Katalin Susztak, a professor of internal medicine, nephrology, and genetics at the Perelman School of Medicine never envisaged she would one day pioneer groundbreaking advancements in kidney disease treatment. Yet, an unforeseen twist during her postgraduate training set her on a path of exploration to unravel the intricacies of the kidney and revolutionize the way kidney disease is identified, prevented, and managed.
It was during medical school in Hungary, where she was born and raised, that Susztak discovered her fascination with research to understand how organs and the human body works.
Her interest in kidney disease was sparked during her intern year when she saw a patient whose illness was caused by defects in the exact same transporter protein she had studied in graduate school.
According to Susztak, few new approaches had worked to treat or cure kidney disease over two decades, between 2000-2019 when she embarked on her career in this field, and the understanding of how the kidney helps the body get rid of waste remains incomplete. As she began developing her own research lab as a principal investigator, Susztak and her team looked at how more than one million people worldwide die of kidney failure each year—despite existing therapies that include drugs, dialysis and transplants. “We have to change that,” she said.
It was the early 2000s, when scientists were just starting to study gene expression changes in a genome-wide level, not just one gene at a time, which was immediately appealing for Susztak. She decided to analyze biopsy samples collected from patients with kidney disease using these genomics tools to take an open-ended or unbiased look at all the genes expressed in the samples. The goal was to identify new genes and molecular pathways for the development of diabetic kidney disease, the most common cause of renal failure in patients.
When Susztak moved to Penn Medicine, her team doubled down to tackle kidney disease using a variety of approaches. First, they started to focus on characterizing the genetic underpinning. Kidney function has a strong heritable component, meaning it tends to run in families, so by collecting genetic and kidney function data for more than 1.5 million people, her team was able to generate a genetic map of where the likely causal genes reside in the genome. Second, Susztak’s team expanded the use of tools for analyzing kidney tissue not only just how the expression of genes change (genomic) but also how genes are organized and regulated (epigenetics) as well as studying kidney proteins and metabolites at a global scale.
A critical limitation of prior work has been that the kidney is a very complex organ made of more than 30 different cell types. Nearly five years ago, Susztak’s lab made a major advancement for kidney disease when a single-cell tool—the first of its kind at Penn Medicine—became available for their use to pinpoint which kidney cells were responsible for different disease types at a cellular and molecular level. “It was transformative and accelerated our research and we were able to connect different subtypes of kidney disease to different cell types in the kidney,” says Susztak.
Now, thanks to the combination of human genetic information and variety of single-cell tools, her team has identified hundreds of genes likely contributing to kidney dysfunction. From this long list, Susztak’s lab has already characterized the role of nearly half a dozen specific genes to better understand why people develop kidney disease and how the diseases progress. Furthermore, Susztak has made her comprehensive datasets available to the public, via generating and maintaining a website where other scientists can look up and analyze her results and discover new genes.
This story is by Lauren Malecki. Read more at Penn Medicine News.
