Explore This Laboratory

About the Lab

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.

Research Projects

Comparative analysis of circulating exosomal RNA profiles in melanoma responders/non-responders to systemic therapy

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 approximately 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.

Correlative assessment of patterns of BRAF-resistance and predictive markers of response

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.

Research Positions

We are currently recruiting for a postdoctoral position. Ideal candidates would have an MD/PhD or PhD in one of the following:

  • Genetics
  • Immunology
  • Molecular and/or cellular biology
  • Bioinformatics

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Publications

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