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Principal Investigator: SIMON R BEST
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2021
Award: $22,318
Funding agency: National Institute on Deafness and Other Communication Disorders
Dr. Simon Best is a junior faculty member in the Department of Otolaryngology – Head and
Neck Surgery at the Johns Hopkins School of Medicine where his clinical practice is dedicated
to voice and airway disorders. With the support of this Mentored Career Development Award,
Dr. Best seeks to better understand the immunologic environment that allows Human
Papillomavirus types 6 and 11 to elude the immune system and cause Recurrent Respiratory
Papillomatosis (RRP). Dr. Best will enhance his research knowledge and skills with coursework
in immunology, biostatistics, and clinical trial design, and receive directed mentorship by an
interdisciplinary team of experienced researchers. He will be immersed in the interdisciplinary
research environment of the Cervical Cancer SPORE program at Johns Hopkins, which is a
unique center of researchers dedicated to HPV-associated diseases. This award will provide Dr.
Best with the resources that he needs to become an independent investigator and future leader
in the treatment of papillomatosis.
In Aim 1, Dr. Best will build on his prior research experience in papillomatosis to test the
hypothesis that PD-1 and PD-L1 play a role in the immunologic microenvironment in a
population of RRP patients and determine if expression of these markers is correlated with
clinical disease severity. He will also seek to understand the mechanisms that drive PD-L1
expression in papilloma and the functional consequences of this pathway in RRP. In Aim 2, he
will study a mouse model of papilloma to further understand how papilloma develops in
immunocompetent mice, and test if DNA vaccines are able to treat this infection. He will further
determine if blockade of the PD-1 pathway enhances the activity of DNA vaccination in this
murine model of papilloma. Upon successful completion of this project, there will be promising
data to suggest a role for immunologic therapies in RRP, and a better understanding of the
immunologic factors that allow laryngeal papillomas to grow and evade immune-mediated
clearance. Identifying these factors could lead directly to the testing of novel therapeutics in
papillomatosis, as well as suggest generalized mechanisms for how the HPV virus escapes the
immune system. At the conclusion of this award, Dr. Best will have obtained the preliminary
data needed to successfully compete for independent funding and achieve long-term success
as a surgeon-scientist dedicated to this debilitating disease.
Terms: <21+ years old><Activities of Daily Living><Activities of everyday life><Address><Adjuvant><Adult><Adult Human><Aero-digestive Tract><Aerodigestive Tract><Antigen-Presenting Cells><Archives><Assay><Award><B7-H1><B7H1><Bioassay><Biologic Assays><Biological Assay><Biometrics><Biometry><Biostatistics><CD274><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><CSIF><CSIF-10><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Cell Body><Cell Function><Cell Process><Cell physiology><Cell-Mediated Lympholytic Cells><Cells><Cellular Function><Cellular Immune Function><Cellular Physiology><Cellular Process><Cervical Cancer><Cervix Cancer><Childhood><Chronic><Clinical><Clinical Trials><Clinical Trials Design><Color><Communication Disorders><Communication impairment><Communicative Disorders><Cytokine Synthesis Inhibitory Factor><Cytolytic T-Cell><Cytotoxic T Cell><Cytotoxic T-Lymphocytes><DNA><DNA Vaccines><DNA-based therapeutics><Data><Deoxyribonucleic Acid><Differentation Markers><Differentiation Antigens><Differentiation Markers><Disease><Disorder><ELISPOT><Environment><Faculty><Feedback><Funding><Future><Gamma interferon><Generalized Growth><Generations><Goals><Growth><HPV><HPV 6><HPV E6><HPV infection><HPV6><Head and Neck Surgery><Hoarseness><Human><Human Papilloma Virus><Human Papillomavirus><Human papilloma virus 6><Human papilloma virus infection><Human papilloma virus type 6><Human papillomavirus 6><Human papillomavirus infection><Human papillomavirus type 6><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-10><IL10><IL10A><Immune><Immune Interferon><Immune Markers><Immune Targeting><Immune infiltrates><Immune mediated therapy><Immune response><Immune system><Immunes><Immunochemical Immunologic><Immunocompetent><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunologic><Immunologic Factors><Immunologic Markers><Immunological><Immunological Factors><Immunological response><Immunologically><Immunologically Directed Therapy><Immunologics><Immunology><Immunomodulation><Immunotherapy><Infection><Infectious Human Wart Virus><Inflammation><Interdisciplinary Research><Interdisciplinary Study><Interferon Gamma><Interferon Type II><Interferon-gamma><Interleukin 10 Precursor><Interleukin-10><Intervention><Intervention Strategies><Investigators><K-Awards><K-Series Research Career Programs><Kinetics><Knowledge><LYT3><Laryngeal Papilloma><Lead><Lesion><Ligands><Malignant Cervical Neoplasm><Malignant Cervical Tumor><Malignant Neoplasm of the Cervix><Malignant Tumor of the Cervix><Malignant Tumor of the Cervix Uteri><Malignant Uterine Cervix Neoplasm><Malignant Uterine Cervix Tumor><Malignant neoplasm of cervix uteri><Marker Antigens><Measures><Mediating><Mentors><Mentorship><Mice><Mice Mammals><Modeling><Modern Man><Multidisciplinary Collaboration><Multidisciplinary Research><Murine><Mus><Naked DNA Vaccines><Otolaryngology><PBMC><PD 1><PD-1><PD-L1><PD1><PDL-1><PDL1><Papilloma><Papilloma Viruses><Papilloma of the Larynx><Papillomaviridae><Papillomavirus><Papillomavirus Transforming Protein E6><Pathway interactions><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pb element><Peripheral Blood Mononuclear Cell><Play><Population><Pre-Clinical Model><Preclinical Models><Production><Programmed Cell Death 1 Ligand 1><Programmed Death Ligand 1><Quantitative RTPCR><Quantitative Reverse Transcriptase PCR><RT-PCR><RTPCR><Recombinant DNA Vaccines><Recurrent respiratory papillomatosis><Research><Research Career Program><Research Personnel><Research Resources><Researchers><Resources><Reverse Transcriptase Polymerase Chain Reaction><Risk><Role><Sampling><Scientist><Severity of illness><Squamous Papilloma of the Larynx><Staining method><Stains><Subcellular Process><Suppressor Cells><Suppressor-Effector T-Cells><Suppressor-Effector T-Lymphocytes><Surgeon><T Suppressor Cell><T cell infiltration><T cell tumor trafficking><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Testing><Therapeutic><Tissue Growth><Translating><Tumor Antigens><Tumor-Associated Antigen><Tumor-infiltrating immune cells><Up-Regulation><Upregulation><Uterine Cervix Cancer><Vaccination><Viral><Viral Burden><Viral Diseases><Viral Load><Viral Load result><Viral Protein E6><Virus><Virus Diseases><Voice><Voice Hoarseness><Work><aPD-1><aPD1><accessory cell><adulthood><allergic/immunologic body system><allergic/immunologic organ system><anti programmed cell death 1><anti-PD-1><anti-PD1><anti-programmed cell death protein 1><antiPD-1><antiPD1><cancer antigens><cell type><clinical practice><cytokine><cytotoxic CD8 T cells><cytotoxic CD8 T lymphocyte><daily living functionality><disease severity><enzyme linked immunospot assay><exhaust><experience><functional ability><functional capacity><heavy metal Pb><heavy metal lead><host response><human papillomavirus E6 oncoprotein><human tissue><immune cell infiltrate><immune competent><immune function><immune infiltration><immune microenvironment><immune modulation><immune regulation><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based biomarkers><immune-based therapies><immune-based treatments><immuno therapy><immunologic reactivity control><immunologic substance><immunological biomarkers><immunological markers><immunological substance><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><immunosuppressive microenvironment><immunosuppressive tumor microenvironment><interventional strategy><intratumoral immune cell><killer T cell><lFN-Gamma><laser capture microdissection><mRNA Expression><medical college><medical schools><member><mouse model><murine model><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel therapeutics><novel therapy><ontogeny><otorhinolaryngology><papilloma virus Transforming Protein E6><pathway><pediatric><programmed cell death 1><programmed cell death ligand 1><programmed cell death protein 1><programmed cell death protein ligand 1><programmed death 1><programs><qRTPCR><reverse transcriptase PCR><school of medicine><skills><sle2><social role><success><suppressor T lymphocyte><systemic lupus erythematosus susceptibility 2><therapeutic DNA><therapeutic vaccine><thymus derived lymphocyte><treatment vaccines><tumor immune cell><tumor immune microenvironment><tumor-immune system interactions><tumor-specific antigen><vaccine for the treatment><vaccine for treatment><viral infection><virus infection><virus-induced disease><wart virus><αPD-1><αPD1>