Division of Nephrology
Sanna-Cherchi Lab
ENVISIONING SCIENCE-BASED PRECISION MEDICINE THROUGH GENE DISCOVERY AND FUNCTIONAL MODELING
Lopez-Rivera et al., “Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.” N Engl J Med 2017; 376:742-754
Kidney Abnormalities and the 22q11.2 Microdeletion Syndrome
CAKUT phenotypes are described in ~30% of patients with DiGeorge Syndrome (DGS), also known as 22q11.2 Microdeletion Syndrome (MDS). This project follows our major finding that identified the CRKL gene as a key driver of CAKUT phenotypes observed in a subset of patients afflicted with DGS, as well as in patients with sporadic, non-syndromic kidney and urinary tract anomalies. Using a multidisciplinary approach, we are using functional modeling in animals to discover how mutations in Crkl, a molecular adaptor protein involved in cell-to-cell communication, ultimately lead to divergence from normal development.
Investigators: Jeremiah Martino, PhD; Qingxue Liu, MS; Tze Yin (Joanne) Lim, MS
Collaborators: Rosemary Sampogna, MD, PhD
Verbitsky et al., “The Copy Number Variation Landscape of Congenital Anomalies of the Kidney and Urinary Tract.” Nat Genet. 2019 Jan;51(1):117-127
Pleiotropic effects associated with the 16p11.2 microdeletion syndrome
The chromosome 16p11.2 microdeletion syndrome is one of the most common genetic causes of syndromic forms of autism and neuroddevelopmental delay. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome. In a follow-up to these findings, we use multiomic approaches in a Tbx6 mouse allelic series to characterize the dose- and spatial- dependent functions of this transcription factor at a single cell level.
Investigators: Jeremiah Martino, PhD; Gregory Whittemore, MD; Qingxue Liu, MS; Tze Yin (Joanne) Lim, MS; Yask Gupta, PhD
Collaborators: Cathy Mendelsohn, PhD; Benjamin Izar, MD, PhD
Ahram, et al., “Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.” J Am Soc Nephrol. 2023 Jun 1;34(6):1105-1119
Rare variant Analysis and gene discovery in Congenital Obstructive Uropathy
Congenital obstructive uropathy (COU) is a commonly observed urinary anomaly underlying a large fraction of kidney failure in children and young adults. Under the hypothesis that a significant portion of disease is attributable to rare variants with large effect size, we are conducting large-scale exome and genome sequencing studies to identify genes involved in the etiology of disease.
Investigators: Tze Y. (Joanne) Lim, MS; Juntao Ke, PhD
Collaborators: Cathy Mendelsohn, PhD; Ali G. Gharavi, MD
Genome-wide association study in congenital anomalies of the kidney and urinary tract (CAKUT)
The contribution of common variants with small-to-moderate effect size to the genetic architectur of CAKUT is poorly understood. We established a network of collaborators across three continents and enrolled thousands of individuals affected by CAKUT. We are conducting modern GWAS for CAKUT that take into account the contribution of rare highly penetrant single nucleotide and structural variants as well and potential environmental confounders, to dissect the complex polygenic background to congenital urinary tract defects.
Investigators: Tze Y. (Joanne) Lim; Juntao Ke, PhD
Collaborators: Cathy Mendelsohn, PhD; Ali G. Gharavi, MD
Genomic studies in Posterior Urethral Valves (PUV)
Posterior Urethral Valves (PUV) is a rare and severe form congenital urinary obstruction that occurs only in males. The genetic basis of PUV is virtually unknown. We are conducting whole genome sequencing studies in PUV trios (affect children and their unaffected parents) to address the contribution of rare and common de novo and inherited single nucleotide and structural variants in the conding and non coding genome.
Investigators: Yask Gupta; PhD; Tze Y. (Joanne) Lim; Juntao Ke, PhD
Collaborators: Cathy Mendelsohn, PhD
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