Mission

The Silvio O. Conte Center for Stress Peptide Advanced Research, Education, & Dissemination (SPARED) at McLean Hospital combines world-renowned preclinical and clinical researchers in the field of stress biology to comprehensively examine, compare, and contrast the neurobiological effects of CRF and PACAP. These scientific elements include complementary molecular, cellular, circuit, physiologic, and behavioral measures in mice and humans, as well as detailed hypothesis testing in postmortem brain samples obtained from individuals with Post-Traumatic Stress Disorder (PTSD) and healthy controls.

The mechanisms by which stress triggers mood and anxiety disorders remain unclear, which impedes the development of improved therapeutics. CRF (Corticotropin-Releasing Factor) and PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) are peptides with well-validated roles in the biology of stress-related conditions. Genetic alterations in these systems render people more vulnerable to stress, administration of either peptide mimics key stress effects, and both systems are altered by stress. Their high degree of conservation across species suggests that each regulates equally important—yet subtly different—aspects of stress responsiveness. Indeed, a major difference revealed by animal models is that the stressful effects of PACAP system activation tend to be more persistent than those of CRF system activation. Such differences, together with reciprocal, complementary, and homeostatic interactions between the peptides, may explain difficulties in developing CRF antagonist monotherapy for clinical use. Neurobiology-based treatments that reduce stress would have utility across a range of DSM-defined disorders and a major impact on health. The Silvio O. Conte Center for Stress Peptide Advanced Research, Education, & Dissemination (SPARED) will combine world-renowned preclinical and clinical researchers in the field of stress biology to comprehensively that is not the plan examine, compare, and contrast the neurobiological effects of CRF and PACAP.

Our premise is that CRF and PACAP systems are interwoven and must be studied in tandem to understand their individual and interactive roles in stress responsiveness. Our overarching hypothesis is that CRF and PACAP effects can be differentiated, revealing CRF-, PACAP- and CRF+PACAP-predominant signatures that reflect different pathological states. Our strategy is to leverage group discoveries to enable active refinement and increasingly rigorous tests of the overarching hypothesis. Our scientific goals are to promote a mechanistic (cell and circuit-based) understanding of features that distinguish CRF and PACAP effects and facilitate diagnostic and treatment advances that derive from appreciating the contributions of each system. To complement the science, the Center will also support a broad range of training and educational activities, including expansion of outreach programs as well as social media approaches to engage scientists and lay-persons. Our overall Aims provide the basis for synergy that will transform this work from a collection of individual projects into a cohesive Center where each element enriches, and is enriched by, the activities of the others, serving as a resource that benefits the scientific community and beyond.

Aim 1. Collaboration

Bring together leading researchers who are committed to understanding stress and reducing its health burdens by combining new insights on biology with cutting-edge technologies and establish a framework that enables sustained collaboration in the service of advancing discovery and innovation.

Aim 2. Investigation

Use a multidisciplinary, RDoC-compatible approach to conduct high-impact research that transforms our mechanistic understanding of CRF and PACAP systems to facilitate the development of improved diagnostics and therapeutics for a range of DSM-defined disorders that are caused or exacerbated by stress.

Aim 3. Outreach

Implement unique and impactful approaches that enhance education, training, and career development for future generations of translationally-oriented stress researchers.

Aim 4: Innovation

Use information and internet technologies to transform collaboration, investigation, and outreach to achieve broad communication of Center-related activities, including sharing of educational materials and strategies, nimbly disseminating news, and making available data sets.