John Sedor, MD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Inflammation and fibrosis - Signaling and metabolic networks
- Overall areas of interest with key words
- Chronic kidney disease, podocyte, precision medicine, glomerulus
- Tools and expertise of the lab
- Glomerular cell experimental cell systems (Madhavan, JCI Insight, 2017, O’Toole, J. Am Soc. Nephology, 2018, Kim, JBC, 2010, Kim, AJP Renal, 2011)
- Transgenic mice (Bruggeman, J Am Soc Nephrol, 2016, Bruggeman, PLoSOne, 2019)
- Spatial proteomics with APEX2 tag
- Examples of collaborators
- John O’Toole, Leslie Bruggeman – APOL1 and chronic kidney disease
- Oliver Wessely – iPSCs kidney disease pathogenesis
- Anant Madabhushi – computational pathology and kidney disease
- Dana Crawford, Will Bush – registries, clinical information, gene epi
- Lab discoveries
- APOL1 expression is kidney cells mediates disease (Madhavan, JASN, 2011, JCI Insight, 2017, Bruggeman, JASN, 2016 and PlOSOne, 2019)
- Mechanisms of APOL1 injury (Sampson, JASN, 2016, O’Toole. 2018)
- How could these discoveries help patients?
- New therapies that are mechanisms-based
- Define kidney diseases by mechanisms rather than pathologic description
- Predict therapy response using in vitro models derived from patient cells
- Implementation of first precision medicine-based therapies for patients with kidney diseases
- Jayapandian, C.P., Y. Chen, A.R. Janowczyk, M. B. Palmer, C.A. Cassol, M. Sekulic, J.B. Hodgin, S.M. Hewitt, J. O’Toole, P Toro, J.R. Sedor, Barisoni, and A. Madabhushi. Development and evaluation of deep learning-based segmentation of histologic structures in the kidney cortex with multiple stains. Kidney Int. 2020 Aug 21.
- Crawford, D.C., J. Lin, J.N. Cooke Bailey, T. Kinzy, J.R. Sedor, J.F. O’Toole, and W.S. Bush. Frequency of ClinVar pathogenic variants in chronic kidney disease patients surveyed for return of research results at a Cleveland public hospital. Pac. Symp. Biocomp. 25: 575-586, 2020.
- Bruggeman, L.A., Z. Wu, L.Luo, S. Madhavan, P.E. Drawz, D.B. Thomas, L. Barisoni, J.F. O’Toole,and J.R. Sedor. PLoS One. 2019 Oct 29; 14: e0224408.
- Madhavan, S.M., J.F. O’Toole, M. Konieczkowski, L. Barisoni, D.B. Thomas, S. Ganesan, L.A. Bruggeman, M. Buck, and J.R. Sedor. APOL1 Variants Change C-terminal Conformational Dynamics and binding to SNARE protein VAMP8. JCI Insight, 2017 Jul 20;2(14). pii: 92581. doi: 10.1172/jci.insight.92581.
Drs. Sedor and Boron are leading a collaboration of Cleveland biomedical institutions to address gaps in community health and training
Drs. Bruggeman, Sedor and O’Toole will investigate the pathogenic mechanisms of chronic kidney disease to develop greater understanding of genetic susceptibility and develop new treatment strategies.
Dr. Bruggeman shows in a new study that genetic variants to the APOL1 gene are associated with increased risk for pregnancy-induced hypertension in African American women.
By studying a model of HIV-associated nephropathy, a group of kidney disease researchers and clinicians discovered that in patients with the APOL1 risk gene, the presence of an environmental stressor, like a virus, can trigger cell changes that lead to chronic kidney diseases.