A means of preventing renal ischemia reperfusion injury in acute kidney injury.
Hospital-acquired acute kidney injury (AKI) accounts for 22% of all cases worldwide, and an estimated 50% of critically ill inpatients are estimated to suffer from AKI. AKI is associated with high rates of morbidity and mortality and causes 2 million deaths per year. Patients who recover are at a higher risk for subsequently developing chronically kidney disease (CKD); other times, the injury is so severe that it leads to end stage renal disease (ESRD). There are no definitive or effective treatments for AKI, nor are there available interventions to decrease the risk of progression to CKD after AKI.
Technology Description
One of the hallmarks of AKI is damage to renal microvasculature, which alters endothelial function and contributes to hypoxic and inflammatory injury to the renal parenchyma. In AKI, some miRNAs appear to act pathogenically by promoting inflammation, apoptosis, and fibrosis, while others may confer protective benefits. Researchers have obtained preliminary data indicating that the absence of the miR-17~92 cluster makes cells are more susceptible to renal ischemia-reperfusion injury while miR-18a and miR-19b protects against renal IRI, providing evidence for a potential novel therapeutic approach for the treatment of acute kidney injury.Advantages
Novel approach to treating acute kidney injuryApplications
Treating acute kidney injuryStage of Development
In vivo data in mice using mimicsIP Status
Provisional patent application filedRelevant Publications
Jacqueline Ho, Sunder Sims-Lucas, et al. Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury. JASN March 2021, 32 (3) 553-562; DOI: https://doi.org/10.1681/ASN.2020050717
Innovators
Sunder Sims-Lucas, PhD
Director, Histology Core, Rangos Research Center
Assistant Professor, Pediatrics
Director, Student Research Training, Rangos Research Center
Dr. Sims-Lucas’ research focuses on the formation of the kidney and the role of maternal stresses, including diabetes and malnutrition, on the formation of the kidney. His program focuses on acute kidney injury as well as the mechanisms that lead to predisposition to injury. He is a member of the American Society of Nephrology, the North American Vascular Biology Organization, the Vascular Medicine Institute, and the American Society of Physiology.Education
Postdoctoral, Kidney Development, University of Pittsburgh
Postdoctoral, Kidney Development, Nationwide Children’s Hospital
Postdoctoral, Lung Stem Cells, Australian Stem Cell Center
PhD, Kidney Development, Monash University,
BSc, Kidney Development and Anatomy/Physiology, Monash UniversityPublications
Dangle P, Salgado C, Reyes-Mugica M, Schneck F, Ost M, Sims-Lucas S. Testicular Hypoplasia Is Driven by Defective Vascular Formation. Urology. 2017 Mar;101:94-98.
Casinelli G, LaRosa J, Sharma M, Cherok E, Banerjee S, Branca M, Edmunds L, Wang Y, Sims-Lucas S, Churley L, Kelly S, Sun M, Stolz D, Graves JA. N-Myc overexpression increases cisplatin resistance in neuroblastoma via deregulation of mitochondrial dynamics. Cell Death Discov. 2016 Dec 12;2:16082.
Zhang Y, Bharathi SS, Rardin MJ, Lu J, Maringer KV, Sims-Lucas S, Prochownik EV, Gibson BW, Goetzman ES. Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain. J Biol Chem. 2017 Jun 16;292(24):10239-10249.
Mukherjee E, Maringer K, Papke E, Bushnell D, Schaefer C, Kramann R, Ho J, Humphreys BD, Bates C, Sims-Lucas S. Endothelial marker-expressing stromal cells are critical for kidney formation. Am J Physiol Renal Physiol. 2017 Sep 1;313(3):F611-F620.Jacqueline Ho, MD, Msc
Associate Professor, Pediatrics
Director, Pediatric Nephrology Fellowship, UPMC Children’s Hospital of Pittsburgh
Co-Director, Pediatric Scientist Development Program
Dr. Ho’s research focuses on understanding the role of microRNAs in kidney development and disease. Her laboratory has discovered important implications for congenital nephron endowment and subsequent kidney health in children and adults. She is a member of the American Academy of Pediatrics, the American Scoeity of Nephrology, the American Society of Pediatric Nephrology, the International Pediatric Nephrology Association, and the Society for Pediatric Research.Education
Clinical and Research Fellowship, Pediatric Nephrology, Children’s Hospital Boston-Harvard Medical School
Residency, Pediatrics, British Columbia Children’s Hospital
MD, University of Western Ontario
MSc, Developmental Biology, University of Toronto
BSc, Genetics, University of Western OntarioPublications
Hemker SL, Cerqueira DM, Bodnar AJ, Cargill KR, Clugston A, Anslow MJ, Sims-Lucas S, Kostka D and Ho J. Deletion of hypoxia-responsive microRNA-210 results in a sex-specific decrease in nephron number. FASEB J. 2020 Mar 5; doi: 10.1096/fj.201902767R. [Epub ahead of print] PMID: 32141129.
Anslow MJ, Bodnar AJ, Cerqueira DM, Bushnell D, Shrom BE, Sims-Lucas S, Bates CM and Ho J. Increased rates of vesicoureteral reflux in mice from deletion of Dicer in the peri-Wolffian duct stroma. Pediatr Res. 2020 Feb 3;. doi: 10.1038/s41390-020-0788-7. [Epub ahead of print]. PMID: 32015493.
Tan RJ, Li Y, Rush BM, Cerqueira DM, Zhou D, Fu H, Ho J, Stolz D and Liu Y. Tubular injury triggers podocyte dysfunction by β-catenin-driven release of MMP-7. JCI Insight. 2019 Dec 19;4(24). doi: 10.1172/jci.insight.122399. PMID: 31743113.