The Zimmerman lab in the Department of Internal Medicine, Division of Nephrology at OUHSC studies how immune cells influence the development and progression of cystic kidney diseases. Our lab was the first to identify the importance of kidney resident macrophages (KRM) in injury induced cystic kidney disease. We went on to show that a similar population of KRM is present in other species using single cell RNA sequencing. As part of these studies, we identified novel markers of KRM that were capable of identifying KRM in mouse, rat, pig, and human kidney tissues. The current projects in our lab build on these previous studies using state of the art technology including CRISP-Cas9 generated mouse models, flow cytometry, confocal microscopy, and single cell RNA sequencing.
The first project is focused on understanding how T cells influence injury induced cystic kidney disease. This includes the identification of T cell subsets, their localization, and potential function during the initiation and progression of cystic disease. The overall goal of this project is to identify pathogenic and protective T cell populations so that we can target these populations for treatment in patients with cystic disease.
The second major project is focused on understanding the ontological origin of KRM. This includes identification of KRM precursor cells and factors that control the seeding, differentiation, and development of KRM precursors in homeostasis and cystic kidney disease. The overall goal of this project is to leverage our understanding of KRM origin and functions to treat cystic kidney disease patients.
1. Zimmerman, KA.*, Bentley, MR., Lever, JM., Li, Z., Crossman, DK., Song, CJ., Liu, S., Crowley, MR., George, JF., Mrug, M., and Yoder, BK*. 2019. Single-cell RNAseq identifies a core renal resident macrophage signature across species. JASN 30:767-781. PMID: 30948627 **Selected as an F1000 prime manuscript**
Special commentary on manuscript
a. Clatworth, M.R. 2019. How to Find a Resident Kidney Macrophage: the Single-Cell Sequencing Solution. JASN 30:715-716. PMCID: PMC6493991
2. Zimmerman, KA.#, Song, CJ.#, Lever, JM., Crossman, DK., Li, Z., Zhou, J., Crowley, MR., Revell, DZ., Giles, KE., Gonzalez, N., Yan, Z., Shan, D., Benveniste, EN., George, JF., Mrug, M., and Yoder, BK. 2019. Tissue resident macrophages promote renal cystic disease. JASN. 10:1841-1856. PMID: 31337691
3. Larson-Casey, J.L., Vaid, M., Gu, L., He, C., Cai, G., Ding, Q., Davis, D., Berryhill, T.F., Wilson, L.S., Barnes, S., Neighbors, J.D., Hohl, R.J., Zimmerman, K.A., Yoder, B.K., Longhini, A.L., Hanumanthu, V.S., Surolia, R., Antony, V.B., Carter, A.B. 2019. Increased flux through the mevalonate pathway mediates fibrotic repair without injury. J Clin Invest. 129(11):4962-4978. PMID: 31609245
4. Zimmerman, KA., Huang, J., He, L., Li, Z., Fitzgibbon, W.R., Hazard, E.S., Hardiman, G., Mrug, M., Bell, P.D., Yoder, B.K., and Saigusa, T. IRF5 produced by kidney macrophages promotes polycystic kidney disease. Kidney 360
A full list of Dr. Zimmerman's research publications can be found at: https://www.ncbi.nlm.nih.gov/myncbi/1vWJzwb3kLkAi/bibliography/public/