A5012382013- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Ferroptosis and cancer prognosis
- Genetic Syndromes and Imprinting
- Cambodian History and Society
- Kruppel-like factors research
- Multiple Myeloma Research and Treatments
- Inflammatory Biomarkers in Disease Prognosis
- Gut microbiota and health
Cornell University
2023-2025
Weill Cornell Medicine
2023-2025
University of Connecticut
2017-2025
Parker Institute for Cancer Immunotherapy
2024
Swim Across America
2022-2024
New York Proton Center
2023
Kettering University
2022
Memorial Sloan Kettering Cancer Center
2021-2022
UConn Health
2020
Cincinnati Children's Hospital Medical Center
2016
Zinc (Zn) is an essential metal for development and maintenance of both the innate adaptive compartments immune system. Zn homeostasis impacts maturation dendritic cells (DCs) that are important in shaping T cell responses. The mechanisms by which regulates tolerogenic phenotype DCs remain largely unknown. In this study, we investigated effect on DC generation Foxp3(+) regulatory (Tregs) using a model Histoplasma capsulatum fungal infection. Exposure bone marrow-derived to vitro induced...
The majority of JAK2 V617F -negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin ( CALR ), resulting a common carboxyl-terminal mutant fragment (CALR MUT representing an attractive source neoantigens for cancer vaccines. However, studies shown that -specific T cells are rare patients with MPN unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies from two independent cohorts. observed MHC-I alleles...
Identification of neoepitopes that are effective in cancer therapy is a major challenge creating vaccines. Here, using an entirely unbiased approach, we queried all possible mouse model and asked which those mediating tumor rejection and, independently, eliciting measurable CD8 response. This analysis uncovered large trove anticancer have strikingly different properties from conventional epitopes suggested algorithm to predict them. It also revealed our current methods prediction discard the...
Abstract Effective combination immunotherapy regimens increase the success rate of treating cancer patients than either monotherapy alone. Ferroptosis is a novel form cell death that has gained popularity in last decade as potential tool to be used against progression but not had much clinically. Currently, several groups are studying relevance ferroptosis context an attempt expand its clinical translatability well overcome lack response The field though divided regarding nature effects...
Abstract Insertion or deletion of one two base pairs within a coding region causes frameshift, which has the potential to generate neoepitopes (InDel-generated neoepitopes) that lack self-counterpart and are entirely novel. Despite obvious appeal InDel-generated neoepitopes, demonstration such candidate can elicit CD8 T-cell response, no actually control tumors in vivo have been reported thus far. Here, mouse colon carcinoma line, we identify 11 InDels, only generates neoepitope elicits...
ABSTRACT The adaptive immune response is tightly regulated by complex signals in dendritic cells (DCs). Although Th2 polarization dictated defined functional DC subsets, the molecular factors that govern amplitude of these responses are not well understood. Krüppel-like factor 2 (KLF2) a transcription negatively regulates activation numerous to stimuli. Here, we demonstrate suppression KLF2 conditioned DCs preferentially amplifies two model systems, one which prototypical intracellular...
We previously reported that activation of p53 by APR-246 reprograms tumor-associated macrophages to overcome immune checkpoint blockade resistance. Here, we demonstrate and its active moiety, methylene quinuclidinone (MQ) can enhance the immunogenicity tumor cells directly. MQ treatment murine B16F10 melanoma promoted melanoma-specific CD8 + T increased efficacy a cell vaccine using MQ-treated even when lacked p53. then designed novel combination with TLR-4 agonist, monophosphoryl lipid A,...
Identification of neoepitopes that can control tumor growth in vivo remains a challenge even 10 y after the first genomics-defined cancer were identified. In this study, we identify neoepitope, resulting from mutation junction plakoglobin (Jup) gene (chromosome 11), mouse colon line MC38-FABF (C57BL/6). This Jup mutant (JupMUT), was detected during mass spectrometry MHC class I-eluted peptides tumor. JupMUT has predicted binding affinity 564 nM for Kb molecule and higher 82 Db. However,...
Abstract The crosstalk between gut microbiome and anti-tumor immunity has recently gained attention in clinical settings. administration of antibiotics during immune checkpoint blockade (ICB) therapies been correlated with poorer outcomes cancer patients, suggesting that alterations affect overall responses to ICB. establishment microbiota-specific T cell clones tumor cross-reactivity potential was proposed as one the mechanisms linking responses. Vaccine-based strategies aimed at...
Abstract Tumor specific neoantigens, encoded by somatic mutations, are recognized T cells, inducing anti-tumor immune responses. This renders neoantigens viable targets for personalized cancer vaccines. However, the identification of immunogenic remains suboptimal. Understanding how selective pressure-mediated tumor evolution and neoantigen editing contribute to emergence may improve prediction accuracy. In this study, we aimed model heterogeneity under pressure using three preclinical...
Abstract Despite the significant success of immunotherapy, more than 40% cancer patients remain unresponsive or exhibit an insufficient response. Well-designed combinations targeted therapy and immunotherapy have potential to increase effectiveness treatment overcome absence response either alone. Since therapies that enhance tumor antigenicity can immune based therapies, we built a compendium in vitro vivo assays evaluate effect multiple immunogenic drugs. In these assays, use preclinical...
Abstract As tumors evolve, cancer cells acquire somatic mutations and these generate tumor specific neoantigens that are different from self can be recognized by T-cells, inducing anti-tumor immune responses. Such immunogenic antigens effective targets for neoantigen-based vaccines. However, the identification of remains limited with current prediction models. Here we designed mouse experiments to model evolution under pressure its association T-cell clones identify agnostically improve We...
Abstract Background: Immune checkpoint blockade therapeutics have revolutionized cancer therapy. However, most patients are either unresponsive or develop acquired resistance. Understanding patient-specific temporal T cell repertoires in the context of immune interventions will contribute to a better understanding potential improvement strategies for anti-tumor immunity. Current methods understand repertoire changes over time limited due amount material and prohibitive cost. In this study,...
<h3>Background</h3> Cancer treatment using immune checkpoint blockade (ICB) with anti- programmed cell death protein (PD)-1 and anti-cytotoxic T lymphocyte associated (CTLA)-4 has been successful, but primary acquired resistance limits their clinical benefit. Chemotherapeutic agents such as Cyclophosphamide (CTX) are known to induce anticancer immunity improves efficacy of ICBs when used in combination. Exploring means improve the benefit ICB therapies by reorchestrating anti-tumor...
Abstract Somatic mutations in cancer cells can give rise to new MHC epitopes referred as neoepitopes. Neoepitopes have been clearly demonstrated elicit an antigen specific T cell response, which are capable of mediating targeted killing cells. Despite recent advancements, exactly what criteria make a good neoepitope for personalized therapy is currently unknown. Here, using syngeneic tumor C57BL/6 mice, named FABF, we present results exhaustive and exhausting study where tested hundreds long...
Abstract Cancer neoepitopes are the only truly tumor-specific antigens and therefore, most suitable as cancer vaccines. Current methods to predict neoepitopes, based on studies of viral epitopes, emphasize high affinity MHC-peptide interactions. Increasing evidence in human murine models indicates that present neoepitope prediction mostly inaccurate predicting true MHC I-restricted neoepitopes. Here, a completely unbiased approach, all possible mouse tumor model were tested for their ability...
Abstract Immune Checkpoint Blockade (ICB) with anti- programmed cell death protein (PD)-1 and anti-cytotoxic T lymphocyte associated (CTLA)-4 have had immense success in cancer treatment. However, primary acquired resistance to these therapies limits their clinical benefit. Accumulating evidence indicates that chemotherapeutic agents such as Cyclophosphamide (CTX) can induce anticancer immunity stand out particularly promising partners for use combination ICBs. A approach reorchestrate the...
<h3>Background</h3> Immune Checkpoint Blockade (ICB) with anti- programmed cell death protein (PD)-1 and anti-cytotoxic T lymphocyte associated (CTLA)-4 have had immense success in cancer treatment. However, primary acquired resistance to these therapies limits their clinical benefit. Accumulating evidence indicates that chemotherapeutic agents such as Cyclophosphamide (CTX) can induce anticancer immunity improves the efficacy of ICBs when used combination. A combination strategy...
<h3>Background</h3> The majority of JAK2V617F-negative myeloproliferative neoplasms (MPN) have disease-initiating frameshift mutations in calreticulin (CALR) resulting a common novel C-terminal mutant fragment (CALRMUT), representing an attractive source neoantigens for cancer vaccines. However, studies shown that CALRMUT-specific T cells are rare CALRMUT MPN patients, but the underlying reasons this phenomenon unknown. We speculate is due to increased chance immune-mediated tumor rejection...