The Skorecki Lab

Translational Research

Genetics of Kidney Health and Disease Lab


Principal Investigator: Prof. Karl Skorecki

The main focus of research activity at the Kaylie Kidney Health Center of Research Excellence at the Clinical Research Institute at Rambam, is in the genetics of kidney health and disease. The laboratory is led by CRIR Member, Professor Karl Skorecki, and CRIR Associate Member, Professor Daniella Magen, and investigates the entire spectrum from rare high-penetrance mutations causing syndromic and non-syndromic kidney disease in families and extended kindred of the region, all the way to large scale population genetics of Chronic Kidney Disease risk variants. An example of the latter, is the identification of risk variants in the APOL1 gene, which account for a majority of the disparity in risk for chronic kidney disease in populations of Sub-Saharan African ancestry. Some 100 million people worldwide carry the high risk genotype at this locus, first reported by our group more than a decade ago, followed by extensive investigation of mechanisms and therapeutic approaches. The normal function of the APOL1 gene product is to confer protection against Trypanosoma disease in Sub-Saharan Africa, with the risk variants providing protection against a broader spectrum of virulent trypanosomal strains. With the identification of the gene product as a target for prevention and therapy of causally associated Chronic Kidney Disease, small molecule drug discovery and gene therapy approaches are been pursued vigorously in the lab, and also at numerous research centers worldwide. The research team also studies splicing, protein processing and trafficking, as part of the clarification of mechanisms of kidney cell injury with stimulated expression of the risk variant gene products. In collaboration with Professor Adi Livnat at the University of Haifa, the laboratory has also been interested in understanding the origination of these and other population-specific mutations, with the finding of non-random directional de novo germline mutagenesis. To advance to higher throughput, and clarify population level mechanisms, members of the laboratory are collaborating with Dr. Liran Shlush and his colleagues at the Weizmann Institute, in ultra-sensitive mutation detection methodologies. 

Professor Magen and her team focus on monogenic high-penetrance syndromic and non-syndromic kidney disease causing genetic mutations. A most current ongoing active example is a research project aimed at deciphering the role of a novel disease-causing variant in one of the MAPKs genes, in the pathogenesis of a hereditary multi-organ syndrome associated with skin, hair, and kidney defects. Functional analysis of the mutant gene product sheds light on previously unrecognized molecular pathways involved in epidermal and renal tissue development.

The research methodologies and approaches include a combination of human genetics with functional genomic models, including yeast, flies, murine genetics, induced pluripotent stem cell derived human kidney cells with genome editing, data science and computational approaches. Clinical translation also includes clinical research studies of kidney protective drugs, such as members of the gliflozin family, with collaborative research teams in Nigeria.

Given the variety of research infrastructure resources required, the laboratory also has extended resources at the Ruth and Bruce Rappaport Faculty of Medicine, which results in amplification of research technological capacities.

The Skorecki Lab

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