I am a physician-scientist with a strong interest and a translational approach to investigation of solid tumor malignancies at the cellular and molecular level. As a fellowship-trained and practicing medical oncologist and neuro-oncologist, I have a strong interest in a ‘bedside-to-bench-and-back’ approach to translational oncology and laboratory research. At the national level, I serve on the American Society of Clinical Oncology (ASCO) Scientific Committee for GI Cancers. Identifying pertinent clinical problems in oncology that can be investigated in the laboratory setting is a high priority for our research program and collaborative efforts.
I. Intercellular Communication in Cancer:
My lab primarily focuses its work on studying intercellular communication via cellular extensions called tunneling nanotubes (TnTs, or TNTs, for short). These structures are long, thin, spontaneously forming actin-based cellular extensions that occur in a variety of cell types including inflammatory cells (e.g. B cells, macrophages), neurons, and more recently being examined in malignant cells. When examined in vitro, TnTs are differentiated from other actin-based structures such as filopodia, invadopodia, and lamellopodia by their characteristic non-adherence to the substratum. Furthermore, once they attach to nearby or distant cells in culture, they form direct connections that serve as conduits for intercellular transport of a variety of cellular cargo and contents, including but not limited to lipophilic vesicles, Golgi vesicles, and even mitochondria. To date, there have been relatively few studies of TnTs in cancer, particularly in primary cancer cells or tumors. Much remains unknown about these structures, including their in vivo relevance. Our team was the first to demonstrate, using confocal microscopy, presence of nanotubes in intact malignant tumors. To date, we have demonstrated nanotubes in several invasive malignancies such as mesothelioma and lung adenocarcinoma from surgically resected tumors from human patients [Lou et al., PLoS ONE, 2012], and more recently in orthotopic animal models including osteosarcoma. Our collaborative team believes that TnTs are an underexplored yet potentially important mode of intercellular communication in cancer and play a heretofore unassessed role in tumor-stromal cross-talk in the complex and heterogeneous tumor microenvironment.
Ongoing projects on TnTs in our lab include the following:
- Investigation of the underlying function of TnTs and relevance to invasive cancers. We are actively investigating whether TnTs serve as a selective and unique conduit for cellular cargo that drive vital cellular processes, including carcinogenesis and metastasis.
- Investigation of the mechanisms of TnT formation and maintenance in cancer.
- Identifying differences in TnT formation in malignant vs. precursor or stromal cells, and identification of cellular biomarkers that contribute to selectivity of TnT formation.
II. Translational Research Program
Novel biomarkers of chemoresistance in ovarian cancer:
An additional project in our lab involves a biomarker-based clinical trial in collaboration with the UMN Gynecologic Oncology group, with the purpose of identifying novel biomarkers of chemoresistant ovarian cancers. We are enrolling patients and collecting tumor specimens at the time of debulking surgery, as well as serum samples at the time of diagnosis and longitudinally throughout their care, with the purpose of correlating potential biomarkers that may predict which patients harbor tumors most susceptible to developing resistance to platinum-based chemotherapy, a major obstacle to treatment of these patients. We also have ongoing collaborations to isolate circulating tumor cells (CTCs) to perform pharmacogenomic profiling and correlate these findings to platinum-resistance as well.