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Maria Carla Carisi, PhD




Research Fellow




Postdoctoral Research Fellow




M. Carla Carisi’*, Martha Bishop*, Madison Sangster*, Yulia Grishchuk*

Characterization of in vitro and in vivo models of the neurodegenerative disorder BPAN

My main interests are neuroscience and gene therapy applied to rare diseases, fields in which the MGH is a pioneer organization. As a woman in STEM, being part of such an inclusive organization is a privilege, one that I do not take for granted. Millions of girls around the world do not have access to education, nor are encouraged to pursue science due to the absence of role models. Participating to the Women in Medicine and Science Symposium and sharing research interests with brilliant women in the field will be an enriching and valuable growth experience.


Beta-Propeller Protein-Associated Neurodegeneration (BPAN) is a-rare neurologic disease associated with early developmental delays and progressive neurodegeneration starting in adolescence. This X-linked disease is caused by mutations in the WDR45 gene encoding WIPI4 protein, involved in autophagosome formation. The goal of this study is to phenotype a novel CRISPR-engineered BPAN mouse model for preclinical therapy development.


Based on disease presentation in patients, we selected a battery of behavioral tests to establish disease-relevant outcome measures for future preclinical testing: open field (spontaneous and exploratory activity, motor and cognitive function), rotarod (motor function, balance, coordination), fear conditioning (learning and memory) and an autistic/social activity test.


We have created and currently testing the first experimental cohort of WDR45 c.ex9+g>a/Y and WDR45 +/Y (WT) mice. WDR45 c.ex9+g>a/Y demonstrate reduced exploratory activity and hyperactive behavior starting at 2 months of age, which is consistent with clinical observations of attention deficits and hyperactivity in BPAN children.


Our observations of the early behavioral deficits in WDR45 c.ex9+g>a/Y mice in the form of hyperactivity and reduced exploratory activity, mimic major cognitive deficits observed in BPAN patients and suggest that this mouse model can be an accurate model of the disease for future therapy testing.