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Research directions:

My laboratory studies respiratory immunology under homeostasis and disease conditions. The long-term goals of the laboratory are to develop novel ideas and methods for the induction of strong respiratory antiviral and anti-tumor immunity, and to target host immune regulatory networks for the control of acute and/or chronic disease (such as long-lasting COVID-19 symptom) development following respiratory viral infections including influenza, SARS-CoV-2 and respiratory syncytial virus (RSV). These research areas are of clinical relevance and might be translatable in the identification of novel preventive and therapeutic approaches.

Current research directions: T cell biology: CD8+ cytotoxic T lymphocytes (CTLs) are crucial for clearing virus-infected or transformed cells. The lab is interested in the transcriptional and metabolic regulation of CTL responses in vivo. The lab has recently identified a couple of key transcription factors required for sustaining robust CTL responses in vivo during viral infections or cancer. The lab is currently investigating the up- and downstream signals regulating the function of these transcription factors, and the effects of these transcription factors in the metabolic and epigenetic modulation of CTL responses against respiratory viral infection and cancer. Additionally, the lab has identified a novel tissue-resident CD4+ T helper cell (TRH) population in the respiratory tract. We are actively investigating whether targeting TRH cells could promote superior mucosal anti-viral and anti-tumor immunity following vaccination or checkpoint blockade therapy respectively. We believe this area of work will help to design better lung mucosal vaccination or immunotherapy strategies against respiratory pathogens or cancer.

Macrophage function in pulmonary inflammation, injury and repair: A rapid and well-controlled anti-viral immunity is the key for containing respiratory viral infections. Conversely, sustained and exaggerated immune responses can cause “cytokine storm”, leading to severe tissue damage and acute host diseases. My lab is interested in dissecting the molecular and metabolic mechanisms underlying the development of exuberant myeloid cell (particularly macrophage) inflammatory responses following infection. Using both animal models and clinical samples, we are evaluating several novel macrophage-targeted compounds or repurposed drugs in dampening severe pulmonary inflammation and host co-morbidities following respiratory viral infections.

Tissue recovery and chronic sequelae following respiratory viral infection: Following the clearance of viral pathogens, prompt and complete repair of the injured lung tissue is required for the restoration of normal pulmonary homeostasis and function. Conversely, failure of complete tissue recovery often leads to lung fibrosis and other chronic pulmonary conditions. For instance, a significant proportion of COVID-19 survivors have been lately reported with the development of chronic respiratory and extra-respiratory symptoms months after viral clearance (COVID-19 “long haulers”). The lab is actively studying how do dysregulated macrophage and T cell responses drive chronic pulmonary sequelae and/or other long-term tissue conditions following viral clearance in both animal and clinical studies. We are also evaluating the potential of a couple of biologics in ameliorating chronic host sequelae.

Interplay between aging and respiratory infections: Aging is associated with dramatically increased risk of developing severe diseases following respiratory viral infections including influenza and SARS-CoV2. We are studying the mechanisms of age-associated decline in pulmonary immunity. Furthermore, we are interested in examining the mechanisms by which respiratory viral infections exacerbate tissue senescence and/or accelerate organ aging. Ultimately, the lab is hoping to develop various means to enhance respiratory immunity during aging, and to dampen age-associated co-morbidities that may be caused or accelerated by viral respiratory infections.