Diseases Commons^™

Towards The Synthesis Of Dragonamide E And Analogs Thereof, Dante Glover

Chemistry Theses

Leishmaniasis is a disease caused by a parasite spread through the female sand fly. It is categorized as a Neglected Tropical Disease and can cause very severe symptoms, even death, if left untreated. Symptoms include skin lesions that can cause permanent scarring, and mucosal membrane infections that can cause facial deformities. More aggressive forms of leishmaniasis can lead to infections of internal organs like the liver and/or spleen and can lead to death. Drug resistance of these parasites has rendered treatment limited and the side effects of which can be harmful as well.

Scientists looking towards new treatments for tropical …

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …

Testing Elicitors Of Homologous Jadr2 Proteins To Regulate Natural Product Production, Carzon J. Williams, Emilee A. Patterson, Allison S. Walker

SPARK Symposium Presentations

The growing threat of antimicrobial resistance (AMR) has and will contribute to global economic and public health concerns in the foreseeable future leading into 2050. As mortality rates derived from AMR are projected to reach 10 million if no viable solution is found to combat it through hastened drug discovery. The use of natural products to mitigate AMRs effects is viable as more than 50% of FDA approved drugs are natural products. These natural products are synthesized by biosynthetic gene clusters (BGC), found in bacteria with a regulatory protein not allowing transcription until unbound . Current methods of eliciting the …

Evaluating The Market Withdrawal Of Andexanet Alfa, Jordyn Linfield, Addisyn Cooper, Alexander Defranco, Emma Gerding, Jessica Kelley, Tyler Henney, Connor Dains, Brenna Hissong, Brittany Bates

Pharmacy and Wellness Review

The coagulation cascade comprises intrinsic, extrinsic, and common pathways that converge when thrombin converts fibrinogen (factor I) into fibrin, leading to fibrin mesh formation, stabilization of the platelet plug, and ultimately thrombus formation. Inhibition of the coagulation cascade can be achieved with a variety of anticoagulant medications, including direct oral anticoagulants (DOACs). The mechanism of action of DOACs is to inhibit either factor Xa or thrombin. Reversal of anticoagulation remains an important clinical consideration when managing patients on DOACs who experience serious bleeding events. Andexanet alfa is a recombinant, modified human factor Xa protein previously indicated for patients receiving rivaroxaban …

Symmetrical Drug-Related Intertriginous And Flexural Exanthema Associated With Tirzepatide, William Goodman, Karan Pandher, Mahaa Ayub

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Developing Antibodies Against Galectin-3 And Galectin-9 To Target Endometriosis, Ashleigh Burger, Noah Farnsworth, Jared J. Reisnouer, Cheyenne Vue

2026 Symposium

Endometriosis is a disease characterized by pelvic pain and the formation of endometrial-like tissue on the outside of the uterine lining. This condition affects nearly 10% of women across the globe and confirming whether someone has endometriosis requires visualization in surgery. While the specific causes of this disease remain unclear, the over-expression of the Galectins 3 and 9 in ectopic endometrial tissues suggests a role in the development and maintenance of the condition. Monoclonal antibodies (mAbs) are highly specific proteins with potential as diagnostic or treatment tools. The goal of this study is to generate antibodies against Gal3 and Gal9. …

Quantifying Black Carbon Concentrations In Georgia And Analyzing Associated Public Health Risks, Khloe R. Osborne

Honors Theses

Quantifying Black Carbon Concentrations in Georgia and Analyzing Associated Public Health Risks

One of the most daunting challenges of the industrial world is air pollution. Within this broad spectrum, there is an inhalable particle group named PM2.5, which contains black carbon. Black carbon has evidence that supports the generation and worsening of adverse health impacts, which may include birth complications, cognitive deficits in children, pulmonary aggravation, asthma, cardiovascular issues, neurological degenerative patterns, and cancer risk. This is especially seen in vulnerable populations, like children, elderly, and those who already suffer from weakened health, many of which reside in the southern …

In Patients With Acne Vulgaris, How Do Standard Acne Treatments Combined With Adjunct Microbiome-Targeted Therapies Compare To Standard Acne Treatments Alone In Affecting Clinical Outcomes?, Sree Gowri Sudharshan

Rowan-Virtua Research Day

Background: Acne vulgaris is a very common chronic skin condition that occurs when hair follicles become clogged with oil, dead skin cells, and bacteria. Nearly 50 million Americans are affected annually, and it usually occurs around puberty. Due to rising antibiotic resistance and unwanted side effects to current mediations, emerging research on the role of skin and gut microbiome in acne development is of interest.

Hypothesis: Adjuvant microbiome-targeted therapies may offer better clinical outcomes than standard acne treatments alone.

Methods: Literature search performed in PubMed and Embase using keywords related to acne vulgaris, microbiome-targeted therapies, and targeted acne treatments. Of …

Resensitization Of Clinical Isolates Of Mdr-Acinetobacter Baumannii To Antibiotics Using Bacteriophage Therapy, Priyal Gajera, Valerie J. Carabetta

Rowan-Virtua Research Day

Introduction:

Antibiotic resistance poses a major global health threat, particularly with multidrug-resistant (MDR) pathogens such as Acinetobacter baumannii, which exhibits resistance to multiple antibiotic classes, including carbapenems.¹ As conventional treatments become less effective, alternative therapies such as bacteriophage therapy are gaining attention. Bacteriophages offer targeted antibacterial activity and may enhance antibiotic efficacy or resensitize resistant strains. This study investigates the synergistic effects of bacteriophage ΦCO03 combined with antibiotics against MDR A. baumannii.

Methods:

Clinical isolates (M20, M5) of A. baumannii were cultured in LB broth at 37°C. Bacteriophage ΦCO03 was isolated and purified using plaque assays. Synergy between phage …

Resensitization Of Clinical Isolates Of Mdr-Acinetobacter Baumannii To Antibiotics Using Bacteriophage Therapy, Zainab Mubasher, Valerie J. Carabetta

Rowan-Virtua Research Day

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen notorious for causing severe infections in immunocompromised patients, particularly those with prolonged hospitalizations or invasive procedures1. Originally susceptible to many antibiotics in the 1970s, this bacterium has since evolved extensive resistance, making it one of the most challenging members of the ESKAPE group of multidrug-resistant (MDR) pathogens2. Its ability to survive in harsh environments and acquire resistance determinants has led to its classification as a “red alert” pathogen by health authorities worldwide. The increasing prevalence of MDR A. baumannii infections in healthcare settings underscores an urgent need for alternative treatment strategies as conventional …

Sex Differences In Insulin Resistance And Triglyceride/Hdl-Cholesterol Ratio In Human Subjects, Jiyoon Jung, Lakshman Segar, Christine Whitehair, James Bailey, Ashley Coleman, George Scott

Rowan-Virtua Research Day

Background: Insulin resistance (IR) plays a major role in dyslipidemia and the associated cardiovascular disease risk. To date, it remains unclear as to how IR alters plasma lipid profile in males versus females. The present study is an initial step to determine sex-specific differences in IR and plasma lipid profile using 40 μL of capillary blood. Methods: 19 adults aged 30-64 were recruited from Rowan Medicine-Sewell clinics, with 13 participants (9 males, 4 females) consenting to the study. After collecting 40 μL of capillary blood via finger prick, the samples were analyzed for glucose, triglyceride (TG), and HDL-cholesterol (HDL-C) using …

Bacteriophage Therapy Vs. Standard Antibiotics: A Review Of Treatment Efficacy For Recurrent Pediatric S. Pyogenes (Gas) Infections, Kartik Kannan Oms-I, Karina Malhotra Oms-I, Gabrielle Coccio Oms-I, Janhavi Belwalkar Oms-I, Jason Rienzo Oms-I, Samay Shukla Oms-I, Valerie J. Carabetta Phd

Rowan-Virtua Research Day

Background: Antibiotic resistance poses a growing threat to pediatric infectious disease management, particularly in the treatment of Streptococcus pyogenes (GAS) infections.¹ While β-lactam antibiotics remain the first-line standard of care, their utility is limited by allergy prevalence and rising resistance among alternative antibiotic agents, such as macrolides, lincosamides, and tetracycline.^2,3 Given these trends, bacteriophage therapy has emerged as a promising adjunctive treatment modality, offering targeted bacterial lysis while sparing commensal microbiota.⁴

Methods: A systematic literature search was conducted across PubMed and Embase (2000–2025) using terms related to antibiotic resistance, Streptococcus pyogenes, bacteriophage therapy, and pediatric populations. …

Efficacy Of Omalizumab And Exposure Immunotherapy In Reducing Allergic Immunological Response, Joshua James Novello, Michelle Lau, Josephine L. Miner, Mudassir A. Rahmani, Kimran Sandhu, Taha Umar

Rowan-Virtua Research Day

Background: Food allergy negatively impacts numerous children in the United States. Oral immunotherapy (OIT) and biologic therapy (omalizumab) are emerging promising strategies for desensitization. This literature review aims to compare the effectiveness of omalizumab and oral immunotherapy in pediatric populations.

Hypothesis: If the use of omalizumab therapy is used to treat children with food allergies compared to OIT, then there would be higher desensitization, lower post-treatment IgE levels, higher IgG4 levels, and decreased chance of a positive skin prick test.

Methods: PubMed, Embase, and The Lancet databases were searched using PRISMA guidelines to locate peer-reviewed studies evaluating …

Understanding The Role Of Toxs As A Bile Sensing Component Of The Toxrs Virulence Regulatory System In Vibrio Spp., Minje Kim

Dartmouth College Ph.D Dissertations

Pathogenic Vibrio bacteria, such as V. cholerae and V. parahaemolyticus, colonize in the human small intestine to cause severe gastrointestinal disease. During the infection, these bacteria encounter bile salts, antimicrobial cholesterol metabolites secreted into the intestine. Pathogenic Vibrio species have evolved to utilize bile salts as signals to regulate virulence. The signaling depends in part on ToxRS, a conserved co-component transmembrane transcription regulator. ToxRS consists of the transcription factor ToxR and its membrane-tethered binding partner ToxS. ToxS is required for ToxR stability and full transcriptional activity. Although bile salts are known to influence ToxRS-dependent virulence gene expression, the molecular …

Investigating The Synthesis And Antibacterial Activity Of A Main-Chain Cationic Polymer, Emily Smith

Honors Theses

Antibiotic resistance is a growing threat to public health. Due to the overuse of antibiotics in agriculture, the overprescription of antibiotics, and the misuse of antibiotics by patients, antibiotic resistance is spreading at an alarming rate. As antibiotic resistance spreads, the antibiotics we depend on to treat common infections become ineffective. Therefore, it is imperative to develop novel treatments for infections that do not increase the prevalence of antibiotic resistance. One treatment being explored is the use of synthetic polymers with antibacterial properties. Synthetic polymers are advantageous because they can be synthesized from widely available precursors and their structure is …

Mechanisms Of Binding And Immune Escape Resistance For Broadly Neutralizing Antibodies Targeting Distinct Conserved Sars-Cov-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling And Energy Landscape Analysis, Mohammed Alshahrani, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The continued evolution of SARS-CoV-2 has enabled an escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes—SCORE-A, SCORE-B, and SCORE-C—retains remarkable activity against even the most recent JN.1-derived sublineages. Here, we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions …

Improving Glp-1 Ra Initiation In Primary Care Through A Paper-Based Clinical Decision Support Tool, Carissa R. Bowery, Karen Carver

Epsilon Sigma at-Large Research Conference

Title: Improving GLP-1 RA Initiation in Primary Care Through a Paper-Based Clinical Decision Support Tool

Authors: Carissa R. Bowery, MSN, FNP-C; East Tennessee State University College of Nursing. Karen M. Carver, PhD, APRN, FNP-C; East Tennessee State University College of Nursing

This quality improvement project focuses on improving evidence-based pharmacologic management of adults with type 2 diabetes mellitus (T2DM) and obesity through implementation of a paper-based clinical decision support (CDS) tool in primary care. The aim is to increase initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among eligible patients and improve provider adherence to current clinical guidelines.

Processes: This …

Albumin Use In Cardiopulmonary Bypass Pump Prime And Its Association With Postoperative Renal Function And Acute Kidney Injury: A Scoping Review, Hannah Talbot

Student Works

ABSTRACT

1.Structured summary:

Background: Cardiopulmonary bypass (CPB) is associated with significant hemodilution, inflammatory activation, and alterations in renal perfusion, all of which may contribute to postoperative acute kidney injury (AKI). Albumin is frequently used as a component of CPB pump prime due to its oncotic properties and potential to mitigate fluid shifts and support intravascular volume. However, the extent to which albumin-containing priming solutions influence postoperative renal outcomes remains unclear.

Objective: This scoping review aimed to map the available literature examining the use of albumin in CPB pump prime and its reported effects on renal function and the incidence …

Brain Delivery Of Antibody-Derived Biologicals For Alzheimer’S Disease: An Updated Narrative Review, Rachita K. Sumbria, Ruben J. Boado

Pharmacy Faculty Articles and Research

Antibodies directed against β-amyloid (Aβ) have been developed for the treatment of Alzheimer’s disease (AD). However, the in vivo central efficacy is reduced by the poor penetration of antibodies across the blood–brain barrier (BBB). In addition, these antibodies have been associated with adverse effects like amyloid-related imaging abnormalities. Thus, the development of new antibody-based therapies for AD with improved transport across the BBB may improve efficacy and reduce adverse effects. Antibodies targeting the BBB transferrin receptor (TfR) are able to cross the BBB through receptor-mediated transcytosis, producing a global distribution throughout the brain. Along the same line, bispecific antibodies directed …

Structural Transformation Of A Hydrogel-Forming Cell Division Protein Zapb Of Multidrug Resistant Klebsiella Pneumoniae With Small Molecules, Ayesha Khan, M. Iqbal Choudhary, Sumaira Javaid, Humaira Zafar, Innokentiy Maslennikov, Atia-Tul Wahab

Pharmacy Faculty Articles and Research

Septal ring assembly protein ZapB (EMR18431.1) is involved in Z-ring formation, and nucleoid segregation during the bacterial cell division . It promotes cell division in the initial stages of the cell cycle through direct interaction with FtsZ, thus stimulating Z-ring assembly. The ZapB inhibition can make bacterial cell susceptible to primary antibiotics, and therefore considered as an important approach for adjuvent therapy against MDR bacterial infections. Hence in the current study, ZapB protein of multidrug resistant Klebsiella pneumoniae was cloned, and expressed in E. coli system. To understand its role, and to assess the mechanism of ZapB activation, the characteristic …

The Effects Of Body Mass Index On Fertility And In Vitro Fertilization, Morgan R. Kidd

Honors College Theses

In-vitro fertilization (IVF) is the most widely used type of assisted reproductive technology for treating infertility arising from a number of conditions. As obesity rates continue to climb in the United States, infertility has been discovered to have a direct correlation. Individuals that fall below or above the healthy body mass index range are found to have disrupted regulation of the hypothalamic-pituitary-gonadal axis, resulting in diminished reproductive health. Those that are diagnosed as infertile due to conditions caused by the effects of low body mass index or high body mass index may seek assisted reproductive technologies to intervene in achieving …

Rapid Resolution Of Psoriatic Arthritis Symptoms Following Initiation Of A Glp-1 Receptor Agonist, Joseph E. Capito, Kate Gelman

Faculty & Staff Scholarship

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used for the management of type 2 diabetes mellitus (T2DM) and obesity, with growing evidence of their anti-inflammatory effects. We report the case of a 54-year-old woman with obesity, T2DM, and biopsy-confirmed plaque psoriasis who developed joint pain and stiffness consistent with psoriatic arthritis (PsA). Her symptoms persisted despite appropriate trials of topical corticosteroids, calcipotriene, and oral apremilast. She also declined methotrexate due to concerns about side effects. Imaging of her hands revealed distal interphalangeal joint space narrowing, marginal erosions, and periosteal reaction, supporting the diagnosis of PsA. The patient was …

Infectious Retinitis Associated With Jak Inhibitors: The Ongoing Duality Of Jak Inhibitors, Jose S. Pulido, Fukutaro Mano, Marcello Casella, Susumu Ishida

Wills Eye Hospital Papers

PURPOSE: To discuss the recent evidence that Janus kinase (JAK) inhibitors can cause viral retinitis.

METHODS: A commentary on the case report in this issue and a review of cases in the literature.

RESULTS: A total of 6 cases have now been reported of cytomegalovirus retinitis associated with Jak inhibitors. Additionally, there was a case of bilateral toxoplasma retinitis and a case of herpetic scleritis.

DISCUSSION: It is important to be aware of the potential blinding complications associated with JAK inhibitors and if the patient complains of acute vision loss and/or floaters, the patient should be emergently referred to a …

A Study Of Awareness Of Antiseptics And Disinfectant Use Among Allied Health Sciences Students And Interns Of A Tertiary Care Hospital, Pooja M, Puneeth A, Sharmi Nm

Digital Journal of Clinical Medicine

Background:

Antiseptics and disinfectants are among the most vital tools in infection prevention and control (IPC), especially in healthcare settings where the risk of hospital-acquired infections (HAIs) remains a significant concern. This study aims to assess the awareness and knowledge of antiseptics and disinfectants among Allied Health Sciences (AHS) students and interns, identify knowledge gaps at different stages of training, and recommend educational interventions.

Methods:

This was a cross-sectional, questionnaire-based study conducted among 1st to 3rd-year AHS students and interns at a tertiary care hospital. Data were collected using a validated questionnaire via a Google form after obtaining approval from …

Selectivity Modulation Of Small Cationic Membrane-Active Cyclic Peptides With Broad-Spectrum Activity Against Bacteria And Fungi, Sandeep Lohan, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Kaustav Das Gupta, Shakti Singh, Keykavous Parang

Pharmacy Faculty Articles and Research

To investigate how ring size and backbone flexibility influence antimicrobial potency and cytotoxicity, we synthesized a series of macrocyclic peptides of lead peptide p1 (c[Arg-Arg-arg-arg-dip-Trp-dip]) by incorporating Gly, 2-aminoethoxyacetic acid (EAA), or 2,4-diaminobutyric acid (Dab). Two optimized peptides, 6b and 10b, retained broad-spectrum activity against drug-resistant Gram-positive (MIC, 1.5–6.2 μg/mL) and Gram-negative bacteria (MIC, 4–25 μg/mL), as well as pathogenic fungi, while exhibiting enhanced selectivity for microbial cells. Their therapeutic indices (TI ∼407 and ∼394, respectively) were ∼2-fold higher than p1, indicating improved safety. Both peptides remained effective against Gram-negative pathogens beyond the reach of daptomycin, were rapidly bactericidal, and …

Plasma Ca125 Levels As A Predictor Of Major Adverse Cardiac Events In Patients With Acute Coronary Syndrome: A Six-Month Follow-Up Study, Nazlı Dilek Çolak, Turgut Karabağ, Onuralp Çalışkan, Songül Tezcan

Journal of the Saudi Heart Association

Objectives: Carbohydrate antigen 125 (CA125) is associated with different cardiovascular conditions. This study aimed to determine CA125 levels in patients with acute coronary syndrome (ACS) and the potential relationship between major adverse cardiac events (MACE) in the short-term following.

Methods: This prospective cohort study was conducted in a coronary care unit between May and November 2022. Plasma CA125 levels were measured only once upon hospital admission. Patients were followed for six months. All-cause mortality, recurrent acute coronary syndrome, requirement for revascularization, decompensated heart failure, cardiogenic pulmonary edema, atrial fibrillation, and stroke were recorded as MACE.

Results: A total of 127 …

Disruption Of Proteoglycan 4 (Prg4)-Cd44 Signaling Modulates Chronic Synovitis In Conditionally Inactivated Mice, Khaled A. Elsaid, Ling Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Gregory D. Jay

Pharmacy Faculty Articles and Research

Background

Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 inhibits synovial macrophage (SM) activation via xanthine oxidase (XO) and hypoxia inducible factor alpha (HIF-1α) suppression. We aimed to evaluate the contribution of PRG4-CD44 interaction to synovial homeostasis and investigate PRG4’s signaling dysfunction in synovial tissues from patients with osteoarthritis (OA). We hypothesized that CD44 mediates synovitis due to PRG4 loss and that PRG4 signaling dysfunction is associated with high-grade synovitis in OA.

Methods

Prg4^{FrtloxP/FrtloxP} are transgenic mice wherein tamoxifen (TAM) inactivates the Frt allele and creates a knockout state (Prg4^{FrtKO/FrtKO …}

Phytic Acid (Insp6) Activates Hdac3 Epigenetic Axis To Maintain Intestinal Barrier Function, Sujan Chatterjee, Zachery Sin, Nguyen Tran, Loretta Vierra, Anuj Shukla, Tam Tran, George Koshkaryan, Kevin Ritter, Xue Bessie Sue, Saharat Jolak Ragsac, Seungman Park, Qian Liu, Richard Van, Katherine Huang, Kayci Huff-Hardy, Richard Rood, Anas Gremida, Martin Gregory, Chien-Huan Chen, Mira V. Han, Parakkal Deepak, Adikfi Saiardi, Henning J. Jensen, Prasun Guha

Life Sciences Faculty Research

HDAC inhibition shows promise in cancer treatment but pan-HDAC inhibitors cause gastrointestinal issues in 48% of patients. Understanding HDAC activation mechanisms is crucial to treating diverse diseases beyond cancer. Our study reveals that inositol polyphosphate multikinase (IPMK) and inositol hexakisphosphate (InsP6 or phytic acid), enriched in vegan diets, play essential roles in activating the HDAC3 epigenetic axis and maintaining intestinal barrier integrity. IPMK binds to HDAC3 and drives InsP6 synthesis, which selectively activates HDAC3 at a 10 nM concentration by recruiting the DAD domain of its corepressor protein. IPMK deletion diminishes HDAC3 activation, leading to histone hyperacetylation and MMP gene …

Rare Event: Neonatal Anaphylaxis Following Hepatitis B Vaccination – A Case Series From A Tertiary Care Center In India, Aarthi Ma, Revanth R

Advances in Clinical Medical Research and Healthcare Delivery

We report two cases of anaphylaxis following Hepatitis B vaccination in one-day-old neonates at a tertiary care hospital in India. Both cases presented with similar patterns of cutaneous reactions and respiratory symptoms shortly after intramuscular administration of the Hepatitis B vaccine. To our knowledge, this is among the few documented case series of neonatal anaphylaxis post–Hepatitis B vaccination, underscoring its rarity yet clinical importance. The cases highlight the critical importance of vigilant post-vaccination monitoring and prompt recognition of vaccine-associated adverse events in neonates. This report reviews current literature on anaphylaxis following vaccination and discusses optimal management strategies.

Spatially Distinct Cellular And Molecular Landscapes Define Prognosis In Triple-Negative Breast Cancer, Kavitha Mukund, Darya Veraksa, David Frankhouser, Lixin Yang, Jerneja Tomsic, Raju Pillai, Srijan Atti, Zahra Mesrizadeh, Daniel Schmolze, Jovanny Zabaleta, Xiao-Cheng Wu, Mary-Anne Leblanc, Lucio Miele, Augusto Ochoa, Victoria Seewaldt, Shankar Subramaniam

School of Medicine Faculty Publications

Triple-negative breast cancer (TNBC) is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors influence outcomes, but their inherent molecular and cellular heterogeneity are increasingly acknowledged as crucial determinants. Here, we report on the spatio-molecular heterogeneity underlying TNBC tumors in a retrospective, treatment-naive cohort with differential prognoses (17 good prognoses [GPx] >15-year survival and 15 poor prognoses [PPx] < 3-year survival]) profiled using GeoMx Digital Spatial Profiler. Analyses reveal that epithelial and microenvironment (TME) states are transcriptionally distinct between groups. Invasive GPx epithelia show an increase in immune transcripts, with a more immune-rich TME (via IF). PPx epithelia, in contrast, are more metabolically and translationally active, with a mesenchymal/fibrotic TME. Pre-cancerous epithelia in PPx exhibit a presence of aggressiveness, marked by increased EMT signaling and complement activity. We identify distinct epithelial gene signatures for PPx and GPx that can accurately classify diagnostic samples and likely inform therapy.