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Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner 2022 Clemson University

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection ...


The Herpes Simplex Virus Type-1 (Hsv-1), Vc2 Live-Attenuated Vaccine Strain Induces Robust Antitumor Immune Responses And Ameliorates Intra-Tumor Immunosuppression In An Immunocompetent B16f10-Derived Murine Melanoma Model, Ifeanyi Kingsley Uche 2022 Louisiana State University and Agricultural and Mechanical College

The Herpes Simplex Virus Type-1 (Hsv-1), Vc2 Live-Attenuated Vaccine Strain Induces Robust Antitumor Immune Responses And Ameliorates Intra-Tumor Immunosuppression In An Immunocompetent B16f10-Derived Murine Melanoma Model, Ifeanyi Kingsley Uche

LSU Doctoral Dissertations

Current cancer immunotherapies include immune checkpoint inhibitors, adoptive cellular therapy, and cancer vaccines. While some of these therapies have met with great clinical success, they are associated with several limitations. Oncolytic virotherapy (OVT) has emerged as a bonafide promising immunotherapy, that uses viral infection to liberate tumor antigens in an immunogenic context to promote the development of anti-tumor immune responses. At present, Talimogene laherparepvec (T-VEC; Imlygic™), a modified type 1 herpes simplex virus (HSV-1) is the only FDA approved OVT for human cancer treatment (melanoma). While T-VEC is associated with limited response rates, its modest efficacy supports the continued development ...


Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby 2022 Edith Cowan University

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby

Research outputs 2022 to 2026

Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced ...


Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear MD, PhD 2022 Virginia Commonwealth University

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

Undergraduate Research Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice ...


Methods For Characterization Of Cl-001 Derived Exosomes As A Stimulating Agent For Nk Cells For Immunotherapy, Ilana Gomez Diaz 2022 University of Central Florida

Methods For Characterization Of Cl-001 Derived Exosomes As A Stimulating Agent For Nk Cells For Immunotherapy, Ilana Gomez Diaz

Honors Undergraduate Theses

The immune system is a complex set of cells in the body that work to prevent disease or infection by recognizing and eliminating foreign material or unhealthy cells. One essential type of immune cell that is part of the innate immune response are Natural Killer (NK) cells. These cytotoxic effector lymphocytes can detect certain unhealthy cells, such as cancer cells, that normal B and T cells would miss. For example, many tumor cells have evolved to bypass immune system surveillance by not expressing major histocompatibility complex class I molecules (MHC class I), on their surface, reducing recognition by cytotoxic T ...


Determinants Of Precocious B-Cell Aging In European Adolescents Living With Perinatally Acquired Hiv-1 After Over 10 Years Of Suppressive Therapy [Preprint], Alessandra Ruggiero, Katherine Luzuriaga, Paolo Palma 2021 University of Verona

Determinants Of Precocious B-Cell Aging In European Adolescents Living With Perinatally Acquired Hiv-1 After Over 10 Years Of Suppressive Therapy [Preprint], Alessandra Ruggiero, Katherine Luzuriaga, Paolo Palma

UMass Chan Medical School Faculty Publications

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2nd year of life and achieved virus suppression within the 1st year of ART, with majority of patient maintaining suppression until analysis and 5/40 ...


Newer Horizon Of Mesenchymal Stem Cell-Based Therapy In The Management Of Sars-Cov-2-Associated Mucormycosis: A Safe Hope For Future Medicine, Alok Raghav, Syed Ghazanfar Ali, Goo-Bo Jeong, Kirti Amresh Gautam, Shahid Banday, Qazi Noorul Mateen, Prashant Tripathi, Richa Giri, Saurabh Agarwal, Manish Singh, Haris M. Khan 2021 Ganesh Shankar Vidyarthi Memorial Medical College

Newer Horizon Of Mesenchymal Stem Cell-Based Therapy In The Management Of Sars-Cov-2-Associated Mucormycosis: A Safe Hope For Future Medicine, Alok Raghav, Syed Ghazanfar Ali, Goo-Bo Jeong, Kirti Amresh Gautam, Shahid Banday, Qazi Noorul Mateen, Prashant Tripathi, Richa Giri, Saurabh Agarwal, Manish Singh, Haris M. Khan

COVID-19 Publications by UMass Chan Authors

SARS-CoV-2-infected patients are reported to show immunocompromised behavior that gives rise to a wide variety of complications due to impaired innate immune response, cytokine storm, and thrombo-inflammation. Prolonged use of steroids, diabetes mellitus, and diabetic ketoacidosis (DKA) are some of the factors responsible for the growth of Mucorales in such immunocompromised patients and, thus, can lead to a life-threatening condition referred to as mucormycosis. Therefore, an early diagnosis and cell-based management cosis is the need of the hour to help affected patients overcome this severe condition. In addition, extended exposure to antifungal drugs/therapeutics is found to initiate hormonal and ...


Neutralizing Antibody-Independent Immunity To Sars-Cov-2 In Hamsters And Hace-2 Transgenic Mice Immunized With A Rbd/Nucleocapsid Fusion Protein [Preprint], Julia T. Castro, Ricardo T. Gazzinelli 2021 University of Sao Paulo, Brazil

Neutralizing Antibody-Independent Immunity To Sars-Cov-2 In Hamsters And Hace-2 Transgenic Mice Immunized With A Rbd/Nucleocapsid Fusion Protein [Preprint], Julia T. Castro, Ricardo T. Gazzinelli

UMass Chan Medical School Faculty Publications

The nucleocapsid (N) and the receptor binding domain (RBD) of the Spike (S) proteins elicit robust antibody and T cell responses either in vaccinated or COVID-19 convalescent individuals. We generated a chimeric protein that comprises the sequences of RBD from S and N antigens (SpiN). SpiN was highly immunogenic and elicited a strong IFNγ response from T cells and high levels of antibodies to the inactivated virus, but no neutralizing antibodies. Importantly, hamsters and the human Angiotensin Convertase Enzyme-2-transgenic mice immunized with SpiN were highly resistant to challenge with the wild type SARS-CoV-2, as indicated by viral load, clinical outcome ...


Leveraging The Treg-Intrinsic Ctla4-Pkceta Signaling Pathway For Cancer Immunotherapy, Hsin-Yu Liu, Christophe Pedros, Kok-Fai Kong, Ann J. Canonigo-Balancio, Wen Xue, Amnon Altman 2021 La Jolla Institute for Immunology

Leveraging The Treg-Intrinsic Ctla4-Pkceta Signaling Pathway For Cancer Immunotherapy, Hsin-Yu Liu, Christophe Pedros, Kok-Fai Kong, Ann J. Canonigo-Balancio, Wen Xue, Amnon Altman

Open Access Publications by UMass Chan Authors

BACKGROUND: Our previous studies revealed a critical role of a novel CTLA4-protein kinase C-eta (PKCeta) signaling axis in mediating the suppressive activity of regulatory T cells (Tregs) in antitumor immunity. These studies have employed adoptive transfer of germline PKCeta-deficient (Prkch (-/-)) Tregs into Prkch (+/+) mice prior to tumor implantation. Here, we extended these findings into a biologically and clinically more relevant context.

METHODS: We have analyzed the role of PKCeta in antitumor immunity and the tumor microenvironment (TME) in intact tumor-bearing mice with Treg-specific or CD8(+) T cell-specific Prkch deletion, including in a therapeutic model of combinatorial treatment. In addition to ...


Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Human Papillomavirus (HPV) induced cancers continue to affect millions of women worldwide, with the five year survival rate hovering just under 60% in some demographics. Therefore there is an unmet need to develop effective, yet, easily administered therapies to treat established HPV genital lesions. Even though immune checkpoint therapy (ICT) is a promising treatment option in some HPV+ cancers, the high cost and associated toxicities are still major concerns for their widespread application. HPV cancers are textbook candidates for therapeutic vaccination intervention because they’re driven by the expression of viral oncoproteins E6 and E7, which serve as ideal tumor ...


Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Glioblastoma is the most common malignant primary brain tumor in adults; the current aggressive treatment results in a 5% five-year survival rate. More effective therapies should be developed. One promising alternative is oncolytic adenovirus, Delta-24-RGD, which elicits cancer cell lysis and immunogenic cell death. In fact, Delta-24-RGD produced complete responses in 20% of recurrent glioblastoma patients through immune mechanisms that activate anti-tumor cytotoxic properties of T-cells. This cytolytic effect can further be enhanced by adding immune agonists, namely OX40L, which engages the OX40 receptor to co-stimulate activated T cells for enhanced proliferation. Hence, we produced the next generation of Delta-24-RGD ...


High-Throughput Human Primary Cell-Based Airway Model For Evaluating Influenza, Coronavirus, Or Other Respiratory Viruses In Vitro, A. L. Gard, Ping Liu, Jennifer P. Wang, Robert W. Finberg, J. T. Borenstein 2021 Draper

High-Throughput Human Primary Cell-Based Airway Model For Evaluating Influenza, Coronavirus, Or Other Respiratory Viruses In Vitro, A. L. Gard, Ping Liu, Jennifer P. Wang, Robert W. Finberg, J. T. Borenstein

COVID-19 Publications by UMass Chan Authors

Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air-liquid interface, in a ...


The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian 2021 Old Dominion University

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages ...


Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng 2021 University of Massachusetts Amherst

Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng

Doctoral Dissertations

Cell surface harbors rich information regarding the status of cell health. Being able to monitor and detect its changes in response to stimuli will provide crucial information in drug discovery, disease diagnosis, and human health. Despite the efforts and breakthroughs made possible through the specific sensing approach, there are significant challenges in extracting the information on the cell surface in a quantitative and reliable way. To address this challenge, I took the approach of array-based, hypothesis-free sensing in which the engineered sensors selectively interact with target analytes, producing a distinct pattern of response that enables analyte identification. This signature-based pattern ...


An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod 2021 Munster Technological University

An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod

International Undergraduate Journal of Health Sciences

Introduction: In Ireland, around 5% of children and 3% adults have food allergy (134,000 people). This current paper describes a survey that was carried out on a subset of service-users with the aim of identifying whether there is a need for increased specialist medical services and/or for a funded charity such as Anaphylaxis Ireland, defunct since 2015.

Materials & Methods: These needs were assessed via an online survey using Google Forms. The survey was conducted from 17-27th February 2020. There were 31 questions in total, relating to topics such as symptoms, clinical wait times, satisfaction with care provided and ...


Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, 2021 Munster Technological University

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences


Report Of The National Institutes Of Health Sars-Cov-2 Antiviral Therapeutics Summit, Matthew D. Hall, James M. Anderson, Celia A. Schiffer, Anthony J. Conley, Mindy I. Davis 2021 National Institutes of Health

Report Of The National Institutes Of Health Sars-Cov-2 Antiviral Therapeutics Summit, Matthew D. Hall, James M. Anderson, Celia A. Schiffer, Anthony J. Conley, Mindy I. Davis

COVID-19 Publications by UMass Chan Authors

The NIH Virtual SARS-CoV-2 Antiviral Summit, held on November 6, 2020, was organized to provide an overview on the status and challenges in developing antiviral therapeutics for COVID-19, including combinations of antivirals. Scientific experts from the public and private sectors convened virtually during a live videocast to discuss SARS-CoV-2 targets for drug discovery as well as the preclinical tools needed to develop and evaluate effective small molecule antivirals. The goals of the Summit were to review the current state of the science, identify unmet research needs, share insights and lessons learned from treating other infectious diseases, identify opportunities for public-private ...


Modeling The Effect Of Igg Subclasses And Specificity In The Translocation Of Monoclonal Antibodies Across The Placental Barrier, Sayuri Tais Miyamoto Magnabosco 2021 Dartmouth College

Modeling The Effect Of Igg Subclasses And Specificity In The Translocation Of Monoclonal Antibodies Across The Placental Barrier, Sayuri Tais Miyamoto Magnabosco

ENGS 88 Honors Thesis (AB Students)

Infections are responsible for over half a million neonatal deaths every year (Lawn et al., 2014). Thus, there is huge interest in leveraging maternal immunization against infectious diseases to grant fetal protection during its development through the vertical transferring of IgG antibodies, the only Ig subclass that can significantly cross the placental barrier. Studies about vertical immunization rely on in-vitro models to extrapolate physiological conditions of the human placenta. The BeWo Transwell model (Bode et al., 2006) presents itself as a reliable model to mimic the transplacental transport mechanism of antibodies (Ellinger et al., 1999; Poulsen et al., 2009). However ...


Hypoxia Acts As An Environmental Cue For The Human Tissue-Resident Memory T-Cell Differentiation Program, Farah Hasan 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Hypoxia Acts As An Environmental Cue For The Human Tissue-Resident Memory T-Cell Differentiation Program, Farah Hasan

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Tissue-resident memory T-cells (TRM) provide frontline defense against viral diseases and can contribute to anti-tumor immunity; however, aside from the necessity of TGF-β, little is known regarding cues for TRM differentiation. Oxygen tension is an environmental cue that distinguishes peripheral tissues from the circulation and here, we demonstrate that differentiation of human CD8+ T-cells under hypoxic conditions in the presence of TGF-β1 led to the development of a TRM phenotype, characterized by a greater than five-fold increase in CD69+CD103+ cells expressing human TRM hallmarks and enrichment for endogenous human TRM gene signatures, including increased ...


Non-Neutralizing Antibodies Targeting The Immunogenic Regions Of Hiv-1 Envelope Reduce Mucosal Infection And Virus Burden In Humanized Mice [Preprint], Catarina E. Hioe, Guangnan Hu, Shixia Wang, Shan Lu 2021 Icahn School of Medicine at Mount Sinai

Non-Neutralizing Antibodies Targeting The Immunogenic Regions Of Hiv-1 Envelope Reduce Mucosal Infection And Virus Burden In Humanized Mice [Preprint], Catarina E. Hioe, Guangnan Hu, Shixia Wang, Shan Lu

UMass Chan Medical School Faculty Publications

Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted ...


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