Leishmaniasis, a neglected tropical infection that affects 600,000 to 1 million people each year, causes enlargement of internal organs like the liver and spleen. Current treatments for leishmaniasis infection can have adverse side effects, creating the necessity for alternative treatment strategies. Studying how this parasitic infection changes the three-dimensional structure of internal organs is imperative to understanding the progression of Leishmaniasis. The spatial arrangement of cells is a key factor in determining how cells within a tissue interact with each other. Cell-cell interactions can direct the progression of disease within tissue, and the host’s immune response to said disease. Current studies of leishmaniasis primarily use immunofluorescence and immunohistochemistry techniques to visualize specific biomarkers within affected organs. Due to the limitations of most microscopes, these procedures must be carried out on thin slices of tissue, meaning they lack crucial architectural information. My research project will focus on the optimization of the Super Ultrafast Multicolor Immunolabeling and Clearing (SUMIC) procedure to clear healthy and Leishmania-infected murine livers. This optimization will increase the quality of liver imaging and provide an opportunity to observe the 3D architecture of the whole liver before and after infection. Tissue clearing is a method used to remove pigmentation from intact organs, effectively rendering them translucent while preserving the organ’s three dimensional architecture. This procedure, along with the use of specific fluorescent tags, light microscopy, and 3D surface rendering, can help researchers visualize different markers within an organ system while maintaining the necessary cell-cell interactions. SUMIC has advantages over other clearing procedures in that it is simple, time-efficient, and inexpensive, making it an attractive procedure for use in a wide range of labs. However, SUMIC is a relatively new clearing method, and has not been extensively used in livers, meaning there is room for improvement within the procedure. For example, a key step in visualizing biomarkers within an organ is the proper tagging of desired proteins and molecules. To optimize results, the target proteins, or antigens, must be readily accessible to the antibody tags used to visualize them. The liver is a very dense organ in terms of tissue structure, so the step to make these antigens accessible should be adjusted accordingly. Thus, I will be optimizing the different solutions and incubation steps with the goal to obtain cleared livers that will be stained with a variety of markers to visualize the blood vessels in this organ. In all, optimization of the SUMIC clearing procedure for liver tissue will lead to improved three dimensional imaging of the liver that can be used to comprehensively investigate leishmaniasis pathology.