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Principal Investigator: CHARLES A O'BRIEN
Organization: UNIV OF ARKANSAS FOR MED SCIS
Fiscal Year: 2024
Award: $2,295,000
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY/ABSTRACT - OVERALL
Conditions such as osteoporosis and osteoarthritis, and malignancies such as breast cancer, negatively
affect the musculoskeletal system, leading to substantial disability and health care costs. Thus, there is an
ongoing need to better understand the causes of these conditions and to support development of more effective
and well-tolerated therapies. The Center for Musculoskeletal Disease Research (CMDR) was established at the
University of Arkansas for Medical Sciences (UAMS) during Phase 1 to meet this need. The scientific theme of
the CMDR is that identification of molecular contributors to musculoskeletal dysfunction and disease will guide
development of effective therapies. To study these conditions, we have assembled teams of junior and
established investigators and supported development of junior investigators to the point of achieving independent
R01-level funding. We also utilize state-of-the-art technologies to analyze gene expression, genetically
manipulate animals, and analyze the skeleton. These complementary approaches, together with access to
clinical investigators and patient samples, have synergized to create a unique and productive research
environment. A key to the continued success of the Center will be to increase the number of investigators whose
research is aligned with our scientific theme via development of more junior investigators and recruitment of new
and established investigators. To accomplish this, in Phase 2 we propose to support the development of 3 Project
Leaders by providing structured mentoring, financial resources, and collaboration with other CMDR investigators
(Aim 1). We will also continue to strengthen the biomedical research infrastructure at UAMS by increasing the
capabilities and utilization of 4 research cores that provide access to rapid, high-quality services and that develop
new approaches, such as CRISPR interference for in vivo loss-of-function studies (Aim 2). To continue building
a critical mass of musculoskeletal investigators and teams, the Center will utilize a Pilot Project Program, targeted
recruitment of investigators with complementary expertise, and incorporation of new and established center
investigators into synergistic and productive research teams (Aim 3). Successful implementation of this
Organization and Management Plan will, in the long-term, lead to a self-sustaining Center of Biomedical
Research Excellence that will generate novel and important results leading to more effective therapies for the
numerous conditions that involve the musculoskeletal system.
Terms: <Achievement><Achievement Attainment><Affect><Animals><Arkansas><Benchmarking><Best Practice Analysis><Bio-Informatics><Bioinformatics><Biomedical Research><Bone Infection><Breast Cancer><COBRE><CRISPR interference><CRISPR-dCas9-mediated repression><CRISPR/dCas9 interference><CRISPR/dCas9-mediated transcriptional inhibition><CRISPRi><Cancers><Center of Biomedical Research Excellence><Centers of Research Excellence><Clinical Investigator><Clustered Regularly Interspaced Short Palindromic Repeats interference><Collaborations><Degenerative Arthritis><Degenerative polyarthritis><Development><Disease><Disorder><Dysfunction><Environment><Faculty><Fertilization in Vitro><Functional disorder><Funding><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Gene Modified><Genetic Models><Goals><Grant><Health><Health Care Costs><Health Costs><Healthcare Costs><Histology><Image><Institution><Investigators><Lead><Malignant Breast Neoplasm><Malignant Neoplasms><Malignant Tumor><Measures><Medical><Mentors><Mice><Mice Mammals><Molecular><Molecular Analysis><Multiple Myeloma><Murine><Mus><Musculoskeletal><Musculoskeletal Diseases><Musculoskeletal System><NIGMS><National Institute of General Medical Sciences><Osteoarthritis><Osteoarthrosis><Osteomyelitis><Osteoporosis><Patients><Pb element><Phase><Physiopathology><Pilot Projects><Plasma-Cell Myeloma><Play><Population><Productivity><Research><Research Infrastructure><Research Personnel><Research Resources><Research Support><Researchers><Resources><Sampling><Science><Scientist><Services><Skeleton><Structure><Technology><Test-Tube Fertilization><Transcript Expression Analyses><Transcript Expression Analysis><Universities><analyze gene expression><benchmark><bone><bone imaging><bone scanning><degenerative joint disease><developmental><disability><effective therapy><effective treatment><experience><gene expression analysis><gene expression assay><gene manipulation><gene modification><genetic manipulation><genetically manipulate><genetically modified><genetically perturb><heavy metal Pb><heavy metal lead><hypertrophic arthritis><imaging><in vivo><innovative technologies><locomotor system><loss of function><malignancy><malignant breast tumor><mouse model><murine model><musculoskeletal disorder><myeloma><myelomatosis><neoplasm/cancer><new approaches><novel><novel approaches><novel strategies><novel strategy><osteoarthritic><pathophysiology><pilot study><programs><recruit><repressing CRISPR-dCas9 system><semen cryopreservation><skeletal abnormality><skeletal imaging><skeletons><sperm cell cryopreservation><sperm cryopreservation><sperm freezing><spermatozoa cryopreservation><success><synergism><transcriptional profiling><web tool><web-based tool>