National Disease Research Interchange

RESEARCH RESOURCE FOR HUMAN ORGANS AND TISSUES

TISSUE PROCUREMENT CENTER (TPC) SUPPORTING THE SOMATIC MOSAICISM ACROSS HUMAN TISSUES (SMAHT) NETWORK - PROGRAM DIRECTOR/PRINCIPAL INVESTIGATOR (BELL, THOMAS, J.): PROJECT SUMMARY: THE SOMATIC MOSAICISM ACROSS HUMAN TISSUES (SMAHT) NETWORK PROJECT WILL ESTABLISH THE FIRST COMPREHENSIVE PUBLIC RESOURCE CORRELATING GENETIC VARIATION DUE TO SOMATIC MOSAICISM IN HUMAN TISSUES FROM ALL DEVELOPMENT LAYERS IN THE HUMAN BODY. THE SMAHT NETWORK WILL HAVE MULTIPLE CENTERS TO SUPPORT THE ADVANCEMENT OF THREE PRIMARY INITIATIVES: 1) SOMATIC VARIANT DISCOVERY, 2) DATA ANALYSIS AND NETWORK ORGANIZATION, AND 3) TECHNOLOGY AND TOOL DEVELOPMENT. THE DATA FROM THE SMAHT NETWORK PROJECT WILL PROVIDE AN UNPARALLELED RESEARCH RESOURCE FOR INVESTIGATORS TO GAIN NEW INSIGHTS ON GENETIC VARIATION DUE TO SOMATIC MOSAICISM PROCESSES IN HEALTHY HUMAN TISSUES. IN ADDITION TO CAPITALIZING ON NEW EMERGING METHODOLOGIES TO STUDY SOMATIC MOSAICISM IN HUMAN TISSUES, THE SMAHT PROGRAM INCLUDES AN ETHICAL, LEGAL, SOCIAL IMPLICATIONS (ELSI) STUDY TO FURTHER OUR UNDERSTANDING OF THE ELSI FACTORS IN HUMAN TISSUE DONATION FOR SOMATIC MOSAICISM RESEARCH. TO SUPPORT THE ADVANCEMENT OF THE SMAHT NETWORK PROJECT, THIS PROPOSAL WILL ESTABLISH A TISSUE PROCUREMENT CENTER (TPC) THAT WILL PROVIDE THE SMAHT NETWORK WITH MULTIPLE, HIGH QUALITY HUMAN TISSUE SAMPLES FROM THE SAME INDIVIDUAL ACROSS ALL THREE DEVELOPMENTAL LAYERS FOR THEIR EXPERIMENTAL ANALYSIS. TO MEET THE CHALLENGES FOR SMAHT NETWORK, OUR PROPOSAL IS UTILIZING A MULTI-INSTITUTIONAL EFFORT WITH EXTENSIVE EXPERTISE IN HUMAN TISSUE COLLECTION, RESEARCH, PATHOLOGY, IMAGING, BIOBANKING, AND ELSI STUDY ANALYSIS. THIS SPAN OF EXPERTISE IS ESSENTIAL FOR THE TPC TO SUCCESSFULLY DELIVER WELL-ANNOTATED, SUITABLE TISSUE SAMPLES TO SUPPORT THE GENERATION OF RELIABLE AND REPRODUCIBLE RESULTS AND DATA INTERPRETATIONS FROM THE SMAHT NETWORK EXPERIMENTAL PROCEDURES. IN ADDITION, THE TPC WILL LEAD THE SMAHT NETWORK ELSI STUDY TO SHED LIGHT ON THE ELSI-SPECIFIC FACTORS IN HUMAN TISSUE DONATION FOR SOMATIC MOSAICISM RESEARCH. TO ENABLE A MORE EXTENSIVE ANALYSIS OF THESE FACTORS, THE SMAHT NETWORK ELSI STUDY WILL INCLUDE EVALUATIONS ON TISSUE REQUESTERS (TRS) AND FAMILY DECISION MAKERS (FDMS). COLLECTIVELY, OUR TPC TEAM IS COMMITTED TO ESTABLISHING AN UNEQUALED TPC FOR THE SMAHT NETWORK PROGRAM TO SUPPORT THE ADVANCEMENT OF SOMATIC MOSAICISM RESEARCH, THE ASSOCIATED ELSI FACTORS, AND ULTIMATELY THE DEVELOPMENT OF NEW CLINICAL APPROACHES TO TREAT DISORDERS DRIVEN BY GENETIC VARIATIONS FROM SOMATIC MOSAICISM IN HUMAN TISSUES. RELEVANCE: THE SOMATIC MOSAICISM ACROSS HUMAN TISSUES (SMAHT) NETWORK PROJECT WILL PROVIDE THE FIRST COMPREHENSIVE PUBLIC RESOURCE OF ANALYZING GENETIC VARIATION DUE TO SOMATIC MOSAICISM IN HUMAN TISSUES FROM ALL THREE DEVELOPMENTAL LAYERS. THE SMAHT NETWORK PROGRAM WILL CREATE A NEW, STATE-OF-THE-ART RESEARCH RESOURCE TO SUPPORT NEW DISCOVERIES IN THE BIOLOGY AND DISEASE MECHANISMS THAT ARE PROPELLED BY SOMATIC GENOMIC ALTERATIONS IN HUMAN TISSUES AND FACILITATE THE DEVELOPMENT OF NEW CLINICAL APPROACHES FOR DISORDERS DERIVED FROM SOMATIC GENETIC VARIATIONS. OMB NO. 0925-0001/0002 (REV. 03/2020 APPROVED THROUGH 02/28/2023) PAGE CONTINUATION FORMAT PAGE

PEDIATRIC BIOSPECIMEN PROCUREMENT CENTER (BPC) SUPPORTING THE DEVELOPMENTAL GENE EXPRESSION (DGTEX) PROJECT - PROGRAM DIRECTOR/PRINCIPAL INVESTIGATOR (BELL, THOMAS, J.): PROJECT SUMMARY: ACCELERATING SCIENTIFIC DISCOVERIES ACROSS THE ENTIRE SPECTRUM OF PEDIATRIC RESEARCH REQUIRES ADVANCING OUR CURRENT UNDERSTANDING OF THE UNIQUE MOLECULAR PROFILES AND PHYSIOLOGIES IN ALL HEALTHY TISSUES ACROSS THE HUMAN BODY. THE DEVELOPMENTAL GENOTYPE-TISSUE EXPRESSION (DGTEX) PROJECT WILL ESTABLISH THE FIRST COMPREHENSIVE PUBLIC RESOURCE CORRELATING GENE EXPRESSION AND GENETIC VARIATION IN PEDIATRIC TISSUES FROM ALL MAJOR ORGAN SYSTEMS IN THE HUMAN BODY. THIS PROJECT WILL IDENTIFY THE MOLECULAR PROFILES IN ~30 DISTINCT TISSUE TYPES FROM FOUR DEVELOPMENTAL GROUPS: EARLY POST-NATAL, EARLY CHILDHOOD, PRE-PUBERTAL, AND POST-PUBERTAL. DGTEX WILL CAPITALIZE ON NEW EMERGING METHODOLOGIES TO CAPTURE DETAILED EVALUATIONS ON THE DEVELOPING BRAIN AND INCLUDE OPTIONS FOR SINGLE CELL ANALYSIS ON MULTIPLE TISSUES. TO ADVANCE OUR UNDERSTANDING OF THE ETHICAL, LEGAL, SOCIAL IMPLICATIONS (ELSI) IN PEDIATRIC TISSUE DONATION, DGTEX ALSO INCLUDES AN ELSI STUDY TO ANALYZE THESE FACTORS. THE DATA FROM DGTEX WILL PROVIDE AN UNRIVALED RESEARCH RESOURCE FOR CLINICIANS AND SCIENTISTS TO GAIN NEW INSIGHTS ON THE MOLECULAR MILESTONES OF REGULATORY PROCESSES THAT DIRECT THE DEVELOPMENT OF HEALTHY TISSUES. TO SUPPORT THE ADVANCEMENT OF DGTEX, THIS PROPOSAL WILL ESTABLISH THE PEDIATRIC BIOSPECIMEN PROCUREMENT CENTER (BPC) TO PROVIDE THE PEDIATRIC LABORATORY DATA ANALYSIS COLLECTION CENTER (LDACC) WITH SUITABLE TISSUE SAMPLES FOR THEIR ANALYSIS. OUR PROPOSAL INCLUDES A MULTI-INSTITUTIONAL EFFORT WITH EXTENSIVE EXPERTISE IN PEDIATRIC RECOVERIES, RESEARCH, PATHOLOGY, IMAGING, BIOBANKING, BRAIN RESEARCH, AND CUTTING-EDGE MOLECULAR TECHNIQUES, SUCH AS SINGLE CELL ANALYSIS. THE OBJECTIVES FOR OUR BPC RECOVERY TEAM WILL BE LED BY A COLLABORATIVE EFFORT AMONGST: 1) NATIONAL DISEASE RESEARCH INTERCHANGE (NDRI) TO PROVIDE PROJECT MANAGEMENT AND COORDINATE THE RECOVERY COLLECTION EFFORT FROM A NETWORK OF TSS, 2) CHILDREN'S HOSPITAL OF PHILADELPHIA (CHOP) TO PROCESS, STORE, AND COORDINATE PATHOLOGICAL REVIEW OF ALL NON-BRAIN TISSUES AND MANAGE THE BIOINFORMATICS WORKFLOW, AND 3) NEUROBIOBANK AT UNIVERSITY OF MARYLAND (NBB-MARYLAND) TO PROCESS, STORE, AND PROVIDE PATHOLOGICAL REVIEW OF BRAINS. THIS BREADTH OF EXPERTISE IS ESSENTIAL FOR THE BPC TO PROVIDE WELL-ANNOTATED, SUITABLE BIOSPECIMENS TO ENABLE RELIABLE AND REPRODUCIBLE RESULTS FROM THE LDACC'S CUTTING-EDGE EXPERIMENTAL METHODS AND RIGOROUS DATA INTERPRETATIONS. IMPROVING OUR UNDERSTANDING OF ELSI-SPECIFIC CHALLENGES IN PEDIATRIC TISSUE DONATION IS AN UNMET NEED FOR THE RESEARCH COMMUNITY. TO ENABLE A MORE COMPLETE ANALYSIS OF THESE CHALLENGES, JOHNS HOPKINS ALL CHILDREN'S HOSPITAL (JHACH) WILL COORDINATE THE DGTEX ELSI STUDY TO INCLUDE EVALUATIONS OF TISSUE REQUESTERS (TRS) AND FAMILY DECISION MAKERS (FDMS) OF DECEASED AND AT-RISK CHILDREN. COLLECTIVELY, OUR BPC TEAM IS COMMITTED TO DEVELOPING AN ALL-ENCOMPASSING, UNPARALLELED BPC FOR THE DGTEX PROJECT TO EMPOWER THE ADVANCEMENT OF PEDIATRIC RESEARCH, ELSI CHALLENGES, AND THE DEVELOPMENT OF NEW CLINICAL APPROACHES TO TREAT PEDIATRIC DISORDERS. OMB NO. 0925-0001/0002 (REV. 03/2020 APPROVED THROUGH 02/28/2023) PAGE CONTINUATION FORMAT PAGE

HUMAN TISSUE AND ORGAN RESEARCH RESOURCE

TISSUE PROCUREMENT CENTER (TPC) SUPPORTING THE SOMATIC MOSAICISM ACROSS HUMAN TISSUES (SMAHT) NETWORK - PROGRAM DIRECTOR/PRINCIPAL INVESTIGATOR (BELL, THOMAS, J.): PROJECT SUMMARY: THE SOMATIC MOSAICISM ACROSS HUMAN TISSUES (SMAHT) NETWORK PROJECT WILL ESTABLISH THE FIRST COMPREHENSIVE PUBLIC RESOURCE CORRELATING GENETIC VARIATION DUE TO SOMATIC MOSAICISM IN HUMAN TISSUES FROM ALL DEVELOPMENT LAYERS IN THE HUMAN BODY. THE SMAHT NETWORK WILL HAVE MULTIPLE CENTERS TO SUPPORT THE ADVANCEMENT OF THREE PRIMARY INITIATIVES: 1) SOMATIC VARIANT DISCOVERY, 2) DATA ANALYSIS AND NETWORK ORGANIZATION, AND 3) TECHNOLOGY AND TOOL DEVELOPMENT. THE DATA FROM THE SMAHT NETWORK PROJECT WILL PROVIDE AN UNPARALLELED RESEARCH RESOURCE FOR INVESTIGATORS TO GAIN NEW INSIGHTS ON GENETIC VARIATION DUE TO SOMATIC MOSAICISM PROCESSES IN HEALTHY HUMAN TISSUES. IN ADDITION TO CAPITALIZING ON NEW EMERGING METHODOLOGIES TO STUDY SOMATIC MOSAICISM IN HUMAN TISSUES, THE SMAHT PROGRAM INCLUDES AN ETHICAL, LEGAL, SOCIAL IMPLICATIONS (ELSI) STUDY TO FURTHER OUR UNDERSTANDING OF THE ELSI FACTORS IN HUMAN TISSUE DONATION FOR SOMATIC MOSAICISM RESEARCH. TO SUPPORT THE ADVANCEMENT OF THE SMAHT NETWORK PROJECT, THIS PROPOSAL WILL ESTABLISH A TISSUE PROCUREMENT CENTER (TPC) THAT WILL PROVIDE THE SMAHT NETWORK WITH MULTIPLE, HIGH QUALITY HUMAN TISSUE SAMPLES FROM THE SAME INDIVIDUAL ACROSS ALL THREE DEVELOPMENTAL LAYERS FOR THEIR EXPERIMENTAL ANALYSIS. TO MEET THE CHALLENGES FOR SMAHT NETWORK, OUR PROPOSAL IS UTILIZING A MULTI-INSTITUTIONAL EFFORT WITH EXTENSIVE EXPERTISE IN HUMAN TISSUE COLLECTION, RESEARCH, PATHOLOGY, IMAGING, BIOBANKING, AND ELSI STUDY ANALYSIS. THIS SPAN OF EXPERTISE IS ESSENTIAL FOR THE TPC TO SUCCESSFULLY DELIVER WELL-ANNOTATED, SUITABLE TISSUE SAMPLES TO SUPPORT THE GENERATION OF RELIABLE AND REPRODUCIBLE RESULTS AND DATA INTERPRETATIONS FROM THE SMAHT NETWORK EXPERIMENTAL PROCEDURES. IN ADDITION, THE TPC WILL LEAD THE SMAHT NETWORK ELSI STUDY TO SHED LIGHT ON THE ELSI-SPECIFIC FACTORS IN HUMAN TISSUE DONATION FOR SOMATIC MOSAICISM RESEARCH. TO ENABLE A MORE EXTENSIVE ANALYSIS OF THESE FACTORS, THE SMAHT NETWORK ELSI STUDY WILL INCLUDE EVALUATIONS ON TISSUE REQUESTERS (TRS) AND FAMILY DECISION MAKERS (FDMS). COLLECTIVELY, OUR TPC TEAM IS COMMITTED TO ESTABLISHING AN UNEQUALED TPC FOR THE SMAHT NETWORK PROGRAM TO SUPPORT THE ADVANCEMENT OF SOMATIC MOSAICISM RESEARCH, THE ASSOCIATED ELSI FACTORS, AND ULTIMATELY THE DEVELOPMENT OF NEW CLINICAL APPROACHES TO TREAT DISORDERS DRIVEN BY GENETIC VARIATIONS FROM SOMATIC MOSAICISM IN HUMAN TISSUES. RELEVANCE: THE SOMATIC MOSAICISM ACROSS HUMAN TISSUES (SMAHT) NETWORK PROJECT WILL PROVIDE THE FIRST COMPREHENSIVE PUBLIC RESOURCE OF ANALYZING GENETIC VARIATION DUE TO SOMATIC MOSAICISM IN HUMAN TISSUES FROM ALL THREE DEVELOPMENTAL LAYERS. THE SMAHT NETWORK PROGRAM WILL CREATE A NEW, STATE-OF-THE-ART RESEARCH RESOURCE TO SUPPORT NEW DISCOVERIES IN THE BIOLOGY AND DISEASE MECHANISMS THAT ARE PROPELLED BY SOMATIC GENOMIC ALTERATIONS IN HUMAN TISSUES AND FACILITATE THE DEVELOPMENT OF NEW CLINICAL APPROACHES FOR DISORDERS DERIVED FROM SOMATIC GENETIC VARIATIONS. OMB NO. 0925-0001/0002 (REV. 03/2020 APPROVED THROUGH 02/28/2023) PAGE CONTINUATION FORMAT PAGE

HTORR COLD STORAGE TEMPERATURE MONITORING MODERNIZATION - PROJECT SUMMARY: THE HUMAN TISSUE AND ORGAN RESEARCH RESOURCE (HTORR) IS A DIVISION OF THE NATIONAL DISEASE RESEARCH INTERCHANGE (NDRI), A NOT-FOR-PROFIT NIH-FUNDED ORGANIZATION WHOSE MISSION IS TO PROVIDE THE BIOMEDICAL RESEARCH COMMUNITY WITH HUMAN TISSUES FOR RESEARCH. THE IMPORTANCE OF HUMAN TISSUES FOR USE IN RESEARCH IS CONTINUALLY GROWING AND EVOLVING AS NEW TOOLS AND TECHNOLOGIES ARE DEVELOPED, REQUIRING THE RESOURCES SUPPORTING THIS RESEARCH TO EVOLVE AS WELL. THE PRIMARY OBJECTIVE OF OUR R24 EQUIPMENT PROGRAM GRANT SUBMISSION TO THE ACTIVE PAR-24-028 “MODERN EQUIPMENT FOR SHARED-USE BIOMEDICAL RESEARCH FACILITIES: ADVANCING RESEARCH- RELATED OPERATIONS” PROPOSAL IS TO MODERNIZE OUR COLD STORAGE MAPPING AND TEMPERATURE MONITORING INFRASTRUCTURE AND CAPABILITIES FOR THE BIOREPOSITORY TO ENSURE THAT THE RESOURCES AVAILABLE TO THE RESEARCH COMMUNITY CAN CONTINUE TO MEET THE EVER-CHANGING NEEDS. IMPORTANTLY, THIS MODERNIZATION WILL ALLOW FOR IMPROVED CONTROL, CONSISTENCY, AND DOCUMENTATION OF SAMPLE MANAGEMENT, WHICH IS AN IMPORTANT STEP IN FACILITATING RESEARCH RIGOR AND REPRODUCIBILITY THROUGHOUT THE RESEARCH COMMUNITIES THAT WE SERVE.