Alavi-Dabiri Postdoctoral Fellowship Awardee: Dr. Rebecca Ahrens-Nicklas

The Alavi-Dabiri fellowship was created in 1997 by Drs. Abass and Jane Alavi to honor their nephew, Ramin Dabiri, who has a developmental disability, and his parents, Maryam Alavi and John Dabiri. This award, which is administered by the IDDRC, provides one year of support to a postdoctoral fellow who works under the mentorship of one or more members of the IDDRC.
 

Rebecca Ahrens-Nicklas, MD,PhD,
was awarded the Alavi-Dabiri
Fellowship

The 2015 awardee is Dr. Rebecca Ahrens-Nicklas, a fellow in the Divisions of Human Genetics and Metabolism at CHOP. She received her MD/PhD in 2010 from the Cornell/Sloan-Kettering/Rockefeller tri-institutional program. Her mentors are Dr. Eric Marsh, Assistant Professor of Neurology, and Dr. Beverly Davidson, Professor of Pathology and Laboratory Medicine and Director of the CHOP Center for Cellular and Molecular Therapeutics.

Dr. Ahrens-Nicklas' proposal, “Electrophysiologic Consequences of Inborn Errors of Metabolism,” focuses on Juvenile Batten Disease (JBD), a lysosomal storage disorder which causes vision loss, seizures and relentless neurologic decline. Affected patients harbor mutations in the gene coding for CLN3, a lysosomal membrane-associated protein. Proposed functions of CLN3 in the central nervous system include autophagy, vacuolar maturation, endocytosis, and vesicle transport. It is still unclear how mutations in this disease give rise to the devastating phenotype, but it is known that the brain suffers the intra-lysosomal accumulation of toxic substances. Dr. Ahrens-Nicklas will carefully characterize disease manifestations in a mouse model of JBD by deploying EEG monitoring, behavioral analysis, histopathology and electrophysiologic study of neural networks utilizing voltage-sensitive dye imaging technology. This information, Dr. Ahrens-Nicklas notes, is necessary to evaluate the efficacy of selected therapeutic interventions, including gene therapy. As the Alavi-Dabiri awardee, Dr. Ahrens-Nicklas will enjoy access to several IDDRC research core facilities, including the Neuroimaging andNeurocircuitry Core, the Preclinical Models Core (animal behavioral testing) and the Biostatistics and Bioinformatics Core (statistical analysis and experimental design).

 

Dr. Ahrens-Nicklas writes: “Ultimately, I am interested in understanding how inborn errors affect neuronal networks, and if therapies can normalize nervous system function. Given that these networks are established during fetal development, postnatal treatment may never fully reverse neurologic phenotypes. One could imagine that early (perhaps even prenatal) intervention may be more efficacious, albeit technically challenging. Therefore, in the future, I would like to investigate the utility of pre-symptomatic or prenatal therapeutics in JBD and other metabolic disorders.”