Pathology Commons^™

Myo5b And The Polygenic Landscape Of Very Early-Onset Inflammatory Bowel Disease In An Ethnically Diverse Population, Ashleigh Watson, R Alan Harris, Amy C Engevik, Numan Oezguen, Maribeth R Nicholson, Sarah Dooley, Rachel Stubler, Lisa Forbes Satter, Lina B Karam, Richard Kellermayer

Faculty, Staff and Students Publications

Background: Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients.

Methods: Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored …

Elucidating The Impact Of Ribosome Biogenesis On Breast Cancer, Amr Rafat Elhamamsy

All ETDs from UAB

Ribosome biogenesis, a complex and multi-step process that occurs predominantly in the nucleolus, plays a critical role in cellular function by mediating protein synthesis through the assembly of ribosomal RNAs (rRNAs) and ribosomal proteins into functional ribosomes. In cancer, dysregulation of this process is linked to the development of specialized ribosomes (onco-ribosomes) that support oncogenic translation programs, enhancing tumor progression and therapeutic resistance. This dissertation explores the interplay between ribosome biogenesis and cancer, focusing particularly on the role of RNA Polymerase I (RNA Pol I) activity under hypoxic conditions and rRNA modifications in breast cancer. My first study elucidates the …

A Thermodynamic Bottleneck In The Tca Cycle Contributes To Acetate Overflow In Staphylococcus Aureus, Nabia Shahreen, Jong-Sam Ahn, Adil Alsiyabi, Niaz Bahar Chowdhury, Dhananjay Shinde, Sujata S. Chaudhari, Kenneth W. Bayles, Vinai Chittezham Thomas, Rajib Saha

Journal Articles: Pathology and Microbiology

During aerobic growth, S. aureus relies on acetate overflow metabolism, a process where glucose is incompletely oxidized to acetate, for its bioenergetic needs. Acetate is not immediately captured as a carbon source and is excreted as waste by cells. The underlying factors governing acetate overflow in S. aureus have not been identified. Here, we show that acetate overflow is favored due to a thermodynamic bottleneck in the TCA cycle specifically involving the oxidation of succinate to fumarate by succinate dehydrogenase. This bottleneck reduces flux through the TCA cycle, making it more efficient for S. aureus to generate ATP via acetate …

Quaternized Chitosan Derivatives Inhibit Growth And Affect Biofilm Formation Of Staphylococcus Aureus, Alex Miranda, Nichole D. Brandquist, Kristen Johnson, Elena Muldiiarova, Aleksandr Fadeev, Mahboubeh Ghanbari, Jennifer L. Endres, Kenneth W. Bayles, Jason N. Mactaggart, Denis Svechkarev, Marat Sadykov, Yury Salkovskiy

Journal Articles: Pathology and Microbiology

Antimicrobial resistance (AMR) poses a global health threat, severely impeding the effective treatment of bacterial infections and jeopardizing the safety of routine medical procedures. Methicillin-resistant Staphylococcus aureus (MRSA) is particularly problematic because of its resistance to beta-lactams and the ability to form resilient biofilms. Conventional antibiotics, including last-resort options, have serious side effects and may contribute to further resistance. Chitosan, a natural biopolymer, offers a promising alternative due to its biocompatibility and antimicrobial properties, though its effectiveness against biofilms is limited. Recent studies suggest that increasing the positive charge density and adding hydrophobic moieties to chitosan, can enhance its antimicrobial …

Interferon-Gamma Receptor Signaling Regulates Innate Immunity During Staphylococcus Aureus Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Rachel W. Fallet, Tammy Kielian

Journal Articles: Pathology and Microbiology

A craniotomy is a neurosurgical procedure performed to access the intracranial space. In 3-5% of cases, infections can develop, most caused by Staphylococcus aureus biofilm formation on the skull surface. Medical management of this infection is difficult, as biofilm properties confer immune and antimicrobial recalcitrance to the infection and necessitate additional surgical procedures. Furthermore, treatment failure rates can be appreciably high. These factors, compounded with rapidly expanding rates of antimicrobial resistance, highlight the need to develop alternative treatment strategies to target and reverse the immune dysfunction that occurs during biofilm infection. Our recent work has identified CD4+ Th1 and Th17 …

Cd4+ T Cell-Innate Immune Crosstalk Is Critical During Staphylococcus Aureus Craniotomy Infection, Gunjan Kak, Zachary A. Van Roy, Rachel W. Fallet, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed …

Pgc-1Α Activation To Enhance Macrophage Immune Function In Mycobacterial Infections, Joel R. Frandsen, Zhihong Yuan, Brahmchetna Bedi, Zohra Prasla, Seoung-Ryoung Choi, Prabagaran Narayanasamy, Ruxana Sadikot

Journal Articles: Pathology and Microbiology

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a …

Extracellular Adherence Proteins Reduce Matrix Porosity And Enhance Staphylococcus Aureus Biofilm Survival During Prosthetic Joint Infection, Mohini Bhattacharya, Tyler D. Scherr, Jessica Lister, Tammy Kielian, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

Biofilms are a cause of chronic, non-healing infections. Staphylococcus aureus is a proficient biofilm-forming pathogen commonly isolated from prosthetic joint infections that develop following primary arthroplasty. Extracellular adherence protein (Eap), previously characterized in planktonic or non-biofilm populations as being an adhesin and immune evasion factor, was recently identified in the exoproteome of S. aureus biofilms. This work demonstrates that Eap and its two functionally orphaned homologs EapH1 and EapH2 contribute to biofilm structure and prevent macrophage invasion and phagocytosis in these communities. Biofilms unable to express Eap proteins demonstrated increased porosity and reduced biomass. We describe the role of Eap …

Species-Specific Discrimination Of Bacterial Biofilms Using A Ratiometric Fluorescence Sensor Array And Machine Learning, Ritika Gupta, Aayushi Laliwala, Elena Muldiiarova, Kenneth W. Bayles, Denis Svechkarev, Marat Sadykov, Aaron M. Mohs

Journal Articles: Pathology and Microbiology

Biofilms are intricate bacterial communities encased in a self-produced extracellular matrix (ECM) of DNA, lipids, proteins, and polysaccharides. The diverse ECM composition across bacterial species significantly influences the progression of biofilm-associated infections, making precise identification crucial for effective treatment. Traditional methods such as biochemical assays, MALDI-TOF mass spectrometry, DNA sequencing and culturing provide valuable insights but have notable drawbacks, including time-consuming procedures, high costs, and the need for specialized equipment and trained personnel. These limitations hinder the rapid and widespread adoption of biofilm identification in clinical settings, underscoring the need for more streamlined, accurate, and accessible methods. In this study, …

Mcl Or Dlbcl - Make Right Choice!, Mohammed Shafeay, Mirza Baig, Astrid Sacasa, Ram Madasu, Delbert Benzenhafer, Alexey Glazyrin

East Florida Division GME Research Day 2025

No abstract provided.

Primary Cardiac Lymphoma: A Rare Diagnosis, Astrid Sacasa, Betty Kirimi, Mohtashim Naeem, Susana Ferra

East Florida Division GME Research Day 2025

No abstract provided.

Myxoid Variant: An Unusual Presentation Of Low-Grade Epithelioid Mesothelioma, Racquel Fournet, Robert Bender, Rohit Jaishankar, Alexey Glazyrin

East Florida Division GME Research Day 2025

No abstract provided.

Performance In Grading Of Well Differentiated Pancreatic Neuroendocrine Tumors (Wdpannet) Using The 2019 World Health Organization (Who) Classification Of Tumors Of The Digestive System. Experience Of A Community Teaching Hospital., Astrid Sacasa, Gul Emek Wymer, Susana Ferra

East Florida Division GME Research Day 2025

CONTEXT: The WHO Classification of Tumors of the Digestive System (2019) categorizes WDPanNETs as grade 1 (G1), grade 2 (G2) or grade 3 (G3) by mitotic count and proliferative index (KI67). We examined the performance of pathologists and pathology trainees in grading WDPanNET according to the 2019 WHO Classification.

DESIGN: One H&E and KI-67 slides of eleven WDPanNET cases from our 2023 archives (7 G1, 1 G2 and 3 G3) were blindly evaluated by 2 junior residents (PGY-1), 2 senior residents (PGY-3), 2 pathologists without formal gastrointestinal training (NOGIP) and 2 pathologists with formal gastrointestinal training (GIP), provided with the …

Staphylococcus Aureus Encodes Four Differentially Regulated Pyruvate Transporters, Jennifer L. Endres, Cleofes Sarmiento, William Xiao, Marat R. Sadykov, Kenneth W. Bayles, Mckenzie K. Lehman

Journal Articles: Pathology and Microbiology

The success of Staphylococcus aureus as a pathogen is attributable, in part, to its ability to exploit the diverse nutrient sources available during infection. Critical to this success are the pathways involving pyruvate that serve as a nexus for energy production, oxidative metabolism, and biosynthetic processes. When available, bacteria acquire pyruvate from the environment to fuel growth. Recently, LrgAB was identified as a pyruvate transporter under microaerobic conditions, leading us to speculate that S. aureus encodes other pyruvate transporters that are active during aerobic growth. In this study, we used the toxic pyruvate analog, 3-fluoropyruvic acid (3-FP), to isolate mutants …

Establishing A Variant Allele Frequency Cutoff For Manual Curation Of Medical Exome Sequencing Data, Kate Sears, Caylin Hickey, Ryan Vincent, Jennifer Stocks-Candelaria, Jason Tate, Cody Bumgardner, Shulin Zhang, Justin B. Miller

Pathology and Laboratory Medicine Faculty Publications

Medical exome sequencing pipelines consist of various preprocessing steps to prioritize credible causal variants before a pathologist or variant curation scientist manually interprets potential findings that are then reported to patients. The variant allele frequency (VAF), reported as the fraction of sequencing reads supporting a variant call, can be used to screen for technical artifacts, yet a specific filtering threshold has yet to be established. A total of 13,122 manually curated variants, sequenced from 289 patients using the Agilent SureSelect Focused Exome enrichment kit at the University of Kentucky Clinical Genomics laboratory from October 2019 to May 2023, were evaluated. …

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

Folliculin (Flcn) In Thyroid Tumors: Incidence, Significance, And Role As A Driver Gene And Secondary Alteration, Faisal Hassan, Camryn Slone, Robert J. Mcdonald, Julie C. Dueber, Adeel M. Ashraf, Melina Windon, Oliver J. Fackelmayer, Cortney Y. Lee, Therese J. Bocklage, Derek B. Allison

Pathology and Laboratory Medicine Faculty Publications

Thyroid carcinomas are driven by diverse molecular alterations, but the tumor suppressor gene folliculin (FLCN), best known for its role in Birt–Hogg–Dubé (BHD) syndrome, has received limited attention in thyroid tumors. Here, we describe two thyroid tumors with pathogenic FLCN alterations—one germline and one somatic—and analyze the broader prevalence and significance of FLCN in thyroid carcinomas using multiple large sequencing datasets, including ORIEN-AVATAR. Patient 1, with a germline FLCN mutation and a history of BHD syndrome, presented with a well-circumscribed oncocytic adenoma. Molecular testing confirmed biallelic FLCN inactivation, but no additional mutations or aggressive features were observed, and the patient …

Malignant Adenomyoepithelioma Of The Breast, Cole Daisley, Susana Ferra

East Florida Division GME Research Day 2025

No abstract provided.

Mesonephric-Like Carcinoma Of The Endometrium In A 73-Year-Old Female, Cameron Summers-Powell, Carina Ferraris, Zoyla Almeida, Susana Ferra, Mirza Baig

East Florida Division GME Research Day 2025

Introduction: Mesonephric-like carcinoma (MLC) is a newly described malignant tumor that represents 1% of endometrial cancers. The etiology of this disease is currently unknown but immunohistochemical expression with GATA-3, PAX-8 and TTF-1 and lack of ER/PR positivity can aid in correct diagnosis.

Case Summary: A 73-year-old female presented to the hospital with post-menopausal bleeding, an initial hysteroscopy identified a lesion suggestive of endometrial cancer. Ultimately, the patient underwent a hysterectomy and a bilateral salpingectomy/oophorectomy. Chemotherapy ensued due to metastatic disease. At 7 months post-op, the patient appeared to be doing well.

Results: Grossly, the lesion was 5.5 cm and appeared …

Carcinoma With Osteoclast-Like Giant Cells: A Rare Histologic Variant Of Breast Cancer, Robert Bender, Makenna Bowman, Matthew Lee, Susana Ferra

East Florida Division GME Research Day 2025

Introduction: Osteoclast like giant cells (OGCs) can be found in various tissues such as the gallbladder, liver, pancreas, and thyroid. In breast cancer, the presence of OGCs is a rare finding. Currently knowledge of such cases is limited, with approximately 200 reported cases of osteoclast like giant cells (OGCs) among all breast carcinomas. Among the breast cancers that are classified as rare, those with OGCs make up only 0.5-1.2% of cases.

Case Description: An 80+ year-old female presented with a palpable left breast lesion initially suspected by mammography as a benign lesion. She eventually underwent breast core biopsy revealing hormone …