Joel Spencer
Intravital Imaging of the Endogenous Mouse Thymus
Hematopoietic cell transplantation (HCT) remains an important treatment for hematologic malignancies such as multiple myeloma, lymphoma, acute leukemias, and myelodysplastic syndromes. A key component of HCT is the cytotoxic preconditioning required to reduce the burden of malignancy, suppress the host immune system, and enable engraftment and tolerance of the donor hematopoietic cells. Unfortunately, preconditioning regimens invariably damage healthy tissues where donor cells engraft and expand (e.g., bone marrow and thymus), leading to significant morbidity and mortality. Much effort has been made to understand how the bone marrow regenerates after HCT, helping drive the development of better treatments. The thymus, however, is relatively understudied despite its importance as a key organ in the adaptive immune system where is serves as the main site for T cell development. Previous imaging studies have relied on thymus transplantation models or ex vivo culture systems, but to date, it has been impossible to directly image the endogenous mouse thymus in vivo. The teleost fishes are potential alternatives suitable for live imaging of the endogenous thymus, but recent data showing redundant cytokine networks in teleost fish suggests their T cell development differs significantly from mammals which have a critical dependence on the cytokine IL7. To overcome these limitations, we developed two-photon intravital imaging of the endogenous thymus in live mice and studied the blood vascular network and hemodynamics in a model of cytotoxic preconditioning. To our knowledge, we are the first to record blood flow in individual cortical capillaries of the endogenous mouse thymus before and after total body irradiation. Intravital imaging of the endogenous mouse thymus has opened up new ways for us to study the effects of cytotoxic preconditioning on the thymus and provides a potentially game-changing tool for the field to investigate thymus regeneration and T cell biology.
Bio: Dr. Joel A. Spencer has been an Assistant Professor of Bioengineering at the University of California, Merced, since 2017. He received his BS in Biological Sciences from the University of California, Irvine, in 2002 and his PhD in Biomedical Engineering from Tufts University in 2012. He has spent his career designing and applying novel optical technologies to fundamental questions in biology and medicine leading to 31 co-authored peer-reviewed publications. He built one of the first hybrid two-photon imaging/oxygen measurement systems that could simultaneously record high-resolution video and quantitatively measure tissue oxygen concentration in sub-cellular volumes in vivo. He used this unique capability to uncover the anatomically varying landscape of oxygenation in the bone marrow and hematopoietic stem cell niche, providing new insights into the role of oxygen in hematopoiesis. Since joining UC Merced, he has focused his efforts on developing optical imaging and sensing systems and methods to study the cellular and non-cellular factors involved in hematopoiesis, bone marrow transplantation, immune development, cancer therapy, and tissue regeneration. He especially focuses on developing techniques well-suited for intravital observation in pre-clinical models.
