Resnick, Adam Cain PHD

This new R25 program, responsive to PAR-22-195, plays a crucial role in the INCLUDE project (Investigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Each year, we recruit,train, mentor, and provide career advice to a cohort of 16 post-graduate participants dedicated to mastering Down syndrome (DS) clinical research. Despite the swift growth of INCLUDE, there are still too few laboratories led by Down syndrome expert scientists and too few new clinical trainees with expertise in Down Syndrome. In full compliance with NOT-OD-25-090 (Notice of Civil Rights Term and Condition of Award), this program is available for all qualified American Citizens and Permanent Residents. Under the direction of multiple Principal Investigators, Ann Cohen, PhD (Pitt); Benjamin Handen, PhD (Pitt); Elizabeth Head, PhD (Irvine); Adam Resnick, MD, PhD (CHOP); Jonathan Santoro, MD (USC-Keck); and Gerald Schatten, PhD (Contact PI, Pitt), with Co-Investigator Calvin Simerly, PhD (Pitt), the ICRT initiative proposes five specific aims: I. Annual ICRT courses covering DS through the entire lifespan; II. Ongoing Mentoring; III. Fostering Intra-INCLUDE Collaborations and Partnerships; IV. Responsible Conduct for Research training to ensure full compliance with NIH and Institutional guidance, regulations and law; and V. Quantitative Independent Evaluations to track Participants’ Careers, comprehensively and longitudinally, to ensure that ICRT is a wise, effective investment. ICRT will meet and exceed the PAR’s mandate of training the next generation of DS clinical researchers, 80 additional clinical investigators, and thereby improving the quality of life and health span of those with Down syndrome.

– Overall. People with Down syndrome are strongly predisposed to develop a wide range of comorbidities that shorten their lifespan and decrease their quality of life, such as Alzheimer’s disease, congenital heart disease, leukemias, autoimmune disorders, and diverse neurological conditions. The proposed activities under this project seek to create a world-class resource for collaborative discovery, data sharing, data access, and integrative analysis that would enable novel investigations into all DS comorbidities across the lifespan and further integrating across datasets for related diseases occurring in the general population, thus paving the way for a precision medicine approach to DS. Furthermore, this resource and associated platforms will also have broader impacts by empowering physicians, educators, government officials, and advocates with the tools required to elicit evidence- based transformative action in the clinic, the classroom, the government, and society at large.

– Overall. People with Down syndrome are strongly predisposed to develop a wide range of comorbidities that shorten their lifespan and decrease their quality of life, such as Alzheimer’s disease, congenital heart disease, leukemias, autoimmune disorders, and diverse neurological conditions. The proposed activities under this project seek to create a world-class resource for collaborative discovery, data sharing, data access, and integrative analysis that would enable novel investigations into all DS comorbidities across the lifespan and further integrating across datasets for related diseases occurring in the general population, thus paving the way for a precision medicine approach to DS. Furthermore, this resource and associated platforms will also have broader impacts by empowering physicians, educators, government officials, and advocates with the tools required to elicit evidence- based transformative action in the clinic, the classroom, the government, and society at large.

PROJECT NARRATIVE – Overall People with Down syndrome are strongly predisposed to develop a wide range of co-occurring conditions that shorten their lifespan and decrease their quality of life, such as Alzheimer’s disease, congenital heart disease, autoimmune disorders, and diverse neurological conditions. The proposed activities under this project seek to further develop a world-class resource for collaborative discovery, data sharing, data access, and analysis that would enable novel investigations of DS across the lifespan, thus paving the way for a precision medicine approach to DS. Furthermore, this resource and associated platforms will also have broader impacts by empowering physicians, educators, government officials, and advocates with the tools required to elicit evidence- based transformative action in the clinic, the classroom, the government, and society at large.

The Kids First Data Resource will aggregate genetic and clinical data from childhood cancer and structural birth defect patient cohorts, empowering researchers to search, aggregate and analyze the data to uncover entirely new ways of understanding childhood cancer and structural birth defects. The Kids First Data Resource will 1) serve as a centralized data hub to integrate dispersed data sources and provide harmonized data sets 2) provide easy access to and querying of disparate data sets via a web portal for researchers without bioinformatics expertise 3) provide tools for analyzing large and complex data sets encompassing genetic sequence and clinical data. By increasing the utility of genetics data, the Kids First Data Resource will maximize the potential to yield novel discovery and better understanding of genetic etiology underlying childhood cancer and structural birth defects for improved treatment and outcomes.

The mission of the INCLUDE Data Coordinating Center is to accelerate research that benefits individuals with Down syndrome (DS) by facilitating access and analysis of data from cohort studies of people with DS. This award will fund the development of an immersive summer course in data sciences known as the Data Science for Developing Scholars in Down Syndrome Research (DS3), which will provide training in the basics of generation, identification and collection of high content multidimensional datasets; their management, analysis and visualization; as well as development of key professional skills required for the career advancement of trainees.

The INCLUDE Data Hub has reached a significant milestone (MVP launch) featuring both open-access and controlled data. Investing in INCLUDE infrastructure that can serve controlled access data directly will empower more researchers with richer data; increasing the probability of advancing DS research. We will design, build, and integrate a Clearinghouse with the INCLUDE DRS Server and the NIH Researcher Auth Service (RAS) to create a secure and compliant system to serve controlled data within the INCLUDE Data Hub.

The respective biorepositories of the Children’s Hospital of Philadelphia and the Crnic Institute Human Trisome Project Biobank will partner with the INCLUDE Data Hub to support the proposed development of a centralized biorepository data resource to coordinate a single biospecimen data repository or a network of repositories curating and distributing tissue specimens, cell lines, and associated derived analytes such as DNA, RNA, metabolites or proteins relevant to Down syndrome research. Coordinating the linkages between samples, clinical data, and derived biosample characterization data and/files such that a federated framework of queryable samples are available as an integrated resource to the investigator community remains a fundamental challenge. This project will address this unmet need in the field.

This is a proposal to support the design of a pilot data portal for sharing and analysis of data from experimental models of Down syndrome, and to enhance the security ecosystem of the existing researcher portal known as the INCLUDE Data Hub. The activities supported by this award will enable the future creation of an Experimental Models Portal within the INCLUDE Data Hub, while also supporting full compliance with advanced security standards.

– Overall. People with Down syndrome are strongly predisposed to develop a wide range of comorbidities that shorten their lifespan and decrease their quality of life, such as Alzheimer’s disease, congenital heart disease, leukemias, autoimmune disorders, and diverse neurological conditions. The proposed activities under this project seek to create a world-class resource for collaborative discovery, data sharing, data access, and integrative analysis that would enable novel investigations into all DS comorbidities across the lifespan and further integrating across datasets for related diseases occurring in the general population, thus paving the way for a precision medicine approach to DS. Furthermore, this resource and associated platforms will also have broader impacts by empowering physicians, educators, government officials, and advocates with the tools required to elicit evidence- based transformative action in the clinic, the classroom, the government, and society at large.