A Multi-Disciplinary Center
Our center is made up of faculty from six University of South Carolina colleges. Together, we're working to create a self-sustaining, nationally recognized, multi-disciplinary center for dietary supplement and inflammation research.
Areas of Interest
- Study the role of a new Chinese herb-derived selective Toll-like receptor antagonist (Sparstolonin B) as an anti-inflammatory agent to treat atherosclerosis
- Anti-inflammatory capabilities of plant polyphenols for the treatment of Alzheimer’s Disease
- American Ginseng-mediated autophagy and suppression of inflammation in pathological cardiac remodeling and dysfunction
- Macrophage-induced inflammation in high fat diet enhanced breast cancer: benefits of Quercetin
Current Research Projects
Insights into Anti-Inflammatory Capabilities of Plant Polyphenols for Treatment of Alzheimer’s Disease
Principal Investigator: Melissa Moss, Ph.D.
The global aim of our research is to use biomedical engineering and molecular biology tools to study the mechanism responsible for changes in protein folding, cell-protein interaction, and inflammatory immune response to misfolded proteins in Alzheimer’s Disease. Alzheimer’s Disease is characterized by deposits of aggregated amyloid-b protein (Ab) within the brain parenchyma and cerebrovasculature. This pathology is coupled with elevated inflammatory response. AD brains with Ab deposits co-localized with vessel-associated immune cells exhibit a compromised blood-brain barrier (BBB) integrity.
The goal of the current study is to expand on our preliminary
- Interaction of soluble Ab aggregates, but not monomeric Ab with cerebrovascular endothelial cells, is responsible for inflammatory responses such as increased endothelial expression of adhesion molecules, increased monocyte adhesion and reduced permeability when tested in vitrocultures.
- These inflammatory responses by aggregated Ab are mediated via NF-kB signaling, where reactive oxygen species (ROS) induced by aggregated Ab serve as second messengers.
We will test the hypothesis that plant polyphenols will reduce Ab-induced inflammatory responses in endothelial cells by interfering with both Ab aggregation and ROS second messengers. We will test if plant polyphenols act as aggregation inhibitors to attenuate Ab-induced vascular inflammatory responses. Combinations of polyphenols that are synergistic in action as demonstrated by their ability to reduce NF-kB signaling, exhibiting similar anti-oxidant capabilities and varying ability to inhibit Ab aggregation, will be identified. These studies will form the basis for future therapeutics development for the treatment of Alzheimer’s disease using plant polyphenols.
American Ginseng-mediated Autophagy and suppression of inflammation in Pathological Cardiac Remodeling and Dysfunction
Principal Investigator: Taixing Cui
The global aim of our research includes studying the role of inflammation in cardiovascular disease with emphasis on identifying alternative therapeutic strategies to manage complications of cardiovascular disease.
The goal of the current study is to expand on our preliminary results that the protective effect of American ginseng extract against cardiac dysfunction is:
- due to enhanced autophagy and suppression of oxidative stress through activation of Nrf2 signaling in cardiomyocytes.
- a unique modulatory effect on inflammatory responses in macrophages via orchestrating NF-kB and STAT pathways.
In this proposal we will determine:
- the role of autophagy and Nrf2 in regulating the American ginseng-mediated suppression of oxidative stress and inflammatory cytokine production in macrophages as well as oxidative stress, hypertrophic growth and cell death in cardiomyocytes.
- the efficacy of hexane fraction of American ginseng on autophagy and Nrf2 pathway in cardiomyocytes and macrophages respectively.
- the efficacy of hexane fraction of American ginseng on the suppression of maladaptive cardiac hypertrophy and dysfunction via activating both myocardial autophagy and Nrf2 in the heart. These studies may have profound implications on the clinical utility of American ginseng as an alternative medicine for the treatment of heart diseases.
- Recent Publication
- Find Taixing Cui on PubMed
Therapeutic potential of resveratrol in depression-cardiovascular disease
Principal Investigator: Susan K Wood
Stress exposure precipitates psychiatric disorders such as depression in susceptible individuals. Depression is not only the leading cause of disability in the U.S. but it increases one’s risk of cardiovascular disease. The long-term goal of our work is to identify neurobiological mechanisms that cause individuals with depression to be at greater risk of developing cardiovascular disease.
Recent data suggests that inflammation may be the link between depression and cardiovascular disease. Using a resident-intruder paradigm of social stress in rats, we previously identified a susceptible population of rats that developed behavioral and neuroendocrine endpoints related to depression and evidence of cardiovascular dysfunction. In these studies we will test the hypothesis that circulating cytokines and cytokines within stress-sensitive brain regions drive the vulnerability to depression and cardiovascular disease.
These studies will test the efficacy of the potent plant-based anti-inflammatory, resveratrol, to inhibit the effects of social stress on neuroinflammation, indices of cardiovascular disease and depressive-like behaviors in a stress-susceptible population.
- Aim 1 will utilize cardiovascular telemetry to examine the cardioprotective effects of resveratrol on stress-induced cardiac dysfunction.
- Because neuroinflammation is gaining recognition for its role in depression and cardiovascular disease, Aim 2 will test the notion that neuroinflammation within the stress-sensitive brain region, the locus coeruleus, is capable of altering neuronal activity and thereby drives the stress-induced depressive-like phenotype.
- Studies in Aim 3 will use resveratrol to establish a role for neuroinflammation in altered serotonin metabolism following social defeat in another stress-sensitive brain region, the dorsal raphe.
The implications of these studies seek to establish a therapeutic role for natural bioactive compounds with potent anti-inflammatory properties in treating stress-induced depression and cardiovascular disease in stress susceptible individuals.
Diet-induced regulation of inflammation in prostate cancer
Principal Investigator: Dev Karan
The global aim of our research includes understanding the role of inflammation-associated molecules in the development and progression of prostate cancer and harnessing the power of immune system to improve its preventive and therapeutic efficacy against developing neoplastic cells and/or established cancer cells.
The goal of the current study is to expand on our observation that Withaferin-A (WFA) from the plant Withania somnifera inhibits expression of NLRP3 inflammasome (multi-protein complexes including NLRP3, IL-1β, IL-18) and therefore test the hypothesis that intake of dietary agent WFA will provide an anti-inflammatory environment in the prostate gland to prevent tumor development.
In this proposal we will:
- determine the mechanism of WFA-mediated regulation of inflammatory cytokines.
- determine WFA-targeted modulation of inflammation in vivo and inhibition of prostate cancer cell growth.
We will specifically test WFA-induced polarization (tumor promoting or tumor suppressive) of macrophages in the prostate gland and understand the role of macrophage inhibitory cytokine-1 (MIC-1) and assess the WFA-induced functional activity of NK cells in vitro and in immune competent mice.
Past Research Projects
Chinese herb, Sparganium stoloniferu-derived Sparstolonin B (SsnB) as an anti-inflammatory and anti-atherogenic agent
Principal Investigator: Daping Fan
The global aim of our research is to promote the regression of atherosclerotic plaques through restoring macrophage cholesterol homeostasis and controlling macrophage inflammation.
The goal of the current study is to expand on our preliminary results that SsnB:
- has potent anti-inflammatory effects on macrophages by blocking Toll-like receptor 2 (TLR2) and TLR4 signaling.
- diminishes the ability of activated endothelial cells to attract monocyte for adhesion and decreases arterial smooth muscle cell migration.
- effectively suppresses inflammatory response in mice.
We will test the hypothesis that SsnB can be developed as an anti-atherosclerosis agent by virtue of its selective inhibitory effects on TLR2 and TLR4 signaling.
To test this hypothesis, we propose three specific aims:
- SA1: To elucidate the molecular mechanism by which SsnB blocks TLR2 and TLR4 signaling. We will express and purify the Toll/IL-1 receptor (TIR) domains of TLRs, the adaptor proteins TIRAP/Mal and MyD88 and examine the binding of SsnB to these proteins.
- SA2: To examine the effects of SsnB on resident vascular cells. We will test the hypothesis that SsnB suppresses the inflammatory phenotype in arterial endothelial and smooth muscle cells by blocking TLR2 and TLR4 signaling.
- SA3: To test the hypothesis that SsnB attenuates atherogenesis in mice. LDL receptor (LDLR) deficient mice will be fed high fat diet to induce hypercholesterolemia and atherosclerosis. SsnB will be administrated to test if it attenuates atherogenesis in these mice.
Macrophage-Induced Inflammation in High Fat Diet Enhanced Breast Cancer: Benefits of Quercetin
Principal Investigator: Angela Murphy
The global aim of our research involves investigations of dietary and physical activity interventions to reduce macrophage-induced inflammation in cancer. The goal of the current study is to determine the effects of dietary quercetin on inflammation and subsequent tumor progression and overall survival in a mouse model of high-fat diet (HFD) enhanced breast cancer (BrCA).
We will test the hypothesis that the mechanism of action of quercetin on the regulation of MΦ-induced inflammation in HFD-enhanced BrCA is mediated through SIRT1.
- elucidate the stage-specific effects of quercetin on inflammation in HFD-enhanced BrCA.
- evaluate whether MΦs are a target for the anti-inflammatory effects of quercetin in HFD-enhanced BrCA.
- determine whether SIRT1 is a mediator of the effects of quercetin in the regulation of MΦ-induced inflammation in HFD-enhanced BrCA.
This investigation proposes to prevent incidence and progression of HFD-enhanced BrCA by using a dietary food component that targets inflammation, the mechanistic core of this disease.
Our Supporting Cores
Our center and researchers are support by various cores across campus.
The administrative Core will provide oversight on all aspects of the COBRE.
Specific aims are to:
- facilitate mentoring of target faculty, enhance use of research resources and monitor the transition of target faculty into independent, well-funded investigators.
- recruit 10 new tenure-track faculty and provide them seed funds to initiate research on dietary supplements and inflammation.
- oversee the financial and personnel management of all the projects and cores as well as develop long term goals.
Long-term objectives include:
- Advancement of entrepreneurial activity, including submission of SBIR/STRR grants and establishment of start-ups
- Development of NIH Program Project grants (PPGs)
- Submission of NIH training grants.
- Facilitating clinical research and trials.
Combined, these activities should lead to the development of a critical mass of highly-competitive scientists supported through NIH R01/Program Projects/Career Development Awards/Training Grants serving the local, regional and national unmet needs in the area of Dietary Supplements and Inflammation.
Microscopy & Imaging Core
The Microscopy and Imaging Core will be housed in the existing Instrument Resource Facility (IRF) at the University of South Carolina School of Medicine which is a core facility providing a wide range of biotechnology and technical expertise to researchers in the state of South Carolina.
The core will provide access to a range of imaging technology for monitoring changes to the whole animal to ultrastructural level. At the whole animal level, ultrasound and fluorescence techniques will be available to determine how inflammation and applied diets affect the experimental animals. At the histology/light microscopy and immunohistochemistry levels, a full range of equipment is available for preparation and imaging of tissues. Isolated cell behavior will be monitored in culture by a spinning disk confocal microscope and localization and co-localization of molecules expressed during the process of inflammation will be monitored by multi-labeling confocal imaging.
Finally, ultrastructural changes in cells will be imaged by electron microscopy to determine changes at the sub-micron level of resolution. A full range of image analysis hardware and software is also available to quantify the structural changes which occur during inflammation in the cells, tissues and organs and how these changes are affected by the various dietary supplements. All equipment and technical expertise is available in the IRF for completion of the experiments proposed by the Target Investigators. There will be three faculty members and four technicians affiliated with the IRF available for assistance with experimental design, operation of equipment and training on imaging instrumentation.
Flow Cytometry and Cell Sorting Core
The Flow Cytometry and Cell Sorting Core, is housed in the established Instrument Resource Facility (IRF) at the University Of South Carolina School Of Medicine. This core will be supervised
by the current Director of the Flow Cytometry lab. There will be two faculty members
affiliated with the IRF available for assistance with experimental design, operation
of equipment and training on micro-fluidics instrumentation.
The core will provide all of the technology and expertise required to study changes in the cell composition of circulating blood cells as well as tissues and organs, changes in cell number and ratios, the status of various states of cell differentiation and apoptosis and the expression patterns of signaling molecules such as cytokines essential in studying the process of inflammation. Many of these changes can be closely monitored by flow cytometry, cell sorting and various other techniques based on micro-fluidic biotechnology such as multiplex ELISA assays for proteins and real time PCR for RNA.
Immune Monitoring Core
The Immunologic Monitoring Core will assist target faculty of the COBRE to pursue high-quality research by monitoring immune cell functions following treatment with the dietary supplements in models of inflammatory disease. The Core will characterize the immune status before, during and after treatment of diseased animals with the plant products so as to provide insights into their prognostic and therapeutic effects.
The Core will:
- offer state-of-the-art resources to pursue cellular and molecular immunological assays so as to enable cutting-edge research on the projects.
- provide technological assistance and training in the use of major equipment by the users.
- participate in experimental design and selection of appropriate assays, troubleshooting and interpretation of results.
- develop and standardize new technologies by evaluation of sensitivity, specificity and reproducibility.
- aid in data collection, evaluation and analysis as well as sharing of data.
There are two major components of this core:
- Serve as a resource of multi-user equipment
- Perform Immune Function Assessment, including:
- evaluation of the general health status.
- Level I immunological testing which includes a variety of assays that examine the functions of T cells, B cells, NK cells and dendritic cells.
- Level II immunological testing of the genetic, transcriptional and epigenetic mechanisms underlying immune dysregulation.
This Core will complement other cores and lead to integration between projects and cores. This core could be used for translational studies in the future.