Target Faculty Grant (Direct funding of $150,000, for a period of one year):

The COBRE (Center of Biomedical Research Excellence) will provide funding to perform research in inflammation and dietary supplements for junior Tenure track and nontenure track investigators (with preference given to tenure-track Assistant Professors) as Target faculty. A junior investigator is defined as an individual who does not have or has not previously had external, peer-reviewed Research Project Grant (RPG) such as R01 or Program Project Grant (PPG) support from either Federal or non-Federal sources for which the individual is named as the PD/PI. Those who have NIH R03, R21, or other similar types of grants are eligible to apply. Since the COBRE Target Faculty have to devote 50% effort towards this grant, those who currently have an NIH K award or equivalent with more than 50% effort on the Career Development Award are not eligible. Candidates who are now or have previously received support from another COBRE grant as Target Faculty are also not eligible to apply. 

Funded investigators will be expected to submit a Research Project Grant before the end of the funding year and demonstrate an effort to move toward independent research support. Upon receiving R01 type of funding, investigators will be considered “graduates” of the COBRE program. Details on the COBRE can be found on the following website:

https://www.nigms.nih.gov/Research/DRCB/IDeA/pages/COBRE.aspx

All successful proposals must be compliant with all NIH regulatory criteria such as human subjects, vertebrate animals, biohazards, etc., (if applicable) in order to receive final NIH approval.

Pilot Project Grants (Direct funding of $50,000, for a period of one year):

The NIH COBRE on Dietary Supplements and Inflammation will provide funding to support research in Dietary Supplements and Inflammation to Tenure-track, Tenured, and nontenure-track faculty who do not currently have R01 or equivalent grants as PI or who are not currently Target Faculty on any COBRE grants. Consideration will be given to the research productivity of the investigator and their ability to attract independent funding from NIH or other funding agencies. Tenured faculty interested in applying should demonstrate a desire to begin research outside their current field. 

All successful proposals must be compliant with all NIH regulatory criteria such as human subjects, vertebrate animals, biohazards, etc., (if applicable) in order to receive final NIH approval.

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
results that:

1. 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 vitro cultures.
2. 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.

• Recent Publications
• Find Melissa Moss on PubMed

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:

1. due to enhanced autophagy and suppression of oxidative stress through activation of Nrf2 signaling in cardiomyocytes.
2. 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

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.

1. Aim 1 will utilize cardiovascular telemetry to examine the cardioprotective effects of resveratrol on stress-induced cardiac dysfunction.
2. 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.
3. 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.

Find Susan Woods on PubMed

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:

1. determine the mechanism of WFA-mediated regulation of inflammatory cytokines.
2. 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.

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:

1. 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.
2. 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.
3. 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.

• Find Daping Fan on PubMed
• Recent Publications

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. 

We will:

• 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.

• Find Angela Murphy on PubMed
• Recent Publications

Principal Investigator: Jabbarzadeh, Ehsan

Project Goals:

Aim 1. Determine the in vitro potential of resveratrol to mediate osteogenic differentiation and inflammatory response in 3D scaffolds.

Hypothesis: We hypothesize that resveratrol-incorporated PLGA scaffolds will modulate the inflammation response of M1 macrophages and promote a phenotypic switch into wound-healing, anti-inflammatory M2 macrophages.

Aim 2. Determine the in vivo potential of resveratrol incorporated scaffolds to mediate inflammatory response and promote the neogenesis of bone and angiogenesis.

Hypothesis: We hypothesize that resveratrol-nanoparticle included PLGA sintered microsphere scaffolds can alleviate host immune response, and enhance vascular growth and ultimate bone healing.

Beyond the scope of this proposal, this approach enables efforts to prospectively engineer inflammatory response by “dialing” the appropriate degree of resveratrol release profile. The proposed studies are translational as they provide critical new insight into the principal mechanisms of directed angiogenesis and inflammation in porous biomaterials. The proposed approach is transformative as it tackles a confounding barrier in regenerative medicine with applicability to many other musculoskeletal tissue engineering approaches in addition to bone. Insufficient vascularization of implantable scaffolds is a profound barrier in regenerative medicine. Our results will impact the field as this strategy can work in different materials and is scalable to larger scaffolds.

Principal Investigator: Gower, Michael

Project Goals:

AIM 1: Employ biomaterial based gene delivery to promote brown adipose tissue (BAT) gene expression in white adipose tissue (WAT). The peritoneal fat is a depot of WAT that exhibits long-term transgene expression following implant of PLG scaffolds that release lentiviral vectors. We propose to implant scaffolds in the peritoneal fat that release vectors encoding for PRDM16 and PGC-1α, transcriptional coactivators required for expression of BAT genes within WAT. We will first investigate, in vitro, the ability PRDM16 and PGC-1α gene delivery to induce BAT gene programs in WAT cell lines and isolated white adipocytes. We will use our in vitro data to determine the number of viral particles and ratio of particles encoding for PRDM16 and PGC-1α to deliver in vivo on vector releasing scaffolds. Following implant we will characterize adipocytes within the implant site by morphology, cell surface markers, and gene expression.

AIM 2: Employ localized release of resveratrol to promote thermogenesis in engineered BAT. Resveratrol, a natural polyphenol found in red wine, modulates energy homeostasis by activation of SIRT1, a deacetylase that recruits coactivators PGC-1α and PRDM16 to the transcription factor PPARγ, leading to induction of BAT genes and repression of WAT genes. We propose to encapsulate resveratrol within scaffolds for BAT engineering and investigate its effect on thermogenesis, weight loss, insulin resistance, and hyperlipidemia when implanted in the peritoneal fat of mice fed a diabetogenic diet.

Principal Investigator: Chatterjee, Saurabh

Principal Investigator: Koh, Ho-Jin

Principal Investigator: Testerman, Traci

Principal Investigator: Colpitts, Tonya

Principal Investigator: Chanda, Anindya

Principal Investigator: Lizarraga, Sophia

Principal Investigator: Jarzynski, Mark

Principal Investigator: Gomez, Gregorio

Allergic disease is the fifth leading chronic disease in the United States. A major contributing factor to allergic inflammation including asthma is Prostaglandin D2 (PGD2) produced by mast cells, the cell type responsible for IgE-mediated immediate hypersensitivity reactions.  Therefore, targeting the arachidonic acid pathway in mast cells to inhibit PGD2 biosynthesis is one strategy to significantly limit allergic inflammation.  Recently, we discovered that Resveratrol, a natural plant-derived polyphenol, selectively inhibited IgE-dependent PGD2 production from human skin mast cells.  We further showed that Resveratrol inhibited FcεRI-induced expression of cyclooxygenase 2 (COX-2), a key enzyme in the arachidonic acid pathway that is directly involved in PGD2 biosynthesis. The central question of this study is: how does Resveratrol inhibit FcεRI-induced COX-2 expression and PGD2 production in mast cells?  Interestingly, miR-155 has been implicated as a positive regulator of COX-2 expression in different cancers, macrophages, airway smooth muscle, and in the severity of allergic asthma in mice.  Indeed, our miRNA array analysis and qRT-PCR validation studies revealed a positive correlation between miR-155 and COX-2 expression in human primary mast cells following FcεRI crosslinking.  Moreover, we found that Resveratrol significantly inhibited FcεRI-induced expression of miR-155 expression as well as COX-2.  Given that miRs negatively regulate target genes, these data suggest that miR-155 targets a repressor of COX-2.  Our in silico pathway analysis has identified several negative regulators of COX-2 such as ATF3, SOCS-1, SHIP-1, and PPARG, as potential targets of miR-155 in human and murine mast cells.  Thus, we hypothesize that Resveratrol inhibits allergic inflammation by regulating the expression of miR-155 in mast cells leading to increased induction of the repressors and consequently diminishing COX-2 expression and PGD2 biosynthesis.  Our study will (1) Characterize the effect of Resveratrol on the FcεRI-induced miRNA expression profile in situ-matured mast cells from human and mouse, (2) Identify the COX-2 repressor targeted by miR-155, and define the mechanism by which Resveratrol inhibits FcεRI-induced COX-2 expression and PGD2 biosynthesis in mast cells, and (3) Characterize the effects of dietary Resveratrol on airway remodeling and hyper-responsiveness in a mast cell dependent model of allergic asthma, and identify associated miRNAs.  To define the role of miR-155-5p in allergic asthma and the efficacy of Resveratrol in inhibiting disease development, we will also use miR-155-5p transgenic (Tg) and knockout (KO) mice in our model.  Overall, this study will shed new light on the role of miR-155 in the ability of Resveratrol to selectively inhibit FcεRI-induced COX-2 and PGD2 production in mast cells, thereby, attenuating allergic inflammation.

Principal Investigator: Testerman, Traci

Inflammatory bowel disease (IBD) afflicts over one million Americans, causing considerable suffering and lost work time.  The direct and indirect costs of IBD were estimated to be between $14.6 and $31.6 billion in 2014.  Furthermore, IBD greatly increases the risk of developing colorectal cancer.  Bacteria are now believed to be key players in both IBD and colorectal cancer.   A number of Helicobacter species infect the human colon and are known to cause colitis and colon cancer in colitis-prone mouse strains.  We have exciting data showing that H. muridarum exacerbates dextran sulfate sodium (DSS) induced colitis in wild-type mice.  There are no studies on the immune response triggered by H. muridarum.  Thus, this EHH species offers a unique experimental model to understand how colitis is triggered in an immunologically normal animal following a chemical insult.  Recent studies have shown that dietary indoles, such as Indole-3-carbinol (I3C), derived from cruciferous vegetables, have a number of anti-inflammatory and anti-carcinogenic properties.  Our preliminary studies showed that I3C attenuates H. muridarum+DSS-mediated exacerbation of colitis and inflammation in the colon. Furthermore, we noted that I3C treatment decreases the expression of miR-874, which targets FOXP3, and increases that of miR-30b which targets for RORC (RORγt) as well as increases miR-5112 that targets IL-17. Based on these data, in the current study, we will test the central hypothesis that I3C attenuates colitis and inflammation induced by H. muridarum through alterations in the expression of miRs that promote a switch in T cell differentiation from Th17 to Tregs.  The mechanisms of colitis exacerbation involving inflammation by H. muridarum are also not known.  Thus, it is critical to understand the nature of immune response against Helicobacter species in IBD.  To that end, we will simultaneously explore immunological and regulatory changes induced by these two agents.  First, we will examine the T cell responses occurring during DSS-mediated colitis with and without H. muridarum infection and with and without I3C treatment.  Our primary focus will be regulatory T cells (Treg), which are critical for intestinal homeostasis.  Next, we will determine whether H. muridarum can trigger colitis in Aryl hydrocarbon receptor (AhR)-deficient mice which fail to generate enough Tregs and are more susceptible to colitis.  These mice will also be used to test the efficacy of I3C, which has been known to act as an AhR ligand.  Finally, we will determine whether specific microRNA species induced by I3C contribute to the Treg response by changing FoxP3 expression both in vitro and in vivo.  Together, the insights gained from these experiments will be essential for understanding the mechanisms of action of I3C and could lead to additional highly targeted treatments.  This project will not only characterize the nature of immune response triggered by H. muridarum during DSS-induced colitis but also test the mode of action of I3C on H. muridarum associated colitis.  These data will support future explorations to investigate the role of other Helicobacter species in clinical IBD and the potential use of I3C in the treatment of IBD.

Principal Investigator:  Lizzarga, Sofia

Growing evidence strongly suggests a correlation between prenatal inflammation and autism; yet the mechanisms that underlie this correlation are largely unknown. The pathophysiology of autism is proposed to arise from defects in neuronal circuitry. Animal models of prenatal exposure to maternal immune activation (MIA) demonstrate that the offspring exhibit abnormal behaviors reminiscent of autistic human behaviors. The increase in autism-like behaviors in MIA animal models is mediated by the pro-inflammatory cytokine IL-17A. IL-17A is produced by CD4+T cells (TH17 cells) and activates the NF-κB signaling pathway in vitro. Resveratrol is a plant derived polyphenolic compound that suppresses IL-17A and has both anti-inflammatory and neuroprotective properties6-8. Interestingly, resveratrol has been shown to ameliorate autistic-like behaviors in a rodent model of ASD. Despite the available data on the role of inflammation in ASD etiology, there is a significant gap in knowledge regarding how inflammation affects the development of human neuronal circuitry. Here we will test the hypothesis that increased levels of IL-17A will impair the development of neuronal connectivity and that resveratrol can serve as a therapeutic modality through inhibition of IL-17A downstream signaling. The rationale for the proposed studies is that, determining the contribution of the different components of the Central Nervous system (CNS) and immune system will allow us to dissect the cellular mechanisms that underlie the role of neuronal inflammation in ASD pathology. The long-term goal of this project is to uncover the mecha- nisms underlying the pathology of autism associated with defects in neuronal connectivity that are induced by prenatal inflammation. The objectives of this application are: 1) to develop stem cell derived neural models and determine the effect of pro-inflammatory cytokines during neuronal development in vitro (Aim-1); 2) to investigate potential chromatin regulatory pathways that might underlie the effect of inflammation during neuronal develop- ment in vivo and in vitro (Aims 2-3); 3) to ascertain the therapeutic potential of plant supplements (i.e. resveratrol) in the pathology of autism (Aim1, 2 & 3). To address the objectives of this application, a combination of state of the art approaches including stem cell based and mouse models, imaging, transcriptome, epigenetic and bio- chemical technologies will be used. We expect that the objectives proposed in this application will provide: 1) clear mechanistic information on how neuronal inflammation might disrupt the normal development of human neuronal circuitry; 2) a testable pre-clinical model for dietary supplements such as resveratrol in the treatment of autism.

Principal Investigator: Chatterjee, Saurabh

Project Summary/Abstract: With obesity assuming pandemic proportions across the developed nations (USA, continental Europe) and emerging economies of India and China, it is estimated that 20-30% of this huge population will develop fatty liver disease (NAFLD). A sizable proportion (roughly 120 million) of those affected with NAFLD will have steatohepatitis and the disease progression is believed to be dependent on the built environment and diet. In spite of the enormous health risk, no suitable treatment regimen has been established so far due to the complications of the disease itself, following multiple risk factors of steatosis, metabolic disorder, inflammation and abnormal endocrine function. Andrographolide (ANDL) is a unique plant derivative which has shown profound caloric restriction, anti-inflammatory and metabolic signaling modulation properties. The use of this compound as a preventive and therapeutic agent in NAFLD is of immense importance to this very significant health risk. Importantly, identifying newer epigenetic modulating function of ANDL in NAFLD would go a long way in targeting effective therapy in this disease. In the current study, we will test the central hypothesis that oral administration of andrographolide (ANDL) attenuates NAFLD via its actions on miR-21-induced inflammatory checkpoints in sinusoidal endothelial dysfunction, stellate cell activation, TGF-beta signaling and defective macroautophagy. The long term objective of this project is to design a comprehensive experimental and preclinical evidence of a treatment regimen that derives from natural dietary supplements with proven anti- inflammatory potential against NAFLD. About seventy-five percent of obese subjects have hepatic steatosis, and about 20% of these individuals develop inflammatory liver disease marked by necroinflammation, a rise in inflammatory cytokines, and some degree of fibrosis. This advanced stage of the disease progression often leads to cirrhosis and autoimmune complications because of the highly inflammatory microenvironment. Because NAFLD has been shown to derive its progression and severity from an underlying condition of obesity and hepatic inflammation, it is imperative that Andrographolide, which has a potent anti-inflammatory effect, might restrict the progression of steatosis to steatohepatitis and thwart the development of more severe complications like hepatocellular carcinoma. The novel role of andrographolide as an epigenetic regulator in NAFLD therapy has never been explored. This project will aim to utilize the supplementation of andrographolide in steatotic mice to abrogate the progression of steatohepatitis following methionine choline deficient diet exposure by its effective regulation of miR21 via NF-kB inhibition leading to suppression of sinusoidal endothelial dysfunction, inflammation and defective autophagy. This project proposes to utilize the COBRE funds to generate sufficient evidence of andrographolide as a potential anti-inflammatory and epigenetic regulator as part of its therapeutic effect in NAFLD. 

Principal Investigator: Kubinak, Jason

Principal Investigator: Xiao, Shuo

The administrative Core will provide oversight on all aspects of the COBRE.

Specific aims are to:

1. facilitate mentoring of target faculty, enhance use of research resources and monitor the transition of target faculty into independent, well-funded investigators.
2. recruit 10 new tenure-track faculty and provide them seed funds to initiate research on dietary supplements and inflammation.
3. 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.

Core Members

• P. Nagarkatti
• M. Nagarkatti
• Carver
• McDonald
• Ray
• Davis
• Sodetz

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.

Core Director

• Robert Price

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.

Core Director

• Udai Singh

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:

1. Serve as a resource of multi-user equipment
2. 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. 

Core Members

• Narendra Singh