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Kerstin Nündel takes on devastating disorder with Target Identification in Lupus grant

UMMS immunologist seeks to elucidate the roles of B cells, TLR9 and AXL in complex autoimmune disease

By Sandra Gray

UMass Medical School Communications

October 19, 2016
  Kerstin Nündel, PhD

Kerstin Nündel, PhD

UMass Medical School investigator Kerstin Nündel, PhD, is poised to help unravel the mysteries of lupus with a Target Identification in Lupus grant from the Lupus Research Alliance. Dr. Nündel, instructor in medicine in the Division of Rheumatology, will use the three-year, $574,000 grant to examine how the white blood cells called B cells go haywire in some individuals to cause the organ damage that is the hallmark of lupus.

“B cells are important for protecting you against viruses or bacteria, but if something goes wrong, they cause autoimmune disease,” said Nündel. “We are trying to understand how.”

More than 1.5 million Americans have lupus, a mysterious and devastating illness that strikes each patient differently. Symptoms may affect many different body systems, including joints, skin, kidneys, blood cells, heart and lungs. Its unpredictable symptoms and progression make targets for drug treatment elusive; only one new drug for lupus has been approved in the last 50 years.

Target Identification in Lupus grants fund innovative research conducted with state-of-the-art techniques that accelerate the development of new treatments for lupus. Prior to her 2014 promotion to instructor, Nündel was a postdoctoral fellow in the lab of Ann Marshak-Rothstein, PhD, professor of medicine in the Division of Rheumatology. Dr. Marshak-Rothstein's research group was the first to propose that a class of proteins called toll-like receptors (TLR) could have a primary role in lupus. Recent Marshak-Rothstein lab studies in which Nündel has been involved explores how one in particular, TLR9, protects against lupus. The work Nündel will conduct with the new grant builds on her previous discovery that TLR9 in B cells regulates a molecule called AXL in one of the pathways they study.

“Preliminary studies show that AXL causes migration, as when cancer metastasizes,” said Nündel. “Since one of the unexplored venues in autoimmune diseases is how B cells actually cause end organ damage like kidney failure, I am interested if AXL is the molecule that gets the B cells to the kidneys in lupus patients.”

While Nündel’s work involves basic science in mouse models, the alliance is funding her work for its potential to lead to treatments for lupus in humans. She is already formulating her next goals. “Our ultimate translational goal would be to target AXL with drugs that are already known to be effective in cancer cells,” she said. “If these drugs work in the pathway I am studying they could possibly be used to treat lupus patients.”

Related stories on UMassMedNow:
Ann Marshak-Rothstein awarded Lupus Insight Prize
UMMS researcher receives $1 million award for lupus work