LSU Biomedical Collaborative Research Program

2016-2017

Bilateral Transfer of Motor Skills and Brain Activation Patterns: A First Step to Determine Whether Rehabilitation Protocols using Transfer Are Appropriate for Older Individuals

Arend Van Gemmert (LSU A&M) and Owen Carmichael (PBRC)

This project aims to produce data critical for success to develop and get externally funded a proposal addressing whether bilateral transfer of learning protocols developed using college aged adults applies to rehabilitative settings with older adults. Before it can be determined how to optimally maintain and restore motor skills in older adults, it needs to be determined what brain circuitry healthy young individuals recruit (using fMRI) when they perform known and learned motor tasks. This project satisfies this need and thus it establishes methods and preliminary data needed for future investigation into the viability of bilateral transfer of learning approaches in the elderly.

Computational Fluid Dynamics and Pediatric Airway Obstruction: Methodology and Potential Applications

Michael Dunham (LSUHSC-NO) and Keith Gonthier (LSU A&M) 

The proposed research will computationally examine airflow within the laryngotracheal airway of children. The investigators plan to construct three-dimensional patient specific airway models that will be subjected to high-fidelity computational fluid dynamics (CFD) evaluations under simulated physiologic conditions. Predictions will be used to identify, interpret, and catalog important aerodynamic parameters that characterize airflow efficiency and airway surface stress distributions, and to develop diagnostic and staging techniques for pediatric airway disease and surgical prototyping. Techniques developed during the project may be used to refine the computational analysis of upper respiratory airflow and extend its application in a clinical setting.

The Effect of Screen-Time Exposure and Sedentary Behavior on Preschool Children’s Fundamental Motor Skill Acquisition

Kip Webster (LSU A&M) and Amanda Staiano (PBRC)

Early interventions are critical in curbing the childhood obesity epidemic and setting children up for a healthy trajectory in life. In response to the critical need for effective obesity reduction interventions in young children, a new collaboration between Co-PI Elizabeth "Kip" Webster, PhD, Assistant Professor in the LSU School of Kinesiology, and Co-PI Amanda Staiano, PhD, Assistant Professor at Pennington Biomedical Research Center, has emerged that will unite each investigator’s expertise in preschool children’s fundamental motor skills (Webster) and early childhood obesity and sedentary behaviors (Staiano). The proposed project is an ancillary project that will add new assessments of fundamental motor skills to a parent study awarded to Dr. Staiano (parent funding from the National Institutes of Health, U54 MD 008602). The proposed project will collect feasibility and pilot data to position Drs. Webster and Staiano to be competitive for external funding, including specific calls by the National Institutes of Health (e.g. PAR-15-346 and PA-14-177).

The Role of Maternal Adipose Tissue in the Preeclamptic-like BPH/5 Mouse

Jennifer Sones (LSU A&M) and Leanne Redman (PBRC)

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by a sudden rise in maternal blood pressure during the second half of gestation and is one of the leading causes of maternal and perinatal morbidity/mortality. There is no way to positively predict which pregnant women will develop PE; however, a number of maternal conditions have been labelled as risk factors, such as chronic hypertension, pre-gestational diabetes, and increased adiposity. To study the origins of PE, our laboratory utilizes BPH/5, an inbred genetic mouse that exhibits the cardinal signs of PE along with increased reproductive white adipose tissue (rWAT) deposition compared to control mice. Preliminary data in BPH/5 pregnant mice suggests calorie restriction and reduction of rWAT prevents adverse pregnancy outcomes in this model. The overarching aim of our proposal is to test the central hypothesis that maternal adiposity plays a key role in the development of PE-associated adverse pregnancy outcomes in BPH/5 mice with rWAT serving as a source of inflammatory signals to the maternal-fetal interface.

Role of Type 7 Adenylyl Cyclase in Innate Immunity

Masami Yoshimura (LSU A&M) and Guoshun Wang (LSUHSC-NO)

Our overarching hypothesis is that AC7 is a pivotal regulator in innate immunity, and is therefore a potential therapeutic target for immune diseases. This joint investigation aims to interrogate how AC7 loss-of-function in innate immune cells, such as macrophages and neutrophils, undermines their immune capacities. Completion of the proposed research will verify the role of AC7 in phagocytic host defense.

Virtual Reality Exposure Therapy for Post-Traumatic Stress Disorder in Civilian Gunshot Victims: A Design and Feasibility Trial

Erich Conrad (LSUHSC-NO), Jennifer Hughes (LSUHSC-NO) and Xin Shane Li (LSU A&M)

The proposed project would develop, standardize, and pilot test Virtual Reality Exposure Therapy (VRET) for post-traumatic stress disorder (PTSD) in gunshot victims. By investigating a novel intervention that draws on basic, specialized, and applied sciences, this study would promote a multidisciplinary, translational approach to clinical problem-solving. If our aims are achieved, we will be the first team to develop and test VRET to treat PTSD in gunshot victims.

 

Previous Awards - 2015-2016

Mechanisms of sigma66-RNAP: CT663-mediated transcriptional regulation

Megan Macnaughtan (LSU A&M) and Li Shen (LSUHSC-NO)

This project aims to explain the developmental cycle and virulence program in Chlamydia trachomatis (CT). Chlamydiae are medically and agriculturally important bacterial pathogens that cause a wide variety of diseases in humans and animals. In this application, Macnaughtan and Shen seek to define the functional and structural relationships of a protein complex containing an initiation factor (σ66), the core enzyme of RNA polymerase (RNAP), and the CT663 protein. This protein complex is important in the transcriptional machinery of CT. The proposed study will test the hypothesis that the functional and structural relationships of the protein complex impact transcription during the CT developmental cycle.

Novel MicroRNA based therapeutic approaches to suppress breast tumor growth using SPECT imaging

Michael Mathis (LSU A&M) and Suresh Alahari (LSUHSC-NO)

Previous work in Mathis’s and Alahari’s labs has identified a novel protein, Nischarin, which blocks tumor cell migration and invasion and can work as an inhibitory agent in breast cancer growth. This protein inhibits cell proliferation and cell invasion, which may explain its effect on tumor growth and metastasis. The objective of this study is to determine whether the suppression of specific RNAs (miR-27b and miR-23b) result in an increase of Nischarin and the robust inhibition of tumor growth. This will be observed in real time using single-photon emission computed tomography (SPECT) imaging. The proposed study will elucidate the significance of RNA suppression in breast cancer formation and validate its function as a novel therapeutic strategy for highly advanced breast cancers.

Cellular Scaffolds: A novel approach for the production of functional, implantable microvascular networks

Todd Monroe (LSU A&M), Dan Hayes (LSU A&M) and Frank Lau (LSUHSC-NO)

Tissue engineering has the potential to revolutionize medicine, but significant hurdles remain. Prominent among these is the ability to create functional, implantable microvascular networks (MVNs). Using biotechnology that allows cell sheets to be stacked, Monroe and Lau will create thick, multilayer cellular constructs with intact extracellular matrices and tight cellular junctions to form MVNs that are perfusable in vitro. These technologies are well developed, making this a highly feasible approach. In keeping with the NIH’s stated goal of encouraging collaborations between the life and physical sciences, this project will ensure that the entire production is undertaken with optimal consideration of both physical (channel design, fluid dynamics, perfusion methodology, etc.) and biological (cellular development, co-culture conditions, physiological considerations, etc.) aspects.

Cell traction force measurement to investigate tumor-suppresive function of Nischarin

Kidong Park (LSU A&M) and Suresh Alahari (LSUHSC-NO)

Nischarin is a newly discovered protein that suppresses cancer invasion and metastasis. In a recent study, Nischarin expression has been shown to be lower in breast cancer tissues, and additional decreases in Nischarin expression are observed in the breast cancer tissues of patients with lymph node metastasis. However, the effects of Nischarin on cellular mechanics and cancer invasion have not been fully investigated. During this project, the cell traction force (CTF) of breast cancer cells with different expression levels of Nischarin will be measured in various conditions to investigate how Nischarin regulates cell mechanics in cancer invasion. The proposed research will allow us to expand our understanding of how Nischarin regulates migration, motility, and invasiveness of the breast cancer cells and to develop a CTF measurement technique with clinical applications.

Cardio-pulmonary responses in mice following inhalation exposure to environmentally persistent free radicals

Arthur Penn (LSU A&M), Kurt Varner (LSUHSC-NO), Tammy Dugas (LSU A&M) and Alexandra Noel (LSUA&M)

Inhaled environmentally persistent free radicals (EPFRs)—a unique particle-pollutant system that forms during combustion processes—can penetrate deep into the lungs and move into the blood, potentially producing systemic and localized oxidant and inflammatory reactions. The project’s working hypothesis is that inhaled EPFRs at environmentally relevant concentrations will induce cardio-respiratory inflammation and oxidative stress responses, which will drive altered pulmonary, cardiac, and vascular functions in mice. The proposed experiments will use a new customized whole-body inhalation system the researchers have developed to examine the health impacts of “real world exposures” to inhaled EPFRs in mice. It is predicted that this new customized exposure system will model (in mice) human inhalation exposures to airborne particulates containing EPFRs.

Phenotypic and transcriptomic analyses of Vibrio cholerae colonial phase variants

Gregg Pettis (LSU A&M) and Christopher Taylor (LSUHSC-NO)

The bacterium Vibrio cholerae causes cholera, the devastating diarrheal disease that affects millions of people worldwide each year. V. cholerae produces an exopolysaccharide (Vibrio polysaccharide, VPS) that aids in formation of biofilms. VPS production and biofilm formation appear to be important for V. cholerae survival in aqueous systems and for its ability to establish infections. Strains of V. cholerae belonging to the O1 and O139 serogroups are responsible for the current cholera pandemic. Pettis and Taylor are interested in identifying the genes that are important for VPS production and biofilm formation in V. cholerae and have previously identified such genes in the O1 serogroup. In the proposed research, similar phenotypic and transcriptomic analyses will be performed on phase variants belonging to an O139 serogroup strain, as well as comparative analyses of the O1 and O139 transcriptomes.

GUMBOS, a new therapeutic approach for the prevention and treatment of gonorrhea

Isiah Warner (LSU A&M) and Jeffrey Hobden (LSUHSC-NO)

Neisseria gonorrhoeae is a sexually transmitted pathogen that infects over 820,000 Americans annually, with Louisiana ranking #1 per capita in new cases of gonorrhea. Complications of infection include pelvic inflammatory disease, infertility, arthritis, and an increased susceptibility to HIV/AIDS. An increasing concern is the development of multi-antibiotic resistant N. gonorrhoeae. In response to this global crisis, Warner and Hobden have developed a strategy for creating novel antimicrobial agents known as GUMBOS (Group of Uniform Materials Based on Organic Salts). The objective for this project is to synthesize and test new and existing GUMBOS against antibiotic-susceptible and antibiotic-resistant clinical isolates of N. gonorrhoeae. Our long-term objective is to have a bank of GUMBOS that can be used as alternative therapy for gonorrhea, particularly for strains of N. gonorrhoeae resistant to conventional antibiotic therapy.

Additive manufacturing and stem cell recruitment for enhancing osseointegration

Shaomian Yao, Shengmin Guo (LSU A&M) and Thomas Lallier (LSUHSC-NO)

Dental implants are a preferred method for the replacement of missing teeth. Osseointegration, the connection of the implant to the surrounding bone, is critical for successful implantation. The shortfalls of current dental implants include the slow or incomplete osseointegration and the gradual loss of osseointegration over time. This research aims to address these shortfalls through the recruitment of endogenous mesenchymal stem cells (MSCs) to implants for rapid osteogenesis and the modification of the internal 3D structures of implants. The long-term goal is to use advanced manufacturing 3D printing techniques to generate patient-specific implants capable of rapid formation of strong osseointegration. This project will not only have a significant impact on the application of guided bone regeneration in dental implantology, but also on the improvement of the design and fabrication of other bone implants.