Integrated Calendar

In functional MRI (fMRI) anatomical localization is typically provided by a Magnetization Prepared Gradient Echo (MPRAGE) pulse sequence with an echo-planar-imaging (EPI) sequence used for the blood-oxygen-level-dependent (BOLD) contrast images. Unfortunately, EPI suffers from geometric distortions due to magnetic field inhomogeneities so the acquired data needs to be distortion-corrected prior to analysis, inevitably introducing errors into the data. In previous work we have described a multi-inversion EPI sequence that is distortion matched to the BOLD data. By exciting multiple slices sequentially with varying inversion times and fitting the data to a model quantitative T1 maps were generated for anatomical localization albeit at the cost of relatively lengthy scan time. In this talk I will describe an optimized version of the sequence that uses concepts originally developed for optimized MR Fingerprinting to accelerate the acquisition 4-5 fold. The utility and versatility of our method is demonstrated in vivo on both 3T and 7T scanners.

Neurodevelopmental disorders encompass a wide range of childhood-onset medical conditions caused by different genetic mutations and interaction with environmental factors, affect ~2% of the population, and are a leading cause of intellectual disability and autism spectrum disorder. Evidence is accumulating that either loss or gain in dosage of proteins involved in cognitive and behavioural processes can be deleterious to the nervous system by causing a failure in the ability to maintain neuronal homeostasis. My studies are focused on the MECP2 duplication syndrome, one of the most common genomic rearrangements in males, characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. To determine whether the phenotypes of MECP2 duplication are reversible upon normalization of MeCP2 levels, I first generated and characterized a new mouse model that over-expresses a conditional allele of Mecp2 that could be deleted in the adult animal (Nature 2015). Upon normalization of MeCP2 in adult symptomatic mice, several phenotypes were rescued at the behavioral, physiological, and molecular levels. Next, I reduced MeCP2 using an antisense oligonucleotide (ASO) strategy, which has greater translational potential. I found that ASO treatment induced a broad phenotypic rescue in adult symptomatic MECP2 duplication mice, abolished abnormal EEG discharges and behavioral seizures, and corrected abnormal gene expression in the hippocampus. I am currently characterizing a novel “humanized” mouse model of MECP2 duplication syndrome that will precisely mimic the human condition by having two copies of human MECP2 and no copies of the mouse gene. These mice will serve as the ideal model for preclinical tests as they represent the closest construct validity model for the human condition. In addition, I am generating and characterizing neurons and cortical spheroids induced from patients’ derived pluripotent stem cells (iPSCs).

The integrity of the genome transmitted to the next generation intrinsically relies on cells of the germ line. Processes that ensure germ cell development, genomic stability, and reproductive lifespan are essential for the long-term success of a species. Dónal O'Carroll is interested in characterizing spermatogonial stem cell (SSC) populations that support fertility as well the regenerative capacity of the testis throughout adult life. In addition, O'Carroll lab tackles fundamental questions regarding the mammalian male germ line and heredity from an RNA perspective. Specifically, their research explores the contribution of non-coding RNA (miRNA, piRNA and lncRNA) and RNA modification pathways within germ cell development as well as testicular homeostasis/regeneration. The research objectives focus on the contribution of these emerging pathways on the underlying circuitry of self-renewal that underpins the SSC, as well as the coordination of the various cellular/differentiation processes of spermatogenesis.