• Dopamine Regulation of Fear Processing and Social Motivation: Implication for Common Psychiatric Comorbidities

      Lee, Jason ChiaTse; Brain and Behavior Discovery Institute (8/3/2017)
      Psychiatric disorders such as post-traumatic disorders and schizophrenia often present with common comorbidities such as increased depression, anxiety, and decreased social motivations. However, the underlying neural circuit that may account for occurrence of multiple psychiatric comorbidities remained unidentified. The dopamine system has been known to play prominent roles regulating emotional states and motivations. We therefore hypothesized that alteration in the dopamine system may lead to comorbidities such as negative mood and social isolation commonly observed in many psychiatric disorders. In this thesis work, we first examined how the dopamine system processes known triggers of psychiatric disorders, such as fear-charged stimuli. We then examined how the dopamine system regulates normal social interactions as well as how an altered dopamine system affects social interactions
    • The Role of RYBP in the Regulation of Apoptosis

      Novak, Rachel Lynn; Georgia Cancer Center (6/5/2014)
      The tumor suppressor Tp53 is the most frequently mutated gene in human cancer. Tp53 encodes a sequence specific transcription factor termed p53 that activates a number of biological programs contributing to tumor suppression, most notably, the promotion of cell cycle arrest and apoptosis. To identify new regulators of p53’s transcriptional activity, we performed a yeast 2-hyrbid screen and have identified Ring 1 YY1 Binding Protein (Rybp) as a novel p53-interacting partner. Consistent with its role as a transcriptional repressor, we have demonstrated that Rybp inhibits p53-mediated transcription. In addition, Rybp forms a trimeric complex with the critical negative regulator of p53, Mdm2. Mdm2 is an E3 ligase that ubiquitinates p53, targeting it for degradation, and expression of Rybp enhances the Mdm2-mediated ubiquitination. To further investigate the role of Rybp in the regulation of endogenous p53 stability we constructed a recombinant adenovirus expressing Rybp (Ad-Rybp). Ad-Rybp infection inhibited the accumulation of p53 and the induction of p53 target genes in response to genotoxic stress. However, interpretation of the results was confounded by Ad-Rybp infection reducing global mRNA levels. Despite inhibition of p53, Ad-Rybp was a powerful inducer of apoptosis, and we investigated this in more detail. Analysis of a panel of tumor cell and untransformed cell types revealed that Ad-Rybp infection specifically induces apoptosis in tumor cells but not in normal diploid cells. Furthermore, at a low multiplicity of infection, Ad-Rybp sensitizes tumor cells to apoptosis in the presence of the death receptor ligands, Tumor Necrosis Factor alpha (TNFα) and TNF related apoptosis inducing ligand (TRAIL). These results suggest that the tumor-specific killing properties of Rybp may be exploited for therapeutic advantage.
    • Regulation and Function of the Major Stress-Induced HSP70 Molecular Chaperone in vivo: Analysis of Mice with Targeted Gene Disruption of the HSP70.1 or HSP70A1

      Huang, Lei; Georgia Cancer Center (6/3/2002)
      (First Paragraph) The cellular response to stress, including exposure to environmental (UV radiation, heat shock, heavy metals), pathological (infection, fever, inflammation, malignancy, ischemia) or physiological (growth factor, hormonal stimulation, tissue development) stimuli is represented at the molecular level by synthesis of groups of protein named heat shock proteins [hsp(s)] (Benjamin 1998; Feder and others 1992; Jolly and Morimoto 2000; Li and Mivechi 1986; Lindquist 1986; Smith 1998). The presence of hsp(s) protect host cells from the damage caused by thermal stress, and after induction of hsp expression, cells are protected well from higher temperatures than they can normally tolerate. This phenomenon is defined as themiotoleranee (Gemer 1975; Li and Mivechi 1986). The protective role of hsp(s) is attributed to several functional properties, including active participation in maintaining proteins in their native correctly folded states, promoting degradation and refolding of misfolded proteins, and minimizing aggregation and incorrect interactions between proteins (Agashe and Hartl 2000; Gething and Sambrook 1992). In addition, hsp(s) can function in cellular protection by modulating the engagement and progression of apoptosis induced by a variety of stress stimuli (Beere and Green 2001). Besides the recognition of the cytoprotective function of hsp(s) under stress conditions, widespread clinical interests exist in their chaperone function during a range of human pathologies, including neurodegenerative conditions, such as amyloidosis, prion disease, and Alzheimer's disease, and cardiovascular diseases, such as myocardial ischemia, cardiac hypertrophy, stroke, and blood vessel injury (Benjamin 1998; Planas and others 1997; Smith 1998).
    • DEVELOPMENT OF TRANSGENIC ZEBRAFISH MODEL FOR INVESTIGATION OF THE FUNCTION OF MICROGLIA

      Sura, Survasha; Department of Biological Sciences; Department of Biochemical and Molecular Biology; Georgia Cancer Center; Augusta University; Rajpurohit, Surendra K (2019-02-13)
      Zebrafish have emerged as a powerful model organism for elucidating the development and function of microglia. Generation of new transgenic reporter lines and imaging tools strengthen the zebrafish model in microglia study�in-vivo. The aim is to develop a novel compound transgenic line to study the inflammatory process mediated by NF-kB in microglia cells. This novel compound transgenic line will establish a new model for microglia study. To generate the novel compound zebrafish transgenic model for microglia, we are crossbreeding microglia transgenic line zebrafish (Tg(mpeg1:mCherry) with the NF-kB Tg(6xNFkB:EGFP) transgenic progeny. We first generate a heterozygous F1 progeny which will be bred to generate an F2 homozygous progeny. Once the F1 progeny of the Microglia-NfkB transgenic line is developed, they will be crossbred to develop the Homozygous compound transgenic line. Fluorescent Microscopy will be used to screen the larvae generated from the breeding events. By developing the compound transgenic line, we are optimizing microglia isolation and sorting methodology by using the related antibodies as the marker. The NF-kB microglia transgenic line will provide a unique platform for drug screening to address microglial based ailments, thus furthering the understanding and treatment of human disease.
    • Global Health Needs Assessment at the Medical College of Georgia

      Tipler, Pam; Wyatt, Tasha R; Medical College of Georgia (Augusta University, 2018-01-19)
    • Evaluation of colonoscopy and sigmoidoscopy utilization for colorectal cancer screening in Georgia

      Ansa, Benjamin E.; Hoffman, Zachary; Lewis, Nicolette; Johnson, J. Aaron; Augusta University (2018)
    • Evaluation of blood stool test utilization for colorectal cancer screening in Georgia

      Ansa, Benjamin E.; Lewis, Nicolette; Hoffman, Zachary; Johnson, J. Aaron; Augusta University (2018)
    • Race/ethnicity differences in access to opioid agonist treatment (OAT)

      Covington, Katherine; Chung, Yunmi; Johnson, J. Aaron; Krawczyk, Noa; Augusta University; Johns Hopkins University (2018)
    • Narcan (naloxone nasal spray) availability in Georgia retail pharmacies

      Johnson, J. Aaron; Chung, Yunmi; Covington, Katherine; Augusta University (2018)
    • Determinants of adherence to physical activity guidelines among adults with and without diabetes

      Ansa, Benjamin E.; Covington, Katherine; Augusta University (2017-10)
    • Syphilis rates and trends in the Central Savannah River Area of Georgia and South Carolina

      Stone, Rebecca; Chung, Yunmi; Ansa, Benjamin E.; Augusta University (2017-10)
    • Trends in HIV testing among adults in Georgia: analysis of the 2011-2015 BRFSS data

      Ansa, Benjamin E.; Smith, Selina A.; Chung, Yunmi; White, Sashia; Augusta University (2017-04)
    • Questionnaire Design and Responsiveness in a Data Capture Tool for Student Sharing of Experiences of Statewide Clerkship Sites

      Zheng, Stephanie; Behrman, David; Agrawal, Parth; Basco, Brian; Ball, Charlotte; Rose, Jennifer; Miller, Samel; Wood, Elena (2017-03)
      Positive clerkship experiences and student performance in the clinical years has been correlated to perceived quality of education and specialty choice amongst medical students [1-3]. The Medical College of Georgia uses a distributed campus model with more than 250 clerkship rotation sites across the state and beyond, making student clerkship choices imperative to their development as physicians. We developed a survey to collect both quantitative and qualitative data from students during their clerkship years and a system to distribute that information to students. The data allowed us to evaluate the effectiveness of various question formats through responsiveness, the length of responses, and time spent on the survey. In addition to this, we looked at the number of responses per clerkship in order to see whether or not our survey was getting information about all of the 3rd year rotations. We aspire to take these findings and utilize them to expand t he program and improve the questionnaire in order to yield more responsiveness from students.
    • An Investigation of the Chronic Disease Self-Management Program - Assessing CDSMP Facilitators' Perceptions of the Program's Effect

      Hillman, L. M.; Anderson, C.; Stoodt, G.; Department of Medicine; Augusta University (2017-03)
      Chronic conditions are public health threats. The Chronic Disease Self-Management Program (CDSMP) is an evidence-based disease management program that addresses personal self-management of chronic conditions. The CDSMP involves peer trainers who instruct and assist with chronic disease preventive measures. Although disease management demonstrates promise to improving patient self-maintenance, previous researchers have not evaluated how the program affects program leaders. The purpose of this study was to discover how self-help leaders feel about the CDSM program. The overarching research question asked about perspectives that self-help leaders had toward the program. Through a narrative qualitative approach, the perceptions of peer leaders were examined to determine if the program was personally beneficial. Guided by the social cognitive theory, a purposeful convenience sample of 20 participants completed the study. The participants were practicing peer trainers in the CDSMP prog ram. Data analysis included hand coding using open and axial coding and content analysis. Study findings included themes surrounding how the CDSMP program benefits health in general as well as the management of facilitators’ own chronic diseases, health behaviors, and increased quality of life. The ability for chronic disease management leaders to experience positive effects of the program they administer may result in positive social change. This awareness can positively affect social change by enhancing an already established evidence-based community health program with stronger and better-equipped leaders.
    • Chetomin as a Potent Hsp90 Inhibitor

      Leibou, Stav; Lu, Sumin; Debbab, Abdssamad; Chadli, Ahmed; Georgia Cancer Center (2017-03)
      Molecular chaperones have been the focus of intense research for their important role in cancer cell homeostasis. Heat shock protein 90 (Hsp90) promotes metastasis, evasion of apoptosis, and proliferative angiogenesis in tumors through preserving the stability and functionality of its client proteins [1]. While the first generation of Hsp90 inhibitors has proven effective in hindering Hsp90 function, they have shown low clinical efficacy in part due to the induction of anti-apoptotic proteins Hsp27, Hsp40, and Hsp70 [2,3]. It is therefore our objective to develop novel efficacious Hsp90 inhibitors without these detrimental effects. During our screen for novel Hsp90 inhibitors, we found that the natural product, Chetomin, is a potent inhibitor of the Hsp90 machine chaperoning activity. Our in vitro data using human and murine mammary carcinoma cell lines suggest that Chetomin is effective in causing degradation of several known Hsp90 physiological client proteins that are crucial to cancer cell proliferation and survival. While the molecular mechanism by which Chetomin inhibits the Hsp90 function is still unclear, our data suggests that Chetomin is highly efficacious in killing cancer cells without induction of the anti-apoptotic proteins as does the first generation of Hsp90 inhibitors making Chetomin a promising new therapeutic agent.
    • The impact of general experience with patients on baseline measures of confidence in an SBIRT training program

      Johnson, J. Aaron; Chung, Yunmi; Brown, Shilpa P.; Augusta University (2016-10)