Intravital Microscopy Core

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The project completed last year (see previous Annual report, 2024) resulted in 5 publications. The CCR IVM Core is currently completing the following projects: 1) Role of PKI in basal squamous cell carcinoma in the skin; Investigator Ramiro Iglesias-Bartolome (LCMB) Basal squamous cell carcinoma, a common skin cancer, rarely causes death. Worldwide, non-melanoma skin cancers result in over 65,000 deaths annually (2020), and in the U.S., basal cell carcinoma causes over 2,000 deaths yearly (2023). Protein Kinase Inhibitor (PKI) modulates intracellular signaling pathways, influencing tumor suppression, proliferation, and differentiation. This project aims to determine how PKI regulates the initiation and spatial dynamics of tumor cell distribution in basal squamous cell carcinoma. Using a genetically engineered mouse model, we followed the initiation and progression of basal squamous cell carcinomas in the ear and pinpointed the changes in distribution of the tumor cells over time. 2) Role of GEMesys in blocking tumor growth - Investigator Rosandra Kaplan (POB) Soft tissue sarcomas cause approximately 55,000 deaths globally each year (2020), and over 5,000 annually in the U.S. (2023). GEMesys is a mesenchymal cell line engineered to express hyaluronidase (Hyal), which degrades hyaluronan - a structural ECM component implicated in tumor stiffness and immune evasion. This project evaluates how GEMesys affects tumor ECM composition and growth from early to late cancer stages. Using a genetically engineered mesenchymal cell line (GEMesys) that expresses Hyal, we monitored how GEMesys treatment is able to reduce tumor-HA and Collagen from early to late stage of cancer. 3) B-Cell Apoptosis in vivo using intravital FLIM - Investigator Christian Mayer (EIB) Non-Hodgkin B-cell lymphomas caused over 250,000 deaths worldwide in 2020 and more than 20,000 in the U.S. annually as of 2023. B-cell apoptosis is a key regulator of humoral immune homeostasis and plays a critical role in preventing lymphoproliferative disorders. This study investigates the kinetics of activated B-cell death in primary immune tissues. Using a genetically engineered mouse that expresses an apoptosis reporter in B cells, we examined the kinetics of activated B-cell death that regulates the homeostasis of humeral response in bone marrow and spleen. 4) Measuring the mechanical properties of tumor microenvironment during melanoma progression in vivo - Investigator Glenn Merlino (LCBG) Melanoma accounts for over 55,000 deaths worldwide (2020) and more than 8,000 deaths annually in the U.S. (2023). Tumor microenvironment stiffness influences cancer progression, metastatic potential, and immune response. This study measures biophysical changes in the tumor microenvironment during melanoma progression. Micro-sized fluorescent beads were used to track the biophysical properties of melanomas microenvironment in a transgenic mouse as the tumor progresses from early to late stage. 5) Nuclear expulsion in breast cancer - Investigator Li Yang (LCBG) Breast cancer caused more than 680,000 deaths globally in 2020 and over 43,000 deaths in the U.S. in 2023. Nuclear expulsion is a rare phenomenon observed during cell death, potentially induced by chemotherapeutic stress. This project explores nuclear expulsion events following chemotherapy in breast cancer cells. Using a genetically engineered mouse that expresses nuclear GFP, we followed the event of cell death followed by nuclear expulsion in breast cancer upon chemotherapy treatment. 6) Role of smurf2 during tumor progression - Investigator Ying Zhang (LCMB) Head and neck cancers caused over 380,000 global deaths in 2020 and more than 15,000 deaths in the U.S. annually as of 2023. Smurf2 is an E3 ubiquitin ligase that regulates TGF-beta signaling and has been linked to both tumor suppression and promotion. This project investigates how Smurf2 affects immune cell distribution in the tumor microenvironment. Using a genetically engineered mouse model in combination with 4NQO treatment that induces head and neck cancer, we monitored the distribution of myeloid cells in the tumor microenvironment from early to late stage with and without the presence of Smurf2. 7) Role of neutrophils in prostate cancer bone metastasis - Investigator Leah Cook (CIL) Prostate cancer caused more than 375,000 deaths globally (2020) and over 35,000 deaths in the U.S. annually as of 2023. Neutrophils can support or suppress metastasis depending on tumor stage and immune context. This project examines how neutrophils influence prostate cancer cell fate in bone metastasis. Using a genetically engineered mouse model we monitored the interactions of neutrophils with prostate cancer cells in determining their cell faith from early to late stage of cancer progression. 8) Role of necrosis genes in blood clots - Investigator Zheng Gang Liu (LCMB) Sepsis-related conditions caused over 11 million deaths worldwide in 2020 and approximately 270,000 annually in the U.S. (2023). Necrosis genes regulate inflammatory cascades during systemic inflammation and influence vascular dynamics. This project explores the role of necrosis genes in regulating inflammation-induced blood flow alterations. Using a mouse model of systemic inflammation that resembles clinical sepsis, we examined the role of necrosis genes that control systemic inflammation by measuring the flow rates of red blood cells and platelets in liver. 9) Role of TGF-beta in mammary tumorigenesis - Investigator Lalage Wakefield (LCBG) Breast cancer remains one of the most prevalent and deadly cancers with over 680,000 global deaths in 2020 and more than 43,000 in the U.S. (2023). TGF-beta plays a dual role in cancer-acting as a suppressor early and promoter later by modulating immune response and metastasis. This project examines dynamic TGF-beta signaling during metastatic breast cancer progression. Using a genetically engineered mouse model of metastatic mammary cancer with TGF-beta labelling in Green, we installed a flexible window on the fat pad and monitored the distribution of TGF-beta active cells from early to late stage of tumorigenesis.