Dr. Jonathan Santoro is a clinician-scientist focused on exploring the interface between vascular disease,
cerebrovascular disease (CeVD) and inflammation in persons with Down syndrome (DS). This five-year
mentored career development award will provide him with advanced training and skills in population-based
data analysis, biostatistics, neuroimaging, and clinical trials development to ensure a successful transition to
an independent research career. The outlined proposal builds on previously published work by Dr. Santoro and
leverages a mentorship team of experts in DS, neurodevelopment, vascular disease, and cerebrovascular-
inflammatory disorders in persons with DS at his home institution and other large academic DS centers.
Research Context: Persons with DS have an increased risk of early CeVD, specifically moyamoya syndrome,
and the initial presentation is often irreversible neurologic insult secondary to cerebrovascular accident. For
persons with DS, there exists no validated means of assessing risk for CeVD. This K23 career development
builds on previous work by Dr. Santoro who identified non-invasive ways to screen for CeVD in children with
DS. This study will prospectively asses blood pressure (BP) in persons with DS and subsequently use this to
predict pre-symptomatic CeVD (Aim 1). Next, this study will compare gold standard CeVD neuroimaging
studies to various non-invasive, low-cost, biometric tools such as repeated BP measurements, transcranial
Doppler ultrasound and neurocognitive testing to assess internal and predictive validity of these measures in
the prediction of CeVD (Aim 2). As persons with DS are established to have immune dysregulation and
systemic inflammatory profiles, we will also explore the role of systemic and vascular inflammatory biomarkers
in the development of CeVD with the goal of identifying contributory inflammatory cascades that could be
targeted with therapeutic interventions geared towards preventing CeVD in subsequent studies (Aim 3).
Career Development Plan: Dr. Santoro will complete coursework in healthcare and science communication,
data analysis, epidemiology, clinical trial design and biomedical informatics. This plan also will strengthen his
competence in both bioinformatics and neuroimaging and be supplemented by institutional workshops and
seminars. This experiential learning is designed to promote knowledge and skillset development needed to
both execute his research and ensure that skills are developed for his transition to an independent researcher.
Dr. Santoro’s career development goals will be supported through close mentorship by an experienced and
committed interdisciplinary team and a combination of didactic, experiential, and team-based learning. This
proposal and subsequent R01 proposals seek to improve the neurologic care of young persons with DS.