The Heersink School of Medicine has awarded the annual Multi-Investigator Program Award to three research investigators for the 2021-2022 cycle: Timmy Lee, M.D., Bruce Korf, M.D., Ph.D., and David Pollock, Ph.D.
The Multi-Investigator Program Award is unique to Heersink School of Medicine; it invites the applications of exploratory and developmental grants with interrelated projects, at least three principal investigators on the project, and requires allows a request of more dollars than the standard modular budget.
Funding is $150,000 for two years which began March 1 this year.
These awards exemplify why research at Heersink is unique: robust collaborative research.
The purpose of these grants is to enable Heersink faculty members to organize and integrate multi-disciplinary teams of accomplished investigators that will compete successfully for long-term support from funding agencies. Additional financial support will provide the award-winning teams with an opportunity to advance their studies.
Timmy Lee, M.D.Timmy Lee, M.D., David G. Warnock Endowed Professorship, professor in the Division of Nephrology, and vice chair of Research in the Department of Medicine, was awarded a Multi-PI Award for his study “Tissue Engineered Arteriovenous Fistula Model with Atherosclerosis for Studying Venous Endothelial Cell Autophagy.”
When asked how a multi-disciplinary approach will contribute to the study’s success, Lee said his multi-disciplinary team includes Ho-Wook Jun, Ph.D., a biomedical engineer with extensive expertise in biomaterials in the vascular bed, a vascular biologist—Jeonga Kim, Ph.D., associate professor in the Department of Medicine—who has expertise and available tools to study autophagy and atherosclerosis, and himself, a translational researcher in vascular access and nephrologist.
“Our expertise allows us to use state of the art biomedical engineering technology, advanced imaging tools, and translational animal models to investigate endothelial autophagy, and atherosclerosis and chronic kidney disease (CKD) to better understand why arteriovenous fistulas do not successfully develop,” he explained.
Lee said the study’s relevance to human disease is due to the arteriovenous fistula being the dialysis patient’s lifeline for the hemodialysis procedure. “Our study will provide new insights into the mechanisms of arteriovenous fistula maturation failure in end stage kidney disease patients,” he said. “[It will] facilitate new therapeutic development, which will help improve morbidity and mortality for end stage kidney disease patients.”
Lee is looking forward to the future, as the funding will help his study’s longevity. “This award will provide vital resources to generate preliminary data for a successful multiple-PI NIH R01 submission. Our results will not only help us develop new therapies for improving arteriovenous fistula maturation for hemodialysis patients, but will also have broad implications for other vascular conditions such as peripheral arterial disease, coronary artery disease, and postangioplasty restenosis,” he said.
Bruce Korf, M.D., Ph.D.Bruce Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Endowed Chair in Medical Genetics, associate dean for Genomic Medicine, chief genomics officer at UAB Medicine, and co-director of the UAB-HudsonAlpha Center for Genomic Medicine, was awarded a Multi-PI Award for his study UAB Gene Therapy Neurofibromatosis Program.
Korf has been long-interested in neurofibromatosis, funding the Neurofibromatosis Clinical Trials Consortium and researching treatment of neurofibromatosis for decades.
The Multi-PI Award will support Korf’s ongoing service to finding treatment for neurofibromatosis. His team includes David Bedwell, Ph.D., professor and chair of the Department of Biochemistry and Molecular Genetics, Robert Kesterson, Ph.D., professor in the Division of Genetics Research, and Deeann Wallis, Ph.D., associate professor in the Division of Genetics Research.
When asked about his priorities with the grant, he said, “Our goal is to develop new approaches to treatment of neurofibromatosis, which is a genetic disorder that causes tumors to form all over the body. In addition, it causes learning disabilities, problems in bone growth, and increased risk of malignant tumors.”
“We hope to develop methods to either restore function to the gene that has been damaged by mutation, or to find ways to either edit or replace the defective gene,” he explained. “There are many different types of gene mutations that can be responsible for neurofibromatosis.”
A collaborative, interdisciplinary approach to researching neurofibromatosis is critical. “Our multi-disciplinary team is developing multiple approaches that we hope will be effective in treating the condition. This involves the use of cell culture and animal systems, requiring expertise that spans multiple disciplines, and requiring a team approach.”
Korf said his and his team’s main desire is to develop new approaches to treatment of neurofibromatosis that will ultimately reduce the medical burden of the disorder.
Additionally, Korf explained that the award is valuable in the present moment but also for future research. “This award will permit us to develop preliminary data that we hope will result in NIH funding to allow us to expand and accelerate our efforts to develop new treatments for neurofibromatosis.”
David Pollock, Ph.D.David Pollock, Ph.D., professor in the Division of Nephrology, was awarded a Multi-PI Award for his study “APOL1 gene variants and ET-1 as predictors of sickle cell nephropathy.”
The overall goal of the proposed research is to determine whether the combination of elevated ET-1 and APOL1 mutations result in earlier progression end-stage kidney disease in sickle cell anemia patients. The AMC21 grant will allow the team to generate additional preliminary data in pediatric patients to justify a larger study that would justify applying for NIH support. Furthermore, studies with mouse models are expected to provide mechanistic for the use of these markers to or even potential mechanisms for therapeutic interventions.
Sickle cell disease is the most common inherited blood disease that primarily impacts individuals of African descent. Chronic kidney disease is a major cause of complications and contributes to the early mortality in these individuals, but there are no means of identifying who is at risk.
“Importantly, we have begun to establish a large pediatric cohort with sickle cell disease and hope to develop a means of identifying the age at which kidney disease progression occurs. Our collaborators at St. Jude Children’s Research Hospital have identified APOL1 mutations that are correlated with proteinuria while our group at UAB have observed a similar correlation with the circulating endothelial factor, endothelin,” Pollock said. Their plan is to examine each of these factors in a combined cohort. “The mouse models needed to study mechanisms of kidney injury with APOL1 variants are available, yet how they may contribute to sickle nephropathy has not been previously examined.”
The current goal of the study is to gather both clinical and mechanistic rationale for their hypothesis that the combination of two factors, elevated ET-1 and APOL1 mutations, predict risk of early progression to chronic kidney disease.
Pollock’s multi-disciplinary team from UAB includes Jeffrey Lebensburger, M.D., director of Pediatric Hematology Section in the Division of Pediatric Hematology Oncology and professor in the Department of Pediatrics, Jennifer S. Pollock, Ph.D., professor in the Division of Nephrology, and Malgorzata “Gosia” Kasztan, Ph.D., assistant professor in the Department of Pediatrics in Pediatric Hematology. Nationally, Rima Zahr, M.D., pediatric nephrologist in the Department of Pediatrics at St. Jude Children’s Research Hospital, is also part of the study.