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Graduate College Post-Comp Research Awards - Spring 2019

  • Mengya Wang (Pharmacology Graduate Student, Russo lab) - Migraine is a prevalent neurological disease, affecting approximately 12% of Americans. Although prevalent, the mechanisms underlying migraine remain elusive and effective treatments are lacking. Alpha-calcitonin gene-related peptide (CGRP) is considered a major player in migraine pathophysiology. However, the location and mechanisms of CGRP in migraine have not been elucidated. The goal of my research is to identify the brain regions regulated by CGRP to induce migraine-like behaviors (e.g. light aversion). Previous studies in our lab have shown that intracerebroventricular injection of CGRP into wildtype mice induced light aversion. This suggests a role of central CGRP in migraine-like behaviors. One potential candidate site in the central nervous system (CNS) is the cerebellum. The cerebellum serves as a sensory and motor integrative center, is activated during migraine attacks, produces CGRP, and has the most CGRP binding sites in the CNS. Based on these observations, we hypothesized that cerebellar CGRP induces migraine-like behaviors. In order to test this hypothesis, we first measured CGRP expression in the cerebellum. We detected RNAs for both CGRP and its receptor subunits. CGRP immunoreactivity was detected in Purkinje cells and deep cerebellar nuclei. Direct CGRP delivery to the cerebellum induced light aversion in mice, which suggests that CGRP in the cerebellum is sufficient to induce light aversion. We created a CGRP sensitized mouse model to further test the role of cerebellar CGRP in migraine. The results will shed light on the underlying brain regions critical for migraine-like behaviors.
  • Chandra Maharjan (Pharmacology Graduate Student, Quelle lab) - Pancreatic neuroendocrine tumors (PNETs) are rare, indolent malignancies with a growing incidence rate. Advanced PNETs are clinically challenging because they are largely refractory to standard therapeutics and lack reliable biomarkers for early stage diagnosis. Molecular mechanisms governing PNET pathogenesis are also incompletely understood, although increasing evidence suggests dysregulated Akt/mTOR and RB1 signaling help drive the disease. RABL6A, a novel oncogenic protein, regulates both those pathways and is a binding partner of the ARF tumor suppressor, which is frequently inactivated in PNETs. We discovered RABL6A gene is amplified in PNETs, and our knock-down studies showed it is required for PNET survival and proliferation. We hypothesize RABL6A is a critical central regulator of PNET development and progression. My project employs an unbiased genetic screening tool called Sleeping Beauty transposition to identify additional molecular targets that function downstream to RABL6A and promote PNET pathogenesis. Furthermore, we are studying the in vivo role of RABL6A in PNET development and progression by using a genetically engineered mouse PNET model. Together, findings from these studies will advance our understanding of PNET pathogenesis and help to establish RABL6A and/or its targets as potential PNET biomarkers and chemotherapeutic targets.
Date: 
Saturday, December 1, 2018