Life Sciences Commons^™

Assessment Of Anti-Hiv-1 Guide Rna Efficacy In Cells Containing The Viral Target Sequence, Corresponding Grna, And Crispr/Cas9., Alexander G Allen, Cheng-Han Chung, Stephen D. Worrell, Glad Nwaozo, Rebekah Madrid, Anthony R. Mele, Will Dampier, Michael R. Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing system has been shown to be effective at inhibiting human immunodeficiency virus type 1 (HIV-1). Studies have not consistently used a trackable dual reporter system to determine what cells received the Cas9/gRNA to determine the overall knockdown of HIV. Some studies have used stably transduced cells under drug selection to accomplish this goal. Here a two-color system was used that allows tracking of viral protein expression and which cells received the CRISPR/Cas9 system. These experiments ensured that each gRNA used was a perfect match to the intended target to remove …

Inhibiting Effects Of Methyllycaconitine (Mla) On Pnu-282987 Induced Neurogenesis In Blast-Exposed Mouse Retinas, Nastia Zhiyew Chan

Honors Theses

Irreversible vision loss can be caused by retinal damage, disease, or aging. In recent years, the prevalence of ocular damage due to blast trauma has been increasing due to the modernization of warfare. Adult mammalian retinal neurons were previously thought to lack the capacity for regeneration to reverse vision loss, which deemed the effects of many ocular damages permanent. However, recent studies from this lab have shown that PNU-282987, an agonist to the alpha 7 subtype of neural nicotinic acetylcholine receptors, will result in neural regeneration in adult mammalian cells. For this research project, I will be using Methyllycaconitine (MLA), …

The Effect Of Callery Pear (Pyrus Calleryana) On Soil Macrofauna (Diplopoda And Oligochaeta), Joseph M. Mcgee

Biology Theses

Callery pear (Pyrus calleryana) is a relatively recent invader of North America. Its ecological effects are still being explored, including those affecting soil macrofauna such as millipedes (Diplopoda) and earthworms (Clitellata: Oligochaeta). These animals play important roles in many soil processes so understanding how they respond to invasive species is vital to soil health. A previous study exploring potential herbicide control was completed in 2019, however as of 2022 there are still treatment zones with little to no Callery pear alongside fully invaded plots, providing an optimal habitat mosaic for comparison. This allowed us to pursue two research …

Precision Medicine, Ancestry, Genetics And Race, Lucio Miele

School of Medicine Faculty Publications

DiscoverBMB, March 25 - 28, 2023, Seattle, WA

Pancreatic Cancer: Advances And Challenges, Christopher J Halbrook, Costas A Lyssiotis, Marina Pasca Di Magliano, Anirban Maitra

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant efforts have largely defined major genetic factors driving PDAC pathogenesis and progression. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this review, we highlight the foundational studies that have driven our understanding of these processes. We further discuss the recent technological advances that continue to expand our understanding of PDAC complexity. We posit that the clinical translation of these research endeavors will enhance the currently dismal survival rate of this recalcitrant …

Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A …

A Reduced Pancreatic Polypeptide Response Is Associated With New-Onset Pancreatogenic Diabetes Versus Type 2 Diabetes, Phil A Hart, Yogish C Kudva, Dhiraj Yadav, Dana K Andersen, Yisheng Li, Frederico G S Toledo, Fuchenchu Wang, Melena D Bellin, David Bradley, Randall E Brand, Kenneth Cusi, William Fisher, Kieren Mather, Walter G Park, Zeb Saeed, Robert V Considine, Sarah C Graham, Jo Ann Rinaudo, Jose Serrano, Mark O Goodarzi

Faculty, Staff and Student Publications

PURPOSE: Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM).

METHODS: Subjects with new-onset DM (<3 >years' duration) in the setting of PDAC (PDAC-DM, n = 28), CP (CP-DM, n = 38), or T2DM (n = 99) completed a standardized mixed meal tolerance test, then serum PP concentrations were subsequently measured at a central laboratory. Two-way comparisons of …

Targeting Mirnas And Other Non-Coding Rnas As A Therapeutic Approach: An Update, Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Faculty, Staff and Student Publications

Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such …

The Role Of Extracellular Vesicles In Cancer, Raghu Kalluri, Kathleen M Mcandrews

Faculty, Staff and Student Publications

Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via packaging and transfer of bioactive constituents to impact the biology and function of cancer cells and cells of the tumor microenvironment. Here, we review recent advances in understanding the functional contribution of EVs to cancer progression and metastasis, as cancer biomarkers, and the development of cancer therapeutics.

New Perspectives On Foot Segment Forces And Joint Kinetics - Integrating Plantar Shear Stresses And Pressures With Multi-Segment Foot Modeling, Dustin A. Bruening, Spencer R. Petersen, Sarah T. Ridge

Faculty Publications

The role of the foot in gait is not well understood, in part due to challenges in capturing and utilizing segmental ground reaction forces. The purposes of this study were to 1) develop methodology to integrate plantar pressure/shear stresses with a multi-segment foot model, and 2) generate and display key normative data from this combined system. Twenty-six young healthy adults walked barefoot (1.3 m/s) across a pressure/shear sensor with markers matching a published 4-segment kinetic foot model. A novel anatomical/geometric masking method was developed that successfully separated regions aligned with model segmentation. This template-based method can be automated and customized …

Mechanisms Of Response And Resistance To Combined Decitabine And Ipilimumab For Advanced Myeloid Disease, Livius Penter, Yang Liu, Jacquelyn O Wolff, Lin Yang, Len Taing, Aashna Jhaveri, Jackson Southard, Manishkumar Patel, Nicole M Cullen, Kathleen L Pfaff, Nicoletta Cieri, Giacomo Oliveira, Seunghee Kim-Schulze, Srinika Ranasinghe, Rebecca Leonard, Taylor Robertson, Elizabeth A Morgan, Helen X Chen, Minkyung H Song, Magdalena Thurin, Shuqiang Li, Scott J Rodig, Carrie Cibulskis, Stacey Gabriel, Pavan Bachireddy, Jerome Ritz, Howard Streicher, Donna S Neuberg, F Stephen Hodi, Matthew S Davids, Sacha Gnjatic, Kenneth J Livak, Jennifer Altreuter, Franziska Michor, Robert J Soiffer, Jacqueline S Garcia, Catherine J Wu

Faculty, Staff and Student Publications

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were …

Immune Checkpoint Therapy-Current Perspectives And Future Directions, Padmanee Sharma, Sangeeta Goswami, Deblina Raychaudhuri, Bilal A Siddiqui, Pratishtha Singh, Ashwat Nagarajan, Jielin Liu, Sumit K Subudhi, Candice Poon, Kristal L Gant, Shelley M Herbrich, Swetha Anandhan, Shajedul Islam, Moran Amit, Gayathri Anandappa, James P Allison

Faculty, Staff and Student Publications

Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.

Energy Availability In Female Collegiate Beach Volleyball Athletes, Meghan Thomas

Undergraduate Research Competition

BACKGROUND: Energy availability (EA) is the amount of energy available for normal physiological processes and is defined as energy intake (kcals) minus exercise energy expenditure (kcals) relative to fat free mass (FFM). Low-energy availability (LEA; i.e., energy intake < 30 kcal/kg FFM/d) causes Relative Energy Deficiency in Sport, which results in various negative health and performance outcomes. A recent study reported 81% of the female collegiate athletes examined exhibited LEA. Of the 18-collegiate beach volleyball (BVB) athletes studied, average EA across 7 days was determined to be 12.44 kcal/kg FFM/d. Notably, this is a 7-day snapshot that may not reflect chronic dietary or training patterns. To our knowledge, no study has examined EA across the 10-week competitive season in this population. Therefore, the purpose of this cross-sectional study is to establish the risk of LEA in female collegiate BVB athletes across the competitive season. METHODS: We plan to recruit 18 female collegiate BVB athletes. Each subject will complete an initial visit where anthropometrics, resting metabolic rate (RMR), nutrition knowledge, psychological skills and maximal aerobic capacity will be tested. During weeks 1, 5, and 9 of the competitive season, in addition to initial testing, energy intake (ASA 24) and energy expenditure (GT9X-Link) will be assessed to calculate EA. Countermovement vertical jump height, velocity, and power (GymAware) will be used to assess performance. Results will be analyzed using repeated measures ANOVA and Pearson Correlations. EXPECTED RESULTS: It is hypothesized that LEA will be present and EA will decline as the season progresses.

A Fisher Indole Synthesis Approach To Phidianidine Analogues, Anna Tingler, Trinity Ghering, Samuel Ross

Undergraduate Research Competition

Naturally occurring products are molecules that are found in the natural world without the aid of humans. Aspirin and opium are famous examples of this classification of molecule. Another example of natural products that are less known are the phidianidines. Phidianidines A & B were isolated from a shell-less mollusk, Phidiana militaris. These molecules are comprised of a 1,2,4-oxadiazole ring, an indole and an aminoalkylguanadio group. These compounds have exhibited striking pharmacological behavior such as that of neutralizing reactive oxygen species and acting as an agonist for the μ-opioid receptor. In recent years, the synthesis of phidianidine analogues has replaced …

The Importance Of Processing And Understanding Bacteriophages, Alexandra Greco, Emily Bishop, Emma Hofseth, Kelsi Phelps

Undergraduate Research Competition

There are many bacteria that are increasingly becoming antibiotic resistant resulting in a new prevalent medical issue. Bacteriophages are evolutionary virus weapons that infect and fight against these infectious bacteria that give rise to Bacteriophages the most abundant biological entity found in nature, outnumbering all life combined, with a total estimated population of 1031. As part of BIOL 302L - Phage Discovery, we focused on identifying phages from individually collected soil samples found regionally in South Carolina. Through a series of experiments, we were able to identify and amplify two newly discovered phages that infect Mycobacterium Smegmatis following the protocols …

Utilizing 3d Printing As A Method Of Engaging Students And Assisting In The Learning Of Spatially Challenging Concepts, Gregory Thompson

Undergraduate Research Competition

Molecular structures, spatial arrangements, bond angles and stereochemistry are examples of topics that chemistry students struggle to grasp because it can be difficult to visualize how they work. 3D printing offers a way for instructors to provide students with molecular models to allow them to experience hands-on learning to better understand these concepts. The aim of this research is to design a method of remotely monitoring as well as controlling the 3D printer, and to explore what molecular editing programs could be useful in creating 3D models to print. To address the former, the software, Octoprint, will be used in …

Effect Of Lactate Dehydrogenase In Alzheimer's Disease Using Fruit Fly Model, Hannah Mccutcheon, Elizabeth Mccrea

Undergraduate Research Competition

The common fruit fly (Drosophila) was used as a model organism to investigate the function of lactate dehydrogenase gene (LDH) in Alzheimer’s disease. Human Alzheimer’s genes were implemented into fruit flies to examine the neurodegenerative properties of the disease since humans and fruit flies share a similar genetic makeup. When human Alzheimer’s gene is given to the fruit flies, they exhibit similar intellectual and physical defects as seen in humans. In previous experiments, it was found that down regulating certain genes allowed the transgenic flies to live longer and reduced their locomotor deficiencies. Lactate dehydrogenase (LDH) is one of the …

Electromyographical Difference Between Tonal And Free Weight Exercises, Sophia Brettler

Undergraduate Research Competition

The purpose of this study is to compare muscle activation between Tonal and traditional free-weight exercises. The Tonal is a digital weight system that can add up to 200 pounds of resistance. The Tonal also features unique exercise modes such as Smart Flex. Smart Flex utilizes Tonal's digital weights system to intelligently match the resistance to the exerciser by continuously adding or subtracting weight depending on when their muscles are at their strongest and weakest during an exercise. For this study, participants will complete 3 separate visits, visit one will include one repetition maximum testing and familiarization and visits 2-3 …

Genome Annotation Of Phages Phayeta And Greco Etereo, Warren Earley, Nestor Llanot Arocho, Brittaney Mazen

Undergraduate Research Competition

Phages are viruses that infect specific bacterial cells in order to reproduce. Many of these phages can infect and kill medically relevant bacterial species. As part of SEA-PHAGES, Coastal students have discovered two phages, Phayeta and Greco Etereo, that infect Mycobacterium smegmatis, which is closely related to the causative agent of tuberculosis. For our purposes we are annotating the phages Phayeta and Greco Etereo and comparing them to other previously annotated phages to help determine the function of the genes they contain. By doing this comparative analysis, we are increasing the understanding of phage biology and the roles of individual …

A New Approach To The Core Of Flinderole C, Ana Pettijohn, Claire Romain

Undergraduate Research Competition

The flinderoles A-C are a class of anti-malaria bisindole alkaloids from plants of the Flindersia genus. Flinderole C was specifically from the Papua New Guinean plant called F. amboinensis and is the most potent antimalarial of the group. Malaria is a parasitic infectious disease usually found in the hot, tropic regions of the world, such as parts of Africa. It is estimated that nearly half the world's population lives in an area where it is endemic. Furthermore, malaria was estimated to have caused over 600,000 deaths in 2020. While measures to limit the spread of the disease lessen its impact, …

Discovery And Characterization Of A Prophage Encoded Anti-Crispr Against The Type Iv-A Crispr System, Andrew Williams

Student Research Symposium

CRISPR Systems are adaptive immune systems in bacteria used to defend against mobile genetic elements such as bacteriophages, or bacterial viruses, and plasmids. They use a protein complexed with a guide RNA to target the protein to a foreign invader and neutralize it by cleaving its genetic information. In order to survive and keep infecting bacteria, bacteriophages likewise have developed machinery used to inhibit CRISPR immunity in the form of anti-CRISPR (Acr) proteins. The type IV-A system is a recently discovered and characterized system by the Jackson lab. It has been shown to defend against plasmids, but further data on …

Native Plant Bacteria Significantly Enhance Plants’ Growth, Ty Wilson, Katie Hewitt

Student Research Symposium

Microbes are among the planet's most diverse organisms and influence plant growth and development. Plant-microbe interactions enable plants to survive in many different environments, particularly in harsh climates where climate factors and nutrient availability stress plants. Microbes help plants acquire nutrients, assist in pathogenic repulsion, and increase drought tolerance. Plants native to the Intermountain West region are drought-resilient and are acclimatized to dry and arid climates. We are isolating plant growth-promoting bacteria (PGPB) from various native plants of the IW region. Ceanothus velutinus is one such plant. We isolated several PGPBs from this plant and tested 18 bacteria for plant …

Selecting Salt Tolerant Penstemon Plants For Landscape Use, Ziuri Wang

Student Research Symposium

The Intermountain West is currently experiencing extreme drought, which escalates in severity due to warmer temperatures resulting from climate change, less predictable precipitation patterns, and rapid population growth. Additionally, landscape irrigation consumes a significant portion of portable water, for example, in Utah, landscape irrigation accounts for 50-65% of urban water demand. For water conservation, local green industries found a great alternative water for landscape irrigation, which is reclaimed water. However, the reclaimed water usually has high salt levels, which negatively impacts plants growth and survival. Penstemon is a native plant to North America, it has long-lasting bloom, colorful flowers, and …

Overcoming Seed Dormancy: A Critical Challenge For Rangeland Species, Fnu Surbhi

Student Research Symposium

The mechanisms of seed dormancy serve the purpose of delaying germination until conditions become conducive for the survival of seedlings (Fenner et al., 1985). This study aimed to determine the effect of temperature treatments on the dormancy release of five wildland forbs and legumes, 3 species (Utah sweetvetch, Lewis flax and Showy goldeneye) showed faster germination at room temperature and 2 were found highly dormant and germinated only at chilling temperature. Understanding how seeds from various species responds to different temperature can help us identify and eliminate the associated dormancy barriers.

The Effectiveness Of Housing First In Improving Mental Health Outcomes Among Homeless Individuals: A Rapid Review, Nya Harper

Student Research Symposium

Objective: The purpose of this study was to review primary research regarding the efficacy of a Housing First (HF) intervention compared to existing treatments for improving mental health outcomes in homeless adults with mental illness.

Methods: A rapid review was conducted from the PubMed database using a predetermined search protocol and inclusion criteria to identify eligible articles.

Results: HF was significantly more effective at helping homeless adults with mental illness become stably housed. HF groups’ subjective measures of mental health were not consistently higher than usual treatment groups.

Conclusion: Evidence supports the efficacy of HF over existing treatments in a …

Study On In Vitro Seed Germination And Seedling Development Of New Phalaenopsis Hybrid, Prakriti Nepal

Student Research Symposium

Phalaenopsis sp., commonly known as moth orchids, is one of the most popular orchids sold as cut flowers or potted plants because of their high ornamental value. Cross pollination of seed parent (Phalaenopsis mannii x Phalaenopsis ‘Yaphong Javaking’) and pollen parent (Phalaenopsis schilleriana) was conducted to obtain hybrids which presumably possess the combined traits and characteristics from the parent plants. Seeds were collected 112 days after hand pollination and sown in five germination media: half-strength Murashige and Skoog Medium (⅟2 MS), Vacin and Went Medium (VW), Orchid Seed Sowing Medium (OSSM), BM-1 Terrestrial Orchid Medium (BM-1), and Knudson C Orchid …

Mapping Of Corticotropin-Releasing Factor (Crf) Receptors In The Coyote Brain, Rachel Tong

Student Research Symposium

Forming strong social bonds is essential to our everyday life and is part of what makes us human. The loss of a loved one often results in grief, stress, and loneliness, and the stress response system of the body has been implicated in the physiological symptoms associated with grieving. The hormone that initiates the stress response in the body is called corticotropin releasing factor (CRF), which acts via binding to CRF receptors (CRFR). Coyotes are an appropriate animal model to study social bonds and social loss because they display monogamy and pair bonding, which is a trait seen in human …

The Water To Land Transition: Changes In Frog Skin Across Development, Kayla Hancey

Student Research Symposium

Amphibians are vulnerable to changes in the environment due to their permeable skin. As the climate changes, the resilience of different species can be illuminated by traits that vary across clades. Skin changes during metamorphosis provide details that may help us anticipate desiccation risk. It is useful to understand histological details in a relatively successful species, such as the American green tree frog (Hyla cinerea) when determining species survivorship. Documentation of skin changes including gland development in H. cinerea has never been done.

Does Fiber Reduce Weight Gain And Improve Metabolism?, Sky Jones

Student Research Symposium

Dietary fiber has a large impact on the microbiota composition and metabolic activity via the provision of fermentable substrates, yet, to date, there has been very little attention paid to modeling the fiber composition of rodent diets to that of humans. We propose to use nutrient density, a form of allometric scaling, to formulate metabolically stressful diets with fiber intake levels at the US average (50% AI), the IOM recommended level (100% AI), and a higher level (150% AI). The primary endpoint we focus on in this study is oral glucose tolerance, as high-fiber diets have been shown to prevent …

Evaluating Two Penstemon Species For Salinity Tolerance, Asmita Paudel

Student Research Symposium

Penstemons are among the most attractive native flowers of North America with high aesthetic importance in urban landscape. Limited studies have been conducted previously to determine their salt tolerance. In this study, we examined how salinities ranging from the electrical conductivity (EC) of 1.0 to 10.0 dS·m-1 affected the growth and physiology of two penstemons [Penstemon barbatus ‘Blue’ (rock candy series beardtongue) and Penstemon strictus ‘Rocky Mountain’ (Rocky Mountain beardtongue)]. Salinity stress reduced the growth rate and biomass production of penstemon species. Penstemon barbatus had slight foliar salt damage with an averaged visual score of 3.2 (0 = dead, 5 …