Katherine Bull

The development of new therapies for kidney disease is hampered by limited understanding of the underlying mechanistic pathways at the cellular level.  Our objective is develop a variety of clinical models and tools and establish new approaches to interrogate tissue cellular pathology. We apply gene editing, single cell transcriptomics, and renal and immune phenotyping, including multiomic and spatial approaches to models and human samples. 

In particular our work focuses on immune mediated glomerular protein leak, a hallmark of many renal pathologies, including lupus nephritis, IgA nephropathy and Focal Segmental Glomerulosclerosis (FSGS). 

Examples of our work

Finding patterns of glomerular immune infiltration  in lupus nephritis by high resolution spatial transcriptomics 

In collaboraation with Heather Harrington (Mathematics), we applied topological data analysis to address the challenge of cellular deconvolution in sub cellular resolution spatial transcriptomics. We dynamically consider the local transcriptomic context to improve cell labelling, and use this new method, TopACT, to define a ring-like glomerular immune distribution in lupus nephritis. 

The effects of immune complex deposition on glomerular renal cells in lupus nephritis

Autoimmune renal disease such as occurs in Systemic Lupus Erythematosus (SLE) is characterised by the deposition of immune complexes in the renal glomeruli, but little is understood about the cellular responses in the tissue that ultimately lead to renal failure for some patients with SLE. Using inducible models and spatial transcriptomics we are interrogating cellular signals and cross talk in the kidney. 

The role of Prolidase in autoimmunity and T cell fate

Deficiency in the metalloproteinase prolidase results in a very rare condition with recurrent infections and in some cases autoimmune features including renal immune complex disease. In vivo knock out of the PEPD gene has identified key functions for prolidase in autoimmunity, renal disease and T cell differentiation. 

Collaborators 

Heather Harrington, Mathematics Institute, University of Oxford and Max Plank Institute of Molecular Cell Biology and Genetics, Dresden. 

Richard Cornall, University of Oxford

John Todd / Diabetes and Inflammation Laboratory, University of Oxford 

geneTIGA consortium https://www.genetiga-horizon.eu/