Browsing 2016 Graduate Research Day by Title
Now showing items 8-9 of 9
Salubrinal Mediated Fetal Hemoglobin Induction Through The PERK-eIF2α-ATF4 Signaling PathwaySickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene affecting ~100,000 people in the United States. These individuals suffer from hemolytic anemia, pain, and progressive organ damage. The best therapeutic intervention in SCD is fetal hemoglobin (HbF) induction by pharmacologic agents, however, Hydroxyurea is the only FDA-approved drug with proven efficacy. The goal of this project is to discover drugs that induce HbF by novel mechanisms for SCD treatment. Salubrinal (SAL), a selective inhibitor of eukaryotic initiation factor 2α (eIF2α), was shown to increase HbF levels by enhancing γ-globin mRNA translation. These findings lead us to test the hypothesis that SAL activates the PERK-eIF2α-ATF4 stress response, as a mechanism of HbF induction in erythroid progenitors. Studies were conducted in K562 and erythroid progenitor generated from CD34+ stem cells treated with SAL (5, 12, and 18µM) for 48hr. RT-qPCR and western blot were used to measure γ-globin mRNA and HbF protein levels respectively. Preliminary data revealed a dose-dependent increase for HbF levels in K562 and erythroid progenitors treated with SAL. Flow cytometry showed an increase in the number of cells producing HbF (%F-cells). Furthermore, eIF2α and ATF4 levels were increased by SAL in K562 cells. These findings suggest SAL mediates HbF induction through eIF2α/ATF-4 signaling; future studies using the preclinical sickle cell mouse model will be investigated.
Understanding and Promoting Breastfeeding among African American Woman of the Rural SouthAfrican American women (AAW) have lower rates of breastfeeding (BF) than whites and other U.S. minority groups. Along with its many maternal and child health benefits, research indicates BF can reduce the risk of developing triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with higher mortalities and incidence in AAW. Thus, increasing BF can be an important strategy for addressing breast cancer health disparities.This research seeks to ultimately determine whether increased awareness that BF reduces breast cancer and TNBC risk will positively alter AAW’s BF decision-making. A survey and an in-depth interview based on the Theory of Planned Behavior framework are used to examine AAW’s perceptions of breast cancer risk and prevention as well as their beliefs, attitudes and motivations that underlie BF decision-making. Preliminary analysis of 10 interviews to date showed that all of the participants had an intention and desire to BF, but many (n=6) lacked a realistic plan to manage BF and address expected barriers. When asked about breast cancer, most (n=8) demonstrated fear and avoidance of the topic. There was a general lack of knowledge, but excitement about the benefits of BF on TNBC prevention. Dissemination of this new evidence may be useful in guiding BF promotions among AAW. Also, there was a clear disconnect in BF intention versus action in this population. Further analysis will identify intervening factors that bridge the gap.