Research projects
The Markovic Melanoma Research Lab has multiple research projects that fall under three major research themes. Our research is geared toward finding novel treatments or drug combinations for metastatic melanoma, with the goals of expanding options for patients and improving outcomes.
Our three research themes are:
- Understanding immune homeostasis in patients with cancer.
- Developing platform nanomedicines to target agents that are toxic to tumors.
- Designing novel vaccine strategies and adjuvants.
Comparison between pregnancy and tumor malignancy
Using a systems biology approach, we're studying immune tolerance and induction of labor during pregnancy. With this work, we hope to gain a better scientific understanding of immune regulation, which could be applied to metastatic cancer. Information gathered from this study could be used to generate new therapeutic treatments in oncology.
Mechanisms of nodal metastasis
In this research area, we're studying the mechanisms by which melanoma induces regional immunosuppression before there's clinical evidence of nodal metastasis.
This project integrates both clinical and basic science approaches by using fresh lymphatic tissue from patients and examining secreted melanoma-derived extracellular vesicles in this system for their ability to drive immunosuppression.
By identifying the factors present in the vesicles, which are responsible for mediating this process, we hope to develop novel therapeutic targets to counteract nodal metastasis.
Multiplex immunofluorescence (MxIF)
This project focuses on immunofluorescence analysis of melanoma tumors to identify cell populations within the dense heterogenous population of the tumor microenvironment and how cell populations correlate with treatment outcomes.
NanoString GeoMx digital spatial profiling
This project focuses on the proteomic differences between melanoma tumors from patients who have a positive response to immunotherapy and those who don't. Our goal is to understand the protein expression and pathways that may clarify why some patients respond differently to immunotherapy.
Targeted nanomedicines
Chemotherapy remains a common systemic therapy for most cancers, including melanoma. The major hurdle of chemotherapy is that it destroys healthy tissue while killing tumors cells.
Our goal in targeted nanomedicine research is to find ways to target the chemotherapy agent to the tumor by noncovalently binding therapeutic antibodies to chemotherapy agents. Therapeutic antibodies are specific to proteins expressed by tumors. By targeting the drug to the tumor, antitumor efficacy is increased while damage to healthy tissue is minimized.
Vaccine development
With increasing use of immunotherapy, including anti-PD-1, in the clinical setting, we're assessing patient T-cell responses before and after PD-1 therapy.
Along with determining T-cell receptor usage in patients who respond to PD-1 therapy relative to those who don't respond, we're conducting DNA sequencing of tumor samples before and after PD-1 treatment.
By performing these two analyses in conjunction, our team hopes to learn what tumor antigens T cells recognize in patients who respond and then use that knowledge to develop new vaccine strategies.