2020 |
Lomvardas, Stavros [⬀] Overdevest, Jonathan B |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Deciphering Mechanisms of Covid-19 Induced Anosmia @ Columbia University Health Sciences
Project Summary/Abstract In this Competitive Revision proposal, we seek to investigate the non-cell autonomous effects of Covid- 19 infections in olfaction. Our preliminary data suggest that induction of pro-inflammatory/antiviral pathways result in disruption of inter-chromosomal genomic interactions, and downregulation of Olfactory Receptor (OR) gene expression. Since antiviral responses are expected be elicited upon Covid-19 infection, we hypothesize that disruptions in nuclear architecture and OR expression account for the reported olfactory deficits in infected patients. Thus, we propose to analyze human autopsies of the olfactory epithelium, to decipher whether Covid- 19 infections disrupt genomic interactions required for OR transcription. We will complement our studies in human autopsies with experiments using mice infected with SARS-CoV-2. RNA-seq, in situ HiC and immunohistochemistry experiments in human and mice will reveal the molecular mechanisms by which Covid- 19 induces olfactory dysfunction. Our experiments will provide critical insight to the mechanisms by which the virus hijacks molecular and physiological processes of the host cell, opening new potential avenues for the prevention, diagnosis and treatment of Covid-19 infection.
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0.943 |
2021 |
Overdevest, Jonathan B |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. |
Neurocognitive & Neuropsychiatric Impact of Chemosensory Alterations: Implications of Olfactory Dysfunction in Covid-19 @ Columbia University Health Sciences
PROJECT SUMMARY Smell loss is a common neurosensory disability accompanying infection with SARS-CoV-2 novel coronavirus. The frequency and persistence of alteration in the ability to smell, or olfactory dysfunction (OD), observed during the COVID-19 pandemic highlight a knowledge gap, where risk factors predicting post-viral OD and subsequent neurological dysfunction remain poorly understood. This K23 proposal will characterize epidemiological risk factors associated with OD following COVID-19 infections, which in turn may signify risk for neurocognitive and neuropsychological impairment in daily functioning and quality of life. As a career development award, this proposal will provide Dr. Jonathan Overdevest, MD, PhD, an Assistant Professor in the Department of Otolaryngology-Head and Neck Surgery at Columbia University Irving Medical Center (CUIMC) with structured training to establish an independent career in the study of olfactory dysfunction and neurocognition. Under the guidance of his primary mentor, D.P. Devanand, and an experienced team of experts, Dr. Overdevest will develop domain expertise in the design and analysis of chemosensory-focused neuroepidemiologic studies using patient-oriented research (POR) methodology. Building upon preliminary data evaluating prevalence and persistence of OD in a vulnerable minority population served by CUIMC, Dr. Overdevest will develop the framework for a longitudinal cohort study within this multi-ethnic population. The research in Aim 1 will investigate epidemiologic risk factors for primary and persistent OD following COVID-19 infection by evaluating OD with subjective functional domain and test-based objective tools. In Aim 2, he will study the relationship between persistent OD and neurological, neurocognitive, and neuropsychiatric functioning using validated measures from the multilingual NIH Toolbox assessment battery. He will then extend this preliminary work into the realm of neuroimaging by leveraging existing local research infrastructure and the expertise of his mentorship team to develop pilot data correlating features of OD and neurologic outcomes with anatomic and inflammatory changes in the brain. These studies will inform strategies for counseling the public about demographic risk factors for experiencing COVID-19 related OD, associate risks for additional neurological disabilities, and provide the foundation for future investigation into imaging modalities to evaluate the central processing of olfaction and monitor outcomes of clinical trials for OD interventions.
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0.943 |