Digital Commons Network^™

A Non-Antibiotic-Disrupted Gut Microbiome Is Associated With Clinical Responses To Cd19-Car-T Cell Cancer Immunotherapy, Christoph K Stein-Thoeringer, Neeraj Y Saini, Eli Zamir, Viktoria Blumenberg, Maria-Luisa Schubert, Uria Mor, Matthias A Fante, Sabine Schmidt, Eiko Hayase, Tomo Hayase, Roman Rohrbach, Chia-Chi Chang, Lauren Mcdaniel, Ivonne Flores, Rogier Gaiser, Matthias Edinger, Daniel Wolff, Martin Heidenreich, Paolo Strati, Ranjit Nair, Dai Chihara, Luis E Fayad, Sairah Ahmed, Swaminathan P Iyer, Raphael E Steiner, Preetesh Jain, Loretta J Nastoupil, Jason Westin, Reetakshi Arora, Michael L Wang, Joel Turner, Meghan Menges, Melanie Hidalgo-Vargas, Kayla Reid, Peter Dreger, Anita Schmitt, Carsten Müller-Tidow, Frederick L Locke, Marco L Davila, Richard E Champlin, Christopher R Flowers, Elizabeth J Shpall, Hendrik Poeck, Sattva S Neelapu, Michael Schmitt, Marion Subklewe, Michael D Jain, Robert R Jenq, Eran Elinav

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals …

Clinical Outcomes Of Immune Checkpoint Inhibitor Diabetes Mellitus At A Comprehensive Cancer Center, Rebecca Jeun, Priyanka C Iyer, Conor Best, Victor Lavis, Jeena M Varghese, Sireesha Yedururi, Veronica Brady, Isabella C Glitza Oliva, Ramona Dadu, Denai R Milton, Kristy Brock, Sonali Thosani

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a rare adverse event. In this study, we characterize clinical outcomes of patients with ICI-DM and evaluate survival impact of this complication on melanoma patients.

Research design & methods: We conducted a retrospective review of 76 patients diagnosed with ICI-DM from April 2014 to December 2020.

Results: 68% of patients presented in diabetic ketoacidosis, 16% had readmissions for hyperglycemia, and hypoglycemia occurred in 70% of patients after diagnosis. Development of ICI-DM did not impact overall survival or progression-free survival in melanoma patients.

Conclusion: Development of ICI-DM is associated with long-term insulin dependence …

Cell-Typing And Interaction Analysis Of The Immune Compartment Of The Tumor Microenvironment Using High-Resolution Omics Modalities, Courtney Taylor Schiebout

Dartmouth College Ph.D Dissertations

Single-cell RNA-sequencing (scRNA-seq) has provided a new frontier for the investigation of complex tissues. One ideal candidate for the utilization of this method is the tumor microenvironment (TME). The TME is often host to a complex set of cell populations and behaviors that can be highly influential for cancer inhibition or progression. This is especially true of the immune compartment of the TME: the presence of certain types of immune cells in the TME and their expression profiles can significantly affect cancer prognosis in some cases. By providing individual cell-level gene expression data, scRNA-seq can be highly informative for characterizing …

Intergenerational Change In Hiv/Aids-Related Stigma In Cato Manor, Mijin Cho

Independent Study Project (ISP) Collection

In South Africa, the world’s epicenter of the HIV/AIDS pandemic, HIV-related stigma and stigma-enforcing stereotypes continue to serve as major health barriers to receiving adequate HIV prevention and treatment. While there continues to be a rise in research and advocacy, there is a need to study HIV stigma through a multigenerational lens that addresses the changing HIV/AIDS stigma in the post-apartheid era. Using qualitative methodology, this study aims to explore the generational differences in perceived HIV stigma between females in their 20s and above 50 years of age (as denoted by “50s+”) living in Cato Manor, South Africa. The study …

Up-03 Identifying The Determinants Of Pediatric Vaccine Uptake During The Covid-19 Pandemic, Colleen Phan, Brandon Mercardo, Justin Travis Ph.D., Ginny Webb Ph.D.

SC Upstate Research Symposium

COVID-19 has caused over a million deaths in the United States. Preventative measures such as masks, social distancing, and vaccination have been implemented to fight against the disease. Unfortunately, a large subset of Americans opposed these efforts.

SC DHEC reports that as of January 2023, only 53.9 % of eligible South Carolinians have been fully vaccinated against COVID-19. Previous studies have shown vaccine hesitancy is influenced largely by personal concerns about vaccine development, peer vaccination status, and general skepticism of immunization.

Hesitancy towards pediatric vaccination is particularly concerning because unvaccinated children can act as vessels to exponentially accelerate COVID-19 transmission. …

Small Molecule Compounds, Active Ingredients Of Tcm, As Novel Therapeutics For Eosinophilic Esophagitis, Anish Maskey

NYMC Student Theses and Dissertations

Eosinophilic Esophagitis (EoE), a chronic inflammatory condition of the esophagus, characterized by esophageal dysfunction and eosinophilic inflammation. Current treatments for EoE include dietary elimination and swallowed steroids. Recently, Dupixent was approved for the treatment of EoE, but it has side effects such as eye inflammation and eczema. Traditional Chinese Medicine (TCM) practice has been used to improve GI symptoms in EoE patients. Two key active ingredients of a TCM formula, 7,4’-Dihydroxyflavone (DHF) and Berberine (BBR), have shown remarkable results in treating EoE.

To understand the role of two active ingredients in EoE, different experimental models were used. First, a computational …

Time And Temperature Stability Of Tritrichomonas Foetus In Phosphate-Buffered Saline As Evaluated By A Reverse Transcription Real-Time Pcr Assay And Field Analysis, Duan S. Loy, Renata Spuri Gomes, Enakshy Dutta, Bruce W. Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Tritrichomonas foetus (TF) is a significant reproductive pathogen of cattle, and sample collection, handling, transport, and testing are significant hurdles to surveillance programs. Recent methods have been developed that allow for the direct detection of TF using a reverse transcription real-time PCR (direct RT-qPCR) approach. To evaluate these methods, a comparative analysis was conducted to assess the technical performance of this assay with a commercially available real- time PCR (qPCR) assay. In addition, the evaluation of two types of collection media (PBS and TF transport tube) was conducted that evaluated sample stability from 0 to 3 days when stored at …

Partial Characterization Of Plasmodium Falciparum Genes Implicated In Altered Artemisinin Stress Response, Caroline F. Simmons

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic illness caused by the Plasmodium spp., with an estimated 247 million malaria cases reported in 2021 across 84 endemic countries. Treatment of the deadliest malaria parasite, P. falciparum, relies on artemisinin combination therapies (ACTs). However, while ACTs have greatly decreased malaria mortality, this progress is threatened due to artemisinin (ART) partial resistance and ACT failure in Southeast Asia and Sub-Saharan Africa. SNPs to the Kelch13 (K13) gene are a well-characterized marker for ART resistance. However, increasing evidence that resistance to ART mediated by genes not related to K13 SNPs prompts the need to characterize other novel …

Role Of Nod2 Receptor In Immune Response To Staphylococcus Aureus, Precious Mckenzie, Aparna Palakodeti Ph.D

Research Days

Staphylococcus aureus, a gram-positive, commensal bacterium, causes several opportunistic diseases and infections in humans. Furthermore, some strains of S.aureus have developed resistance to antibiotics such as methicillin and pose a health risk. Pattern Recognition Receptors (PRRs) on host immune cells recognize specific components of S.aureus cell wall and mount an immune response against the bacteria. One such PRR is the Nuclear Oligomerization Domain 2 (NOD2) receptor which is present in the cytosol of host immune cells. NOD2 recognizes Muramyl-Dipeptide (MDP), a component of the peptidoglycan cell wall of several bacteria including S. aureus. The binding of MDP to NOD2 allows …

Impact Of Testosterone Use On The Vaginal Microbiota Of Transgender Men, Including Susceptibility To Bacterial Vaginosis: Study Protocol For A Prospective, Observational Study, Christina A. Muzny, Olivia T. Van Gerwen, Julia A. Schroeder, Emma Sophia Kay-Duncan, Krishmita Siwakoti, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Jacob H. Elnaggar, Ashutosh Tamhane, Dustin Long, Nicholas Van Wagoner, Evelyn Toh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will …

Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters

USF Tampa Graduate Theses and Dissertations

This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …

Rna Virus-Mediated Changes In Organismal Oxygen Consumption Rate In Young And Old Drosophila Melanogaster Males, Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel Smith Jr, Stephanie Dickinson, Andrew Brown, Maria De Luca, Ashley Turner, Stanislava Chtarbanova

Research, Publications & Creative Work

Aging is accompanied by increased susceptibility to infections including with viral pathogens resulting in higher morbidity and mortality among the elderly. Significant changes in host metabolism can take place following virus infection. Efficient immune responses are energetically costly, and viruses divert host molecular resources to promote their own replication. Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood. RNA virus infection of Drosophila melanogaster with Flock House virus (FHV) is an effective model to study antiviral responses with age, where older flies die faster than younger flies due …

Atlas Of Ticks (Acari: Argasidae, Ixodidae) In Germany: 1st Data Update, Franz Rubel, Stefan Zaenker, Alexander Weigand, Dieter Weber, Lidia Chitimia-Dobler, Olaf Kahl

Harold W. Manter Laboratory of Parasitology: Library Materials

The first data update of the atlas of ticks in Germany published in 2021 is presented here. This atlas provides maps based on georeferenced tick locations of 21 species endemic in Germany as well as three tick species that are regularly imported to Germany. The data update includes the following numbers of newly georeferenced tick locations: 17 Argas reflexus, 79 Carios vespertilionis, 2 Dermacentor marginatus, 43 Dermacentor reticulatus, 4 Haemaphysalis concinna, 3 Haemaphysalis punctata, 3 Hyalomma rufipes, 3 Ixodes apronophorus, 9 Ixodes arboricola, 1 Ixodes ariadnae, 30 Ixodes canisuga, …

Relationship Between Treatment Comorbidities And Hiv Viral Suppression Among People Who Live With Aids In Johannesburg., Nwogo Immaculata Ekeji, Tolulope A. Osoba, Hebatullah Tawfik, Mehdi Agha

Journal of Social, Behavioral, and Health Sciences

HIV has globally infected over 37.9 million people, of which 28.2 million (73%) are on antiretroviral treatment, and 66% of those on treatment are virally suppressed. In South Africa, however, low rate of viral suppression (47%) among people living with HIV is a major health problem that has continued to fuel HIV prevalence. A cross-sectional quantitative research design was used to investigate the relationship between treatment comorbidities and viral suppression among HIV-infected adults aged 18–49 who were diabetic, had cancer, or tuberculosis in Johannesburg. HIV Care Continuum formed the theoretical framework for this research. An existing HIV-infected patient de-identifiable dataset …

Syndemics And Social Factors: Infectious Disease Patterns Within The Population Of People Experiencing Homelessness In The United States, Kathleen Berzonsky

Honors Program: Senior Projects (Public)

Individuals experiencing homelessness are at increased risk of suffering from infectious diseases. This is due to a number of social factors and healthcare disparities, as well as the idea of syndemics, by which diseases cluster together to worsen disease burden. Current intervention strategies approach treatment from a post-infection perspective, but reducing transmission rates of infectious diseases within the population of people experiencing homelessness will require a shift in the healthcare framework. The issue of people experiencing homelessness must be viewed through a biosocial lens, focusing on preventative care and treatment. I provide an overview of the social factors governing infectious …

Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability, Jennifer N Pearson-Smith, Ruth Fulton, Christopher Q Huynh, Anna G Figueroa, Gia B Huynh, Li-Ping Liang, Lindsey B Gano, Cole R Michel, Nichole Reisdorph, Richard Reisdorph, Kristofer S Fritz, Eric Verdin, Manisha Patel

Faculty, Staff and Students Publications

Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons …

Characterization Of Tick And Host-Associated Factors Linked To Induction Of Alpha-Gal Syndrome., Surendra Raj Sharma, Surendra Raj Sharma

Dissertations

Alpha-Gal Syndrome (AGS) is a delayed allergic reaction caused by specific IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-gal) present in red meat. AGS is a growing concern globally, with over 34,000 confirmed cases in the United States alone. Studies have linked AGS to tick bites, which sensitizes hosts against α-gal antigens and elevates α-gal specific IgE. This dissertation investigates the role of tick and host-associated factors in AGS development. Microbiome analysis of Am. americanum ticks revealed a comprehensive core microbiome profile and showed that new Fransiella-like endosymbionts dominate and outcompete conventional tick Coxiella endosymbionts. Ticks subjected to tetracycline treatment showed …

In Silico Binding Of 2-Aminocyclobutanones To Sars-Cov-2 Nsp13 Helicase And Demonstration Of Antiviral Activity, Thahani S. Habeeb Mohammad, Yash Gupta, Cory T. Reidl, Vlad Nicolaescu, Haley Gula, Ravi Durvasula, Prakasha Kempaiah, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

The landscape of viral strains and lineages of SARS-CoV-2 keeps changing and is currently dominated by Delta and Omicron variants. Members of the latest Omicron variants, including BA.1, are showing a high level of immune evasion, and Omicron has become a prominent variant circulating globally. In our search for versatile medicinal chemistry scaffolds, we prepared a library of substituted α-aminocyclobutanones from an α-aminocyclobutanone synthon (11). We performed an in silico screen of this actual chemical library as well as other virtual 2-aminocyclobutanone analogs against seven SARS-CoV-2 nonstructural proteins to identify potential drug leads against SARS-CoV-2, and more broadly against coronavirus …

Behavioural Defences Against Parasites Across Host Social Structures, Sebastian Stockmeier, Yuko Ulrich, Gregory F. Albery, Sylvia Cremer, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

1. Animals exhibit a variety of behavioural defences against socially transmitted parasites. These defences evolved to increase host fitness by avoiding, resisting or tolerating infection.
2. Because they can occur in both infected individuals and their uninfected social partners, these defences often have important consequences for the social group.
3. Here, we discuss the evolution and ecology of anti-parasite behavioural defences across a taxonomically wide social spectrum, considering colonial groups, stable groups, transitional groups and solitary animals.
4. We discuss avoidance, resistance and tolerance behaviours across these social group structures, identifying how social complexity, group composition and interdependent social relationships may contribute to the …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

A Draft Of The Genome Of The Gulf Coast Tick, Amblyomma Maculatum, Jose M.C. Ribeiro, Natalia J. Bayona-Vásquez, Khemraj Budachetri, Deepak Kumar, Julia Catherine Frederick, Faizan Tahir, Brant C. Faircloth, Travis C. Glenn, Shahid Karim

Faculty Publications

The Gulf Coast tick, Amblyomma maculatum, inhabits the Southeastern states of the USA bordering the Gulf of Mexico, Mexico, and other Central and South American countries. More recently, its U.S. range has extended West to Arizona and Northeast to New York state and Connecticut. It is a vector of Rickettsia parkeri and Hepatozoon americanum. This tick species has become a model to study tick/Rickettsia interactions. To increase our knowledge of the basic biology of A. maculatum we report here a draft genome of this tick and an extensive functional classification of its proteome. The DNA from a single …

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Eczema Monkeypoxicum In A Female Patient With Atopic Dermatitis, Emma Napoli, Madeline Frizzell, Clark Gravell, Sergio Vallejo, Shasta Theodore, Karen Chen, Huma Siddiqui, Justin Dunn, Dora Marrufo, Jose Cadena, Patrick J Danaher

Faculty, Staff and Student Publications

A female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat.

Urinary Cd163 Is A Marker Of Active Kidney Disease In Childhood-Onset Lupus Nephritis, Haleigh Inthavong, Kamala Vanarsa, Jessica Castillo, M John Hicks, Chandra Mohan, Scott E Wenderfer

Faculty, Staff and Students Publications

OBJECTIVE: The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients.

METHODS: Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K.

RESULTS: Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated …

Fine Needle Aspiration Of Pancreatic Lesions Focusing On Secondary Tumors With Emphasis Of Metastatic Breast Cancer: A Clinicopathological Study With Follow-Up, Maria Yanqing Chen, Neda Zarrin-Khameh, Ya Xu

Faculty, Staff and Students Publications

BACKGROUND: The data on metastatic tumors to the pancreas diagnosed by fine needle aspiration (FNA) biopsy is limited. We report our experience of FNA of primary and secondary pancreatic tumors emphasizing metastatic breast cancer in the pancreas.

METHOD: Total 274 cases of pancreatic FNA in 10 years were retrospectively reviewed. Literature review of metastatic breast cancers to the pancreas was performed.

RESULTS: Out of the 274 cases, 7 (7/274, 2.6%) cases were non-diagnostic, 46 (46/274, 16.8%) cases were negative for malignancy, and 40 (40/274, 14.6%) cases were under the category of atypical cells. There were 133 (133/274, 48.5%) cases diagnosed …

Corrigendum To 'The Hemophilia Joint Health Score Version 21 Validation In Adult Patients Study: A Multicenter International Study' [Research And Practice In Thrombosis And Haemostasis, 6/2, (2022) E12690], Adrian Minford, Leonardo R Brand Ao, Maha Othman, Christoph Male, Rezan Abdul-Kadir, Paul Monagle, Andrew D Mumford, Dorothy Adcock, Björn Dahlbäck, Predrag Miljic, Maria T Desancho, Jun Teruya

Faculty, Staff and Students Publications

This corrects the article "The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study" in volume 6, e12690.

Association Of IsvSa3 With Multidrug Resistance In Salmonella Enterica Isolates From Cattle (Bos Taurus), Gentry L. Lewis, Robert J. Fenton, Etsuko Moriyama, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Salmonella enterica is, globally, an important cause of human illness with beef being a significant attributable source. In the human patient, systemic Salmonella infection requires antibiotic therapy, and when strains are multidrug resistant (MDR), no effective treatment may be available. MDR in bacteria is often associated with the presence of mobile genetic elements (MGE) that mediate horizontal spread of antimicrobial resistance (AMR) genes. In this study, we sought to determine the potential relationship of MDR in bovine Salmonella isolates with MGE. The present study involved 111 bovine Salmonella isolates obtained collectively from specimens derived from healthy cattle or their environments …

Analysis Of Acquired Resistance Mechanisms To Osimertinib In Patients With Egfr-Mutated Advanced Non-Small Cell Lung Cancer From The Aura3 Trial, Juliann Chmielecki, Tony Mok, Yi-Long Wu, Ji-Youn Han, Myung-Ju Ahn, Suresh S Ramalingam, Thomas John, Isamu Okamoto, James Chih-Hsin Yang, Frances A Shepherd, Krishna C Bulusu, Gianluca Laus, Barbara Collins, J Carl Barrett, Ryan J Hartmaier, Vassiliki Papadimitrakopoulou

Faculty, Staff and Student Publications

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation …

Alternative Splicing Mediates The Compensatory Upregulation Of Mbnl2 Upon Mbnl1 Loss-Of-Function, Larissa Nitschke, Rong-Chi Hu, Andrew N Miller, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

Loss of gene function can be compensated by paralogs with redundant functions. An example of such compensation are the paralogs of the Muscleblind-Like (MBNL) family of RNA-binding proteins that are sequestered and lose their function in Myotonic Dystrophy Type 1 (DM1). Loss of MBNL1 increases the levels of its paralog MBNL2 in tissues where Mbnl2 expression is low, allowing MBNL2 to functionally compensate for MBNL1 loss. Here, we show that loss of MBNL1 increases the inclusion of Mbnl2 exon 6 and exon 9. We find that inclusion of Mbnl2 exon 6 increases the translocation of MBNL2 to the nucleus, while …

The Immunomodulating Effects Of Delta-9 Tetrahydrocannabinol (Thc) And Cannabidiol (Cbd) In The Context Of Infection, Rose D. Goodman, Kate Rouse, Victor Jimenez

Annual Research Symposium

No abstract provided.