also benefit from transcriptomic and genomic analyses of tumor biopsies.
While significant progress using serial tumor biopsy specimens of patients on targeted therapy has elucidated the various pathways of resistance, identification of real-time, minimally invasive means to monitor changes in tumors would represent a significant advance in the clinical management of melanoma.
To this end, patient sera-derived exosomes may be used as a liquid biopsy, as they contain double-stranded DNA that spans the entire tumor genome and mRNA/miRNA signatures that could predict response to treatment and monitor for recurrence.
Exosomes dynamically sample the cells’ genome and miRNA transcriptome, offering unique insights into tumor progression, response, and recurrence over time. We hypothesize that circulating exosomal mRNA/miRNA profiles can accurately inform on clinical changes in patient with metastatic melanoma, and that such exosomal signatures correspond with treatment response or resistance to current immunotherapies.
This work utilized a co-clinical assessment of human tumors and a genetically-engineering mouse model of melanoma in order to understand the mechanism of resistance to BRAF-targeted therapy. I participated in hypothesis generation, tumor collection, data analysis, in vitro validation studies and manuscript preparation.
The goal of this study was an improved understanding of the process of resistance in patients on BRAF-targeted therapy and the identification of novel targets of intervention or as rationale for new combinatorial therapies.
A secondary goal was the establishment of predictive markers or response to BRAF-targeted therapy and current work is ongoing to validate a panel of proliferative and immune markers identified in this project that predict responsiveness to BRAF-targeted therapy.
We are currently recruiting for a Postdoctoral position.
Ideal candidates would have an MD/PhD or PhD in genetics, immunology, molecular and/or cellular biology, or bioinformatics.
CVs can be sent to email@example.com
See a list of Dr. Boland's publications on PubMed http://www.ncbi.nlm.nih.gov/pubmed/?term=boland+gm
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