My role in basic and clinical research has largely derived from my position as Director of the Molecular Biology Core in the Section of Pulmonary Medicine. In that capacity, I have generated and characterized lung-specific overexpressing transgenic and null mutant mice to study in vivo roles and the effect of various cytokines in the pathogenesis of asthma, acute lung injury, pulmonary vascular disease, pulmonary fibrosis and emphysema. 

My current research interest is to define the molecular mechanism regulating pulmonary fibrosis and emphysema. Although cigarette smoke (CS) is a common risk factor for the development of these pathologies, the mechanism underlying this divergent tissue response of CS exposure has not been clearly understood. Interestingly, we have found that the TGF-b Tg mice in different genetic backgrounds demonstrated divergent tissue phenotypes of pulmonary fibrosis and emphysema. This observation led to the identification of genetic factors that modulate TGF-b effector function. Through extensive haplotype analysis and mRNA expression arrays, we further determined potential genetic modifiers. More recently, my lab has focused on defining the mechanism of vascular and tissue remodeling associated with dysregulated expression of Chitinase/Chitinase-like proteins(C/CLP). Using expertise in developing genetically modified mice and animal models, I will be able to determine specific pathogenetic mechanism of various lung diseases characterized by inflammation and remodeling that is essential for further development of therapeutic intervention on these diseases.

KDDF-Bioneer-201312-11 (Lee/Chae)                        2/11/2014- 10/10/2015            

Korea Drug Development Fund (KDDF)                      $227,273 

Selection of optimized lead compounds for preclinical studies for idiopathic pulmonary fibrosis using a novel RNAi-based nanoparticle technology SAMiRNA

Bioneer, a biotech company in Korea, developed Self Assembled Micelle-inhibitory RNA (SAMiRNA) technology as a novel and effective siRNA delivery method.  In this project, the effectiveness of this SAMiRNA approach against pulmonary fibrosis will be determined through a variety of in vivo and in vitro evaluations and also using TGF-b transgenic mice developed by our laboratory as an animal model of pulmonary fibrosis.  Thus, successful completion of this project will lead to the development of new drug for the effective intervention of pulmonary fibrosis.

Role: Principal Investigator

 

1 R01 HL115813-01A1 (Lee)                                    7/1/14 – 6/31/18                        

NIH / NHLBI                                                               $254,707

Chitinase 1 as a Biomarker and Therapeutic Target in Scleroderma Lung Disease

This grant proposes to define the roles and effects of chitinase1 in the pathogenesis of Scleroderma-associated interstitial lung disease. The studies in this project will evaluate the levels of chitinase1 in the blood or tissues of Scleroderma patients and controls to identify chitinase1 as a potential biomarker or a therapeutic target for this disease.

Role:  Principal Investigator

 

1U01 HL 108638-01 (Elias)                                        8/15/11 – 6/30/15                                

NIH / NHLBI                                                               $396,455                     

YKL-40 in Idiopathic Pulmonary Fibrosis and Kidney Transplantation

This grant is designed to evaluate circulating YKL-40 as a biomarker for disease progression in IPF and urinary YKL-40 as a predictor of delayed graft function after renal transplantation. These studies will also evaluate the utility of YKL-40 as a therapeutic target in both disorders.

Role:  Co-Investigator

 

P01 HL114501-01A1 (Choi)                                       4/1/13 – 3/31/18                                  

NIH / NHLBI                                                               $225,000

Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers

The focus is on the mechanisms that underlie the observation that cigarette smoke exposure and TGF-1 can contribute to the pathogenesis of COPD and IPF. Project 3 is based on evaluations of 10 different inbred murine backgrounds which define genetic modifiers that likely determine if TGF-1 causes fibrosis versus emphysema. These studies will define the expression of these modifiers in COPD and IPF and will define their roles in these biologic responses.

Role:  Co-PI, Project 2

 

5 U01 HL108634 (Zhou/Elias)                                    9/1/13- 8/31/14                         .

NIH/NHLBI                                                                 $61,538

MAPGen Knowledge Base (MAPGenKB) and Coordination Center

In this ancillary project, we will measure the levels of YK-40 in patients with atherosclerosis, hypertension, metabolic syndromes and visceral fat accumulation.  In addition, we will evaluate the roles of cell cycle regulation and the mitochondrial function in animal model of the diseases.

Role: Co-Investigator

 

1 UH2 HL 123876-01   (Chupp/Elias)                        7/1/14 – 6/30/19                                    

NIH/NHLBI                                                                 $458,188

Preclinical Development of a Novel Anti-YKL-40 Biologic to Treat Severe Asthma

We will complete the pre-clinical development of a humanized monoclonal antibody against the chitinase-like-protein, YKL-40, for the treatment of severe asthma.  A companion diagnostic test will also be developed to measure YKL-40 in the serum that is drug-bound or free for monitoring the bioavailability, dosing, and biologic effect. The results will generate a novel therapeutic against a validated mediator of inflammation and remodeling in asthma and will lead to an Investigational New Drug (IND) application following the conclusion of the award.

Role:  Co-Investigator

 

NIH/ NHLBI                                                                10/1/14 to 9/30/15                               

R56 HL 119511-01A1 (Bridge Award) (Kang)

NLRX1 and MAVS in cigarette smoke-induced inflammation and alveolar remodeling  

The goal of this grant is to define the roles of novel mitochondrial molecules called NLRX1 and MAVS in the development of COPD.  In addition, we will explore whether interventions that restore suppressed NLRX1 or modulate this pathway have therapeutic potential in a murine COPD model.

Role:  Co-Investigator

1981-1993   Full scholarship from Hanyang University for undergraduate and graduate courses, Hanyang

University, School of Medicine, Seoul Korea

1992-1993   Scholarship from Korean Public Health Institution, Seoul Korea

2005            Innovative Research Award, American Thoracic Society

1987 – 1992    Teaching Assistant, Hanyang University School of  Medicine

1993 – 1995    Research Scientist, Division of Biotechnology, Korea National Institute of Health (KNIH)

1995 – 1996    Full-time Instructor, Hanyang University School of Medicine

1997 – 1998    Visiting fellow, LMM, NIAID, NIH

1998 – 1999    Post-doctoral fellow, Yale University School of Medicine

2000 – 2001    Associate Research Scientist, Yale University School of  Medicine

2002 – 2007      Assistant Professor of Medicine, Yale University School of Medicine

2007 – 2009       Visiting Professor, Hanyang University School of Medicine

2002 -  2014      Director, Molecular Biology Core, Section of Pulmonary, Critical Care & Sleep Medicine, Yale                                              University School of Medicine, New Haven, CT

2008 – 2014       Associate Professor of Medicine, Yale University School of Medicine

2014 – Present   Professor, Dept of Molecular Microbiology and Immunology,

                           Division of Biology and Medical Sciences, Brown University
 

Based on my resarch experience and expertise in Genetics and immunobiolgy, I am mainly involved in mentoring of undergraduate, graduate and pre- and postdoctoral fellows.