Mentor: Dr. Lucia Notterpek
College of Medicine
"I applied to the Scholars program to further my interest in research and specifically the sciences involved in my lab. Additionally, I was intrigued by the capabilities of the Scholars program to act as a forum for sharing and discussing research with fellow scholars at the symposium. My goals for the academic year are to learn useful research skills and techniques, as well as develop a sense of independence in the lab. Also, I hope to foster my critical thinking and problem solving skills through challenges I face in the lab."
- Mathematical applications towards biological sciences
- Florida Bright Futures
- Dean's List, 2010
Hobbies and Interests
- Learning new things
- Sharing knowledge
Role of HSP70 in Reducing Peripheral Myelin Protein 22 Aggregation
Charcot-Marie-Tooth disease refers to a group of hereditary peripheral neuropathies, of which type 1A (CMT1A) is known to be the most common. It is largely linked to the duplication in a gene encoding for a myelin protein, Peripheral Myelin Protein 22 (PMP22). PMP22 is a hydrophobic, tetraspan membrane glycoprotein expressed mainly in Schwann cells, but also expressed in the epithelia and fibroblasts. The gene was discovered in primary mouse embryonic fibroblasts (MEFs), arrested in the Go phase of cell cycle. Although the function of PMP22 is not yet clear in the non-neural tissues, it is thought to function as a compact myelin protein in the peripheral glia. In normal Schwann cells, only 20% of the newly-synthesized PMP22 is successfully trafficked to the membrane whereas the remaining 80% is degraded by the proteasome machinery. In CMT1A, this balance is disrupted due to duplication or point mutations in the Pmp22 gene, resulting in the formation of polyubiquitinated PMP22 aggregates. These structures are surrounded by components of the autophagic machinery and heat shock proteins. My USP research project is intended to investigate if there is a direct role of the 70 kilo-Dalton heat shock protein, known as HSP70, in reducing or clearing PMP22 aggregates. To accomplish this goal, I will use primary mouse embryonic fibroblasts (MEFs) isolated from wild-type (Wt) and HSP70-deficient (knockout; KO) mice. Both genotype MEFs will be treated with proteasome inhibitors like lactacystin, to induce protein aggregation. Since it has been shown that in the presence of such an inhibitor, PMP22 aggregation is encouraged in rat Schwann cells, the same will be evaluated in MEFs. Techniques such as Western blotting and immunocytochemistry will be used to compare the levels of accumulated polyubiquitinated substrates and the number of cells with aggregates in these MEFs, in the presence and absence of HSP70. Further, I plan to transfect the KO MEFs with an HSP70-overexpression plasmid and subject these transfected cells to lactacystin. The number of transfected KO MEFs with lactacystin-induced aggregates will be compared with non-transfected KO MEFs. This will allow us to determine if HSP70 alone can aid in preventing intracellular aggregates.