Pulmonology 2023

Improving influenza vaccine responses by ubiquitin ligases in B cells


Dr. Emily Moser

Email
emily.moser@medicine.ufl.edu

Phone
(352) 273-8740

Faculty Department/Division
Pulmonary, Critical Care, and Sleep Medicine

This project is primarily:
Basic

Research Project Description:
Current vaccines for influenza induce strong antibody responses, but don’t elicit long-term protection because of antigenic drift and shift. An improved vaccine would elicit antibodies against conserved antigens, providing cross-protection against new influenza variants. This project will identify new pathways in B cells that regulate development of cross-protective antibodies. We previously identified that a ubiquitin ligase, Itch, limits selection of activated B cells prior to differentiation into plasma cells. We hypothesize that Itch limits development of cross-protective antibodies after influenza infection. We will use mouse-adapted influenza virus infection in WT mice or mice lacking Itch in B cells. The medical student will be responsible for determining how well serum antibodies from these mice neutralize homologous and heterologous influenza virus strains in vitro.

Does this project have an international component or travel?
No

Interstitial lung disease in patients with autoimmune features


Diana Gomez

Email
diana.gomezmanjarres@medicine.ufl.edu

Phone
(773) 398-6739

Faculty Department/Division
Pulmonary, Critical Care, and Sleep Medicine

This project is primarily:
Clinical

Research Project Description:
Patients with connective tissue diseases tend to have pulmonary involvement but the optimal management for these patients is unclear. Most of the available literature is based on small cohorts. This is a collaboration between the rheumatology and pulmonary departments. We plan to study the patients seen in both clinics and describe demographics, pulmonary tests, chest imaging findings, respond to therapy, and clinical outcomes.

Does this project have an international component or travel?
No

The role of Sirt3 pathway in alpha-1 anti trypsin deficiency mediated liver disease


Mrs. Nazli Khodayari

Email
Nazli.khodayari@medicine.ufl.edu

Phone
(352) 443-1874

Faculty Department/Division
Pulmonary, Critical Care, and Sleep Medicine

This project is primarily:
Basic

Research Project Description:
Alpha-1 Antitrypsin Deficiency (AATD) is a rare genetic disease caused by the misfolding and accumulation of alpha-1 antitrypsin (AAT) and manifests in the lung and liver. AATD is caused most often by a single amino acid substitution at amino acid 342 in the ZAAT protein, resulting in misfolding and accumulation of ZAAT in the endoplasmic reticulum (ER) of hepatocytes. Hepatic ZAAT polymerization results in reduced secretion levels of AAT into the bloodstream. Lack of AAT function in the lungs causes AATD mediated lung disease. Retained ZAAT is eliminated by ER-associated degradation and autophagy, however the accumulation of polymerized AAT in the liver is theorized to be the main cause of liver disease in AATD individuals. We hypothesized that proteins such as Sirt3 that regulate degradation pathways in the cells play critical roles in quality control of AAT. In this study, utilizing RNA analysis, protein analysis, immunoprecipitation, and in-vitro cell localization assays, we will investigate the role of Sirt3 in the pathophysiology of AATD mediated liver disease in the context of dysregulation of Chaperone-Mediated Autophagy (CMA). We hypothesize that upregulation or induction of Sirt3 can decrease levels of intracellular AAT through activating the CMA pathway and would be a potential therapeutic target moving forward for AATD individuals.

Does this project have an international component or travel?
No