Life Sciences Commons^™

Embracing Ai/Ml In Genetic Counseling: A Nationwide Survey On Program Leaderships’ Perspectives And Curriculum Integration, Kyla Holmes

KGI Theses and Dissertations

This study aimed to examine the attitudes and preparedness of genetic counseling program directors and faculty leadership in incorporating artificial intelligence and machine learning (AI/ML) into their curricula and its effect on core competency proficiency. AI/ML has been instrumental in creating and maintaining vital analytical tools and models employed by genetic counselors (GCs). However, research on the attitudes of faculty leadership in charge of training future GCs is limited. A nationwide survey conducted between November 2022 and February 2023 gathered 15 respondents holding diverse academic positions in genetic counseling program curriculum development. The majority of respondents had encountered AI/ML in …

The Development Of A Primer Payload With Microparticles For Uti Pathogen Identification Using Polythymidine- Modified Lamp Primers In Droplet Lamp, Jonas Otoo

KGI Theses and Dissertations

Nucleic acid amplification tests (NAATs) are among the diagnostic tests with the highest sensitivity and specificity. However, they are more complex to develop than other diagnostic tests such as biochemical tests and lateral flow immunoassay tests. Polymerase chain reaction (PCR) is the gold standard for NAATs. PCR requires thermal cycling to achieve clonal amplification of the target pathogen DNA for diagnosis. Thermal cycling poses a challenge in the development of PCR diagnostics for point-of-care (POC) settings. Loop-mediated isothermal amplification (LAMP) offers an isothermal method for NAATs diagnostics. The advancement of the microfluidics field significantly enhances the development of LAMP diagnostics …

Using Computational Fluid Dynamics And Optical Sensor Technology To Scale Cell Culture Platforms, Mandar Makwana

KGI Theses and Dissertations

Different cell culture vessels ranging from micro scale to laboratory scale to commercial scale play critical role in upstream process development for biologics manufacturing. Based on the mode of operation, cell culture vessels have different hydrodynamic environments, making it challenging to scale. Integrated approaches using computational tools supported by experimental studies can overcome these challenges. Computational Fluid Dynamics (CFD) is one such tool that can simulate hydrodynamics within the cell culture vessels and can provide insights at macro and micro-scale. Accuracy of a CFD model significantly depends on the fluid model and assumptions. Traditionally, simple two-equation fluid models were developed …

Intrinsically Disordered Protein Regions In Human Evolution And As Therapeutic Targets, Karen Paco Mendivil

KGI Theses and Dissertations

Intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) fail to form stable structures but have important biological functions via interacting with various molecular partners (proteins, DNA, RNA, glycosaminoglycans). We hypothesized that IDPRs are potential targets for therapeutics development because they are reservoirs of evolutionary innovation, and they play crucial roles in adaptation to pathogens.

We first studied the evolution of IDPRs in the human proteome and compared it with the proteome of non-human primates. We have found that evolutionary young protein-coding genes have included low conserved regions in the N-terminal part of proteins, and such regions are linked to high …

Point Of Care Infectious Disease Diagnosis Via Isothermal Nucleic Acid Amplification Integrated Into A Sample To Answer Device, Abrar Al Maghribi

KGI Theses and Dissertations

Sexually transmitted infections caused by Chlamydia trachomatous (CT) and Neisseria gonorrhea (NG) are often under-diagnosed, miss-diagnosed, and not properly treated, leading to long term complications such as ectopic pregnancy and infertility, and to emergence of drug resistance. Dengue virus (DENV) infections can cause dengue fever (DF), which if not properly managed can lead to Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), causing significant morbidity and mortality. In both cases, early and accurate detection at the point of care is critical to facilitate proper patient care and disease management. Nucleic acid amplification tests (NAATs) provide suitable sensitivity and specificity, …

Primer Payload System For Higher-Order Multiplex Lamp: Design And Development Of Unit Processes, Tochukwu Dubem Anyaduba

KGI Theses and Dissertations

Design and Development of Platforms for the Application of Loop-mediated Isothermal Nucleic Acid Amplification, LAMP, in the Diagnosis of Polymicrobial Diseases

Tochukwu Dubem Anyaduba, Travis Schlappi (PI)

For the past two decades, several isothermal nucleic acid amplification technologies have emerged. These are mostly in response to the need for robust molecular diagnostic tools amenable to point-of-care and limited-resource settings. Of these, loop-mediated isothermal amplification, LAMP, stands out as a highly specific and rapid alternative to the polymerase chain reaction, PCR. One of LAMP's significant characteristics involves using four essential and two loop (rate increasing) primers to recognize six to eight …

Modeling Residence Time Distribution Of Chromatographic Perfusion Resin For Large Biopharmaceutical Molecules: A Computational Fluid Dynamic Study, Kevin Vehar

KGI Theses and Dissertations

The need for production processes of large biotherapeutic particles, such as virus-based particles and extracellular vesicles, has risen due to increased demand in the development of vaccinations, gene therapies, and cancer treatments. Liquid chromatography plays a significant role in the purification process and is routinely used with therapeutic protein production. However, performance with larger macromolecules is often inconsistent, and parameter estimation for process development can be extremely time- and resource-intensive. This thesis aimed to utilize advances in computational fluid dynamic (CFD) modeling to generate a first-principle model of the chromatographic process while minimizing model parameter estimation's physical resource demand. Specifically, …

The Shape Of Metabolism: Mitochondrial Dynamics, Remodeling, And Bioenergetic Reprogramming In Disease, Carl Decker

KGI Theses and Dissertations

Mitochondria are dynamic, double-membrane bound hubs of bioenergetics, cell signaling, and redox balance that exist as an oscillating network of fused superstructures and smaller, single organelles. Importantly, their position at the junction of catabolic and anabolic metabolism connects these morphological fluctuations to larger cellular metabolic programs, which in turn have implicated mitochondrial dynamics in a number of disease states and a varied set of cell phenomena. For example, differentiation of memory t-cells is dependent on mitochondrial network morphology, and in particular on remodeling dynamics that yield fused mitochondrial assemblies favoring oxidative phosphorylation-driven metabolism. In contrast, many cancers have been shown …

Which "Me" Am I Going To Be Today? Exploring Genetic Counselors' Attitudes On Expressing Their "Authentic Self" In The Workplace, Brynna Nguyenton

KGI Theses and Dissertations

While professional organizations expect their employees to adhere to a cohesive image based on the social contract of professionalism, the modern workplace is growing increasingly diverse and freedom of self-expression is challenged by these traditionally defined norms. This study seeks to define these societal expectations and their implications in the context of a rapidly changing professional landscape. Individuals portray their true identities, or “authentic selves,” through their internal beliefs and external appearance, so naturally, these expressions may contradict the expectations for their professional appearance. Previous research has investigated professionalism, authentic selfhood, and the genetic counseling profession on separate levels, but …

The Psychosocial Effects Of Unexpected Findings On Direct To Consumer Genetic Testing, Emily Wiseman

KGI Theses and Dissertations

Direct to Consumer (DTC) genetic testing has grown in popularity since its inception in 2010. Consumers can now order DTC tests giving them more information on their ancestry, health and ethnicity than ever before. With more information and more consumers taking the tests, this has allowed for the opportunity of unexpected findings to be generated from the tests. Previous studies have shown that consumers can learn about a health risk they were previously unaware of, and this can impact the health management and surveillance practices of consumers receiving them. Additionally, studies have shown that ethnicity results can impact consumers’ previously …

Risk Reducing Mastectomies Among Women With Mutations In Moderate Penetrance Breast Cancer Susceptibility Genes, Jacob Comeaux

KGI Theses and Dissertations

Women who harbor mutations in breast cancer susceptibility genes are at an increased lifetime risk of developing breast cancer and are faced with decisions about managing their risks, including the decision of whether to undergo a risk reducing mastectomy (RRM). While decision making for risk management has been studied extensively for BRCA1 and BRCA2 carriers, there is much less information surrounding risk management for women with mutations in moderate penetrance genes. This is a retrospective study of 280 women undergoing genetic counseling at a Los Angeles-based academic hospital between 2009 and 2019. The study used medical records to examine rates …

Cancer Genetic Counselors’ Perceptions Of Nutritional Recommendations, Breann Reinsch

KGI Theses and Dissertations

Objective: The purpose of this research study is to understand the perspectives of genetic counselors who work with patients in the cancer setting and explore if nutrition is a consideration when counseling patients.

Background: Evidence on the influence of nutrition on cancer risk is increasing with retrospective cohort studies. The American Cancer Society states that smoking, body mass index (BMI), poor nutrition, and excess alcohol consumption are directly linked to cancer occurrences, therefore some cancers may be preventable through lifestyle changes (American Cancer Society, 2016). In cancer genetic counseling sessions, patients are often inquiring about nutritional recommendations. A majority of …

Identifying The Gap: Cancer Genetic Counseling And Testing For Underinsured Patients, Bailey Sanderson

KGI Theses and Dissertations

Background: Health care costs have increased faster than Consumer Price Index leading to patients weighing their options of medical treatment and services. One such service, genetic counseling, has grown 20% annually, in part due to the increased demand of genetic testing. Oncology care is one need for testing because 5-15% of all cancer diagnoses in the United States are inherited. Due to the fact that the Affordable Care Act does not cover all genetic counseling testing needs, and ethnic minorities are less likely to seek testing due to insurance coverage and costs, an increased effort is needed to reach …

Development Of Novel Zika And Anthrax Viral Nanoparticle Vaccines, Elizabeth Henderson

KGI Theses and Dissertations

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of …

Microrna Profiling And Engineering Of Cho Cell Lines Stably Expressing Difficult-To-Express Lysosomal Protein, Ifeanyi Amadi

KGI Theses and Dissertations

Difficult-to-express (DTE) recombinant proteins like multi-specific proteins, DTE monoclonal antibodies and lysosomal enzymes, have seen difficulties in manufacturability using Chinese hamster ovary (CHO) cells and other mammalian cells as production platforms. CHO cells are preferably used for protein production because of their innate ability to secrete human-like recombinant proteins with post-translational modification, resistance to viral infection and familiarity with drug regulators. However, despite huge progress made in engineering CHO cells for high volumetric productivity, expression of DTE proteins like recombinant lysosomal sulfatase represent one of the poorly understood proteins. Furthermore, there are growing interest in the use of microRNAs (miRNAs) …

Targeted Genome-Scale Gene Activation And Gene Editing In Human Cells To Understand Disease Models, Michael De La Cruz

KGI Theses and Dissertations

Since the discovery of sequence directed DNA editing reagents such as CRISPR-Cas9 RNA-guided and TALEN DNA endonucleases, there has been a snowball of advances in the life sciences due to the ability to efficiently edit and control genomes within living cells. CRISPR-Cas9 based genomic tools, which facilitate the high-throughput precise manipulation of genes, allow for unbiased functional genomic screens. We used a human CRISPR-Cas9 Synergistic Activation Mediator pooled library which utilizes an engineered protein complex for transcriptional activation of 23,430 endogenous genes to investigate the development of novel resistance mechanisms to lung cancer targeted therapy, Erlotinib. We set out to …

Novel Low Shear 3d Bioreactor For The Scaled Production Of High Purity Human Mesenchymal Stem Cells, Andrew Burns

KGI Theses and Dissertations

Human mesenchymal stem cells are an ideal candidate for stem cell therapies. They have been researched since the 1960’s and can differentiate into many desired functional cell types without undergoing teratogenesis. However, higher yields are needed for a marketable, successful stem cell therapy. To accomplish this, cells will have to be cultured to expand them to therapeutically relevant dosages for multiple patients. Bioreactor production is an ideal method to solve this problem.

The aim of this thesis is to test and validate a novel bioreactor for the cultivation of human mesenchymal stem cells. In this work, we investigate a novel …

Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez

KGI Theses and Dissertations

Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in …

Optimization Of Recombinant Adeno-Associated Virus (Aav) Vector Production In Saccharomyces Cerevisiae, Juan Aponte

KGI Theses and Dissertations

Recombinant adeno-associated viral vectors (rAAV) are emerging drugs for gene therapy applications. Their non-pathogenic status, low inflammatory potential, availability of viral serotypes with different tissue tropisms, and prospective long-lasting gene expression are important attributes that make rAAVs safe and efficient therapeutic options. One of the main limitations for bringing rAAV gene therapy to the market is the difficulty in supplying enough rAAV vector product. The high vector doses suggested by early clinical data infer the need to scale up production at high volumes in order to satisfy patient demand. Current production platforms such as HEK293 or Sf9 cells are very …

Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande

KGI Theses and Dissertations

Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …

Design And Testing Of Novel Anthrax Vaccines Utilizing A Tobacco Mosaic Virus Expression System, Ryan C. Mccomb

KGI Theses and Dissertations

Anthrax is a potentially fatal disease caused by the bacteria Bacillus anthracis. Infection and disease occur after spores gain entry into the body, germinate into vegetative bacteria, and produce toxin. Bacillus anthracis spores have been engineered as bioweapons and have been used repeatedly in warfare and terrorism to inflict casualties in military and civilian populations. Currently, only one vaccine has been approved for prevention of anthrax in the United States. This vaccine is an undefined product that is difficult to produce, requires a long vaccination schedule, and is reactogenic. Efforts to make an improved anthrax vaccine are being pursued. …