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WashU Center researchers will create maps showing the genetic details of normal and diseased kidneys
Researchers at Washington University School of Medicine in St. Louis have received a grant from the National Institutes of Health (NIH) to establish a pediatric center of excellence in nephrology. The center’s physician-scientists will create high-definition molecular reference maps showing the genetic details of normal and diseased kidneys during different stages of child growth and development. The center team will also launch related educational programs to attract new researchers to the field.
Kidney problems in children can range from short-term treatable disorders to chronic illnesses with devastating long-term consequences, including kidney failure, which requires dialysis treatment and often a kidney transplant. Common causes of kidney disease include birth defects, hereditary diseases, immunological damage, infections, and the consequences of other systemic problems, such as diabetes and hypertension. Children with chronic kidney disease may spend longer in hospital, incur higher health care costs and have a higher risk of death than pediatric patients hospitalized with other chronic conditions, research shows.
“The development of effective methods for the early detection and measurement of the severity of kidney disease in children has lagged in part due to a lack of knowledge about the physiological and pathological changes that occur as the kidney matures,” said co-principal investigator Vikas Dharnidharka, MD, director of the division of pediatric nephrology, hypertension, and pheresis in the medical school’s department of pediatrics. “The molecular patterns generated by our initiative will greatly improve our ability to design effective approaches to intervene and prevent kidney dysfunction.”
Dharnidharka, Alexis F. Hartmann Sr., MD, professor of pediatrics and vice chair of clinical investigations in the department of pediatrics, is also co-medical director of the pediatric kidney transplant program at St. Louis Children’s Hospital, where he treats patients. Nationally recognized for their expertise in the diagnosis and treatment of kidney disease, pediatric specialists at the University of Washington have led St. Louis Children’s to become a major referral center for children with kidney disease.
Sanjay Jain, MD, PhD, professor of medicine in the Division of Nephrology in the Department of Medicine, will serve as co-principal investigator and project leader for the initiative. Jain, a researcher at the school’s Center for Regenerative Medicine, studies the biology of kidney and lower urinary tract stem cells, focusing on their potential to differentiate or remain stable in healthy and diseased states.
His lab explores how the kidneys form, how they connect to the bladder, and how their cellular and molecular makeup changes throughout life. His other NIH projects include the Kidney Precision Medicine Initiative and the Kidney Single Cell and Spatial Molecular Atlas Project under the Human Biomolecular Atlas Project, with funding from the NIH Common Fund, the Kidney Precision Medicine Project, and the National Institute of Diabetes. and Digestive and Kidney Diseases (NIDDK).
The Center of Excellence awards are funded through a highly competitive five-year selection process administered by the NIDDK. Only three such projects receive funding each cycle.
The leaders of the initiative will manage an annual program of pilot projects and various educational initiatives, including an annual research symposium, an eight-week summer internship program and a guest lectures program, all designed to attract new researchers to the the domain. Program funding runs through June 2027.
Researchers will analyze healthy and diseased samples of pediatric kidneys using single-cell and spatial transcriptomics, a molecular profiling method that allows scientists to precisely measure and map where gene activity occurs in a single cell or a group of cells. By comparing how gene expression and cellular functions change during healthy development and disease progression, researchers hope to identify which changes play a role in making and maintaining healthy kidneys and which ones contribute to the disease.
“Our goal is to detail the genetic and cellular mechanisms of childhood kidney failure and its progression to aid in the development of new diagnostic tests, improved drugs, unique personalized therapies, and other clinical improvements that will help us limit or even cure genetic or acquired kidney disorders,” Jain said.
Other University of Washington co-investigators are Michael Rauchman, MD, Chromalloy Professor of Kidney Disease in Medicine; and Joseph Gaut, MD, PhD, Ladenson Professor of Pathology and Immunology. The multidisciplinary team also includes co-investigators Gloria Pryhuber, MD, neonatologist from the University of Rochester, and Michael Eadon, MD, nephrologist from Indiana University.
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