The MCRC has a robust Pilot Project Program utilizing institutional funds. Institutional commitments support comptetive pilot projects addressing the MCRC mission.
Year 1 Pilot Projects:
Pilot Project 1
Paula Ramos, Ph.D.
Systemic lupus erythematosus (SLE) disproportionately affects African Americans (AA). In spite of its higher prevalence and severity, little is known about the etiology of SLE in AA, and the reason for the health disparity is unknown. Since human genome structure at a population level is shaped by adaptation to environmental pressures, one plausible reason for their higher disease risk may be a direct effect of population-specific positive natural selection, causing increased frequency of alleles under positive selection. As such, understanding the contribution of positive selection to the genetic structure of the AA population will provide insights into the areas of genetic anthropology and disease etiology. Given their African and European ancestry, the identification of signatures of selection is complicated by their admixture. Since regions under recent selection may be more easily detected in homogeneous populations, we will use data on the Gullah, which are the most homogeneous population of African ancestry in the U.S. Their ancestors were forcibly brought from the Sierra Leone and Ivory Coast area in West Africa, and were kept in the geographically isolated Sea Islands along the South Carolina and Georgia coasts. Interestingly, an increased familial clustering of autoimmunity in the Gullah suggests that this unique population might be useful for the identification of SLE risk loci in AAs. The long-term goal of this project is to delineate the role of natural selection in the Gullah and understand its contribution to the high prevalence of SLE.
Pilot Project 2
Tammy Nowling, Ph.D.
The study will provide valuable preliminary data supporting applications for extramural funding to elucidate the molecular mechanisms by which the glycosphingolipid metabolic pathway contributes to the progression of nephritis, the efficacy of FDA-approved inhibitors of the pathway in protecting and/or slowing progression of nephritis and whether molecules in this pathway may serve as more sensitive markers of nephritis and/or nephritis flares.We hypothesize that elevated GluCer and LacCer levels increase inflammatory pathways and renal damage in lupus nephritis. Our long-term goal is to reduce the renal damage and slow the progression of nephritis in lupus by utilizing existing novel therapeutic approaches for treating inflammatory renal diseases.
Pilot Project 3
Sibnath Ghatak, Ph.D.
Our long term goal is to determine the roles of TGF-β and/or CD44v6 (hyaluronan receptor) specific microRNAs involved in the pathogenesis of diffuse cutaneous systemic sclerosis (dcSSc) fibrosis that will help us to understand the pathogenesis of dcSSc and to identify novel methods for the diagnosis and treatment of the disease. Increased mortality is associated with African Americans with SSc compared to Caucacians. Ethnic differences in TGF-β effects on related molecules involved in SSc is an important factor underlying the severity of SSc in African Americans.
Year 2 Pilot Projects:
Pilot Project 1
Wei Jiang, M.D.
The goal of the proposed research is to investigate the role of sex hormones in microbial translocation and monocyte activation and how this effects on lupus etiology and pathogenesis. Using gender differences as a model to study gut function, microbial translocation, TLR responsiveness, immune function and lupus disease etiology and pathogenesis, will provide important information in sex differences in healthy individuals and autoimmune diseases such as lupus. Dr. Rockey, an expert in the field of gatroenterology research, will collaborate with Dr. Jiang as a co-investigator to study the role of sex hormones in the gut epithelial function. This expertise will build a research effort in studying gender differences in immune function (both systemic and mucosa) and resultant differences in disease pathogenesis of SLE.
Pilot Project 2
Natasha Ruth, M.D.
The purpose of our proposal is to obtain preliminary estimates of the association between dMRI metrics, current biomarkers (autoantibodies) and neurocognitive impairment in children with SLE. The funding of this pilot project will help support and sustain ongoing research in the area of neuroimaging and NPSLE. This pilot study will also support ethnic disparities research as lupus is known to predominantly affect women and more severly women of color. Our overall hypotheiss is that patients with SLE will have neurocognitive impairment based on formal neurocognitive testing, that serum autoantibodies are not correlative with cognitive impairment and that patients with SLE will exhibit more white matter changes on dMRI that are associated with neurocognitive impairment.
Pilot Project 3
Yunyun Su, M.D.
This proposal is based on a recent observation that endostatin, an anti-fibrotic factor, induces IGFBP-4 and that IGFBP-4 reduces the fibrotic phenotype by reducing extracellular matrix and pro-fibrotic factor production. We propose to delineate the mechanism mediating the anti-fibrotic activity of IGFBP-4. Our research has the potential to better understand the mechanism of action of a novel anti-fibrotic factor, result in the development of intellectual property material, and lead to the development of a therapy for organ fibrosis in systemic sclerosis. Research on IGFBP-4 is based on very recent observations and represents new focus for our research team. Although our group has focused on endostation and peptides derived from it as anti-fibrotic therapy, the identification of IGFBP-4 as another potential anti-fibrotic factor is novel. In addition to the impact of our findings on systemic sclerosis, understanding the mechanism(s) resulting in the anti-fibrotic effects of IGFBP-4 will also have broad impact and will be applicable to other fibrosing conditions such as idiopathic pulmonary fibrosis.
For more information on the Pilot Project Program please contact Dr. Gary Gilkeson (email@example.com).