Researchers at the University of Colorado School of Medicine have been awarded a $2 million grant by the National Institutes of Health (NIH) to contribute to the creation of the Kidney Tissue Atlas that will help improve care to patients with life-limiting kidney diseases.
Over the next five years, Elena Hsieh, MD, associate professor of pediatrics - allergy and immunology, and Joshua Thurman, MD, professor of medicine in the Division of Renal Diseases and Hypertension, and their teams and colleagues on the Anschutz Medical Campus will use multiplexed ion beam imaging (MIBI) technology and spatial transcriptomic platforms to identify critical kidney cells and tissue infiltrating immune cells to promote precision medicine and discover novel therapeutic targets in chronic kidney disease and acute kidney injury.
New technology to gain more insight
The grant is part of the next stage of the NIH’s Kidney Precision Medicine Project, and the Anschutz Medical Campus is a tissue interrogation site, using and developing innovative technologies to analyze human kidney tissue.
“We always say that a biopsy is the gold standard for diagnosing the cause of disease, but how we as a scientific community have been analyzing kidney tissue has been quite primitive,” Thurman says. “We analyze it by light microscopy, and pathologists might stain it for three or four different things. What we are going to be doing as part of this initiative is to take those same biopsy tissues, but then applying this MIBI technology, we’ll be getting single cell resolution with 40-plus different markers.
“Our hope is that, using technologies like this, we will gain so much more insight into what is causing kidney disease progression, leading to better diagnostics and therapies,” says Thurman.
Chronic kidney disease (CKD) is a public health epidemic and along with end stage kidney disease account for more than 20% of Medicare expenditures. Additionally, acute kidney injury (AKI) is a major clinical problem without effective treatments. AKI and CKD are widespread problems that reduce quality of life and often lead to death. The diseases are interrelated, but current tests do not provide the detail needed to make an accurate prognosis. Currently, supportive care is the only therapeutic option for these diseases.
Targeting new potential therapies
In their study, Thurman and Hsieh propose using the types of tests that have been helpful in transforming cancer biology. These tools have allowed much better classification of tumors based on
shared cell types, pathways, and the spatial relationships between cell types and certain tumor areas, rather than simply classifying them based on their histologic appearance or the tissue of origin. With the information they collect, Hsieh and Thurman plan to develop single-cell cellular proteomic and transcriptional maps of the kidney that researchers can use to better target potential therapies.
Their research requires strong skill at the laboratory bench, cutting-edge instrumentation, and deep capabilities in data analysis. At the CU School of Medicine, Hsieh and Thurman will draw on investments previously made by the Dean’s Office in the Human Immunology and Immunotherapy Initiative and the RNA Bioscience Initiative, and the data analytics will be supported by specialists from the Colorado School of Public Health.
“We are proposing to do the single cell protein studies and the single cell transcript studies from basically the same patients and integrate the data, and we got funded because we have the instrumentation to do it,” Hsieh says. “We have the analytical support because of the strengths of the biostatistics and informatics on campus.
“At the School of Medicine, we come with the immunology background, the bench work, the instrumentation, and the experimental side,” Hsieh says. “The School of Public Health houses the people who are also in the grant, and they will do the analytical work, because this is very complex data and new analytical approaches need to be developed.”