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9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Improving The Health Care Of Foster Children Throughout The Us: Texas, A Case Example, Nickolas Agathis, Jean L. Raphael, Christopher Greeley

Journal of Applied Research on Children: Informing Policy for Children at Risk

Children who have been exposed to the foster care system comprise a high-risk, vulnerable, and potentially medically complex population that has both poor health and poor access to health care. This review with Texas as a case example aims to describe the health and health care issues impacting children in foster care (CFCs), the state and federal level mechanisms to ensure appropriate funding for the health care of CFCs, and recent legislative efforts to improve the health and health care access for CFCs. The review discusses potential solutions in regards to improving the health of CFCs through four main domains: …

Unmet Needs Of Unaccompanied Minors From Central America: Perceptions Of Professionals From Multiple Sectors, Sheyla P. Medina, Carol Lewis, Roberta Goldman

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background: In recent years, there has been a significant influx of Central American youth who cross the U.S.-Mexico border without a parent or legal guardian. While federal procedures are established to oversee the treatment and placement of unaccompanied minors, less is known about the needs of unaccompanied minors and available services afterthey are placed in appropriate custody.

Methods: Purposive and strategic sampling of professionals from medical, social work, education and legal fields was conducted. Fourteen informants were recruited across the U.S. for confidential semi-structured interviews, which were audio recorded and transcribed in 2016 to 2017. Standard anthropological …

Discrimination Against Mixed-Status Families And Its Health Impact On Latino Children, Margaret A. Singer Ba, Manuela Gutierrez Velez Bs, Scott D. Rhodes Phd, Mph, Julie M. Linton M.D.

Journal of Applied Research on Children: Informing Policy for Children at Risk

Background and Objective: Restrictive immigration policies and discrimination are associated with negative health outcomes for immigrant and Latino families. Mixed-status families represent a unique subpopulation of Latinos affected by restrictive immigration policies. This qualitative study explored discrimination against mixed-status families and its potential health impact on Latino children from the perspective of Latina mothers.

Methods: In 2017, twenty in-depth interviews with Latina mothers of mixed-status families living in northwestern North Carolina were conducted, transcribed, and analyzed. Constant comparison, an approach to grounded theory development, was used.

Results: Nine themes emerged that reflected experiences with discrimination and its …

Unraveling The Functional Role Of The Orphan Solute Carrier, Slc22a24 In The Transport Of Steroid Conjugates Through Metabolomic And Genome-Wide Association Studies, Sook Wah Yee, Adrian Stecula, Huan-Chieh Chien, Ling Zou, Elena V Feofanova, Marjolein Van Borselen, Kit Wun Kathy Cheung, Noha A Yousri, Karsten Suhre, Jason M Kinchen, Eric Boerwinkle, Roshanak Irannejad, Bing Yu, Kathleen M Giacomini

Faculty, Staff and Student Publications

Variation in steroid hormone levels has wide implications for health and disease. The genes encoding the proteins involved in steroid disposition represent key determinants of interindividual variation in steroid levels and ultimately, their effects. Beginning with metabolomic data from genome-wide association studies (GWAS), we observed that genetic variants in the orphan transporter, SLC22A24 were significantly associated with levels of androsterone glucuronide and etiocholanolone glucuronide (sentinel SNPs p-value

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Faculty, Staff and Student Publications

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Faculty, Staff and Student Publications

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …

Blood Leukocyte Dna Methylation Predicts Risk Of Future Myocardial Infarction And Coronary Heart Disease, Golareh Agha, Michael M Mendelson, Cavin K Ward-Caviness, Roby Joehanes, Tianxiao Huan, Rahul Gondalia, Elias Salfati, Jennifer A Brody, Giovanni Fiorito, Jan Bressler, Brian H Chen, Symen Ligthart, Simonetta Guarrera, Elena Colicino, Allan C Just, Simone Wahl, Christian Gieger, Amy R Vandiver, Toshiko Tanaka, Dena G Hernandez, Luke C Pilling, Andrew B Singleton, Carlotta Sacerdote, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Yun Li, Guosheng Zhang, James D Stewart, James S Floyd, Kerri L Wiggins, Jerome I Rotter, Michael Multhaup, Kelly Bakulski, Steven Horvath, Philip S Tsao, Devin M Absher, Pantel Vokonas, Joel Hirschhorn, M Daniele Fallin, Chunyu Liu, Stefania Bandinelli, Eric Boerwinkle, Abbas Dehghan, Joel D Schwartz, Bruce M Psaty, Andrew P Feinberg, Lifang Hou, Luigi Ferrucci, Nona Sotoodehnia, Giuseppe Matullo, Annette Peters, Myriam Fornage, Themistocles L Assimes, Eric A Whitsel, Daniel Levy, Andrea A Baccarelli

Faculty, Staff and Student Publications

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

RESULTS: Among …

Utilizing Temporal Information In The Ehr For Developing A Novel Continuous Prediction Model, Kang Lin Hsieh

Dissertations and Theses (Open Access)

Type 2 diabetes mellitus (T2DM) is a nation-wide prevalent chronic condition, which includes direct and indirect healthcare costs. T2DM, however, is a preventable chronic condition based on previous clinical research. Many prediction models were based on the risk factors identified by clinical trials. One of the major tasks of the T2DM prediction models is to estimate the risks for further testing by HbA1c or fasting plasma glucose to determine whether the patient has or does not have T2DM because nation-wide screening is not cost-effective.

Those models had substantial limitations on data quality, such as missing values. In this dissertation, I …

Design And Architecture Of An Ontology-Driven Dialogue System For Hpv Vaccine Counseling, Amith Faheem Muhammad

Dissertations and Theses (Open Access)

Speech and conversational technologies are increasingly being used by consumers, with the inevitability that one day they will be integrated in health care. Where this technology could be of service is in patient-provider communication, specifically for communicating the risks and benefits of vaccines. Human papillomavirus (HPV) vaccine, in particular, is a vaccine that inoculates individuals from certain HPV viruses responsible for adulthood cancers - cervical, head and neck cancers, etc. My research focuses on the architecture and development of speech-enabled conversational agent that relies on series of consumer-centric health ontologies and the technology that utilizes these ontologies. Ontologies are computable …

The Biology Of Hope, Fernando Stein M.D.

Journal of Applied Research on Children: Informing Policy for Children at Risk

Children do not immigrate; they flee. I have used this simple phrase during the recent years that I have been thrust into the debate related to the migration of children alone or with families across the southern border of the United States.

The Louisiana Spirit Hurricane Recovery Program: Addressing The Needs Of Children And Adolescents After Catastrophic Hurricanes, Melissa J. Brymer, Tonya Hansel, Alan M. Steinberg, Anthony Speier, Joy Osofsky, Howard Osofsky

Journal of Family Strengths

Aims: The Louisiana Spirit Hurricane Recovery Program was a statewide disaster mental health initiative implemented in response to the 2005 Hurricanes Katrina and Rita. Major components of the program included community-based culturally appropriate outreach strategies, risk screening and triage, and provision of Specialized Crisis Counseling Services (SCCS). The goal was to identify children and families at risk, and deliver services to address current needs and ongoing distress to prevent longer-term mental health problems. Methods: As the behavioral health needs of special populations, including minorities, and children and adolescents often go unmet, the Louisiana Spirit Program addressed this by …

Project Reach: Implementation Of Evidence-Based Psychotherapy Within Integrated Healthcare For Hurricane Harvey Affected Individuals, Lynn M. Hana B.S., Sandra L. Cepeda B.S., Catherine C. Christian B.E., Sophie C. Schneider Ph.D., Ashley M. Shaw Ph.D., Jill Ehrenreich-May Ph.D., Alison Salloum Ph.D., Laurel Williams D.O., Asim A. Shah M.D., Eric A. Storch Ph.D.

Journal of Family Strengths

Project Reach was established to deliver evidence-based mental healthcare services to children and adults affected by Hurricane Harvey and its aftermath. Through Project Reach, an innovative multi-component assessment and treatment service is utilized to identify and treat in integrated healthcare settings both children and adults exhibiting significant behavioral health concerns in Houston. The aim is to provide sustainable, integrated mental health services through primary care and school-based settings to post-Harvey affected individuals whose emotional needs remain unmet. This paper describes the design and implementation of Project Reach as well as special considerations for implementation. The overall goal of Project Reach …

Climate Change And Chagas Disease In The Americas: A Qualitative Systematic Review, Brittany N. Graves

Dissertations and Theses (Open Access)

While many studies have found associations between climate change and factors affecting Chagas disease transmission, the future impact of climate change on the global spread of Chagas disease remains debatable. A qualitative, systematic review was conducted to assess the impact of climate change on Chagas disease transmission in the Americas (Central America, South America, and North America). The literature search was performed in January 2019 using the keywords climate, Chagas, and “trypanosoma cruzi” and the electronic databases PubMed, Scopus, and Ovid. Searches retrieved records from 1982 through 2019. The initial electronic database search identified a total of 191 record documents …

Uses Of Continuous-Time Markov Chain To Describe Longitudinal Patient-Reported Outcomes For Survival Prediction And Dimension Reduction, Ting-Yu Chen

Dissertations and Theses (Open Access)

A patient-reported outcome (PRO) is a type of outcome reported directly from patients, and it has been widely used in medical research and clinical trials to measure a patient’s symptoms, health-related quality of life, physical functioning, and health status. Previous studies have linked PROs to survival outcomes, but most of them only used the PRO information at baseline or at a specific clinical time point [1, 2]. Even though some of these studies collected longitudinal PROs, only few of them evaluated the association between the longitudinal PROs and a survival outcome. One of the major challenges in longitudinal PRO studies …

Hepatitis C Infection In Men Who Have Sex With Men, Jing Zhao

Dissertations and Theses (Open Access)

Hepatitis C virus (HCV) infection is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. Current treatment rates and efficacy are inadequate to manage the disease burden caused by HCV; thus, efforts are needed to control HCV transmission. Besides the well-known transmission routes, which are health-care-associated transmission and transmission through injecting drugs, HCV could also be transmitted by sexual contact, especially among men having sex with men (MSM). MSM also have higher drug use prevalence than the general population, which may contribute to HCV infection by sexual disinhibition and other risky behavior. Since 2000, there have been emerging reports …

Utilization Of Mind-Body Practices For Adults With Fibromyalgia: 2017 National Health Interview Survey, Jennifer Contreras

Dissertations and Theses (Open Access)

Fibromyalgia (FM) is a medical condition characterized by chronic pain and tenderness. Individuals with FM may experience burdensome symptoms, which impact their health-related quality of life. Treatment for FM includes pharmacological and non pharmacological practices. Non-pharmacological treatments for FM include dietary management, routine exercise, and physical and mind-body therapies. There is growing evidence that the utilization of mind-body practices is increasing in the United States, but there have been limited investigations done to observe the use of mind-body practices in the FM population. The purpose of this study is to identify predictors of the use of meditation and/or meditative movement …

Assessing The Readiness Of Relatives To Undergo Cascade Genetic Testing For Inherited Predispositions To Cancer Using The Transtheoretical Model Stages Of Change, Erica M. Bednar

Dissertations and Theses (Open Access)

National guidelines recommend cascade genetic testing (CGT) for blood relatives after a cancer predisposition gene mutation is identified in an individual. Despite recommendations for CGT, only 30-60% of first-degree relatives (FDRs) complete CGT. The proportion of untested relatives who are planning to have CGT is unknown. We used the Transtheoretical Model to assess the readiness (stage of change) for CGT among living, untested FDRs at-risk for a hereditary predisposition to cancer. An anonymous, online survey was open to U.S. adults with an autosomal dominant, adult-onset, hereditary predisposition to cancer. Participants reported demographic information, their genetic testing information, and information on …

Commissioning Of Micro-Cube Thermoluminescent Dosimeters For Small Field Dosimetry Quality Assurance In Radiotherapy, Brandon Luckett

Dissertations and Theses (Open Access)

Small field dosimetry presents complications and uncertainties that could be circumvented by using detectors which are smaller than the radiation field. This study evaluates the reproducibility and accuracy of TLD micro-cubes for use in stereotactic radiosurgery (SRS) remote auditing quality assurance (QA) for treatment centers participating in clinical trials. This study tested the hypothesis that TLD micro-cubes could be commissioned to evaluate small field dosimetry, and provide reproducibility within 3%, as well as assure agreement between measured dose and calculated doses to within 5%.

The aims of this thesis were to characterize and commission TLD micro-cubes as well as to …

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali

Dissertations and Theses (Open Access)

Recently, a novel class of muscular dystrophy has been discovered in a family due to autosomal recessive missense mutation in POGLUT1. Mutation of this enzyme leads to decreased O-glucosyltransferase activity and impaired Notch signaling, the pathways important for skeletal muscle stem cell (satellite cells) quiescence and activation. We hypothesize that reduced POGLUT1 activity and impaired Notch signaling is causative of this limb girdle muscular dystrophy through dysfunction of muscle stem cells and myogenic progenitors.

To test this, we have used iPSCs for disease modeling and rescue experiments. Using a CRISPR based gene targeting method, we aimed to correct the point …

Inhibition Of Urothelial Carcinoma By Type I Interferon Activation Of The Innate And Adaptive Immune Response, Devin Plote

Dissertations and Theses (Open Access)

Bacillus Calmette-Guerin (BCG) is the first line therapy for bladder cancer patients with non-invasive disease. However, roughly 40% of patients exhibit no response, tumor recurrence or tumor progression following BCG treatment. Type I interferon (IFN-I) has potent anti-tumor effects against urothelial carcinoma (UC) and may be an alternative treatment option for patients who do not respond to BCG standard of care. However, the mechanisms that mediate the IFN-I-stimulated immune responses against UC are not fully elucidated. Herein, we evaluated the anti-tumor mechanisms of IFN-I in UC by use of adenoviral interferon-α (Ad-IFNα/Syn3) in human patients, and poly(I:C) or lentiviral IFNa …

The Gsk-3Β-Fbxl21 Axis Regulates Tcap Via Ubiquitin-Mediated Proteasomal Pathway In The Cytoplasm, Jiah Yang

Dissertations and Theses (Open Access)

Protein turnover is one of the most essential mechanisms controlling circadian rhythms. F-Box and Leucine Rich Repeat Protein21 (FBXL21) is a circadian E3 ligase which shows oscillatory mRNA transcripts and protein levels. It was previously found to perform subcellular compartment-specific E3 ligase activities targeting the core clock proteins CRYPTOCHROME(CRY)1/2. Here we identified a new sarcomeric target substrate, Telethonin(TCAP), which also shows circadian oscillation in its mRNA transcript and protein expression and, importantly, interaction with FBXL21 in an anti-phasic manner. Via computational and pharmacological tests, we identified Glycogen Synthase Kinase-3β(GSK-3β) as a regulator of FBXL21. Biochemical and molecular characterizations demonstrated that …

Evaluating The Therapeutic Efficacy Of Grb2 Inhibition In Ovarian Malignancies, Olivia Lara

Dissertations and Theses (Open Access)

Purpose: Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in ovarian cancer models.

Experimental Design: Murine orthotopic models of ovarian cancer (OVCAR5 and SKOV3ip1) were used to study the biological effects of L-Grb2 on tumor growth. In vitro experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanism and potential predictors of tumor response to L-Grb2.

Results: Treatment with L-Grb2 decreased tumor growth …

Identifying And Targeting Adaptive Changes To Bet Inhibition In Ovarian Cancer, Christopher Lafargue

Dissertations and Theses (Open Access)

Purpose: To identify combination strategies using Bromodomain and Extra-Terminal Domain (BET) inhibitors in a mechanism driven fashion to maximize anti-tumor activity, and to determine the efficacy of BET inhibitor combinations in pre-clinical ovarian cancer mouse models.

Experimental Design: We used a novel, previously uncharacterized pan-BET inhibitor, CN210, for all in vitro (MTT, apoptosis, protein expression, reverse phase protein array (RPPA) analysis and in vivo (orthotopic mouse model)) experiments. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib, as well as the mechanistic target of rapamycin (mTOR) inhibitors rapamycin and INK-128 were also used. Statistical analyses of in vitro and in vivo experiments …

An Information Theory Model For Optimizing Quantitative Magnetic Resonance Imaging Acquisitions, Drew Mitchell

Dissertations and Theses (Open Access)

Quantitative magnetic resonance imaging (qMRI) is a powerful group of imaging techniques with a growing number of clinical applications, including synthetic image generation in post-processing, automatic segmentation, and diagnosis of disease from quantitative parameter values. Currently, acquisition parameter selection is performed empirically for quantitative MRI. Tuning parameters for different scan times, tissues, and resolutions requires some measure of trial and error. There is an opportunity to quantitatively optimize these acquisition parameters in order to maximize image quality and the reliability of the previously mentioned methods which follow image acquisition.

The objective of this work is to introduce and evaluate a …

Modeling Proton Relative Biological Effectiveness Using Monte Carlo Simulations Of Microdosimetry, Mark A. Newpower

Dissertations and Theses (Open Access)

Proton therapy is a radiotherapy modality that can offer a better physical dose distribution when compared to photon radiotherapy by taking advantage of the Bragg peak, a narrow region of rapid energy loss. Proton therapy is also known to offer an enhanced relative biological effectiveness (RBE) compared to photons. In the current clinical standard, RBE is fixed at 1.1 at all points along the proton beam, meaning protons are assumed to require 10% less dose than photons to achieve target coverage and organ at risk (OAR) sparing. However, there is mounting clinical evidence, and a significant number of in vitro …

Role Of C-Met And Egfr In Acquired Resistance To Parp Inhibitors In Triple-Negative Breast Cancer, Clinton Yam

Dissertations and Theses (Open Access)

Triple-negative breast cancer is associated with a poor prognosis and treatment options are limited. The Poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and talazoparib, were recently approved for metastatic breast cancer (including triple-negative breast cancer) in patients with a germline BRCA1/2 mutation. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with PARP inhibitors is modest, suggesting the emergence of resistance. We previously demonstrated that c-MET contributes to intrinsic resistance to PARP inhibitors in triple-negative breast cancer. However, whether c-MET plays a role in acquired resistance to PARP inhibitors in triple-negative breast cancer remains unclear. Here, we show …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

The Influence Of The Pep-Pts And Other Metabolic Systems On The Master Virulence Regulator Atxa And To Xin Gene Expression In Bacillus Anthracis, Naomi Bier-Reizes

Dissertations and Theses (Open Access)

AtxA, the master virulence gene regulator in Bacillus anthracis, is a PRD-containing virulence regulator (PCVR) as indicated by the crystal structure, post-translational modifications, and activity of the protein. PCVRs are transcriptional regulators, named for the regulatory domains subject to phosphorylation by the phosphoenolpyruvate phosphotransferase system (PEP-PTS), termed PTS Regulatory Domains (PRD), and for their impact on virulence gene expression. Generally, the phosphorylation of a PCVR regulates protein activity and multimerization. AtxA is phosphorylated at two histidine residues - one in each of its two PRDs. Phosphorylation at position 199 allows for AtxA to positively affect expression of virulence genes, whereas …