Emil Lou Lab

The Lou lab studies intercellular communication via cellular extensions called tunneling nanotubes (TnTs). These long, thin, spontaneously forming actin-based cellular extensions occur in a variety of cell types including inflammatory cells (e.g. B cells, macrophages), neurons, and malignant cells. When examined in vitro, TnTs are differentiated from other actin-based structures such as filopodia, invadopodia, and lamellipodia 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. There have been relatively few studies of TnTs in cancer, particularly in primary cancer cells or tumors: the Lou team was the first to demonstrate, using confocal microscopy, the presence of nanotubes in intact malignant tumors. Click here for confocal and other microscopy videos of this work.

Ongoing projects

• Investigation of the underlying function of TnTs and relevance to invasive cancers, specifically 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.
• Identifying differences in TnT formation in malignant vs. precursor or stromal cells, and identification of cellular biomarkers that contribute to selectivity of TnT formation.

Pertinent publications

• Our lab produced the first publication to demonstrate TNTs exist in intact human tissue specimens: Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma (Publication Link)
• Treatment with tumor-treating fields (TTFields) suppresses intercellular tunneling nanotube formation in vitro and upregulates immuno-oncologic biomarkers in vivo in malignant mesothelioma (Publication Link)
• Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells (Publication Link)
• The first demonstration of intercellular transfer of nucleic acids occurring via TNTs: Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via tunneling nanotubes ( Publication Link)
• Tunneling nanotubes: an alternate route for propagation of the bystander effect following oncolytic viral infection (Publication Link)
• Do tunneling nanotubes drive chemoresistance in solid tumors and other malignancies? (Publication Link)
• Tunneling Nanotubes: Implications for Chemoresistance (Publication Link)
• Tunneling nanotubes and tumor microtubes-Emerging data on their roles in intercellular communication and pathophysiology: Summary of an International FASEB Catalyst Conference October 2023 (Publication Link)
• TNTdetect.AI: A Deep Learning Model for Automated Detection and Counting of Tunneling Nanotubes in Microscopy Images (Publication Link)
• Tunneling Nanotubes between Cells Migrating in ECM Mimicking Fibrous Environments (Publication Link)
• Tunneling nanotubes: A bridge for heterogeneity in glioblastoma and a new therapeutic target? (Publication Link)
• Intercellular Transfer of Oncogenic KRAS via Tunneling Nanotubes Introduces Intracellular Mutational Heterogeneity in Colon Cancer Cells (Publication Link)
• Cellular and Molecular Networking Within the Ecosystem of Cancer Cell Communication via Tunneling Nanotubes (Publication Link)
• A new paradigm for studying intercellular communication and therapeutics in cancer (Publication Link)

Novel biomarkers of chemoresistance in ovarian cancer

A biomarker-based clinical trial in collaboration with the UMN Gynecologic Oncology group, aims to identify novel biomarkers of chemoresistant ovarian cancers. The team enrolled patients and collected tumor specimens at the time of debulking surgery, as well as serum samples at the time of diagnosis and longitudinally throughout their care, to  correlate 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. The team also isolated circulating tumor cells (CTCs) and correlated these findings to platinum-resistance. In JAMA Oncology in 2019, the Lou Lab  reported a correlation between Tumor-Stroma Proportion and Platinum Chemotherapy Resistance in Ovarian Cancer. This work was sponsored by the KL2 Scholars Career Development Program, Clinical and Translational Science Institute, University of Minnesota.

• Emil Lou et al., Tumor-Stroma Proportion as a Predictive Biomarker of Resistance to Platinum-Based Chemotherapy in Patients With Ovarian Cancer
• Analysis of Differentially Expressed MicroRNAs and Circulating Tumor Cells as Predictive Biomarkers of Platinum Chemoresistance in Primary Ovarian Carcinomas: A Prospective Study
• Assessment of Circulating Tumor Cells as a Predictive Biomarker of Histology in Women With Suspected Ovarian Cancer
• Tumor-Stroma Proportion to Predict Chemoresistance in Patients With Ovarian Cancer
• Dr Lou on the Predictive and Prognostic Utility of Tumor Stroma Proportion in Ovarian Cancer
• Tumor-Stroma Proportion May Predict Clinical Outcomes in High-Grade Serous Ovarian Cancer  

AACR Scientist Survivor Program

• Dr. Lou has served as a Scientist Mentor for this Program at the AACR (American Association for Cancer Research) Annual Meetings, 2013-2026.
• Invited guest on Breast Cancer Social Media (#bcsm) blog for updates from #AACR15

Community Outreach and Presentations

• Presentation on “Recent Advances in Cancer Research” at the Roseville Rotary Club’s Rotary Health Day, April 21, 2014.

Community Service

• Grant reviewer for community group applications to the UMN CTSI Office of Community Engagement for Health (OCEH).

Social Media

• Dr. Lou participated in the AACR/ABC News Live Stream Chat on “Breakthroughs in Cancer Research” from the 2015 Annual Meeting.
  Read Article  |  Watch Video
• Article on Dr. Lou’s panel discussion at the Professional Advancement Session on Social Media for Scientists at the 2015 AACR Annual Meeting. Read Article.

Tips to be a Great Patient Advocate

• Dr. Lou's interview with Caringbridge.org

We are grateful to funding agencies that support our work, including the following.

Current Lab Members

• Emma Hawkins
• Phillip Wong, MS

Former Lab Members

• Snider Desir, PhD
• Sophie Korenfeld
• Katherine Ladner, PhD
• Sanyukta (Yuki) Padmanabhan
• William Sperduto, MD
• Venugopal Thayanithy, PhD
• Elizabeth Dickson, MD
• Shoshana Liu, BS
• Akshat Sarkari, BS
• Rojina Sapkota, MS (BICB Program)

• Sara Kugler, MS (BICB Program)

Collaborators

• Dr. Martina Bazzaro
• Dr. Melissa Geller
• Dr. Jerry Lee
• Dr. Amrinder Nain
• Dr. Chirag Patel
• Dr. Clifford Steer
• Dr. Subree Subramanian
• Dr. Deanna Teoh