Digital Commons Network^™

Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan

Dissertations and Theses (Open Access)

Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …

Stromal Fibroblasts Restrain The Rate Of Colon Cancer Progression And Metastasis By Suppressing Regulatory T Cells And Colon Cancer Stem Cells, Changsoo Kwak

Dissertations and Theses (Open Access)

The initiation, progression, and metastasis of tumors involve not only cancer cells, but also the tumor microenvironment, which consists of immune or inflammatory cells, fibroblasts, endothelial cells, and extracellular matrix components (ECM). Fibroblasts are ubiquitous stromal cells that can influence other neighboring cell types through the secretion of chemokines, cytokines, ECM, ECM remodeling enzymes, and other metabolites. Myofibroblasts are a distinct subtype of fibroblasts characterized by expression α-smooth muscle actin (αSMA). These cells are a dominant component of the microenvironment, and a FSP1 and FAP could be a different clone of fibroblasts. Myofibroblasts also have been known to contribute to …

Characterization Of The Role Of The Pkm101-Encoded T4ss Outer Membrane Core Complex In Substrate Transfer, Pilus Biogenesis, And Recipient Cell Contact, Jay E. Gordon

Dissertations and Theses (Open Access)

The bacterial type IV secretion systems (T4SS) encoded on the Escherichia coli pKM101 and R388 conjugative plasmids and the Agrobacterium tumefaciens virB operon are composed of 12 subunits arranged in an architecturally similar fashion. Structural studies of the T4SS from R388 (Trw_R388) highlighted the presence of a distinct outer membrane core complex (OMCC) and inner membrane complex (IMC) joined together by a central stalk. This thesis is focused on the development of the pKM101 model system and the role of an OMCC cap region formed by alpha helical antenna projections (AP) found in VirB10 and TraF_pKM101. …

Detecting And Evaluating Therapy Induced Changes In Radiomics Features Measured From Non-Small Cell Lung Cancer To Predict Patient Outcomes, Xenia J. Fave

Dissertations and Theses (Open Access)

The purpose of this study was to investigate whether radiomics features measured from weekly 4-dimensional computed tomography (4DCT) images of non-small cell lung cancers (NSCLC) change during treatment and if those changes are prognostic for patient outcomes or dependent on treatment modality. Radiomics features are quantitative metrics designed to evaluate tumor heterogeneity from routine medical imaging. Features that are prognostic for patient outcome could be used to monitor tumor response and identify high-risk patients for adaptive treatment. This would be especially valuable for NSCLC due to the high prevalence and mortality of this disease.

A novel process was designed to …

Ms171: Interview With Diana Chow, Diana Shu-Lian Chow Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

Diana Shu-Lian Chow, Ph.D., is an outstanding researcher at the University of Houston College of Pharmacy, where she began her career in 1981. She has authored or co-authored more than 50 peer-reviewed journal articles, three book chapters and more than 200 abstracts presented at national and international scientific conference or meetings. She is the editor of the British Journal of Pharmacology, editorial board member for the Journal of Drug Development and Industrial Pharmacy and a reviewer for more than a dozen journals.

She holds more than 10 U.S. and international patents, and in 2009, the Houston Intellectual Property Law Association …

Ms171: Interview With Margaret Carter Mcneese, Margaret Carter Mcneese M.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Margaret Carter McNeese about her career in the Department of Pediatrics at the Univeristy of Texas Health Science Center at Houston Medical School.

Dr. McNeese’s undergraduate years were spent at Mary Baldwin College in Staunton, Virginia. She went to medical school at The University of Texas Medical Branch at Galveston, where she began her career as a physician and pediatrician. She has been a recipient of many awards, among them the UT Health Science Center at Houston’s President’s Award for Mentoring Women; the Catholic Charity Guild Award for service at the San Jose Clinic, the …

Ms171: Interview With Kathryn Peek, Kathryn Elaine Peek Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Kathryn Elaine Hickman Peek about her career as a biomedical administrator and educator at many institutions in the Texas Medical Center.

Kathryn Elaine Peek, Ph.D. completed her bachelor’s degree in English and embarked on a first career as a public school teacher. She obtained master’s degrees in biology and behavioral sciences at the University of Houston and UH Clear Lake during two stays in the Houston area. She entered the University of Texas Graduate School of Biomedical Sciences at what is now the McGovern Medical School at the age of 39. She graduated with a …

Ms171: Interview With Millicent Goldschmidt, Millicent Goldscmidt Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Millicent Goldschmidt about her career at University of Texas Health Science Center at Houston (UTHealth) where she has held faculty positions in the Department of Diagnostic and Biomedical Sciences at UTHealth School of Dentistry, UTHealth Medical School, and the Graduate School of Biomedical Sciences.

Millicent Edna Goldschmidt, Ph.D., came to the Texas Medical Center after an educational journey that included parental objections and a husband’s ethical concerns about research.

Once in Houston, her professional journey took her to almost every institution in the Texas Medical Center – from Baylor College of Medicine to The University …

Further Advances For The Sequential Multiple Assignment Randomized Trial (Smart), Tianjiao Dai

Dissertations and Theses (Open Access)

ABSTRACT

FURTHER ADVANCES FOR THE SEQUENTIAL MULTIPLE ASSIGNMENT RANDOMIZED TRIAL (SMART)

Tianjiao Dai, M.S.

Advisory Professor: Sanjay Shete, Ph.D.

Sequential multiple assignment randomized trial (SMART) designs have been developed these years for studying adaptive interventions. In my Ph.D. study, I mainly investigate how to further improve SMART designs and optimize the interventions for each individual in the trial. My dissertation has focused on two topics of SMART designs.

1) Developing a novel SMART design that can reduce the cost and side effects associated with the interventions and proposing the corresponding analytic methods. I have developed a time-varying SMART design in …

Latina Women In The United States: Child Care Preferences And Arrangements, Laura Satkowski Ph.D., Rumeli Banik Ph.D., Sonia Roubeni M.A.

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

Formal child care has been associated with myriad benefits for children, such as improvements in cognitive development and language skills. Immigrant children may derive unique benefits from formal child care, as research has also confirmed that center-based child care is associated with gains in English language proficiency and school readiness. However, immigrant families are less likely than nonimmigrant families to enroll their children in formal child care. Considering the growing immigrant population in the US—a large proportion of which is Latino—more research is needed to understand the child care decision-making processes of immigrant Latino families. The current study examined the …

Behavioral Economics And Developmental Science: A New Framework To Support Early Childhood Interventions, Lisa Gennetian, Matthew Darling, J Lawrence Aber

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

Public policies have actively responded to an emergent social and neuroscientific evidence base documenting the benefits of targeting services to children during the earliest period of their development. But problems of low utilization, inconsistent participation, and low retention continue to present themselves as challenges. Although most interventions recognize and address structural and psycho-social barriers to parent’s engagement, few take seriously the decision making roles of parents. Using insights from the behavioral sciences, we revisit assumptions about the presumed behavior of parents in a developmental context. We then describe ways in which this framework informs features of interventions that can be …

Annual Report 2016-2017, Houston Academy Of Medicine - Texas Medical Center Library

Annual Reports: 1943 - Present

This file contains the Annual Report for the library from 2016-2017.

A Life Cycle Approach To The Development And Validation Of An Ontology Of The U.S. Common Rule (45 C.F.R. § 46), Francis Manion

Dissertations and Theses (Open Access)

Requirements for the protection of human research subjects stem from directly from federal regulation by the Department of Health and Human Services in Title 45 of the Code of Federal Regulations (C.F.R.) part 46. 15 other federal agencies include subpart A of part 46 verbatim in their own body of regulation. Hence 45 C.F.R. part 46 subpart A has come to be called colloquially the ‘Common Rule.’

Overall motivation for this study began as a desire to facilitate the ethical sharing of biospecimen samples from large biospecimen collections by using ontologies. Previous work demonstrated that in general the informed consent …

Improving Syntactic Parsing Of Clinical Text Using Domain Knowledge, Min Jiang

Dissertations and Theses (Open Access)

Syntactic parsing is one of the fundamental tasks of Natural Language Processing (NLP). However, few studies have explored syntactic parsing in the medical domain. This dissertation systematically investigated different methods to improve the performance of syntactic parsing of clinical text, including (1) Constructing two clinical treebanks of discharge summaries and progress notes by developing annotation guidelines that handle missing elements in clinical sentences; (2) Retraining four state-of-the-art parsers, including the Stanford parser, Berkeley parser, Charniak parser, and Bikel parser, using clinical treebanks, and comparing their performance to identify better parsing approaches; and (3) Developing new methods to reduce syntactic ambiguity …

Targeting Apoptotic Pathways To Overcome Drug Resistance In Acute Myeloid Leukemia, Rongqing Pan

Dissertations and Theses (Open Access)

Evasion of apoptosis is integral to tumorigenesis and drug resistance. BCL-2 and p53 proteins represent two focal nodes in convergent apoptosis signaling. Upregulation of anti-apoptotic BCL-2 family members and inactivation of p53 functions are two canonical approaches exploited by cancer cells to escape apoptosis. In the current study, we find that BCL-2 protein is highly expressed in acute myeloid leukemia (AML) cells. BCL-2–specific inhibitor ABT-199 potently induces mitochondrial apoptosis in AML cells and effectively kills AML stem/progenitor cells. Our biomarker studies demonstrate that both BH3 profiling and the expression profiling of BCL-2 proteins may serve as predictive biomarkers for the …

Regulation Of Hnrnpa1 By Micrornas Controls The Mir-18a–K-Ras Axis In Chemotherapy-Resistant Ovarian Cancer, Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

The regulation of microRNA (miRNA) biogenesis, function and degradation involves a range of mechanisms, including interactions with RNA-binding proteins. The potential contribution of regulatory miRNAs to the expression of these RNA interactor proteins that could control other miRNAs expression is still unclear. Here we demonstrate a regulatory circuit involving oncogenic and tumor-suppressor miRNAs and an RNA-binding protein in a chemotherapy-resistant ovarian cancer model. We identified and characterized miR-15a-5p and miR-25-3p as negative regulators of hnRNPA1 expression, which is required for the processing of miR-18a-3p, an inhibitor of the

The Neurobiological Mechanisms Of Generalized Anxiety Disorder And Chronic Stress, Michelle A Patriquin, Sanjay J Mathew

Staff and Researcher Publications

Two classification systems are now at the forefront of clinical psychiatric research: (1) Diagnostic and Statistical Manual, Fifth Edition and (2) the National Institutes of Mental Health Research Domain Criteria. Herein, we propose that these two classification systems are complementary rather than mutually exclusive, and when combined provide important information for understanding aspects of the pathophysiology related to Generalized Anxiety Disorder (GAD). The neurobiological literature for GAD and one relevant research domain criteria component, sustained threat, are reviewed from multiple units of analysis (genetic, neuroimaging, neuroendocrine, and psychophysiological). It is hypothesized that generating a comprehensive, biologically based understanding of the …

A Novel Approach To Identifying A Neuroimaging Biomarker For Patients With Serious Mental Illness, Alok Madan, J Christopher Fowler, Michelle A Patriquin, Ramiro Salas, Philip R Baldwin, Kenia M Velasquez, Humsini Viswanath, David L Molfese, Carla Sharp, Jon G Allen, Susan Hardesty, John M Oldham, B Christopher Frueh

Staff and Researcher Publications

Serious mental illness (SMI) is disabling, and current interventions are ineffective for many. This exploratory study sought to demonstrate the feasibility of applying topological data analysis (TDA) to resting-state functional connectivity data obtained from a heterogeneous sample of 235 adult inpatients to identify a biomarker of treatment response. TDA identified two groups based on connectivity between the prefrontal cortex and striatal regions: patients admitted with greater functional connectivity between these regions evidenced less improvement from admission to discharge than patients with lesser connectivity between them. TDA identified a potential biomarker of an attenuated treatment response among inpatients with SMI. Insofar …

A Rare Case Of Erythema Elevatum Diutinum Presenting As Diffuse Neuropathy, G H. Nguyen, E L. Guo, D Norris

Faculty, Staff and Students Publications

No abstract provided.

Influence Of Maternal Breast Milk Ingestion On Acquisition Of The Intestinal Microbiome In Preterm Infants, Katherine E Gregory, Buck S Samuel, Pearl Houghteling, Guru Shan, Frederick M Ausubel, Ruslan I Sadreyev, W Allan Walker

Faculty, Staff and Students Publications

BACKGROUND: The initial acquisition and early development of the intestinal microbiome during infancy are important to human health across the lifespan. Mode of birth, antibiotic administration, environment of care, and nutrition have all been shown to play a role in the assembly of the intestinal microbiome during early life. For preterm infants, who are disproportionately at risk of inflammatory intestinal disease (i.e., necrotizing enterocolitis), a unique set of clinical factors influence the establishment of the microbiome. The purpose of this study was to establish the influence of nutritional exposures on the intestinal microbiome in a cohort of preterm infants early …

Ms 014 Guide To William Fields, Md Papers (1930-1987), William Fields (1913-2004)

Manuscript Finding Aids

The William Fields, MD papers contain scientific meeting booklets, academic books, binders containing case histories, research, symposium notes, and correspondence relating to the publication of his research of materials related to his career in Neurology. The collection consists of five boxes and equals 2.5 cubic feet. See more at MS 014.

Sel: Third Ward Intervention, Mike Malkemes, Joan Waters

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

A review of the effects of generational poverty on the development of children and the well-being of their families is compared with nine years of experience by Generation One, a non-profit organization that operates a school and a revitalization program in the Third Ward of Houston, Texas. Analysis of student behavior and the level and quality of parent involvement points to the children’s lack of self-control (tantrums, disruptions, etc.) and their parents’ limited engagement in school or the community as the key barriers to their learning. In the research of brain/cognitive, language/literacy, personal-social, emotional, and physical development, as well as …

Circumstantial Disconnection: Homelessness And Parental Relationships With Children, Jonathan Holland, David Branham Sr.

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

This article looks at homeless individuals to see how they think their residential situation affects their relationship with their non-homeless children. Using a survey of 75 homeless parents in Houston, Texas this analysis finds that homeless parents of non-homeless children believe that their living situation has a detrimental impact on their relationship with their children. While many respondents felt that they had a good relationship with their children the chances of maintaining a good relationship were less for respondents with adult children than minor children. While a majority of respondents with children felt that finding housing stability would help their …

The Role Of Two Homologous E3 Ligases In Muscle Physiology, Gabrielle F. Gloston

Dissertations and Theses (Open Access)

Ubiquitin-mediated proteasomal degradation is an essential cellular function that is coordinated by three key components: E1 ubiquitin activating enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligases. There are an estimated 600 E3 ligases, some of which share high sequence homology; however, the functional significance often remains unknown. FBXL3 and FBXL21 are two homologous E3 ligases that have previously been reported to dictate circadian periodicity, with FBXL3 being the dominant E3 ligase and FBXL21 playing a regulatory role. A recent Yeast Two-Hybrid screen revealed a new shared target of FBXL3 and FBXL21: Telethonin (also known as TCAP). TCAP is a …

Using Mouse Models To Define How The P53 R72p Polymorphism Impacts The Adverse Effects Of Doxorubicin And Ionizing Radiation, Emily Dominguez

Dissertations and Theses (Open Access)

The single nucleotide polymorphism (SNP) at codon 72 of the tumor suppressor gene p53 codes for either an arginine (R) or proline (P) (p53 R72P). This SNP may impact how cells respond to genotoxic insult. Studies in cell culture and in tissues from mouse models of the SNP indicate that, in response to gentoxic treatment, the two variants may differentially induce apoptosis and expression of p53 target genes. In epidemiological studies, the P variant is associated with decreased cancer survival and increased risk of side-effects from genotoxic cancer treatment. Genotoxic therapy is still the mainstay of cancer treatment, and doxorubicin …

The Role Of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development, Jennifer L. Herold

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of …

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder

Dissertations and Theses (Open Access)

Over the last decade, a paradigm-shift in lung cancer therapy has evolved into targeted-driven medicinal approaches. However, patients frequently relapse and develop resistance to available therapies. Herein, we utilized genomic mutation data from advanced chemorefractory non-small cell lung cancer (NSCLC) patients enrolled in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) clinical trial to characterize novel actionable genomic alterations potentially of clinical relevance. We identified RICTOR alterations (mutations, amplifications) in 17% of lung adenocarcinomas and found RICTOR expression correlates to worse overall survival. There was enrichment of MAPK pathway genetic aberrations in key oncogenes (e.g. KRAS, BRAF, …

Maguk Scaffolds Organize A Key Synaptic Complex In Horizontal Cell Processes Contacting Photoreceptors, Alejandro Vila, Ph.D.

Dissertations and Theses (Open Access)

Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in …

The Role Of Phosphorylation In Pam2 Motif-Containing Proteins Mediated Messenger Rna Deadenylation, Kai-Lieh Huang

Dissertations and Theses (Open Access)

Phosphorylation regulates many cellular processes. However, its role in mRNA deadenylation, a process to remove poly adenosines from the mature mRNA 3’ end tail, is unclear. The length of poly(A) tail determines mRNA stability and translation efficiency. Poly(A)-binding protein (PABP), which binds to newly synthesized poly(A) tails homogeneously and is known as a scaffold protein for PAM2 motif-containing proteins, plays a pivotal role in the shortening of poly (A) tails. This study is to examine the role of phosphorylation of PAM2 motif–containing proteins in regulating their interactions with PABP and mRNA deadenylation function.

The PAM2 motif, a region required for …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations and Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …