Molecular disease mechanisms in kidneys and allografts
Research Group Leader
- Prof. Dr. med. Kai Schmidt-Ott
Researchers
- Irma Karen Lopez-Cayuqueo, PhD, Postdoctoral Researcher
- Dr. rer. nat. Irini Schäfer, Postdoctoral Researcher
- Dr. med. Song Rong, Postdoctoral Researcher
- Dr. rer. biol. hum. Irina Scheffner, Data Scientist
- Shuang Cao, PhD student
- Arnold Tsamo Tetou, PhD student
- Mai Abdelhalim Mohamed, PhD student
- Herle Chlebusch, technical assistant
- Martina Flechsig, technical assistant
Research profile
The kidneys excrete toxins, regulate blood pressure, volume and electrolyte balance and produce hormones. Kidneys are composed of functional units called nephrons, which each consist of more than 20 different cell types. Disorders of embryonic development of the kidney due to genetic or environmental factors lead to congenital defects of the kidney and the urinary tract, arterial hypertension and increased susceptibility to progressive kidney diseases. Kidneys can be injured by hypoxia, ischemia, immunological processes, or toxins. While healthy kidney cells have remarkable potential for repair, this regenerative potential is significantly impaired in aging and in individuals with genetic or developmental predisposition or comorbidities such as diabetes or hypertension. The situation is even more complex in the transplanted kidney allograft, where complex interactions between immunological, infectious, and toxic processes concur in a significant subset of patients. Major goals of modern nephrology include the prevention of progressive injury to the kidney or allograft by nephroprotective measures as well as the development of improved molecular high-resolution diagnostics and targeted therapies.
Our group investigates the molecular and cellular basis of developmental and genetic injury susceptibility, injury response and repair of epithelial cells within the kidney and allograft. We focus on gene regulatory mechanisms that control aspects of epithelial differentiation, regeneration, and homeostasis. Our ultimate goal is to improve the prediction, classification and therapy in patients with kidney disease.
We use high-throughput technologies and bioinformatics approaches and combine them with classical methods of developmental biology and renal physiology as well as genetic and experimental models of renal injury. In addition, we coordinate prospective observational and interventional clinical studies with the aim to characterize the epidemiology, the clinical characteristics and the molecular mechanisms of different kidney diseases and test new therapeutic approaches.
Selected publications
Hinze C, Lovric S, Halloran PF, Barasch J, Schmidt-Ott KM. Epithelial cell states associated with kidney and allograft injury. Nat Rev Nephrol. 2024.
Swolinsky JS, Hinz RM, Markus CE, Singer E, Bachmann F, Halleck F, Kron S, Naik MG, Schmidt D, Obermeier M, Gebert P, Rauch G, Kropf S, Haase M, Budde K, Eckardt KU, Westhoff TH, Schmidt-Ott KM. Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss. Nephrol Dial Transplant. 39:483-495, 2024.
Mansour F, Hinze C, Telugu NS, Kresoja J, Shaheed IB, Mosimann C, Diecke S, Schmidt-Ott KM. The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage. Elife, 11:e80165, 2022.
Hinze C, Kocks C, Leiz J, Karaiskos N, Boltengagen A, Cao S, Skopnik CM, Klocke J, Hardenberg JH, Stockmann H, Gotthardt I, Obermayer B, Haghverdi L, Wyler E, Landthaler M, Bachmann S, Hocke AC, Corman V, Busch J, Schneider W, Himmerkus N, Bleich M, Eckardt KU, Enghard P, Rajewsky N, Schmidt-Ott KM. Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury. Genome Medicine, 14:103, 2022.
Hinze C, Karaiskos N, Boltengagen A, Walentin K, Redo K, Himmerkus N, Bleich M, Potter SS, Potter AS, Eckardt KU, Kocks C, Rajewsky N#, Schmidt-Ott KM#: Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality Gradients. Journal of the American Society of Nephrology, 32:291-306, 2021.
Vukićević T*, Hinze C*, Baltzer S, Himmerkus N, Quintanova C, Zühlke K, Compton F, Ahlborn R, Dema A, Eichhorst J, Wiesner B, Bleich M, Schmidt-Ott KM#, Klussmann E#: Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking. Journal of the American Society of Nephrology, 30:795-810, 2019.
Vigolo E*, Marko L*, Hinze C, Müller DN#, Schmidt-Ullrich R#, Schmidt-Ott KM#: Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury. Kidney International, 95:108-122, 2019.
Hinze C*, Ruffert J*, Walentin K*, Himmerkus N, Nikpey E, Tenstad O, Wiig H, Mutig K, Yurtdas ZY, Klein JD, Sands JM, Branchi F, Schumann M, Bachmann S, Bleich M, Schmidt-Ott KM: GRHL2 is required for collecting duct epithelial barrier function and renal osmoregulation. Journal of the American Society of Nephrology, 29:857-868, 2018.
Werth M*, Schmidt-Ott KM*, Leete T, Qiu A, Hinze C, Viltard M, Paragas N, Shawber CJ, Yu W, Lee P, Chen X, Sarkar A, Mu W, Rittenberg A, Lin CS, Kitajewski J, Al-Awqati Q, Barasch J: Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts. eLife, 6:e24265, 2017.
Marko L*, Vigolo E*, Hinze C, Park JK, Roel G, Balogh A, Choi M, Wuebken A, Cording J, Blasig IE, Luft FC, Scheidereit C, Schmidt-Ott KM#, Schmidt-Ullrich R#, Muller DN#: Tubular Epithelial NF-kB Activity Regulates Ischemic AKI. Journal of the American Society of Nephrology, 27:2658-2669, 2016.
Aue A*, Hinze C*, Walentin K, Ruffert, Yurtdas Y, Werth M, Chen W, Rabien A, Kilic E, Schulzke JD, Schumann M, Schmidt-Ott KM: A grainyhead-like 2/ovo-like 2 pathway regulates renal epithelial barrier function and lumen expansion. Journal of the American Society of Nephrology, 26:2704-15, 2015.
Walentin K, Hinze C, Werth M, Haase N, Varma S, Morell R, Aue A, Pötschke E, Warburton D, Qiu A, Barasch J, Purfürst B, Dieterich C, Popova E, Bader M, Dechend R, Staff AC, Yurtdas ZY, Kilic E, Schmidt-Ott KM: A Grhl2-dependent gene network controls trophoblast branching morphogenesis. Development, 142:1125-1136, 2015.
Paragas N*, Kulkarni R*, Werth M*, Schmidt-Ott KM*, Forster C, Deng R, Zhang Q, Singer E, Klose AD, Shen TH, Francis KP, Ray S, Vijayakumar S, Seward S, Bovino ME, Xu K, Takabe Y, Amaral FE, Mohan S, Wax R, Corbin K, Sanna-Cherchi S, Mori K, Johnson L, Nickolas T, D'Agati V, Lin CS, Qiu A, Al-Awqati Q, Ratner AJ, Barasch J: α-Intercalated cells defend the urinary system from bacterial infection. The Journal of Clinical Investigation, 124:2963-2976, 2014.
Nickolas TL*#, Schmidt-Ott KM*#, Canetta P, Forster C, Singer E, Sise M, Elger A, Maarouf O, Sola-Del Valle DA, O’Rourke M, Sherman E, Lee P, Geara A, Imus P, Guddati A, Polland A, Rahman W, Elitok S, Malik N, Giglio J, El-Sayegh S, Devarajan P, Hebbar S, Saggi SJ, Hahn B, Kettritz R, Luft FC, Barasch J: Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage - A Multicenter Prospective Cohort Study. Journal of the American College of Cardiology, 59:235-244, 2012.
*equal contribution | #Corresponding authors
Selected third-party funding
Deutsche Forschungsgemeinschaft, Collaborative Research Consortium 1365, Renoprotection
Deutsche Forschungsgemeinschaft, Research Unit 2841, Beyond the exome
Deutsche Forschungsgemeinschaft, Graduate School 2318, Tight junctions and their proteins
ERA PerMed, ONAKI-ICI, Towards a personalised management of oncologic patients with acute kidney injury to immune checkpoint inhibitors
Open positions and PhD projects
We welcome applications for postdoc and PhD student positions. If you are interested, please submit your application including a letter of motivation, curriculum vitae and relevant certificates to Nephrologie(at)mh-hannover.de. We aim for an integration of candidates into structured programs (e.g. HBRS-Molecular Medicine).
Contact
Univ.-Prof. Dr. med. Kai Schmidt-Ott
Chief of the Department of Nephrology and Hypertension
Hannover Medical School
OE6840, Carl-Neuberg-Str. 1, 30625 Hannover
Tel: +49 511 532 6320, Fax: +49 511 532-18515
Email: Nephrologie(at)mh-hannover.de