Dyslexia is a learning disability that negatively affects reading, writing, and spelling development at the word level in 5%-9% of children. The phenotype is variable and complex, involving several potential cognitive and physical concomitants such as sensory dysregulation and immunodeficiencies. The biological pathogenesis is not well-understood. Toward a better understanding of the biological drivers of dyslexia, we conducted the first joint exome and metabolome investigation in a pilot sample of 30 participants with dyslexia and 13 controls. In the metabolite analysis, eight metabolites of interest emerged (pyridoxine, kynurenic acid, citraconic acid, phosphocreatine, hippuric acid, xylitol, 2-deoxyuridine, and acetylcysteine). A metabolite-metabolite interaction analysis identified Krebs cycle intermediates that may be implicated in the development of dyslexia. Gene ontology analysis based on exome variants resulted in several pathways of interest, including the sensory perception of smell (olfactory) and immune system-related responses. In the joint exome and metabolite analysis, the olfactory transduction pathway emerged as the primary pathway of interest. Although the olfactory transduction and Krebs cycle pathways have not previously been described in the dyslexia literature, these pathways have been implicated in other neurodevelopmental disorders including autism spectrum disorder and obsessive-compulsive disorder, suggesting the possibility of these pathways playing a role in dyslexia as well. Immune system response pathways, on the other hand, have been implicated in both dyslexia and other neurodevelopmental disorders.
The purpose of this study was to determine the feasibility of a mindfulness-based intervention among pregnant women (12-20 weeks’ gestation) using a mobile meditation app, Calm. This study involved 100 participants who were recruited nationally due to the COVID-19 pandemic. This study was reviewed and approved by the Institutional Review Board of Arizona State University (STUDY STUDY00010467). All participants were provided an informed consent document and provided electronic consent prior to enrollment and participation in this study. This study was a randomized, controlled trial (trial registration: ClinicalTrials.gov NCT04264910). Participants randomized to the intervention group were asked to participate in a minimum of 10 minutes of daily meditation using a mindfulness meditation mobile app (i.e., Calm) for the duration of their pregnancy. Participants randomized to the standard of care control group were given access to the app after they gave birth. Both the intervention and control groups were administered surveys that measured feasibility outcomes, perceived stress, mindfulness, self-compassion, impact from COVID-19, pregnancy-related anxiety, depression, emotional regulation, sleep, and childbirth experience at four time points: baseline (12-20 weeks gestation), midline (24 weeks gestation), postintervention (36 weeks gestation), and follow-up survey (3-5 weeks postpartum). Data is currently being analyzed for publication.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.