COBRE (Phase II) Awards – October 2009

NCRR's Centers of Biomedical Research Excellence (COBRE) support thematic multidisciplinary centers that augment and strengthen institutional biomedical research capacity. This is accomplished by expanding and developing biomedical faculty research capability and enhancing research infrastructure, including the establishment of core facilities needed to carry out the objectives of a multidisciplinary, collaborative program.

Supported by NCRR's Division of Research Infrastructure (DRI), COBREs are led by NIH-funded investigators with expertise central to the theme of the grant proposal. The centers promote collaborative interactive efforts among researchers with complementary backgrounds, skills and expertise. In some instances, COBRE support will facilitate the development of new disease-specific research centers or augment the capability of existing centers. Researchers supported through the COBREs are expected to compete independently for external peer-reviewed grant support.

Louisiana State University

Baton Rouge, La.

Center for Experimental Infectious Disease Research

Principal Investigator
Konstantin G. Kousoulas, Ph.D.
E-mail: vtgusk@lsu.edu

Description:

The Center for Experimental Infectious Disease Research (CEIDR) is led by the Louisiana State University-Baton Rouge (LSU-BR) School of Veterinary Medicine, (SVM) in a strategic alliance with the Tulane National Primate Research Center (TNPRC). Accomplishments by junior investigators (JIs) recruited during the last funding period (2003-2008) includes the award of 4R01, 2R21, 2K22,1K01 and 1 NIH-R01- subcontract, as well as competitive funding from sources other than NIH. Importantly, the institutions were awarded a NIH T32 postdoctoral training grant for veterinarians (TNPRC) and a NIH T35 summer training grant for veterinary students (LSU-SVM). For the next phase, the COBRE will encompass four initial research projects under the direction of new junior investigators working on infectious diseases. The new projects are: host mediators of mycobacterium tuberculosis (MTB) immunopathology; borrelial evasion of innate and adaptive immunity; molecular determinants of rickettsial pathogens in tick hosts; the role of humoral immune responses in control of SIV replication and pathogenesis. Enhancement of the research infrastructure will be achieved by the formation of a Molecular Immunopathology (MIP) Core Laboratory as a consortium of existing LSU-SVM centralized laboratories and TNPRC. Future development of the Center will be achieved through the addition of 4-6 JIs at LSU and TNPRC within the next three years, as well as the hiring of two senior investigators. The proposed research is focused on finding new ways to understand and combat infectious diseases including AIDS, Lyme disease, Tuberculosis and mosquito borne diseases. The work will produce new diagnostics and vaccines to ameliorate these diseases.

Montana State University

Bozeman, Mont.

Center for Zoonotic and Emerging Infectious Diseases

Principal Investigator
Mark Quinn, Ph.D.
E-mail: mquinn@montana.edu

Description:

Zoonotic and emerging infectious diseases represent an increasing threat to global health, and it is essential that we expand our understanding of the pathogenesis and prevention of these diseases because of the increasing density of human populations, the increased exposure to domestic animal populations and the crowding of wildlife into limited areas with frequent human contact. To address the need for infectious disease research capabilities, a COBRE Center of Excellence was established at Montana State University (MSU), with the goal of positioning Montana as a national leader in research on the pathogenesis of zoonotic infectious diseases. Over the past four years, the Center has been extremely successful, resulting in development of infrastructure, recruitment and support of junior investigators and formation of a cohesive Center of investigators. The long-term goal is to establish a sustainable Center of Excellence that is focused on understanding pathogenesis, host immune responses and therapeutic development for zoonotic and emerging infectious diseases of regional and worldwide importance. The second phase of funding will enable the continued development of a pipeline of current junior investigators, so that funding and infrastructure resources are available at critical junctures in their careers. The COBRE will also increase the size, scope and competitiveness of the Center through four new faculty hires and strengthen the infectious disease research infrastructure in Montana through support and enhancement of established core facilities. COBRE II will strengthen and enrich the Center of Excellence in infectious disease research, providing the resources needed to advance the understanding of disease pathogenesis and facilitating development of novel therapeutic treatments.

Oklahoma Medical Research Foundation

Oklahoma City, Okla.

Molecular Mechanisms and Genetics of Autoimmunity

Principal Investigator
John Barker Harley, M.D., Ph.D.
E-mail: john-harley@omrf.org

Description:

The COBRE Program in the “Molecular Mechanisms and Genetics of Autoimmunity” at the Oklahoma Medical Research Foundation (OMRF) has sponsored 14 studies, generated more than 240,000,000 genotypes, published 130 important manuscripts, made possible the funding of multiple NIH grants and resulted in recruiting of eight new faculty members. This COBRE focuses on professional growth through mentoring and through building relevant infrastructure. With its emphasis on mentoring, the COBRE program has changed the scientific culture toward open, mutual encouragement of faculty, whether senior or junior. This has also served to develop careers in science and to produce outstanding scientific results. Each COBRE-funded scientist holds the potential promise for an independent career, producing critical insights and experiments. Scientifically, the scientists will be supported by Nucleic Acid and Data Analysis Cores with mentoring and other functions under an Administrative Core. In addition, the recruiting successes will be continued with a Recruiting Core designed to provide adjunct support to the expansion underway at the OMRF. In the second phase of funding, the goal is to build as many productive scientific careers as possible, to populate our institutions with as many exceptional faculty members as possible, to enhance our international reputation for scientific excellence in autoimmunity and to produce critically important new discoveries in the process. Autoimmune diseases are estimated to afflict as many as 50,000,000 citizens. This COBRE program will study pathways, identify genes and develop knowledge basic to understanding these disorders, concentrating on systemic lupus erythematosus - a potentially deadly autoimmune disease found mainly in young women - so that the new knowledge will lead to new diagnostics, prognostics and therapeutics.

Rhode Island Hospital

Providence, R.I.

COBRE Center for Cancer Research Development

Principal Investigator
Douglas Hixson, Ph.D.
E-mail: douglas_hixson@brown.edu

Description:

The COBRE Center for Cancer Research Development (CCRD) aims to promote the expansion of basic cancer research by creating a supportive research environment that facilitates the transition of promising scientists into independent investigators. The next phase of this award will build on the success of the CCRD in guiding promising junior investigators towards independence. Recognizing the high cancer mortality in Rhode Island, CCRD will continue to support hypothesis driven research in the area of Gl Cancer. The development of new collaborative endeavors focused on stem cells in liver/GI cancer will be overseen by a research development committee. This theme will take full advantage of the strong liver and stem cell research programs already ongoing at Rhode Island Hospital. Five talented investigators with overlapping research interests will generate opportunities for sharing of ideas and productive interaction. While expanding basic cancer research will continue to be the primary mission of CCRD, it will also increase fundraising efforts and augment outreach activities aimed at increasing public awareness of the value of cancer research. Fostering interactions between basic scientists and clinical oncologists through innovative programs driven by clinical observation will also be a high priority. During the next 5 years, CCRD will expand its leadership role in sustaining a dialogue with state and federal legislators and policy makers.

Tulane University School of Public Health and Tropical Medicine

New Orleans, La.

Mentoring a Cancer Genetics Program

Principal Investigator
Prescott Deininger, Ph.D.
E-mail: pdeinin@tulane.edu

Description:

The objective of this COBRE renewal is to continue to develop the research careers of promising junior investigators in cancer genetics and to build core programmatic strength in this area. The five projects in this COBRE focus on several overlapping themes that contribute to an understanding of genetic instability, cellular inflammation, and the cell's responses to these factors. Career development will involve a series of program meetings, exposure to didactic grant-writing sessions, and seminars to develop a highly collaborative environment for both the junior faculty, as well as other members of the Louisiana Cancer Research Consortium (LCRC). The COBRE also provides outstanding core facility development for scientists to make new experiments available to them. The LCRC provides an outstanding interdisciplinary and inter-institutional environment for cancer research involving Tulane University, LSU Health Sciences Center and Xavier University. This COBRE represents the centerpiece of the LCRC and contributed strongly to rebuilding post-Katrina as well as providing the framework that helps guide mentoring and development throughout the LCRC.

This COBRE has been responsible for the success of a number of young faculty obtaining their first NIH R01 funding and is poised for even more growth in the renewal. This will greatly enhance the research funding base and mentoring pool in Southeastern Louisiana. In addition, the scientific programs and cores described provide outstanding and highly translational projects aimed at combating cancer.

University of Arkansas for Medical Sciences

Little Rock, Ark.

Center for Translational Neuroscience

Principal Investigator
Edgar Garcia-Rill, Ph.D.
E-mail: garciarilledgar@uams.edu

Description:

During the initial award phase, the Center for Translational Neuroscience (CTN) generated more than $13 million in new grants to investigators and recruits and published more than 130 articles, chapters, abstracts or presentations. The CTN has devised a new and effective treatment for tinnitus, developed a device as well as a new drug treatment for hyperreflexia and spasticity after spinal cord injury, developed a cure (elimination of symptoms) for spatial neglect, discovered a novel mechanism for sleep-wake control that will also impact the mechanisms behind anesthesia and have begun to decrease the death rate among low-birth-weight babies in the Arkansas. A few of the aims of the next phase of the CTN include: strengthening and augmenting translational neuroscience research through mentoring promising junior clinician and basic scientists; expanding the research programs of early career investigators by forming research teams, including successful, previously supported investigators and new junior investigators mentored by multiple established senior investigators; enhancing the infrastructure critical for expanding translational neuroscience research by supporting, upgrading and expanding our core facilities; and maintaining the successful career development program for junior investigators and instituting a new leadership program for established, early career and junior researchers. Two blocks to translational research have been identified: 1) lack of translation of basic science discoveries into clinical studies; 2) lack of translation from clinical studies into medical practice. The CTN is designed to address blocks to these processes while mentoring promising scientists to careers in translational research. The CTN is a beacon for translational research in Arkansas and is having an impact on the health of its residents.

University of Kentucky

Lexington, Ky.

Center for the Biologic Basis of Oral/Systemic Disease

Principal Investigator
Jeffrey L. Ebersole, Ph.D.
E-mail: jleber2@uky.edu

Description:

The link between chronic oral infections and general health has been recognized since the early 20th century. Retrospective epidemiological studies and prospective longitudinal — as well as intervention — studies have supported that these chronic oral infections with accompanying chronic inflammation associated with various systemic diseases and their sequelae. The award for the Center for the Biologic Basis of Oral/System Diseases (CBBO/SD) addresses major initiatives of the National Institute of Dental and Craniofacial Research regarding improving oral and general health of the U.S. population. The CBBO/SD is organized into three clinical projects: Chronic Inflammation at the Oral and Cervico/Vaginal Mucosa; Physiology of the Stress Response in Patients with Temporomandibular Disorders and Fibromyalgia; Coordinated Oral-Intestinal Immune Response in Patients with Inflammatory Bowel Diseases. The CBBO/SD also has two translational science projects: Ontogeny of Innate Immune Responses at Mucosal Surfaces; and Gene Therapy for Orofacial Pain. These projects enlist junior investigators from the Colleges of Dentistry, Nursing and Medicine, as well as senior mentors/co-investigators from multiple colleges at the University of Kentucky. The theme of the projects focuses on the contribution of chronic inflammation to oral and systemic diseases. The projects engage populations of expectant women, patients with chronic orofacial pain and patients with inflammatory bowel disease. The clinical projects interact with the translational projects at the level of a common understanding of innate immune responses and inflammation and novel therapeutic intervention strategies for chronic orofacial pain. The CBBO/SD provides an infrastructure for development of the junior faculty by providing grants management support, educational opportunities, a biostatistics/bioinformatics core and a clinical research center.

University of Kentucky Research Foundation

Lexington, Ky.

Center for Biomedical Research Excellence in the Molecular Basis of Human Disease

Principal Investigator
Louis Hersh, Ph.D.
E-mail: lhersh@uky.edu

Description:

The Kentucky COBRE aims to enhance the competitiveness of junior faculty at the University of Kentucky through the funding of promising junior faculty and providing state-of-the-art research cores. During the prior five years of this COBRE grant, 22 junior faculty from nine different departments were mentored; eight of them received NIH R01 funding, and an additional four received other forms of extramural funding. Participants in the activities of the Center have included an additional 11 faculty, 11 postdoctoral/research associates and nine graduate students. The members of the Center published more than 175 research papers and made 38 presentations at scientific meetings. The Department of Molecular and Cellular Biochemistry, in which the COBRE is housed, rose from 28th to 12th in NIH rankings, in terms of public medical schools; and 26th, in terms of all medical schools, during the tenure of the COBRE. This was accomplished by increasing NIH grant dollars by over $5 million, excluding the COBRE funds. In the second phase of this COBRE, the Center aims to establish a nationally and internationally recognized research center that will continue to compete effectively for extramural research funding. To accomplish this goal, the Center plans to: expand its critical mass of investigators; enhance the opportunity to translate research to patients by facilitating interactions with clinical faculty; continue the major areas of focus in cancer, diabetes, and neurological diseases and develop core facilities in proteomics, synthetic chemistry, microscopy, and protein characterization.

University of Nebraska Medical Center

Omaha, Neb.

The Molecular Biology of Neurosurgery Systems

Principal Investigator
Shelley D. Smith, Ph.D.
E-mail: ssmith@unmc.edu

Description:

The loss of neurosensory function — particularly the sensations of hearing and vision — has devastating effects on quality of life. Since neurosensory cells of the inner ear and retina are not replaced after damage or degeneration, such losses are permanent. The Nebraska Center for the Molecular Biology of Neurosensory Systems aims to characterize the genetic mechanisms controlling the development and maintenance of neurosensory functions and the corresponding pathology associated with relevant gene mutations to identify potential avenues for intervention. Through a collaboration between the University of Nebraska Medical Center, Creighton University, and Boys Town National Research Hospital, this COBRE will focus its efforts on promising regenerative medicine strategies such as the reconstitution of damaged cells through the use of pluripotent stem cells or de-differentiation and regeneration of post-mitotic cells in the inner ear and retina. The research is facilitated by three scientific cores: 1) a Mouse Genome Engineering core for the development of mouse models; 2) a Microarray core for comprehensive assessment of gene expression levels and determination of possible genetic networks; and 3) a Molecular Phenotyping/Histology core to study the results of experimental alterations. In the second phase of this COBRE project, six junior researchers will have continued support: two are studying the mechanisms of specific syndromes of blindness and deaf/blindness; one is concentrating on the development and enrichment of retinal stem cell populations; and three are studying the molecular pathways of inner ear differentiation with the goal of facilitating sensory regeneration. By studying the genetic controls of development of the sensory cells in the retina and inner ear, the scientists in this Center will determine optimal approaches for therapies utilizing precursor cells that can develop into replacement cells and restore function.

University of Nevada, Reno

Reno, Nev.

Smooth Muscle Plasticity Center of Biomedical Research Excellence

Principal Investigator
Kenton M. Sanders, Ph.D.
E-mail: ksanders@medicine.nevada.edu

Description:

The Smooth Muscle Plasticity Center of Biomedical Research Excellence (COBRE) has expanded the research infrastructure and helped to develop the careers of several highly promising young investigators. The center has a strong thematic focus in smooth muscle biology. Smooth muscles are unique among muscle lineages, because they change phenotype in response to a variety of stimuli. Pathophysiological conditions result from phenotypic changes in smooth muscle tissues, but the cause and consequences of remodeling and hypertrophy are not well understood. Several disease models of smooth muscles will be used to learn how phenotypic change contributes to pathophysiology. The COBRE consists of five projects that are investigating various aspects of smooth muscle plasticity: 1) correlation between structural and motor defects in diabetic gastroparesis; 2) Phopholamban and CaM Kinase II in smooth muscle plasticity; 3) an in vitro model system for determining regulatory mechanisms for smooth muscle mechanics; 4) smooth muscle hypertrophy regulated by microRNAs and their target genes; and 5) stretch-dependent potassium channel regulation in overactive bladder. The projects are supported by core lab facilities in administration and faculty development, molecular expression and transgenics, protein expression and cell morphology, and dynamic imaging. The COBRE will be administered by the Central COBRE Administration, consisting of an administrative assistant and computer specialist, an Internal Advisory Committee (IAC) with mentors for each project leader and an External Advisory Committee (EAC), consisting of leaders in smooth muscle biology. The IAC establishes milestones for career development, performs formative and summative evaluation of progress toward milestones and assists the project leaders in the central goal of developing independent funding and sustainable research careers.

University of New Mexico

Albuquerque, N.M.

COBRE Center for Evolutionary and Theoretical Immunology

Principal Investigator
Eric Loker, Ph.D.
E-mail: esloker@unm.edu

Description:

Research conducted by investigators at the Center for Evolutionary and Theoretical Immunology (CETI) will increase their understanding of the transmission of human parasitic diseases and may lead to the development of new therapeutics. In addition, models of viral diseases will be developed that will improve our ability to predict the spread of epidemics, as well as evaluate effectiveness of different treatment regimes. Through CETI, both junior and senior faculty scholars from the Biology and Computer Science Departments at the University of New Mexico (UNM) and the Los Alamos National Laboratories will undertake research projects that seek to reveal basic design principles of immune systems, that model the interactions between pathogens and immune systems and that explore the evolution of immune responses across animal phyla. These projects will enable a better understanding of how invertebrate vectors transmit infectious diseases, how pathogens defend themselves from immune attack and how the comparative study of immune systems can lead to exciting new conceptual frameworks and paradigms. During the second phase of funding, CETI will improve its mentoring program to develop independently-funded junior investigators. The Center will hire additional CETI-related tenure track faculty and continue to partner with other NCRR programs and the UNM administration to support and improve CETI's core facilities in molecular biology, controlled environments and mass spectrometry/proteomics. The funding will also be applied toward the development of multi-investigator proposals that will enable CETI to seek new ways to promote integration and collaborations among our members and with the New Mexico research community. CETI will increasingly serve as a catalyst to develop new training and biomedical research opportunities in New Mexico.