Digital Commons Network^™

Il-6/Jak1 Drives Pd-L1 Phosphorylation And Glycosylation To Promote Cancer Immune Evasion, Li-Chuan Chan

Dissertations and Theses (Open Access)

Glycosylation of immune receptors and ligands, such as T-cell receptor (TCR), major histocompatibility complex (MHC), and co-inhibitory molecules, regulates immune signaling activation, antigen presentation, and immune surveillance. Recent studies revealed that the glycan structures of co-inhibitory molecules are required for receptor-ligand interaction, a critical feature for activating cancer immune evasion. However, it is unclear how oncogenic signaling initiates glycosylation of co-inhibitory molecules to induce immunosuppression. Here we show interleukin (IL)-6-activated Janus kinase 1 (JAK1) phosphorylates programmed death-ligand 1 (PD-L1)-Tyr112, leading to the recruitment of endoplasmic reticulum (ER)-associated N-glycosyltransferase, STT3A, which catalyzes the glycosylation of PD-L1, contributing to its stability. A …

The Characterization Of T-Cell Manufacturing For Adoptive T-Cell Therapies, Amir Alpert

Dissertations and Theses (Open Access)

Adoptive T-cell therapy using genetically modified T cells has emerged as a potential therapeutic option for several malignancies. Central to the production of the cellular therapy is the manufacturing using a stimulation, genetic engineering, and expansion methodology. Within this framework, there is a delicate balance between expansion of the cells to a therapeutically relevant dosage and the need to retain the proliferative potential of the ‘living drug’. I show that as T-cells are expanded for elongated periods of time, they lose their proliferative potential and become functionally senescent despite the presence of multiple proliferative cytokines. In addition, I show that …

Rejuvenation Of The Epigenetic Landscape Of The Aged Brain Through Manipulation Of Circulating Factors, Edward Koellhoffer

Dissertations and Theses (Open Access)

The aging population of the United States is expanding at an alarming rate. The Center for Disease Control and Prevention estimates that the population of those age 65 years and older will reach over 50 million by 2020 and will double to 100 million by 2060. This will not only put a massive strain on national healthcare resources, but will also increase the number of those who are not able to live and function independently. It is becoming increasingly vital to understand how the brain changes with age and mechanisms to possibly protect and rejuvenate the aged brain to a …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations and Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

Systemic Antibiotic Therapy Reduces Circulating Inflammatory Dendritic Cells And Treg-Th17 Plasticity In Periodontitis, Mythilypriya Rajendran, Stephen Looney, Nagendra Singh, Mahmoud Elashiry, Mohamed M Meghil, Ahmed R El-Awady, Omnia Tawfik, Cristiano Susin, Roger M Arce, Christopher W Cutler

Faculty, Staff and Student Publications

Periodontitis (PD) is a common dysbiotic inflammatory disease that leads to local bone deterioration and tooth loss. PD patients experience low-grade bacteremias with oral microbes implicated in the risk of heart disease, cancer, and kidney failure. Although Th17 effectors are vital to fighting infection, functional imbalance of Th17 effectors and regulatory T cells (Tregs) promote inflammatory diseases. In this study, we investigated, in a small pilot randomized clinical trial, whether expansion of inflammatory blood myeloid dendritic cells (DCs) and conversion of Tregs to Th17 cells could be modulated with antibiotics (AB) as part of initial therapy in PD patients. PD …

Ic 092 Guide To University Of Texas-Houston Health Science Center Internal Medicine Grand Rounds Videos, 1990-2002, University Of Texas Health Science Center At Houston

Institutional Finding Aids

University of Texas-Houston Health Science Center Internal Medicine Grand Rounds videos consists of videos of Grand Rounds and the Clinicopathologic Conference (CPC) from the Department of Internal Medicine in the University of Texas Medical School at Houston. The department provides for the education of students, physicians, and the public in the field of biomedical knowledge. The department provides clinical education, fosters research, and through its clinical services provides patient care ranging from primary to subspeciality care. See more at IC 092.

Ic 072 Gude To Hiv/Aids Houston Collection, 1951-1995, John P. Mcgovern Historical Collections & Research Center

Institutional Finding Aids

The HIV/AIDS Houston collection consists of 6 boxes that contain newspaper clippings, reprinted articles, correspondence, speeches, guidelines, printed material, and newletters that document the early research of AIDS and the impact of AIDS in the Houston area. The collection has several issues of HIV Treatment and RITA! (Research Initiative, Treatment Action) ranging from 2001-2007. The collection encompasses 1951 – 1995 with earlier materials related to studies on the spread of diseases, such as encephalomyelitis in mice. The collection is in fair condition with some water damage. See more at IC 072.

Ic 061 Guide To University Of Texas, Division Of Continuing Education Records, 1950-1981, University Of Texas Division Of Continuing Education

Institutional Finding Aids

The University of Texas, Division of Continuing Education records contains budgets, grant requests, residency programs, faculty and staff, and other materials pertaining to the Post Graduate School of Medicine, Graduate School of Biomedical Sciences, and Division of Continuing Education from 1950-1981. See more at IC 061.

New Morbidities 2.0, Angelo P. Giardino, Robert Sanborn

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

Robert Sanborn and Angelo Giardino's introduction for Volume 4, Issue 1: New Morbidities 2.0

Introducing Foster Care: Challenges And Opportunities To Reducing Health Disparities, Anu Partap

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

Guest editor Dr. Anu Partap introduces Volume 9, Issue 1 of the Journal of Applied Research on Children.

Ic 042 Gude To Texas Children's Hospital Historical Archives, 1953-2003, Texas Children's Hospital

Institutional Finding Aids

Texas Children's Hospital Historical Archives contains 10 cubic feet of processed material and 79 boxes of unprocessed material. The later is labeled as the TCH Historical Archives and arrived in the HRC in 2008. See more at IC 042.

Multistate Outbreaks Of Foodborne Illness In The United States Associated With Fresh Produce From 2010 To 2017, Christina K Carstens, Joelle K Salazar, Charles Darkoh

Faculty, Staff and Student Publications

In the United States, the consumption of fresh fruits and vegetables has increased during recent years as consumers seek to make healthier lifestyle choices. However, the number of outbreaks associated with fresh produce that involve cases in more than one state (multistate) has increased concomitantly. As the distance along the farm-to-fork continuum has lengthened over time, there are also more opportunities for fresh produce contamination with bacterial pathogens before it reaches the consumer. This review provides an overview of the three bacterial pathogens (i.e., pathogenic

Impact Of Technology On Improving Hiv And Tuberculosis Health Outcomes Among African Countries, Sunny Ibeneme

Dissertations and Theses (Open Access)

This study used health analytics approach to evaluate the association between population health outcomes and Information and Communication Technology (ICT) infrastructures at a country level. This study used aggregate data obtained from the World Bank database, and the International Telecommunication Union (ITU) database for 53 African countries for the periods 2000 to 2016, and quantitatively explored the impact of ICT infrastructures’ diffusion on population health outcomes.

ICT data was obtained from the ITU database. Similarly, population health attributes were retrieved from the World Bank database. ICT infrastructure variables used in this study include: internet access, mobile phone use, and fixed …

Identifying Risk Factors Associated With Cardiovascular Disease Risk In Lesbians, Sofia S. Velazquez

Dissertations and Theses (Open Access)

Cardiovascular disease (CVD) is the leading cause of female deaths in the United States (1). While women, in general, are at risk for CVD, current research indicates that sexual minority women (i.e. lesbians and bisexual women [SMW]) may be at greater risk for CVD than heterosexual women. This heightened risk potentially stems from an increased prevalence of traditional CVD risk factors in SMW, creating health disparities between SMW and their heterosexual counterparts (2). Further research into this high-risk population is needed, in order to minimize these disparities.

The purpose of this study was to establish differences in the prevalence of …

Chagas Disease Awareness Amongst Texas Physicians, Gerardo J. Pacheco

Dissertations and Theses (Open Access)

An estimated 300,000 people in the U.S. are living with Chagas Disease (CD), many of whom may not yet know they are infected. Approximately 20% to 30% of individuals with CD are expected to develop clinical symptoms that may manifest as heart disease and result in death if left untreated. The prevalence of CD in humans is not well understood. Given its asymptomatic manifestation and the rarity in cases seen by physicians in general, CD may be under-recognized by physicians.

The purpose of this research was to explore the understanding and knowledge of CD in Texas HCP populations (cardiologists, infectious …

Impacts Of Cold Weather On Health In Texas, Tsun-Hsuan Chen

Dissertations and Theses (Open Access)

Recent events with recorded low temperature and unusual snow accumulation in the United States and Europe have raised the public awareness of the potential health impacts of extreme winter weather. Excessive cold was the leading cause of weather-related death during 2006-2010 in the U.S., accounting for 63% of weather related deaths. Several studies worldwide have demonstrated that, in general, mortality rates are higher in winter compared to summer. Studies have also shown that the association between cold temperature and death vary across cities, regions and countries and is especially relevant with decreasing latitude or in regions with mild winter climate. …

Collateral Benefits Of Diabetes Self-Management Associated With Self-Administered Outpatient Parenteral Antimicrobial Therapy, Anisha P. Ganguly

Dissertations and Theses (Open Access)

Self-administered outpatient parenteral antimicrobial therapy (S-OPAT) is a self-care treatment modality in which patients requiring extended courses of intravenous antibiotics are trained to safely self-administer treatment via an indwelling catheter in their home. Many patients seen in the S-OPAT program have a diagnosis of diabetes and present with infections associated with poor glycemic control, including skin and soft-tissue infections and osteomyelitis. Given the degree of patient activation required to successfully complete the S-OPAT process, we hypothesized that participation in this self-care program may benefit patients in self-management of other chronic health conditions, such as diabetes. The study team included Anisha …

Investigation Of Hantavirus And Leptospira As Possible Contributing Factors Of The Unexplained Kidney Disease Epidemic In Nicaragua, Nicole J. Delgado

Dissertations and Theses (Open Access)

Throughout Latin America, an epidemic of a kidney disease of an unknown etiology has been occurring since the late 1990s, and this disease is being called “Mesoamerican nephropathy.” Mesoamerican nephropathy predominantly affects male sugarcane workers. In Chichigalpa, Chinandega, Nicaragua, there is sugarcane plantation that is being heavily impacted by the Mesoamerican nephropathy epidemic, and they invited researchers from Baylor College of Medicine to investigate the epidemic. The prospective epidemic investigation began in 2015, and it is an ongoing investigation. Based on the compilation of data collected during the preliminary investigation, our hypothesis is that a possible zoonotic disease, such as …

Effects Of Extreme Precipitation On Gastrointesitnal Related Hospital Admissions In Texas, Sharmila Giri

Dissertations and Theses (Open Access)

Extreme precipitation has been implicated in more than 51% of the waterborne disease outbreaks in the United States between 1948-1994. With increased incidence of extreme precipitation projected to be more likely due to ongoing climate change, the burden of waterborne disease is expected to rise even in the United States where drinking water is considered to be one of the safest in the world. In this study we aim to quantify the risk of extreme precipitation on gastrointestinal (GI) related hospital admissions by using meteorological and emergency hospital data from twelve major metropolitan statistical areas (MSA) of Texas from year …

Examining The Effect Of Service Delivery Factors On Timely Initiation Of Tuberculosis Treatment Within Primary Care Settings In Uganda, Michael Juma

Dissertations and Theses (Open Access)

Background: Timeliness of Tuberculosis (TB) treatment is critical to stopping its transmission and preventing disease complications and death. Efficiency in identifying and treating presumptive TB cases is critical to reducing delays.

Aims: We determined the association between health service-related factors and delays in initiating TB treatment within primary care settings in Uganda. Perspectives of healthcare workers on practices underlying healthcare facility level delays were also described.

Methods: A mixed methods study was conducted based on facility-register records of 1199 treated TB cases and key informant interviews with 27 outpatient staffs. Health service-related factors (size, ownership, number of …

Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers To Checkpoint Blockade Immunotherapy, Casey Ager

Dissertations and Theses (Open Access)

Unprecedented durable tumor regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to checkpoint blockade, requiring development of new therapeutic approaches to promote responsivity in patients with these diseases. Both CRPC and PDAC are characterized by an immunosuppressive tumor milieu rich in cells of the myeloid lineage, which regulate T cell activity in many ways independent of the coinhibitory receptor axis. We investigated whether activation of acute inflammatory signaling …

Assembly And Display Of Surface Proteins In Actinomyces Oris, Sara Siegel

Dissertations and Theses (Open Access)

Bacteria are an integral part of human health and disease. In the human host, dental plaques form as a result of up to 700 individual bacterial species colonizing oral surfaces and forming a multispecies biofilm. These biofilms are the cause of prevalent human diseases such as dental caries, gingivitis, and periodontitis. The microbes present in the oral biofilm are highly spatially and temporally structured and require a primary colonizing species to adhere to host tissue. As an important primary colonizer of the oral biofilm, the actinobacterium Actinomyces oris utilizes cell wall anchored proteins and glycoconjugates to initiate adherence to host …

Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez

Dissertations and Theses (Open Access)

IL-1α Blockade Reduces Immune Suppression in the Early Tumor Micro-Environment

Brenda Melendez, B.S.

Advisory Professor: Gregory Lizee, PhD.

Immunotherapy against melanoma has shown great promise in the clinic for treating advanced-stage patients. However, a major barrier against effective T cell mediated cytotoxicity is immunosuppression in the tumor micro-environment. It has been described that tumors secrete pro-inflammatory cytokines capable of modulating immune responses that favors the growth of tumor cells. Specifically, IL-1 plays a critical role in myeloid cell recruitment and activation, which can in turn inhibit T cell activity in vivo. Moreover, IL-1 is also known to up-regulate immune inhibitory …

Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens, Yi Liu

Dissertations and Theses (Open Access)

Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific …

Vaccine Myths: Setting The Record Straight, Julie A. Boom, Rachel M. Cunningham, Lindy U. Mcgee

Journal of Family Strengths

Despite their standing as one of the most remarkable public health achievements, vaccines have been surrounded by dangerous myths since the development of the smallpox vaccine in the 18th century. In recent decades, with the publication of a fraudulent article linking vaccines to autism, the involvement of celebrities in the debate, and the rise of the internet and social media as sources for information for patients, these myths have become more widespread. This paper reviews four common vaccine myths: vaccines cause autism, vaccines are not safe, too many vaccines are given too soon, and the influenza vaccine is not necessary. …

Human Trafficking: It’S Not Just A Crime, Frances H. Recknor, Makini Chisolm-Straker

Journal of Family Strengths

Human trafficking, although commonly conceived of as a crime, is also a matter for the fields of health and public health. Trafficked individuals suffering physical, sexual, and/or psychological abuse can experience acute and chronic health sequelae, bringing them to the attention of health and/or mental health professionals. Communicable infections affect many trafficked individuals and can be transmitted to those not trafficked. The factors that contribute to people being trafficked, like poverty, educational disparities, and systematic oppression based upon identities, are multifaceted and interlinked with other trauma experiences. Incorporation of public health principles into anti-trafficking efforts facilitates a comprehensive and holistic …

8th 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.

An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen

Faculty, Staff and Students Publications

We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …

Development And Commissioning Of An Independent Peer Review System For A Small Animal Irradiator, Mary Peters

Dissertations and Theses (Open Access)

Dosimetry for small animal irradiators lacks the standardization of clinical radiotherapy practice, yet plays a central translational role in human trial design. The purpose of this work was to improve the dosimetric accuracy and consistency of animal studies by developing an independent peer review system to verify dose delivery from animal irradiators. This study focused on the development of a mouse phantom and characterization of the thermoluminescent dosimetry system for a commonly used small animal irradiator.

First, a mouse model and irradiation stand were designed with the purpose of being used in a mailable audit. Two mouse phantoms were machined …

Trichuris Muris Whey Acidic Protein Induces Type 2 Protective Immunity Against Whipworm, Neima Briggs

Dissertations and Theses (Open Access)

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The near full-length recombinant WAP protein (rTm-WAP49), as well …