Graduate Student Directory
|Degree Program:||Molecular, Cellular, and Developmental Biology||Email:||email@example.com|
|Major Professor:||Dr Rekha Patel|
Eukaryotic cell stress is modulated by a variety of stress response signaling pathways to ensure cellular fate. One such pathway has been well characterized for its ability to regulate apoptosis under conditions of viral, oxidative, or endoplasmic reticulum stress via phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) by the interferon inducible RNA activated protein kinase (PKR). My work focuses on characterizing how mutations in the protein activator of this apoptotic signaling pathway results in the phenotype of early onset dystonia/parkinsonism (DYT16).
Dystonia is a genetically heterogeneous movement disorder with mutations in 25 known associated genesand is characterized by involuntary repetitive movements. Dystonia is divided into three categories: primary (idiopathic) dystonia, secondary (symptomatic) dystonia, and pseudo-dystonia. Primary dystonia is specific to patients who are exclusively presenting the phenotype associated with the disease as a result of a mutation in one of the genes linked to the disorder. One type of dystonia, early onset dystonia 16 (DYT16), has been linked to various mutations in the PACT gene (named after its function as the protein activator of protein kinase PKR but designated as PRKRA gene in the Genbank), which has been extensively studied for its role in the apoptotic signaling pathway.
Apoptotic Signaling Pathway
Three ubiquitously expressed proteins, PACT, PKR, and TRBP have been extensively studied for their role in controlling apoptosis. These proteins are members of the double stranded RNA (dsRNA)-binding protein family and have multiple copies of an evolutionarily conserved dsRNA binding motifs. Under stable conditions Protein ACTivator of PKR (PACT) is constitutively phosphorylated on serine 246 and bound to a PKR inhibitory protein, TRBP, rendering the apoptotic signaling pathway inactive. Under conditions of cellular stress PACT is phosphorylated on serine 287 which dissociates the PACT-TRBP complex and results in the formation of PACT-PACT homodimers that interact with the interferon induced RNA activated Protein Kinase (PKR) forming a PACT-PKR complex. This interaction allows the PKR protein to undergo a conformational change exposing ATP-binding sites that allow PKR to become active via a trans-autophosphorylation event. PKR has a stringent specificity toward the alpha subunit of the translation initiation factor 2 (eIF2α) as a target substrate. The phosphorylation of the alpha subunit of eIF2α results in a global shut down of protein synthesis. If this inhibition of protein synthesis is prolonged it leads to apoptosis.
University of South Carolina, MS Biology, Concentration: Molecular Biology Spring 2016-Present
University of South Carolina, B.Sc Biology, Fall 2012-Fall 2015
Toccoa Falls College, Biology Life Sciences Fall 2011-Spring 2012
Biology 101 Laboratory Senior Teaching Assistant, Fall 2016-Present
Graduate Association of Biological Sciences (GABS) Treasurer, Fall 2016-Present
CHEM 101L Fundamental Chemistry I Laboratory, Department of Chemistry and Biochemistry, Spring 2016
BIOL 101L Principles of Biology I Laboratory, Department of Biological Sciences, Summer 2016-Present