LRI Scientists Win $60 Million from NIH to Expand Research
Innovation Drives Powerful New Research Model for Complex Disease
Wednesday, October 1, 2008
A recent analysis shows that 65 percent of the 53 LRI scientists who have completed their 3-year Novel Research grants—an LRI investment of $13.5 million—have successfully proven their innovative hypotheses and gone on to secure nearly $60 million at the National Institutes of Health (NIH) and other agencies to expand lupus research.
“The scope, speed, and consistent pace of this scientific discovery are unprecedented in privatesector lupus research,” said LRI President Margaret Dowd. “We began convinced that the path to a cure lay in freeing investigators to think creatively and imaginatively, so we asked for outside-of-the-box thinking. LRI investigators have turned that box inside-out and upside-down.”
“The LRI strategy of funding novel scientific ideas in lupus has more than demonstrated its power,” adds William E. Paul, MD, chair of the LRI’s Scientific Advisory Board. “The model strengthens the lupus research landscape by moving novel concepts forward to secure large-scale federal funding.”
The LRI invests $300,000 each in grants for innovative projects at academic medical centers nationwide. It’s the only organization pioneering lupus discovery through this bold, high-risk model.
At first, no one else would fund exploration of Dr. Betty Diamond’s novel idea that certain stress hormones might be responsible for allowing toxic antibodies to penetrate the brain in lupus and destroy nerve cells there, causing memory loss, confusion, and other cognitive problems. Now the Feinstein Institute for Medical Research researcher has an LRI-generated NIH program grant for $6.5 million to build on more strategies for dealing with this devastating development.
At first, no one else would fund exploration of Dr. Marcus Clark’s novel idea that the kidneys of people with lupus may actually contain activated B cells that directly promote inflammation and damage in these critical organs. But in his LRI research, Dr. Clark examined small bits of tissue taken from inflamed lupus kidneys—and did in fact find activated B cells. Now the University of Chicago researcher has an NIH grant for $1.1 million to further explore, explain, and expand on this major discovery. “This government grant was funded entirely based on research supported by the LRI,” Dr. Clark said.
At first, no one else would fund exploration of Dr. Elahna Paul’s novel idea that a special mouse model could be used to identify and block pathways of kidney cell activation and associated inflammation and damage in lupus. Now the Massachusetts General Hospital researcher has an NIH grant for $1.6 million to continue this groundbreaking work.
#1 NIH Grant to LRI Researcher Zhixin Zhang, PhD
Dr. Zhixin (Jason) Zhang’s grant proposal was so strong that the National Institutes of Health (NIH) ranked it NUMBER ONE out of 500 applications.
At first, no one else would fund exploration of Dr. Zhixin (Jason) Zhang’s novel idea that the normal immune system process that alters antibody genes—VH replacement—is what goes into overdrive in lupus, causing B cells to make damaging autoantibodies. But with LRI funding, he was able to show that 30 to 60 percent of these genes in people with lupus are in fact generated by this ‘VH replacement’ process, compared with less than 5 percent in healthy people. Now the former University of Alabama researcher, currently at the University of Nebraska, has received two NIH grants totaling $2.9 million to further pursue this discovery and its potential to find an early marker for lupus diagnoses and organ involvement. He’ll also look at whether chronic viral or bacterial infections may actually trigger lupus.
“Without the LRI we wouldn’t have been able to generate
the preliminary data for the NIH grants,” Zhang said.
“LRI support made this happen.”
At first, no one else would fund exploration of Dr. Greg Lemke’s novel idea that a curious family of “TAM” receptors might function as a core ‘control switch’ over the immune system’s inflammatory response. But he was right. Now the Salk Institute for Biologic Studies researcher has grants of $1.4 million from the NIH and others to explore exciting new approaches to mastering this switch—shutting down the uncontrolled inflammation of lupus and other autoimmune illnesses by restoring immune system regulation. “Without the LRI…this fundamental discovery in immunology wouldn’t have happened,” Dr. Lemke said.
At first, no funding group except the LRI would back exploration of Drs. Bevra Hahn and Maureen McMahon’s novel idea that a certain form of the normally “good” HDL cholesterol linked to heart health might play a counterproductive role in lupus and actually promote atherosclerosis. Now the University of California at Los Angeles researchers have various grants totaling over $869,000 to find new ways to detect, prevent and treat lupus related atherosclerosis.
At first, no one else would fund exploration of Dr. Amy S. Major’s novel model for accelerated atherosclerosis in lupus. Dr. Major believed the model held promise for explaining what immune system activities lead to premature atherosclerosis and heart enlargement (cardiomyopathy) in so many people with lupus, raising their risk for heart attack and stroke. Now the Vanderbilt University School of Medicine researcher has an NIH grant for $1.5 million to further develop this animal model and generate techniques for early detection and prevention of lupus atherosclerosis. “I am thrilled that I could provide a great return on your investment in me!” Dr. Major said.
At first, no one else would fund exploration of Dr. Chander Raman’s novel idea that tinkering with a molecule known as CD5 might reprogram the immune system by sounding the death knell for auto-reactive B cells. Now the University of Alabama at Birmingham researcher has an NIH grant for $1.8 million to examine this approach to shutting off the over-reactive immune system. The research may also help with treatments for other immune system illnesses such as MS and rheumatoid arthritis. “There is no way this [NIH] grant would have happened without the LRI,” Dr. Raman said.
At first, no one else would fund exploration of Dr. Christopher Roman’s novel idea that the damaging over-stimulation of the immune system in lupus could be mitigated by inactivating the gene regulatory proteins that his lab discovered control the molecule CD40L and others normally charged with fighting infections. Now the State University of New York Downstate Medical Center (Brooklyn) researcher has an NIH grant for $1.35 million to look deeper into the link between CD40L gene regulation, infection, abnormal behavior in immune system cells, and lupus.
At first, no one else would fund exploration of Dr. Eric Greidinger’s novel approach to predicting lupus organ damage. With LRI funds, he developed a special model to assess the potential of immune system “danger signal” sensors to indicate which organs and tissues in lupus were under imminent attack. Now the University of Miami Miller School of Medicine researcher has a Veterans Administration grant for $650,000 to further study these immune response patterns and their potential for generating new therapies that could convert severe disease to mild disease.
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