ABSTRACT – OVERALL The North Carolina Center for Coastal Algae, People, and Environment (NC C-CAPE) will combine multidisciplinary expertise in ocean and climate science, toxicology, epidemiology, modeling, and community engagement to understand, predict, and reduce risks to human health from cyanobacterial Harmful Algal Blooms (HABs) in coastal waters. Growing threats to ecosystem and human health are expected with the increasing frequency, intensity, and range of cyanobacterial blooms, attributable to eutrophication and climate change. For NC's coastal waters, including US' largest lagoonal estuary, the Pamlico-Albemarle Sound System, concerns about emergent HABs have surged and coincide with reports on cyanobacterial toxin presence, mainly microcystins (MCs), in water and seafood. The transport of toxic algae and MCs along the freshwater-to-marine continuum further increases the potential to spread MC risks across coastal environments. Epidemiological studies measuring the association of MC exposure and liver toxicity, including non-alcoholic fatty liver disease (NAFLD), in rodent models are necessary to determine whether chronic MC exposure is associated with liver toxicity, NAFLD and liver cancer in humans. Most research and environmental testing have focused on a single MC congener but since blooms are associated with mixtures of congeners that vary in toxicity, further data is needed to understand risks that emerge from MC mixtures and inform human health guidelines. NC C-CAPE will investigate the health effects of various MC mixtures, and elucidate links among environmental drivers and HAB dynamics, MC congener composition, and toxin contamination in oysters and blue crabs. Project 1 will advance our understanding of HAB dynamics and MC contamination in seafood, combining state-of-the-art in situ observing technologies and targeted field surveys. In addition, experimental work will elucidate trophic transfer of toxins in oysters and blue crabs. Project 2 will define how MC mixtures influence mechanisms of liver toxicity and resulting risk of adverse health outcomes in regulatory-relevant mammalian models as well as at- risk human populations. Project 3 will integrate highly diverse data sets and coastal circulation modeling within a probabilistic modeling framework to elucidate environmental controls on MC distribution in water and seafood and assess MC exposure risk in a changing climate. The Center's Community Engagement Core will use the principles of data justice, where community members are experts with the capacity to conduct critical and systemic inquiry into their own lived experiences, to address HAB exposure and prevention. The Administrative Core will provide effective fiscal and scientific leadership to promote collaborations across all Center components and beyond. As an integrated whole, NC C-CAPE will provide significant insight to guide efforts to implement effective monitoring approaches, inform guideline values for safe consumption of water and seafood, deliver predictive tools to assess emergent and future toxin exposure risk, and leverage community engagement initiatives to fill data gaps and improve oceans and human health.

PROJECT NARRATIVE – OVERALL The mission of North Carolina Center for Coastal Algae, People, and Environment (NC C-CAPE) is to deliver novel insight and understanding of emergent and future, climate-driven human health risks related to cyanobacterial algal blooms and microcystins in shallow, estuarine environments. The integration of three research projects and a community engagement core will facilitate 1) the characterization of algal composition, microcystin concentrations, and microcystin congener mixtures in water and seafood (oysters and blue crabs) in relation to environmental conditions including toxin transport across the freshwater-to-marine continuum, 2) the examination of the effects of cyanotoxin mixtures on hepatic toxicity, fatty liver diseases, and liver cancers using a combination of a rodent model and a nested case-control study on human populations, 3) the development of predictive models for cyanotoxin risk assessment in the context of climate change, based on diverse algal bloom metrics and environmental covariates, and 4) effective data sharing to prevent bloom exposure of NC coastal communities, activate community science projects that fill data gaps, and improve translation of research findings on oceans and human health to community stakeholders. NC C-CAPE will be a nexus of climate and ocean science, human health, and stakeholder engagement to advance our understanding of harmful algal blooms, and to develop innovative approaches to assess, mitigate and predict their impacts on human health.