Medical Molecular Biology Commons^™

Predictors Of Hiv Molecular Cluster Membership And Implications For Partner Services, Camden J Hallmark, Charles Luswata, Natascha Del Vecchio, Christina Hayford, Ricardo Mora, Michelle Carr, Marlene Mcneese, Nanette Benbow, John A Schneider, Joel O Wertheim, Kayo Fujimoto

Faculty, Staff and Student Publications

Public health surveillance data used in HIV molecular cluster analyses lack contextual information that is available from partner services (PS) data. Integrating these data sources in retrospective analyses can enrich understanding of the risk profile of people in clusters. In this study, HIV molecular clusters were identified and matched to information on partners and other information gleaned at the time of diagnosis, including coinfection with syphilis. We aimed to produce a more complete understanding of molecular cluster membership in Houston, Texas, a city ranking ninth nationally in rate of new HIV diagnoses that may benefit from retrospective matched analyses between …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Comparative Tumor Microenvironment Analysis Of Primary And Recurrent Ovarian Granulosa Cell Tumors, Eleonora Khlebus, Veena K Vuttaradhi, Thomas Welte, Namrata Khurana, Joseph Celestino, Hannah C Beird, Curtis Gumbs, Latasha Little, Alejandra Flores Legarreta, Bryan M Fellman, Tri Nguyen, Barrett Lawson, Sammy Ferri-Borgogno, Samuel C Mok, Russell R Broaddus, David M Gershenson, P Andrew Futreal, R Tyler Hillman

Faculty, Staff and Student Publications

Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary and recurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using “clusterProfiler” and “GSVA” R packages. TME …

Disclosing Quantitative Rt-Pcr Raw Data During Manuscript Submission: A Call For Action, Andreas Untergasser, Jan Hellemans, Michael W Pfaffl, Jan M Ruijter, Maurice J B Van Den Hoff, Mihnea P Dragomir, Douglas Adamoski, Sandra Martha Gomes Dias, Rui Manuel Reis, Manuela Ferracin, Emmanuel Dias-Neto, Ian Marsh, Mikael Kubista, Muller Fabbri, Ajay Goel, Ondřej Slabý, Erik Knutsen, Baoqing Chen, Massimo Negrini, Koshi Mimori, Martin Pichler, Maria Papatriantafyllou, Simone Anfossi, Thomas D Schmittgen, Jim Huggett, Stephen Bustin, Jo Vandesompele, George A Calin, Heroic (The Initiative Group On Qrt Disclosure) Consortium

Faculty, Staff and Student Publications

Accuracy and transparency of scientific data are becoming more and more relevant with the increasing concern regarding the evaluation of data reproducibility in many research areas. This concern is also true for quantifying coding and noncoding RNAs, with the remarkable increase in publications reporting RNA profiling and sequencing studies. To address the problem, we propose the following recommendations: (a) accurate documentation of experimental procedures in Materials and methods (and not only in the supplementary information, as many journals have a strict mandate for making Materials and methods as visible as possible in the main text); (b) submission of RT‐qPCR raw …

Cvam: Cna Profile Inference Of The Spatial Transcriptome Based On The Vgae And Hmm, Jian Ma, Jingjing Guo, Zhiwei Fan, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

Tumors are often polyclonal due to copy number alteration (CNA) events. Through the CNA profile, we can understand the tumor heterogeneity and consistency. CNA information is usually obtained through DNA sequencing. However, many existing studies have shown a positive correlation between the gene expression and gene copy number identified from DNA sequencing. With the development of spatial transcriptome technologies, it is urgent to develop new tools to identify genomic variation from the spatial transcriptome. Therefore, in this study, we developed CVAM, a tool to infer the CNA profile from spatial transcriptome data. Compared with existing tools, CVAM integrates the spatial …

Nothing About Us Without Us: The Roles Of Diverse Stakeholders In Scientific Publishing, Diana M Proctor

Faculty, Staff and Student Publications

No abstract provided.

Point-Of-Care Ultrasound In Airway Evaluation And Management: A Comprehensive Review, Judy Lin, Ryan Bellinger, Andrew Shedd, Jon Wolfshohl, Jennifer Walker, Jack Healy, Jimmy Taylor, Kevin Chao, Yi-Hsuan Yen, Ching-Fang Tiffany Tzeng, Eric H Chou

Faculty, Staff and Student Publications

Airway management is a common and critical procedure in acute settings, such as the Emergency Department (ED) or Intensive Care Unit (ICU) of hospitals. Many of the traditional physical examination methods have limitations in airway assessment. Point-of-care ultrasound (POCUS) has emerged as a promising tool for airway management due to its familiarity, accessibility, safety, and non-invasive nature. It can assist physicians in identifying relevant anatomy of the upper airway with objective measurements of airway parameters, and it can guide airway interventions with dynamic real-time images. To date, ultrasound has been considered highly accurate for assessment of the difficult airway, confirmation …

Candidate Variants In Dna Replication And Repair Genes In Early-Onset Renal Cell Carcinoma Patients Referred For Germline Testing, Elena V. Demidova, Ilya G. Serebriiskii, Ramilia Vlasenkova, Simon Kelow, Mark D. Andrake, Tiffiney R. Hartman, Tatiana Kent, James Virtucio, Gail L. Rosen, Richard T. Pomerantz, Roland L. Dunbrack, Erica A. Golemis, Michael J. Hall, David Y.T. Chen, Mary B. Daly, Sanjeevani Arora

Department of Biochemistry and Molecular Biology Faculty Papers

Background: Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined.

Methods: Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes.

Results: Analysis of whole-exome sequencing (WES) data found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of …

Consensus On The Ras Dimerization Hypothesis: Strong Evidence For Lipid-Mediated Clustering But Not For G-Domain-Mediated Interactions, Dhirendra K Simanshu, Mark R Philips, John F Hancock

Faculty, Staff and Student Publications

One of the open questions in RAS biology is the existence of RAS dimers and their role in RAF dimerization and activation. The idea of RAS dimers arose from the discovery that RAF kinases function as obligate dimers, which generated the hypothesis that RAF dimer formation might be nucleated by G-domain-mediated RAS dimerization. Here, we review the evidence for RAS dimerization and describe a recent discussion among RAS researchers that led to a consensus that the clustering of two or more RAS proteins is not due to the stable association of G-domains but, instead, is a consequence of RAS C-terminal …

Meta-Narrative Review Of Possible Impacts Of Genetic Screening On Treatment Of Breast Cancer, Toqa Al Alawi, Sheza Khan, Ivey Knebel, Steven Luong, Vilma Sanchez, Kamilah Walker-Charles

Research Methods Poster Session 2023

Objective: To examine the impacts of genetic screening on the treatment of breast cancer, in relation to differences, outcomes and decisions in treatment plans or surgery in patients that performed genetic screening versus those that did not.

Background: Genetic screening technology has become commercially available, yet standard preventative care for breast cancer has no genetic screening involved. Genetic screening in breast cancer treatment is performed, but its usage is not standardized.

Methods: Findings were synthesized using the meta-narrative review style to examine articles retrieved from searches of digital databases PubMed and the M.D. Anderson Scholarly Library.

Discussion: Articles were selected …

Serum Micrornas Associated With Concussion In Football Players, Dorota Wyczechowska, Paul Harch, Shelly Mullenix, Erin S. Fannin, Brenda B. Chiappinelli, Duane Jeansonne, Adam Lassak, Nicolas G. Bazan, Francesca Peruzzi

School of Medicine Faculty Publications

Mild Traumatic Brain Injury (mild TBI)/concussion is a common sports injury, especially common in football players. Repeated concussions are thought to lead to long-term brain damage including chronic traumatic encephalopathy (CTE). With the worldwide growing interest in studying sport-related concussion the search for biomarkers for early diagnosis and progression of neuronal injury has also became priority. MicroRNAs are short, non-coding RNAs that regulate gene expression post-transcriptionally. Due to their high stability in biological fluids, microRNAs can serve as biomarkers in a variety of diseases including pathologies of the nervous system. In this exploratory study, we have evaluated changes in the …

Mechanisms Of Chromosomal Instability (Cin) Tolerance In Aggressive Tumors: Surviving The Genomic Chaos, Brittiny Dhital, Veronica Rodriguez-Bravo

Student Papers, Posters & Projects

Chromosomal instability (CIN) is a pervasive feature of human cancers involved in tumor initiation and progression and which is found elevated in metastatic stages. CIN can provide survival and adaptation advantages to human cancers. However, too much of a good thing may come at a high cost for tumor cells as excessive degree of CIN-induced chromosomal aberrations can be detrimental for cancer cell survival and proliferation. Thus, aggressive tumors adapt to cope with ongoing CIN and most likely develop unique susceptibilities that can be their Achilles' heel. Determining the differences between the tumor-promoting and tumor-suppressing effects of CIN at the …

One Population, Multiple Lifestyles: Commensalism And Pathogenesis In The Human Mycobiome, Diana M Proctor, Rebecca A Drummond, Michail S Lionakis, Julia A Segre

Faculty, Staff and Student Publications

Candida auris and Candida albicans can result in invasive fungal diseases. And yet, these species can stably and asymptomatically colonize human skin and gastrointestinal tracts. To consider these disparate microbial lifestyles, we first review factors shown to influence the underlying microbiome. Structured by the damage response framework, we then consider the molecular mechanisms deployed by C. albicans to switch between commensal and pathogenic lifestyles. Next, we explore this framework with C. auris to highlight how host physiology, immunity, and/or antibiotic receipt are associated with progression from colonization to infection. While treatment with antibiotics increases the risk an individual will succumb …

Myod Functions As An Oncogene In Rhabdomyosarcoma By Promoting Survival Through Differentiation And Cyld, Alexander Oles

MUSC Theses and Dissertations

Rhabdomyosarcoma (RMS) is the most common soft tissue cancer among

children, characterized by a skeletal muscle lineage that is impaired from

undergoing terminal differentiation. NF-κB is constitutively active in cancer cells

and plays a critical role in cell survival. Although NF-κB is also activated in RMS,

surprisingly we find that these tumors are less dependent on NF-κB to overcome

stress-induced cell death. Instead, RMS cells survive by being partially

differentiated under the control of the myogenic transcription factor MyoD. Loss of

MyoD or cellular reprogramming dedifferentiates RMS tumor cells and promotes

cell death when exposed to stress. Further, use of …

Novel Mechanisms Of Systemic Sclerosis-Associated Lung Fibrosis, Joe E. Mouawad

MUSC Theses and Dissertations

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disorder that affects the connective tissues and has the highest mortality rate among the rheumatic diseases. One of the hallmarks of SSc is fibrosis, which may develop systemically, affecting the skin and virtually any visceral organ in the body. Fibrosis of the lungs leads to interstitial lung disease (ILD), which is currently the leading cause of death in SSc. The identification of effective treatments to stop or reverse lung fibrosis has been the main challenge in reducing SSc mortality and improving patient outcomes and quality of life. Currently, only two …

Integrated Analysis Of Racial Disparities In Genomic Architecture Identifies A Trans-Ancestry Prognostic Subtype In Bladder Cancer, Baifeng Zhang, Peilin Jia, Jiayin Wang, Guangsheng Pei, Changxi Wang, Shimei Pei, Xiangchun Li, Zhongming Zhao, Xin Yi, Xin-Yuan Guan, Yi Huang

Faculty, Staff and Student Publications

The incidence of bladder cancer and patient survival vary greatly among different populations, but the influence of the associated molecular features and evolutionary processes on its clinical treatment and prognostication remains unknown. Here, we analyze the genomic architectures of 505 bladder cancer patients from Asian/Black/White populations. We identify a previously unknown association between AHNAK mutations and activity of the APOBEC-a mutational signature, the activity of which varied substantially across populations. All significantly mutated genes but only half of arm-level somatic copy number alterations (SCNAs) are enriched with clonal events, indicating large-scale SCNAs as rich sources of bladder cancer clonal diversities. …

Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn

Biomedical Sciences Undergraduate Research

There is current research to suggest that endogenous neuronal regeneration, exogenous neuronal stem cell transplantation and glial cell reprogramming could be prospective therapeutic treatments for neurodegeneration and traumatic injury. With these conditions, there is significant brain atrophy, loss of neurons and loss of synaptic connections which can have devastating effects on executive functioning, cognition, learning and memory. This review will examine these modern approaches to adult neurogenesis, and assess the viable mechanisms and future outlook of these three therapies for neurological regenerative medicine.

The Revolutionary Genome Editor: Crispr-Cas9 Systems, Grace Spade

Senior Honors Theses

Genetic engineering is the modification of an organism's genetic material to alter its traits through adding, deleting, or changing specific genes. CRISPR-Cas9 systems are groundbreaking tools for genetic engineering, in short utilizing a molecule called RNA to guide a protein called Cas9 to a specific location in DNA to add, delete, or replace genes. The history of how the CRISPR-Cas9 systems came into existence, how it was adapted from a natural defense system in bacteria, and its mechanism of action in both are explained. Its applications, both present and future, competing genetic modifiers, advantages and disadvantages, and the ethical dilemmas …

In Vitro Gametogenesis: A Research Timeline And Implications For The Future Of Assisted Reproductive Technology, Nicole Buckley

Senior Honors Theses

The novel reproductive technology, In Vitro Gametogenesis (IVG), includes the process of obtaining mature viable germ cells from pluripotent stem cells. To do so, embryonic stem cells and induced pluripotent stem cells are specified to primordial germ cells and differentiated to form gametes that undergo further maturation, which subsequently may undergo in vitro fertilization to form an embryo. With this capability, IVG holds the power to provide a novel treatment option for human infertility. As of now, research has been conducted on mice successfully, and with limited success in humans. Future research will likely focus on discovering the species-specific differences …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …