ABSTRACT The goal of this Phase 2 CoBRE application is to expand on the accomplishments of Phase 1 in establishing an interdisciplinary and translational Center for Integrative Research on Childhood Adversity (CIRCA) at Oklahoma State University (OSU). Two decades of epidemiological data document that Adverse Childhood Experiences (ACEs) are prevalent and cumulative, have enduring negative consequences for physical and mental health, and cost north America more than $758B in preventable health care. In order to reduce the costly effects of ACEs, research is increasingly focused on identifying mechanisms and processes by which ACEs impact developing nervous, endocrine, metabolic, and immune systems, and intergenerational biobehavioral pathways of transmission, as well as potential pathways for prevention, recovery, and healing. This research is interdisciplinary by design and reliant on a team science approach, requiring researchers with the capacity to collaborate in transdisciplinary teams.14, 15 The goals of CIRCA during Phase 1 were to increase institutional research infrastructure to support a cadre of collaborative investigators achieve independent funding on adversity and resilience. OSU invested approximately $10M in facilities, equipment, faculty, and staff, significantly increasing capacity for biobehavioral research on adversity. The 5 research project leaders (RPLs) and 8 pilot project leaders in Phase 1 obtained $16.3M in external grant support, with an $8.2M increase in NIH funding. Phase 2 will expand and strengthen this interdisciplinary and collaborative center of biomedical research excellence by a) building institutional and center infrastructure using a team science approach; b) supporting and mentoring early-career investigators in their programs of research; c) developing vibrant, sustainable research cores; and d) generating innovative transdisciplinary approaches focused on the synergistic impacts of genetic, biological, environmental, and developmental influences on risk and resilience over the life course. Phase 2 projects will investigate neurobiological mechanisms and developmental processes linking childhood adversity with subsequent health problems using a theoretical framework developed by CIRCA investigators during Phase 1. The proposed research projects and planned pilot projects will be supported by an Administrative Core, a Recruitment, Engagement, Collection, and Assessment (RECA) Core and a Biological Systems Core. Each project will contribute to a common set of biological and behavioral measures, establishing a sustainable CIRCA Databank for current and future research. This proposed Phase 2 CoBRE is highly innovative in that it addresses the need to prepare a new generation of scientists with the capacity to identify and target the biobehavioral and developmental processes linking early life adversity with negative health outcomes. It is significant in that it will create a sustainable center providing opportunities for collaboration and a biobehavioral databank for current and future investigators in a region characterized by high rates of ACEs and historical trauma.

NARRATIVE Adverse Childhood Experiences (ACEs) are a leading public health problem, contributing to poor mental and physical health, substance abuse and other health-harming behaviors, and are often generationally transmitted. In order to reducing the harmful effects of ACEs, research is needed that better explains how childhood adversity affects developing biological systems and how protective experiences can mitigate those effects. The purpose of the Center for Integrative Research on Childhood Adversity (CIRCA) Phase 2 application is to expand on the accomplishments in Phase 1, growing and strengthening a sustainable center that supports researchers with the mentoring, training, and resources to study the effects of ACEs on multiple biological and behavioral systems and identify more effective ways to prevent and treat the effects of ACEs.