U01NS134349

Vanderbilt Center for Undiagnosed Diseases (VCUD) - Project Summary

Undiagnosed diseases (UD) are constellations of significant signs, symptoms and/or test results that are seen by specialists over time without discovery of their cause(s), and for which diagnostic procedures and tests have been exhausted. The goal of the Undiagnosed Disease Network (UDN) is to diagnose UDs and bring answers that give afflicted individuals hope and ways to improve their health.

Our Vanderbilt UDN clinical site (VCUD) is an ideal milieu of excellent patient oriented care, and collaborative research. We formed the VCUD by combining unique Vanderbilt resources with UDN resources to diagnose difficult UDs. Vanderbilt resources include:

1) A productive Clinical and Translational Science Award that hosts a large Clinical Research Center (CRC) that has grown, evolved, and developed an outstanding cohort of clinicians and physician scientists,
2) A strong, dedicated group of pediatricians, internists, neurologists and geneticists,
3) Bioinformatics experts,
4) The BioVU DNA databank and experts,
5) Structural biology investigators,
6) Our EMR and REDCap database, and
7) A strong focus on educating and training the next generation who will help sustain the UDN over the long-term.

We have combined our VCUD team (physicians, bioinformatics experts, research scientists, study coordinator, NPs, GCs), with UDN resources to diagnose UD patients by the following:

A) Gathering and analyzing clinical data to form differential diagnoses (clinical hypotheses),
B) Analyzing next generation sequencing and other test data to form testable gene hypotheses,
C) Utilizing unique VUMC resources including BioVU, PrediXcan, and structural biology to prioritize candidate variants (CV),
D) Determining the functional effects of non-coding CV,
E) Testing and merging our clinical and genetic hypotheses to identify concordant disorders and CV that cause the patients' UD, and
F) Using VCUD studios to discover new diseases and promote translational research to determine mechanisms and lead to treatments.

We hypothesize that we can use VCUD teams to merge patient care with translational research by synergistically combining them with distinct VUMC resources to more efficiently and sustainably diagnose and treat UD patients. Our VCUD structure will provide the workflow, throughput, and passion needed to test our hypotheses and diagnose and provide treatment recommendations.

A key goal in this transition period would be to fully implement a sustainability plan (Specific Aim 3) that is inclusive and relies on a number of resources (institutional, insurance plans, NORD, UDNF, philanthropic).

Vanderbilt University Medical Center

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.310 - Trans-NIH Research Support

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

Diagnostic Centers of Excellence for the Undiagnosed Diseases Network (U01 Clinical Trial Not Allowed) (PAR-23-289)

Amendment Since initial award the End Date has been extended from 04/30/24 to 07/31/28 and the total obligations have increased 336% from $681,250 to $2,970,371.