PROJECT SUMMARY/ABSTRACT A properly functioning and effective immune system is needed to control infection by bacterial, viral and other pathogen invaders, growth of aberrant cells, as well as for proper embryonic development, wound healing, bone remodeling, and other normal homeostatic processes. Thus, understanding the innate and adaptive immune responses and how abnormalities affect human health in chronic inflammatory conditions, during neonatal development and how infectious diseases and cancers subvert or alter these responses is critical to improving our health, not only in the United States, but globally. Closer to home, this unfortunately remains especially true in the state of Louisiana, which ranks near the bottom in many national health studies. For example, human immunodeficiency virus (HIV) age adjusted deaths in the state are more than double the national average, while the state ranks in the top 5 in infections with the sexually transmitted diseases, Syphilis, Gonorrhea and Chlamydia. In addition, as is documented for many states in the south, Louisiana has some of the highest rates of arthritis (affecting ~1 in 4 adults in the state), heart disease and cardiovascular deaths (ranked 46/50 and 48/50 respectively), and cancer-related mortality rates (15-20% higher than the national average) in the nation. These glaring statistics support the need for additional understanding of the pathogenesis of these diseases and new options for therapeutic interventions. One common theme among these different diseases is an aberrant immune response and resulting immunopathologies. Thus, we propose a better understanding of how aberrations in the immune system result in disease is needed. We propose that a targeted growth of an immunology-centric center on our campus at LSUHSC-S will positively influence the health of our citizens. This is especially true as new research shows targeted modifications of the immune response or immunotherapy holds great promise as an effective treatment option to control and eradicate various tumors, for the treatment and mitigation of antibiotic or antiviral resistant infectious diseases, and for the prevention of chronic inflammatory diseases, etc. Diverse research into aspects of immunology, host pathogen interactions, and the immunopathology associated with an abnormal immune response is an important priority at LSU Health Sciences Center Shreveport (LSUHSC-S) within multiple centers and departments. Immunology as a discipline can effectively bridge many centers and departments currently on campus and thus serve as a nucleus for collaborative and synergistic research across diverse disciplines. Immunology as a discipline is now at the forefront of novel therapies to control bacterial infections, viral infections, to treat cancer; thus an expansion and growth of this area at LSUHSC-S will advance the mission of the school to grow basic science that has strong translational potential. The objective of this new COBRE Center for Applied Immunology and Pathological Processes (CAIPP) to establish an independent internationally recognized research and training program at LSUHSC-S. We propose to first mentor and develop federally funded junior faculty research and to develop new infrastructure to support the growth and continued hiring in this important area of biomedical science. Because Dr. Yurochko has 35 years of experience in immunology research, has been a junior PI in a COBRE center, Project Mentor for successful projects and part of a COBRE leadership team, he can draw on a wealth of experiences, along with those of the experienced leadership team, to drive the success of the CAIPP. Second, we propose long term to retain these immunology researchers as they become more senior through promotion, to become an international recognized research hub and to elevate the CAIPP within LSUHSC-S by becoming a state recognized Center. We shall take advantage of the strengths currently on campus and through targeted recruitment to grow the CAIPP COBRE around the focused understanding of “aberrant immune cell function and the resulting immunopathology”. The cores address critical research needs on campus and are ultimately essential for the long-term growth and status of research at LSUHSC-S. The cores build upon existing equipment and infrastructure and bring new expertise not currently available on campus; thus, they fill a needed gap in research infrastructure. Recent polling of the faculty document that all centers and most faculty (>80%) on campus will utilize/require both proposed cores to generate the needed new data for competitive national grant submissions. In summary, the major goals of this CAIPP COBRE application are to: establish a strong and consistent mentorship and professional development program that meet the individual needs of each investigator (and thus are tailored for the needs of that investigator); establish advanced research core facilities that support the university, the region and the state; advance the mechanistic and clinical understanding for how subversion of the immune response and functioning of immune cells influences human health and disease; and lastly to create an academically and financially independent and internationally recognized Center of Excellence. We support these major goals through our initial collaboration within centers and departments within the school and the entire northern region of the state and to then grow this collaboration through engagement and collaborations with colleagues in the rest of the state once we have established the foundation of the proposed CAIPP.

PROJECT NARRATIVE The COBRE Center for Applied Immunology and Pathological Processes (CAIPP) provides a unique interactive training and research environment for investigators to receive mentorship and guidance, while increasing the competitiveness of their research programs for national funding. The proposed Center will allow the development and growth of the key infrastructure needed to support the national competitiveness of not only the members of the CAIPP Center, but of all researchers on campus, the region and the state. We propose new techniques and infrastructure not presently found on campus. We also propose to promote the interaction and synergy of multiple disciplines where appropriate and harness the collective strengths of the collaborative departments and schools within the state and region to drive research competitiveness. Together, the CAIPP will advance new insights and understanding for how when the immune system is dysregulated in either a hyperactive manner as would be seen in the case of chronic inflammatory conditions or when negatively affected such as during infection with viral or bacterial pathogens, serious and often fatal disease pathologies ensue. It is the understanding of the molecular and clinical basis for these diseases and resulting immunopathologies that we hope will lead to new and better ways to detect and treat these various diseases. These proposed studies go hand and hand with the needs of the citizens of the State of Louisiana where diseases associated with altered immune responsiveness take a significant toll on the health of the citizens of the state, as well as financially on the health care system within the state.