Medical Immunology Commons^™

Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Immunotherapies have greatly improved outcomes for patients with renal cell carcinoma (RCC), yet response rates remain suboptimal and the factors promoting therapy resistance versus sensitivity are incompletely understood. Currently, no preclinical model of orthotopic renal cancer exists that permits evaluation of tumor antigen–specific (TAS) CD8⁺ tumor-infiltrating lymphocytes (TILs). To address this deficiency, we developed a mouse renal cancer model that permits tracking of adoptively transferred TAS CD8⁺ T cells. Renca-LUC tumor cells were transduced to express tumor ERK (tERK), a model antigen expressing a one-amino-acid change from wild-type ERK, resulting in recognition by tERK/H-2K^d-specific DUC Thy1.1 …

Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …

Glycoprotein-Specific Transcriptional Response Contributes To Differential Vaccine Protection Against Lethal Ebola Virus Infection, Sheridan B. Wagner, Delphine C. Malherbe, Ethan G. Napier, Andrea Marzi, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 10 ⁷ PFU to provide broader population protection. Identification …

Sex Differences In Allergic Asthma Responses Of Mice Prenatally Exposed To Wood Smoke, Adelynne Walley

Undergraduate Theses, Professional Papers, and Capstone Artifacts

No abstract provided.

The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton

Theses and Dissertations--Pharmacy

Alcohol consumption is widespread in the United States, with 80% of individuals aged 12 and older reporting alcohol use and 1-in-4 engaging in risky drinking behaviors. Alcohol misuse heightens susceptibility to infections and delays wound healing, indicating a disrupted immune system. Previous studies show alcohol rewires immune cells, especially monocytes and macrophages, which play critical roles in tissue homeostasis and host defense.

Using a rhesus macaque model of ethanol self-administration, we demonstrate that after 6-months of drinking, monocytes exhibit decreased cytokine production and significant transcriptomic changes, indicating a hypo-inflammatory state. In contrast, 12-months of chronic alcohol use induces hyperinflammatory responses, …

A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …

Maternal Opioid Use Disorder And Hepatitis C Infection In Pregnancy Reshape The Peripheral Immune Landscape At Term, Brianna M. Doratt, Heather E. True, Sheridan B. Wagner, Delphine C. Malherbe, Zachary M. Reynolds, Cynthia Cockerham, John O'Brien, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Pregnancy requires precisely timed immune adaptations to maintain foetal tolerance while enabling timely initiation of labour, a process often conceptualised as the ‘immune clock’ of pregnancy. Disruption of this immune clock contributes to adverse obstetric outcomes. While maternal opioid use disorder (OUD) is a recognised risk factor for poor maternal and neonatal health, its impact on maternal immune landscape at delivery remains poorly understood.

Methods: We analysed peripheral blood collected from pregnant individuals with and without OUD at time of admission for delivery before the onset of active labour. We employed multiparameter flow cytometry, cytokine profiling, and single-cell-RNA sequencing …

Evaluating The Efficacy And Safety Of Inactivated Dengue Vaccines In Vulnerable Populations, Alaa Daghash

Honors Undergraduate Theses

Dengue virus is a mosquito-borne flavivirus responsible for over 390 million annual cases worldwide. While there are live-attenuated vaccines available to prevent dengue, none are currently approved for use in the United States, and existing platforms pose significant risks of viral reactivation and antibody-dependent enhancement in vulnerable populations, such as pregnant women, children under the age of nine, and the immunocompromised. This widespread exclusion of vulnerable populations exposes a significant vaccine equity gap in dengue prevention, as the populations most at risk for severe dengue are the same ones who are currently excluded from vaccination. In this study, I conducted …

Light-Induced Oslike1 Phosphorylation Enhances Rice Resistance Against Blast Disease, Jiangtao Liu, Lei Su, Wenya Wang, Jintao Wang, Weizhong Chen, Zhixiang Yang, Leiyun Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Zhongqiang Qi, Yongfeng Liu, Yuqiang Liu, Ping Wang, Muxing Liu, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Rice blast caused by Magnaporthe oryzae poses a major threat to world food supply. Conditions conducive to the disease include insufficient light. Our previous studies found that light-dependent phosphorylation of light-harvesting complex II protein (LHCB5) mediates rice immunity; however, the underlying mechanisms, in particular, the upstream regulators of LHCB5 phosphorylation, remain unknown. Here, we show that OsLIKE1 functions as a lectin receptor-like kinase (LecRLK) to play a critical role in rice resistance against M. oryzae. OsLIKE1 interacts with and phosphorylates LHCB5. In addition, we find two phosphorylation sites in the kinase domain of OsLIKE1 important for its auto-phosphorylation and phosphorylation …

Patient-Derived Ovarian Cancer Models Provide Insight Into Cancer Cell-Intrinsic And Immune Cell-Dependent Effects On Therapeutic Response, Parisa Nikeghbal

Biomedical Sciences ETDs

Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and resistance to chemotherapy. This dissertation applies patient-derived organoids (PDOs), xenograft-derived organoids (PDXOs), and humanized xenografts (huPDX) to investigate therapeutic responses and immune interactions. Organoids were shown to retain critical features of the original malignancy. Across platinum-sensitive, -resistant, and -refractory cases, both PDOs and PDXOs exhibited drug sensitivities that aligned with patients’ clinical classifications. Building on this foundation, a drug screen revealed novel strategies. Auranofin restored platinum sensitivity in Notch3-active models, afatinib broadly reduced viability, and adavosertib–gemcitabine and sorafenib–topotecan combinations produced synergy. Extending this work, immune interactions …

T Cell Senescence And Nociplastic Pain: A Proposed Etiological Mechanism, Kayla S. Riggleman

Senior Honors Theses

Nociplastic pain is a newly identified chronic pain phenotype characterized by widespread hyperalgesia and allodynia. Its etiological mechanisms are currently unknown, making medical intervention elusive. The proposed pathophysiological model connects immunosenescence with a degradation of the blood-brain barrier as a result of peripheral inflammation. Neuronal hyperexcitability and glial cell activation result, leading to nociplastic pain. It is currently thought that central sensitization is the key mechanistic driver of nociplastic pain, so this literature review seeks to expound on that. Based on this framework, chimeric antigen receptor (CAR)-T cell therapy and stem cell treatments are proposed therapeutic methodologies to be explored. …

Asymptomatic Cryptococcal Antigenemia: A Multi-Clinic Cross-Sectional Study On The Prevalence, Associated Factors And Predictors Of Three-Month Outcomes Among Antiretroviralnaïve And Antiretroviral-Experienced Hiv Patients In Dar Es Salaam, Tanzania, Mandela Makakala, Mukasa Mohammed, Mabula Mabelele, Kamran Hameed, Philip Adebayo

Internal Medicine, East Africa

Background: Cryptococcal meningitis remains a leading cause of HIV/AIDS-related mortality, predominantly in Sub-Saharan Africa. Current screening and prevention efforts primarily target antiretroviral therapy (ART)-naïve patients, whereas strategies for ART-experienced individuals are less well defined.

Objectives: This study primarily aimed at determining the prevalence of asymptomatic cryptococcal antigenemia (ACA) among ART-naïve and ART-experienced patients, along with associated factors and predictors of three-month outcomes among HIV patients in three HIV clinics in Dar es Salaam, Tanzania. Secondarily, factors associated with serum cryptococcal antigen positivity in the overall study population were also assessed.

Methods: This cross-sectional clinic-based study recruited 273 HIV-positive participants (ART-naïve …

Host-Intrinsic Factors Determine Anti-Tumor Efficacy Of Exercise In Pancreatic Ductal Adenocarcinoma, Sumedha Pareek

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.

In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a …

Giant Cell Arteritis After Mrna Covid Vaccines: Concerning Or A False Alarm?-A Retrospective Cohort Study, Syed M. F. Zabiullah, Rutwik Pradeep Sharma, Roshan Subedi, Viqarunnisa Faaiza Zahid, Yasir Loai, Sarathlal Mannumbethlal, Aatifa Aatifa

Advances in Clinical Medical Research and Healthcare Delivery

Background: The coronavirus disease (COVID-19) pandemic led to the first large-scale rapid deployment of novel messenger RNA (mRNA) vaccines. Although the effectiveness and safety of these vaccines were rigorously studied, post-vaccination adverse events such as giant cell arteritis (GCA) continue to be reported. More than two hundred and sixty three cases of new-onset GCA occurring after mRNA vaccine administration are listed in the Vaccine Adverse Events Reporting System as of October 2024. We aimed to explore the incidence of GCA after mRNA vaccines among patients in our health system and study their characteristics and outcomes.

Methods: We conducted a …

A Case Of Granuloma Annulare Mimicking Candidal Intertrigo In The Groin, Scotty Smith, Patrice Perche, Leonard Gately

School of Medicine Faculty Publications

Granuloma annulare (GA) is a benign, non-infectious granulomatous skin condition of uncertain etiology, often presenting as annular erythematous plaques. While commonly localized to the hands and feet, GA has multiple clinical variants and can mimic other dermatologic conditions, leading to diagnostic challenges. We report a rare case of GA localized to the inguinal region in a 55-year-old female initially treated empirically for candidal intertrigo without improvement. Biopsy demonstrated interstitial histiocytic infiltrates dissecting between collagen bundles with increased dermal mucin, confirming a diagnosis of interstitial GA. The patient was subsequently treated with triamcinolone 0.1% ointment and hydroxychloroquine 200 mg twice daily …

Advancing Peptide-Based Vaccines Against Candida: A Comparative Perspective On Liposomal And Synthetic Formulations, Hong Xin

School of Graduate Studies Faculty Publications

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform's compatibility with clinically approved adjuvants (MPLA and QS-21), …

Use Of Modified Z-Domain Peptides To Specifically Label The Constant Region Of Immunoglobulin G And Vegf, Madeline Allen

Department of Chemistry: Dissertations, Theses, and Student Research

Antibodies are increasingly being used in medicinal therapies due to their ability to specifically bind to a target antigen. This fundamental behavior of antibodies has been used as a key component in drug development to address common problems with traditional drug molecules such as off-targeting, fast drug clearance, and low efficacy. This thesis provides some background into how antibodies can be used as potential treatments for a few diseases. Chapter 1 begins with an overview of the human immune system, and the role antibodies play within it. Then, the variety of ways in which antibodies can be used as medicinal …

Decreased Risk Of Incident Cancer Among Patients With Vitiligo: A Multicenter Retrospective Cohort Analysis, Rahib K. Islam, Ivan D. Nguyen, Kazi N. Islam, Lacey M. Falgout, Jonathan M. Joseph, Collins T. Langley, Christopher J. Haas

School of Medicine Faculty Publications

No abstract provided.

Delayed Diagnosis Of Systemic Lupus Erythematosus Presenting As Autoimmune Hemolytic Anemia: A Case For Heightened Clinical Suspicion, Diana Acosta Pozo, Luis Álvarez Pérez

Research Colloquium

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem involvement, including hematologic manifestations. Autoimmune Hemolytic Anemia (AIHA), though an established feature, is relatively uncommon and may occur early or in isolation. When AIHA presents without overt systemic symptoms, the underlying autoimmune etiology may be overlooked, resulting in delays in diagnosis and treatment. Prompt recognition is essential to prevent unnecessary interventions and prolonged morbidity.

Case Presentation: A 39-year-old woman residing in Texas presented to the Rheumatology office with persistent synovitis and severe transfusion-dependent anemia, requiring red blood cell transfusions every 48 hours for over three months. She …

Identifying Novel Fibrotic Mechanisms Underlying Treatment-Resistant Lower Urinary Tract Dysfunction, Quentin Darcy

Graduate Doctoral Dissertations

ABSTRACT

IDENTIFYING NOVEL FIBROTIC MECHANISMS UNDERLYING TREATMENT-RESISTANT LOWER URINARY TRACT DYSFUNCTION

August 2025

Quentin D’Arcy, B.S., University of Massachusetts Amherst

Ph.D., University of Massachusetts Boston

Directed by Dr. Jill Macoska

Lower urinary tract dysfunction (LUTD) is a common, age-related disease that affects millions of men over the age of 50. Current treatment for this and other related prostate diseases concentrate on decreasing benign prostate growth and relaxing smooth muscle contractions to alleviate urinary voiding symptoms. However, up to 45% of patients with LUTD are treatment-resistant and require surgical intervention to resolve prostate issues. By focusing on the contribution of inflammation-derived …