• 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).
    • CURS Connection September 2020

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2020-09-16)
      Table of Content: CURS Alumni Spotlight: Naomie Jules, BSN; News (Student Research Series, High Five My Faculty); Opportunities to Present (Interdisciplinary Student Conference, Posters at the Georgia State Capitol 2021)
    • Attitudes and Behavior towards Interprofessional Collaboration among Healthcare Professionals in a Large Academic Medical Center

      Ansa, Benjamin E.; Zechariah, Sunitha; Gates, Amy M.; Johnson, Stephanie W.; Heboyan, Vahé; De Leo, Gianluca; Institute of Public and Preventive Health (MDPI, 2020-09-06)
      The increasing rates of comorbidities among patients and the complexity of care have warranted interprofessional collaboration (IPC) as an important component of the healthcare structure. An initial step towards assessing the e ectiveness of collaboration requires the exploration of the attitudes and experience of healthcare professionals towards IPC. This online survey aimed to examine the attitudes of healthcare professionals working in a large public academic medical center toward IPC in patient care and the healthcare team, and their behavior and experience regarding IPC. The rankings, according to the perceived importance among the respondents, of the four Interprofessional Education Collaborative (IPEC) core competencies (values/ethics, roles/responsibilities, interprofessional communication, teams/teamwork) were assessed. There were strong but varying levels of consensus among healthcare professionals (N = 551) that IPC facilitates ecient patient care, improves patient problem-solving ability, and increases better clinical outcomes for patients. They acknowledged that IPC promotes mutual respect within the healthcare team and providers’ ability to make optimal patient care decisions. However, overall more than 35% of the respondents did not attend multidisciplinary education sessions (grand rounds, seminars, etc.), and about 23% did not participate in bedside patient care rounds. Interprofessional communication was ranked as the most important IPEC core competence. Although the attitude towards IPC among healthcare professionals is strongly positive, many healthcare professionals face challenges in participating in IPC. Institutional policies that facilitate interprofessional learning and interactions for this group of healthcare professionals should be formulated. Online distance learning and interactions, and simulation-enhanced interprofessional education, are options for addressing this barrier. Hospital administrators should facilitate conducive work environments that promote IPC, based on IPEC core competencies, and promote programs that address the challenges of IPC.
    • CURS Connection May/June 2020

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2020-06)
      Table of Contents: Happy Birthday SSP!: CURS Summer Scholars Program Turns 10CURS: A Year in Pictures, Reflections by Undergraduate Researchers, Get Involved (Arsenal Undergraduate Research Journal, Seeking CURS Ambassadors, Undergrad Research Advising, and Faculty: Take your UR Mentorship in New Directions)
    • Cell drinking: a closer look at how macropinocytosis drives cholesterol uptake in atherosclerotic vessels

      Lin, Huiping; Vascular Biology Center (Augusta University, 2020-05)
      Atherosclerotic vascular disease is the underlying cause of myocardial infarction, stable and unstable angina, stroke, peripheral artery disease and sudden cardiac death. Collectively, these cardiovascular diseases are responsible for the majority of deaths worldwide. Internalization of modified apolipoprotein B–containing lipoproteins by macrophages through scavenger receptor (SR)-mediated pathways is generally viewed as an essential step for the initiation and progression of atherosclerosis. Our studies were designed to investigate the contribution of receptor-independent LDL macropinocytosis to arterial lipid accumulation and atherosclerosis. We developed novel genetic and pharmacological approaches, utilized high resolution imaging techniques and employed unique in vivo lipid quantification assays to investigate the role of macrophage macropinocytosis in the pathogenesis of atherosclerosis. My results demonstrate that the macropinocytosis inhibitor EIPA and selective deletion of a key pathway regulating macropinocytosis in myeloid cells substantially decreased lesion size in both hypercholesterolemic wild type (WT) and SR knockout (CD36-/-/SR-A-/-) mice. Stimulation of macropinocytosis using genetic and physiologically relevant approaches promotes lipoprotein internalization by WT and CD36-/-/SR-A-/- macrophages, leading to foam cell formation. Serial section high-resolution imaging of murine and human atherosclerotic arteries identified for the first time subendothelial macrophages for the first time that demonstrate plasma membrane ruffling, cupping and macropinosome internalization. Immunoelectron microscopy, 3D reconstruction of macrophage foam cells and in vivo LDL tracking demonstrate macrophage internalization of LDL in human and murine atherosclerotic arteries via macropinocytosis. We next performed a large, unbiased-screen of an FDA-approved drug library to identify clinically relevant therapeutic agents that can be repurposed as pharmacological inhibitors of macropinocytosis. Our studies identified a low MW compound (imipramine) that inhibits macrophage macropinocytosis in vitro and in vivo. Imaging, toxicity and selectivity studies demonstrated that imipramine is a potent (IC50 = 130.9 nM), non-toxic (selectivity index CC50/IC50 > 300) and selective inhibitor of macropinocytosis. Repurposing of imipramine to inhibit macropinocytosis in hypercholesterolemic mice substantially decreased plaque development compared with control treatment. Taken together, our findings challenge the SR paradigm of atherosclerosis and identify inhibition of receptor-independent macrophage macropinocytosis as a new therapeutic strategy that may be beneficial in the treatment of atherosclerosis and its cardiovascular consequences.
    • Genomic Predictions in Uterine Cancers

      Tran, Lynn Kim Hoang; Center for Biotechnology and Genomic Medicine (Augusta University, 2020-05)
      Introduction: Current uterine cancer classification provides suboptimal treatment stratification and often groups together patients with significant differences in survival outcome and/or response. We used transcriptomic information to devise genomic scores for improved prediction of uterine cancer patient outcomes and validated these scores in our institutional cohorts. Project 1: In an early iteration of our gene signature discovery pipeline, we developed USC73, a genomic score for uterine serous carcinoma patients, which grouped patients into a low score (lower 66.7 percentile), good prognosis group and a high score (upper 33.3 percentile), poor prognosis group (5-year overall survival: 83.3% and 13.3%, respectively). USC73 predicts survival independently of stage, and can be combined with stage for further resolution of patient survival. Poor survivors have faster-growing tumors and lower rates of complete response to primary therapy. Project 2: We applied our pipeline to uterine endometrioid carcinoma, the most common histotype of uterine cancer, and developed UEC_IGS, an immune gene score that separates early stage patients into a high lymphocytic infiltration, good prognosis group (IGS 1) and a low lymphocytic infiltration, poor prognosis group (IGS 2). UEC_IGS predicts overall survival independent of grade and treatment. IGS 1 patients have higher levels of CD8+ tumor infiltrating lymphocytes (TILs), more CD45RO+/CD3+ memory T cells, and lower levels of FOXP3+ Tregs compared to IGS 2. Conclusion: Using transcriptomic data, we can reliably stratify uterine cancer patients into good and poor survival groups. This information can be used to facilitate recruitment of only poor prognosis patients into clinical trials, mitigating some heterogeneity in patient response and allowing clinicians to better identify treatments for patients who will not survive on the current therapy. Additionally, biological functions (e.g. cellular proliferation or immune infiltration) are associated with each genomic score, and these can serve as potential pathways to target for improving the outcome of poor survival groups.
    • The Gulf War Women’s Health Cohort: Study Design and Protocol

      Ansa, Benjamin E.; Sullivan, Kimberly; Krengel, Maxine H.; Heboyan, Vahé; Wilson, Candy; Lobst, Stacey; Coughlin, Steven S.; Institute of Public and Preventive Health (MDPI, 2020-04-02)
      Military service and deployment affect women differently than men, underscoring the need for studies of the health of women veterans and their receipt of health care services. Despite the large numbers of women who served during the 1990–1991 Gulf War, few studies have evaluated Gulf War illness (GWI) and other medical conditions specifically as they affect women veterans of the 1991 Gulf War. The objectives of the Gulf War Women’s Health Cohort study are: (1) to establish the Gulf War women’s cohort (GWWC), a large sample of women veterans who served in the 1990–1991 Gulf War and a comparison group of women who served in other locations during that period; and (2) to provide current, comprehensive data on the health status of women who served during the 1990–1991 Gulf War, and identify any specific conditions that affect Gulf War women veterans at excess rates. The study will utilize both existing datasets and newly collected data to examine the prevalence and patterns of Gulf War Illness symptoms, diagnosed medical conditions, reproductive health, birth outcomes and other health issues among women who served during the Gulf War. The Gulf War Women’s Health Cohort study will address the need for information about the comprehensive health of women veterans who were deployed to the Gulf War, and other wars during the Gulf War era.
    • APPLICATIONS OF MACHINE LEARNING TO GENOMICS: STUDIES IN TYPE 1 DIABETES AND CANCER

      Tran, Paul; Center for Biotechnology and Genomic Medicine (Augusta University, 2020-04)
      Introduction: A major aim of modern medicine is to translate basic genomics findings using machine learning and other data analysis methods into clinical tests for improving patient care. Herein, I applied machine learning methods to publicly available genetic and genomic data to address three clinical problems in cancer and type 1 diabetes (T1D) research. Project 1: Cancer classification mostly depends on the anatomic pathology workforce; hence, diagnosis is slow, stepwise, and prone to errors and systemic bias. Using a transcriptome-based cancer classification method, I reconciled the 18% disagreement rate between histology and mutation-based classifier for brain cancer. Project 2: I applied the same transcriptome-based classification method to lung adenocarcinoma and identified 3 novel subgroups comprising ~30% of lung adenocarcinoma. Project 3: The estimated genetic heritability of T1D is up to 80%. Identifying those most genetically susceptible to T1D can lead to reduction of the number of islet autoimmunity cases and the number diabetic ketoacidosis episodes. I developed a genetic risk prediction model using neural networks which performs better than currently published methods. I applied model interpretation methods to the neural network and identified important genetic drivers for characterizing T1D molecular subgroups. Conclusion: These projects are small steps in translating genomic medicine projects to clinical applications but represent a future with more objective and automated tools to aid in clinical decision making.
    • CURS Connection April 2020

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2020-04)
      Table of Contents: Congratulations to Dr. Sabbatini, Biological Sciences: 2020 CURS Mentor Excellence Award, Congratulations Summer Scholars Program Awardees!, Research Week Recap, Get Involved (Arsenal Undergraduate Research Journal and Undergrad Research Advising)
    • CURS Connection March 2020

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2020-03)
      Table of Contents: We're Still Here!, Congratulations Spring Grant Awardees!, Ayala Presents to Georgia Legislators, Take Note (Phi Kappa Phi (would have been) Presenters, Call for Nominations: Mentor Excellence Award), Get Involved (Summer Research Opportunities through NSF and Undergrad Research Advising)
    • CURS Connection February 2020

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2020-02)
      Table of Contents: Student Researcher Spotlight: Vinaya Alapatt, B.S., Meet the CURS Ambassadors, Upcoming Events, Student Resources (Upcoming Workshop: Oral and Poster Presentation Workshop, Undergrads: Publish Your Work!, Phi Kappa Phi Student Research and Fine Arts Conference, Summer Research Opportunities through NSF, Follow Us on Social Media, CURS Advising)
    • CURS Connection January 2020

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2020-01)
      Table of Contents: Congratulations Dr. Brandon Cromer and Dr. Laurence Miller!, Student Research Series: Rachel Hammesfahr, Senior, Biology major and Ananya Chakraborty, Senior, Cell and Molecular Biology Major, Upcoming Events, Faculty Resources (Call for Proposals and Research and Travel Grants), Student Resources (Apply to be a CURS 2020 Summer Scholar and Phi Kappa Phi Student Research and Fine Arts Conference), Summer Research Opportunities through NSF, Advising, Announcements (Follow on social media, chemical and lab safety training, The Arsenal is seeking submissions)
    • CURS Connection November/December 2019

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2019-12)
      Table of Contents: Undergraduate Research Fair a Success, Student Research Series: Kyle Cartledge and Farron Aaronson, Mathematics and Isabella Santana, Cell and Molecular Biology, Georgia Undergraduate Research Conference (GURC), Faculty Resources (Faculty Information Sessions and Call for Summer Scholar Proposals), Student Resources (Vascular Biology Center Tour and High Five My Faculty: CURS Offering New Mentoring Award), Mark Your Calendars!, The 21st Annual Phi Kappa Phi Student Research & Fine Arts Conference.
    • Aspirin Use among Adults with Cardiovascular Disease in the United States: Implications for an Intervention Approach

      Ansa, Benjamin E.; Hoffman, Zachary; Lewis, Nicollette; Savoy, Cassandra; Hickson, Angela; Stone, Rebecca; Johnson, Tara; Institute of Public and Preventive Health (Augusta University, 2019-11-11)
      Cardiovascular disease (CVD) is a major underlying cause of death, with high economic burden in most countries, including the United States. Lifestyle modifications and the use of antiplatelet therapy, such as aspirin, can contribute significantly to secondary prevention of CVD in adults. This study examined the prevalence and associated factors of aspirin use for the secondary prevention of angina pectoris, myocardial infarction (MI), and cerebrovascular disease (stroke) in a sample of American adults. The 2015 Behavioral Risk Factor Surveillance System (BRFSS) dataset was analyzed for this cross-sectional study. Almost 16% of the study population (N = 441,456) had angina, MI, or stroke. Weighted percentages of respondents with angina, MI, and stroke were 4%, 4.3%, and 3%, respectively. Overall, weighted prevalence of daily (or every other day) aspirin use was about 65%, 71%, and 57% among respondents with angina, MI, and stroke, respectively. Factors that were significantly associated with aspirin use included male sex, more than high school education, high blood pressure, diabetes, and less than excellent general health. There were existing differences among individuals with CVD based on diagnosis, demographic and socioeconomic status in the use of aspirin for secondary prevention. Resources for promoting aspirin use should be directed toward groups with lower utilization.
    • Pancreatic cancer survival trends in the United States: 2001 - 2015 SEER 18 data

      Ansa, Benjamin; Institute of Public and Preventive Health (Augusta University, 2019-11-06)
    • CURS Connection October 2019

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2019-10)
      Table of Contents: First Annual Undergraduate Research Fair, #Research News (Calling All Student Researchers and Chemical Safety Partners with CURS: Chemical and Lab Safety Training Comes to Summerville), Student Research Series: Nitish Sood and Anish Sangari, Cell and Molecular Biology, Leslie Duncan, Cell and Molecular Biology, Upcoming Events, Next Steps in Research Workshop, #ResearchNews (Calling Faculty Mentors, Art and Design Meet and Greet, and High Five My Faculty: CURS Offers a New Mentoring Award)
    • CURS Connection September 2019

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2019-09)
      Table of Contents: Communications Student Involved in Multiple Scholarly Projects, High Five My Faculty: CURS Offers a New Mentoring Award, Student Research Series (Justin Brown, English major, Reeya Patel and Chandani Patel, Cell/Molecular Biology), Upcoming Events, #ResearchNews (Last Chance for 2019 GA Undergraduate Research Conference and Calling Faculty Mentors), #InTheKnow (Still Accepting Ambassadors! and Save the Date).
    • CURS Connection August 2019

      Center for Undergraduate Research and Scholarship; Davis, Quentin; Knapp, Melissa; Center for Undergraduate Research and Scholarship (Augusta University, 2019-08)
      Table of Contents: Summer Scholars Symposium, Changes Coming in CURS Grant Opportunities, Student Research Series (Sabrina Nacci, English major, kicked off the Student Research Series (formerly known as Brown Bag), Upcoming Events, #ResearchNews (Call for Abstracts and CURS Ice Cream Social), Call for Nominations: CURS Ambassadors