Research

Our lab uses murine modeling systems, genetically modified mice that we generate and human samples. We attempt to work in an iterative fashion, going from mouse to man and back again, to define basic paradigms of biology and their relevance to important human lung diseases. 

Pulmonary diseases characterized by inflammation, remodeling and abnormal cellular responses are the major focus of our laboratory. We pioneered the techniques that are used to inducibly target genes to the lung and used these and other techniques to define the in vivo roles and effects of IL-11, IL-13, TGF-beta, and VEGF in the pathogenesis of asthma, pulmonary fibrosis, emphysema and acute lung injury. Our studies in COPD are focused on the role of the inflammasome and IL-18, virus-cigarette smoke interaction and the innate immune responses and mitochondrial abnormalities that contribute to these disorders. 

We have also recently focused on the biology of the 18 glycosyl hydrolases, in particular the chitinase-like protein, chitinase-3-like 1 (Chi3l1) and chitotriosiase (also called chitinase 1). These studies demonstrated that the former is an important regulator of anti-pathogen responses which controls cell death, inhibits the inflammasome and other innate immune responses, augments adaptive immunity and stimulates would healing. They also highlighted its important roles in asthma, pneumococcal pneumonia, acute lung injury, COPD and bronchpulmonary dysplasia. The chitinase 1 studies highlight its ability to augment TGF-beta1 responses and its important roles in scleroderma. 


Current Projects

Asthma 

  • cellular and molecular determinants of Th2 inflammation and their relation to obesity
  • Chi3L1(BRP-39/YKL-40) and Chitinase 1 in Th2 Inflammation and Asthma

Pulmonary Fibrosis

  • CHI3LI(YKL-40) and Chitinase 1 as therapeutic targets and biomarkers in Idiopathic Pulmonary Fibrosis, Scleroderma and Hermansky Pudlak Syndrome.
  • In silico and in vivo analysis of genetic modifiers of the tissue effects of TGF-beta 1.

COPD/Emphysema

  • Role of CHi3l1 in injury and repair after cigarette smoke exposure.
  • Role of RIG-like helicase innate immune responses in COPD and aveolar and airway remodeling.
  • Role of mitochondrial injury and quality control in COPD and alveolar and airway remodeling.
  • In silico and in vivo analysis of genetic modifiers of the emphysema-generating effects of TGF-beta 1.

Primary and Metastatic Lung Cancer

  • Role of Chi3l1 and chitinase 1 in the development and spread of cancer in the lung.

Acute Lung Injury and Infection

  • Role of Chi3l1 and chitinase 1 in acute lung injury and infection.