Alondra Schweizer Burguete, PhD

Ph.D. work was with Suzanne Pfeffer in Biochemistry at Stanford University. A method to predict and select surface residues that mediate protein::protein interactions was developed, and selected affinity-altered mutant proteins were assayed for their function in living cells. The interactions between a Rab GTPase and a Golgin, two key players in a vesicle trafficking pathway, were characterized and the studies were extended to an atomic level with Axel Brunger, also at Stanford University.  A structure-derived model that explains how Rab and Arf-family members may interact with the same binding partner at different distances from the cell membrane was generated.  In addition, the first-ever instance of a cooperative relationship between different GTPase family members in directing incoming vesicles to the Golgi membrane prior to fusion, was described.

Postdoctoral work was on the mechanisms behind microsatellite repeat expansion disorders, with Nancy Bonini in Biology at the University of Pennsylvania. Using cell biological and genetic tools at subcellular resolution, we surprisingly found that expanded repeat RNA, linked to ALS/FTD, Huntington’s disease, and the Myotonic Muscular Dystrophies is incorporated into neuritic ribonucleoprotein particles in mammalian primary spinal cord neurons, as well as in induced pluripotent stem cell-derived neurons from expansion carriers. The disease-associated repeats function as RNA localization signals: they assemble into RNA/protein granules that undergo transport into distal segments of neurites, and furthermore, neuritic localization of expanded repeat RNA correlates with loss of primary arbors. The establishment of Drosophila models for repeat RNA toxicity in sensory neurons allowed the identification of striking dendritic arborization defects, and mRNP components were identified as strong modifiers of the expanded GGGGCC repeat-induced phenotype. The human homologues of these modifiers (FMRP, CPEB3, as well as FMRP targets, e.g. PSD-95) were shown to be upregulated in human GGGGCC expansion carrier-derived iPSNs, suggesting disrupted local translational regulation. These findings indicate transport granule dysfunction as a novel disease mechanism that may contribute to microsatellite expansion disorder.
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[Taub Institute for Research on Alzheimer’s Disease and the Aging Brain]

Yarim Lee
Columbia University, Biochemistry Major

Yarim is currently a junior pursuing her bachelor’s degree in Biology at Columbia College. She joined the lab in November 2017 and is investigating the role of microsatellite repeat RNA in neurodegenerative disease using the fruit fly as a model organism. Her future goals are to attend medical school and pursue an MD/PhD program. On her free time she likes to read and spend time with her family and pets.

We are currently accepting applications for postdoctoral and research technician positions. Please inquire with Dr. Burguete.