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Principal Investigator: MAI T DANG
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $238,140
Funding agency: National Cancer Institute
The goal of the proposed 5-year training program is to facilitate Dr. Mai Dang’s full transition to an independent physician scientist. Her work is focused on identifying novel ways to modulate the brain tumor immune microenvironment to improve treatment strategies for pediatric patients. She was recently recruited to Washington University in St. Louis as a tenured-track assistant professor in the Department of Neurology to continue this work with strong institutional support. She will use the next five years of mentored training to acquire additional essential knowledge on immunology and advanced research tools to perform investigations in cancer immunology. While her prior work was specifically on macrophages and microglia, her current proposal will focus on antigen presenting cells and their interaction with the adaptive arm of the immune system. Dr. Dang will be mentored by Dr. Milan Chheda, a physician scientist, whose expertise is on developing new therapies that target glioblastoma brain tumor cancer stem cells and the tumor microenvironment. She will be co-mentored by Dr. David DeNardo, who has expertise in immunology and the tumor microenvironment’s regulation of therapy response in pancreatic and lung cancer. They will be joined by a committee comprised of two highly seasoned mentors, both physician scientists with excellent track record for and commitment to training other physician scientists at WUSTL. Dr. Christine Gurnett is Head of Pediatric neurology, who is highly recognized for her work in the genetics of neurological disorders, and Dr. Joshua Rubin, Professor in Oncology is an expert on pediatric and adult brain tumors. This team is deeply committed to providing Dr. Dang with scientific, technical, and career mentorship to assist her in this launch of her independent research career.
The research goal of this proposal is to identify reversible causes of immune suppression in medulloblastomas treated with radiation and drug treatment. The central hypothesis is that effective tumor immunity after radiation in a pediatric brain tumor will require both reducing suppressive myeloid cells and increasing functional antigen presenting cells. She further hypothesizes that reprogramming myeloid cells may allow for more anti-tumor activity during treatment. She will use advanced tools such as inducible depletion of immune cells and single- cell analysis paired with assays to directly measure the function of antigen presenting cells and cytotoxic T cells to study this hypothesis. Findings from this work will uncover ways to effectively use immunotherapy to augment radiation efficacy to improve overall survival and morbidity for pediatric brain tumor patients.
Terms: <0-11 years old><21+ years old><Ablation><Adult><Adult Human><Affect><Antigen Presentation><Antigen-Presenting Cells><Antigens><Area><Assay><Bioassay><Biological Assay><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood monocyte><Brain><Brain Glioblastoma><Brain Glioblastoma Multiforme><Brain Neoplasia><Brain Neoplasms><Brain Nervous System><Brain Tumors><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><Cancers><Cause of Death><Cell Body><Cell Function><Cell Mediated Immunology><Cell Physiology><Cell Process><Cell Survival><Cell Viability><Cell-Mediated Immunity><Cell-Mediated Lympholytic Cells><Cells><Cellular Function><Cellular Immunity><Cellular Physiology><Cellular Process><Child><Child Youth><Childhood><Childhood Brain Neoplasm><Childhood Brain Tumor><Childhood Malignant Brain Tumor><Children (0-21)><Children's Hospital><Clinical><Coupled><Cytolytic T-Cell><Cytotoxic T Cell><Cytotoxic T-Lymphocytes><Data><Dendritic Cells><Development><Disease remission><Drugs><Dysfunction><Encephalon><Fellowship><Functional disorder><GEM model><GEMM model><Gene Transcription><Genetic><Genetic Transcription><Genetically Engineered Mouse><Goals><Grade IV Brain Astrocytic Neoplasm><Grade IV Brain Astrocytic Tumor><Grade IV Brain Astrocytoma><Head><Heterogeneity><Hortega cell><Immune><Immune mediated therapy><Immune response><Immune system><Immunes><Immunity><Immunological response><Immunologically Directed Therapy><Immunology><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Immunotherapy><Impairment><Infiltration><Innate Immunity><Institution><Intervention><Intervention Strategies><Investigation><Knowledge><Laboratories><Macrophage><Malignant Melanoma><Malignant Neoplasms><Malignant Pancreatic Neoplasm><Malignant Tumor><Malignant Tumor of the Lung><Malignant neoplasm of lung><Malignant neoplasm of pancreas><Marrow Neutrophil><Marrow monocyte><Measures><Mediating><Medication><Medulloblastoma><Melanoma><Mentors><Mentorship><Mice><Mice Mammals><Microglia><Morbidity><Morbidity - disease rate><Murine><Mus><Myeloid Cells><Myeloid-derived suppressor cells><Mφ><NSCLC><NSCLC - Non-Small Cell Lung Cancer><Native Immunity><Natural Immunity><Nervous System Diseases><Nervous System Disorder><Neurologic Disorders><Neurological Disorders><Neurology><Neurosciences><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Granulocyte><Neutrophilic Infiltrate><Neutrophilic Leukocyte><Non-Small Cell Lung Cancer><Non-Small-Cell Lung Carcinoma><Non-Specific Immunity><Nonspecific Immunity><Oncology><Oncology Cancer><Operative Procedures><Operative Surgical Procedures><Pancreas Cancer><Pancreatic Cancer><Patients><Pediatric Hospitals><Pediatric Malignant Brain Tumor><Pediatric Neurology><Pharmaceutical Preparations><Phenotype><Philadelphia><Physicians><Physiopathology><Play><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Population><Position><Positioning Attribute><Pulmonary Cancer><Pulmonary malignant Neoplasm><RNA Expression><Radiation><Radiation therapy><Radiotherapeutics><Radiotherapy><Recurrence><Recurrent><Regulation><Remission><Research><Resistance><Role><Scientist><Seasons><Site><Subcellular Process><Surgical><Surgical Interventions><Surgical Procedure><T cell response><T-Cell Activation><T-Cell Proliferation><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Testing><Therapeutic Intervention><Training><Training Programs><Transcription><Treatment Efficacy><Tumor Cell><Tumor Immunity><Universities><Veiled Cells><Washington><Work><accessory cell><activate T cells><adaptive immune response><adaptive immunity><adulthood><anti-tumor effect><anti-tumor immune response><anti-tumor immunity><antitumor effect><antitumor immunity><arm><cancer immunity><cancer immunology><cancer microenvironment><cancer progenitor><cancer progenitor cells><cancer stem cell><career><cell killing><check point blockade><checkpoint blockade><chemotherapy><child neurology><child patients><childhood brain cancer><clinical training><cytotoxic><developmental><draining lymph node><drug/agent><genetically engineered mouse model><genetically engineered murine model><gitter cell><host response><immune check point blockade><immune checkpoint blockade><immune microenvironment><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><immunogen><immunoresponse><immunosuppressive activity><immunosuppressive function><immunosuppressive microenvironment><immunosuppressive myeloid cells><immunosuppressive response><immunosuppressive tumor microenvironment><improved><improved outcome><intervention efficacy><intervention therapy><interventional strategy><kids><killer T cell><lung cancer><malignancy><malignant progenitor><malignant stem cell><mesoglia><microglial cell><microgliocyte><monocyte><myeloid suppressor cells><myeloid-derived suppressive cells><neoplasm immunology><neoplasm/cancer><neoplastic cell><neuro-oncology><neurological disease><neurooncology><neutrophil><new drug target><new drug treatments><new druggable target><new drugs><new pharmacological therapeutic><new pharmacotherapy target><new therapeutic target><new therapeutics><new therapy><new therapy target><next generation therapeutics><novel><novel drug target><novel drug treatments><novel druggable target><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel pharmacotherapy target><novel therapeutic target><novel therapeutics><novel therapy><novel therapy target><pancreatic malignancy><pathophysiology><pediatric><pediatric brain cancer><pediatric brain neoplasm><pediatric brain tumor><pediatric patients><perivascular glial cell><professor><radiation effect><radiation treatment><recruit><regional lymph node><resistant><response><response to therapy><response to treatment><side effect><single cell analysis><skill acquisition><skill development><social role><suppressive myeloid cells><surgery><tenure process><tenure track><therapeutic efficacy><therapeutic response><therapy efficacy><therapy response><thymus derived lymphocyte><tool><transcriptomics><treatment response><treatment responsiveness><treatment strategy><treatment with radiation><tumor><tumor immune microenvironment><tumor immunology><tumor microenvironment><tumor-immune system interactions><tumors in the brain><youngster>