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Mississippi State University COBRE

Center of Biomedical Research Excellence In Pathogen Host Interactions

Principal Investigator: Stephen B. Pruett

The Phase I COBRE at Mississippi State University (MSU) has catalyzed a transformation in the biomedical research enterprise, particularly in the research focus area of the COBRE, pathogen-host interactions. In the CVM Basic Sciences Department, where most COBRE investigators worked, the research culture has changed; 19 of 20 faculty members now have competitive extramural funding. Furthermore, the total NIH funding amount at Mississippi State University has increased from about $1.4 million in 2012 (just before the Phase I COBRE began) to about $5.4 million in 2016 (year 4 of the Phase I COBRE). Two of our Phase I investigators have graduated to independent status, and all have obtained significant levels of competitive extramural funding. In fact, these two independent Phase I investigators will serve on the Leadership Team in Phase II, which will continue relationships between Phase I and Phase II investigators to build functional teams that will be competitive for collaborative funding efforts. Continuing the transformation of biomedical research at MSU to yield a self-sustaining high level research enterprise is the goal of the Phase II COBRE described in this application. We have identified 5 excellent investigators (two of whom were hired during Phase I) to lead research projects in the Phase II COBRE. The projects include sufficient commonality to allow synergy, and all are novel and have the potential to open new avenues of investigation. For example, two projects focus on vector borne diseases, three projects investigate the role of microbial metabolic adaptations in virulence, and two projects involve Staphylococcus aureus. One of the most positive characteristics of our investigators is the spontaneous development of collaborations between Phase I and Phase II investigators, which has occurred even before the beginning of Phase II. Plans for Phase II take advantage of this by deliberately encouraging continued interactions between Phase I and Phase II investigators both in mentoring and in research collaboration. Each investigator in Phase II has identified a distinguished scientist who is a leader in his/her field of study to serve as an external mentor. Internal mentors (from MSU) will serve as advisors in both scientific areas and in grant writing. All members of the distinguished External Advisory Committee from Phase I have agreed to serve in the same role in Phase II. With funds from Phase I, physical facilities and research infrastructure have been substantially improved by purchase of major equipment, renovation of the HVAC system of 4 labs, and addition of 6 Biological Safety Cabinets. The support of MSU for research in pathogen-host interactions is also illustrated by the university’s substantial investment to acquire a BSL-3 modular lab (1200 square feet with 3 separate labs), which has been commissioned and should be operational by the summer of 2018. A major user will be one of our COBRE Phase I investigators. The proposed Phase II COBRE will allow initiatives begun in Phase I to continue and establish a critical mass of well-funded investigators who can conduct high impact research.

University of Mississippi COBRE

Glycore: Clycoscience Center of Research Excellence

Principal Investigator: Joshua S. Sharp

The University of Mississippi proposes to establish the Glycoscience Center of Research Excellence (GlyCORE), a Phase I Center of Biomedical Research Excellence. Glycoscience is an essential and rapidly emerging field of biomedical science, and the challenging nature of glycoscience research requires tools and expertise that are not commonly found in the biomedical research community. Moreover, the biomedical community is rapidly growing to appreciate the essential role of carbohydrates, with researchers outside of the self-identified “glycoscience” community finding themselves faced with addressing challenging questions in glycoscience as part of the course of their biomedical researchers. GlyCORE will develop and provide resources and expertise in glycoscience to both core glycoscience researchers as well as researchers who encounter questions in glycoscience in the course of their biomedical research programs. GlyCORE will serve researchers at both the University of Mississippi and the Mid-South community through three mechanisms: a Faculty Development program, the establishment of three Research Cores to support glycoscience research, and the establishment of local and regional meetings focusing on questions in glycoscience. GlyCORE's Faculty Development program includes the support of four Junior Investigators establishing their careers in various disciplines in glycoscience. This program includes financial support of the investigators' research efforts, a formal mentoring program, and priority subsidized access to University of Mississippi core facilities. GlyCORE will also support smaller developmental projects through a Pilot Project Program, including financial support and prioritized access to core facilities. GlyCORE's Faculty Development program will also promote recruitment of glycoscience faculty to the University of Mississippi, including the recruitment of a mid-career carbohydrate synthetic chemist to help support expanded services in GlyCORE during Phase II. GlyCORE's Research Cores will establish three new core capabilities at the University of Mississippi that are essential for modern glycoscience: an Analytical and Biophysical Core supporting high resolution chromatography and mass spectrometry analyses; an Imaging Core supporting confocal microscopy with lectin-based and anti- carbohydrate immunohistochemistry imaging; and a Computational and Bioinformatics Core supporting simulations and bioinformatics data analysis to support glycoscience and structural glycobiology. Finally, GlyCORE will establish the University of Mississippi as a regional center for glycoscience in the Mid-South. GlyCORE will host an annual Mid-South Glycoscience Meeting with subsidized access to regional participants, and will host both an annual UM Glycoscience Symposium and monthly glycoscience meetings to highlight the role of glycoscience at the University of Mississippi. Together, these efforts will establish a core of experienced and nationally competitive young faculty in glycoscience, supported by modern research infrastructure and promoted to the glycoscience community as the glycoscience destination in the Mid-South.


COBRE Phase III Transitional Center

Principal Investigator: Soumyajit Majumdar

The Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) at The University of Mississippi School of Pharmacy (UM), initiated ten years ago through a COBRE grant, has developed a multidisciplinary team committed to evaluating the effects of natural products on the central nervous system (CNS). The Center now has the potential to develop and sustain an innovative and independently funded research center focused on treating disorders associated with the nervous system. Faculty in the Center and its academic home, the School of Pharmacy, have already reported groundbreaking observations on the roles of cannabinoids and non-cannabinoids in the etiology of weight control, the control of the immune system, treatment of cancer, control of nausea and vomiting in patients receiving anti-neoplastic treatment, glaucoma, and the development of sigma receptor agonists in the treatment of cocaine and methamphetamine abuse. Also, CORE- NPN-supported investigators have increased their competitiveness by attracting extramural funds and publishing in leading journals of neuroscience. The Center will continue to provide an excellent environment for junior and mid-level investigators through the Pilot Project Program. Investigators will work in close collaboration with leading national centers and scientists studying natural products to carry out the proposed projects that build on these novel insights into the pathophysiology of nervous system disorders. To achieve the goal of establishing an innovative and multidisciplinary Center focused on the use of natural products to manage neuropharmacological disorders, the following Specific Aims are proposed: Specific Aim 1: Administration. To enhance a sound administrative structure that offers strong mentoring for junior scientists, management of the Research Cores, workshops on grant writing/management (pre- and post-award), training in responsible conduct in research, intellectual property development, distinguished lectureship program, and promote the development of the CORE-NPN into an independent Center. Specific Aim 2: Research Core Facilities. To accelerate the research of the CORE-NPN and the associated community through state-of-the-art equipment, cutting-edge techniques, and scientific expertise. Specific Aim 3: Pilot Project Program (PPP). To advance an infrastructure of developmental programs that engage in basic, translational, and entrepreneurial research.

University of Mississippi Medical Center COBRE

Cardiorenal and Metabolic Diseases Research Center

Principal Investigator: John E. Hall

Cardiovascular (CV), renal and metabolic diseases are inextricably linked and are the leading causes of mortality and morbidity in the U.S., especially in Mississippi which has the highest prevalence in the nation of these diseases. Cardiorenal and metabolic disorders usually cluster together and are highly interdependent. Obesity and associated metabolic disorders, such as diabetes, are major causes of CV and renal disease. Abnormal kidney function is an important cause as well as a consequence of hypertension, a key risk factor for CV diseases such coronary artery disease and stroke. Understanding the complex relationships among CV, renal, and metabolic disorders and developing new therapeutic approaches requires a paradigm shift in research that incorporates multidisciplinary integrated approaches, combining the efforts of basic, clinical and population scientists. A major objective of this Phase 2 COBRE proposal is to further develop a leading Cardiorenal and Metabolic Diseases Research Center (CMDRC) that brings together a multidisciplinary group of basic, clinical and population scientists working on a common synergistic theme, and to facilitate their collaborations. The specific aims are: 1) to further develop infrastructure and core facilities that foster excellence in basic, clinical, and population research in cardiorenal and metabolic diseases and increase competitiveness of CMDRC investigators for independent funding from NIH and other national biomedical research programs; 2) to enhance CMDRC mentoring and education programs and research support for promising new investigators so that they can become productive, independent investigators who are also effective collaborators on multidisciplinary research teams; 3) to achieve the specific aims of the research projects described by Junior Investigators in this proposal, and to foster their career development; 4) to further develop a pipeline of diverse postdoctoral fellows, graduate and undergraduate students trained in cutting edge cardiorenal and metabolic diseases research so they become the next generation of researchers in this field; major emphasis is placed on recruiting and mentoring underrepresented minority investigators through partnerships with local institutions and by leveraging training programs at UMMC; 5) to enhance collaborations and interactions among established investigators from multiple disciplines in cardiorenal and metabolic diseases at UMMC, other IDeA supported programs, and external partners; 6) to strengthen cardiorenal and metabolic disease research at UMMC by recruiting new faculty with expertise in clinical and translational research, and in emerging technologies (e.g. in vivo imaging, bioinformatics, and systems analysis) and in areas where there are gaps in CMDRC expertise.


Mississippi Center of Excellence in Perinatal Research

Principal Investigator: Jane F. Reckelhoff

The major goal of the Mississippi Center of Excellence in Perinatal Research (CEPR) is to develop an innovative, independent and sustainable center of excellence in perinatal research and treatment spanning the spectrum from adverse pregnancy to subsequent outcomes in offspring. More specifically, perinatal research encompasses the study of disease states that may occur during gestation and early post-natal development that result in long term consequences in the mother and offspring across their lifespan. Studies will focus on the integrative relationships and health disparities in adverse pregnancy, pregnancy outcomes and developmental programming of cardiovascular, renal, metabolic and behavioral diseases. This is an important area for research especially in light of the increasing evidence of long term health consequences brought about by adverse fetal environment and subsequent low birth weight during pregnancy both for the mother and offspring. An adverse perinatal environment is thought to account at least in part for the development of obesity, cardiovascular, renal, and behavioral diseases later in life for the offspring, and predispose the mothers for increased risk of these diseases with aging. Mississippi has one of the highest rates of preeclampsia, obesity, cardiovascular, renal and metabolic diseases and hypertension in the United States, leading to disproportionate levels of morbidity and mortality in our population. The incidence of preeclampsia is 10% in Mississippi, compared to 5% in the US. The prevalence of children with low birth weight in Mississippi is 12% in Caucasian children and 18% in African American children, compared to 5-8% in the other states. Studies that will provide novel insight into mechanisms responsible for the high rates of these diseases in Mississippi will require a paradigm shift in research that incorporates multidisciplinary integrated approaches, combining the efforts of basic, clinical and population scientists. A major goal of this proposal is to develop a research Center that will provide infrastructure and capacity for a multidisciplinary, diverse group of basic, clinical and population scientists working on the common synergistic theme of perinatal diseases and health disparities and to facilitate their collaborations. The specific aims of the Administrative, Mentoring and Education Core A include the following: 1. To provide overall leadership for development of infrastructure, mentoring programs and research core facilities that foster excellence in perinatal research spanning the spectrum from adverse pregnancy to subsequent outcomes in offspring and will lead to development of an innovative, internationally recognized Center of Excellence. 2. To develop, implement and monitor a Mentoring and Education Program that facilitates development of junior faculty investigators into independent, extramurally (NIH) funded researchers. 3. To develop and implement a Pipeline Grants Program for promising new investigators, with emphasis on recruiting and mentoring under-represented minority investigators. 4. To develop and implement educational programs that will facilitate collaborations and interactions among investigators from multiple disciplines in perinatal research at UMMC. 5. To develop and implement programs for recruiting, training, and mentoring a diverse group of undergraduate students and postdoctoral trainees to provide experience in mentoring for the junior investigators and so that the trainees become the next generation of perinatal researchers. 6. To implement formative and summative evaluation strategies for overall progress and effectiveness of the CEPR junior investigators, programs, and cores. 7. To provide high-level program administrative support and fiscal oversight of all research projects and cores. 8. To organize networking meetings and seminars related to the Center as well as meetings of the Executive Committee, Internal and External Advisory Committees. 9.To ensure that all Center programs, initiatives, policies and reporting mechanisms to UMMC and NIGMS are optimally developed, implemented, and administered within federal granting agency policies and deadlines.