Research Activity

The UC Division of Pulmonary, Critical Care and Sleep Medicine has active and collaborative research programs that include funding from the National Institutes of Health, American Lung Association, Office of Veterans Affairs, Flight Attendants Medical Research Institute, Cystic Fibrosis Foundation and industry partners.

Laboratory of Frank McCormack

Areas of focus include:

Novel Methods of Inhibiting Pandemic Influenza and Viral Pneumonia:
Our research focuses on host-pathogen interaction between Influenza-A, and the airway epithelium in vivo. We are examining the role of the epithelial cell mitogen KGF and other growth factors on Influenza susceptibility and viral production in the lung. Additionally, we are studying the role of pulmonary collectins in the innate defense against viral infection and determining the potential utility of using mutated surfactant proteins as an anti-influenza therapeutic.

Sirolimus safety in patients awaiting transplant:
Sirolimus (Rapamycin) is an effective therapy for lymphangioleiomyomatosis (LAM), but is linked to delayed wound healing properties. Thus, Sirolimus is contraindicated in LAM lung transplant candidates. We are testing the hypothesis that LAM patients can remain on this therapy until they are called up for their lung transplant without an increased risk of developing wound healing complications.

Innovative biomarker panels:
To predict prognosis and therapeutic response in rare lung diseases: VEGF-D is a lymphangiogenic growth factor that has a key role in tumor metastasis. We recently discovered that VEGF-D levels in the blood can predict severity of lymphangioleiomyomatosis (LAM), a rare lung disease.

VEGF-D levels can also predict responses to treatment in LAM patients. We are expanding our search for biomarkers to differentiate between different rare lung diseases and to create a panel of makers that can diagnose different rare lung diseases and inform the risk-benefit analysis of therapies.

Innovative treatments for pulmonary alveolar microlithiasis:
Pulmonary alveolar microlithiasis (PAM) is a rare pulmonary disease associated with accumulation of calcium phosphate crystals in the lung, leading to progressive pulmonary fibrosis, respiratory failure and death. Although almost 600 PAM cases have been reported, mostly in Japan, Turkey, and Europe, there is currently no treatment.

PAM is caused by autosomal recessive mutations in the gene for the sole pulmonary solute transporter responsible for export of phosphate from the pulmonary alveolar lumen, SLC34A2. We have created a mouse model that recapitulates the human disease. We are examining the role of phosphate transporters in the lung with this mouse model and preclinical development of potential therapeutic approaches are currently underway.

Preclinical models of monogenic pulmonary diseases:
Including pulmonary alveolar microlithiasis (PAM), LAM, pulmonary Langerhan’s cell histiocytosis, and pulmonary capillary hemangiomatosis, are employed to search for insights that have the potential to impact human health in a relatively short time frame.

Laboratory of Michael Borchers

My lab is focused on the effects of cigarette smoke exposure on innate and adaptive immune system function and specifically examines the mechanisms by which smoke exposed epithelium communicates with the immune system. We have extensive experience with mouse models of smoke exposure and have published several manuscripts detailing epithelial cell changes and immune function.

We have specifically examined the effects of smoke exposure on the host response to influenza, RSV, and bacterial infections. As Director of the Inhalation Exposure Facility at the University of Cincinnati, my lab has conducted mouse exposures for investigators at the University of Cincinnati, Cincinnati Children’s Hospital, the Cincinnati Veteran’s Affairs Medical Center, Ohio State University, University of Colorado, National Jewish Hospital and University of Pennsylvania.

Laboratory of Dennis McGraw

My laboratory has a longstanding interest in G-protein coupled receptors and how they regulate both airway and vascular smooth muscle tone. The primary focus is devoted to signaling by adrenergic and prostanoid receptors. A major focus at this time is investigation of oxidative stress as an inflammatory mechanism that attenuates the response to b-agonists during more severe asthma exacerbations. Oxidative stress results from the activity of peroxidase enzymes such as eosinophil peroxidase (EPO) and myeloperoxidase (MPO) that are released by infiltrating eosinophils and neutrophils in the asthmatic airway.

Laboratory of Jason Gardner

Crossroads of innate and adaptive immune responses to trauma:
Pneumonia is one of the most common life threatening complication of patients in the intensive care unit. The outcome of pulmonary infection is determined by a delicate balance between appropriate inflammatory responses orchestrating effective clearance of microbes from the lung and excessive inflammatory responses that compromise gas exchange and result in respiratory failure. The research goal is to define the mechanisms which regulate the balance between effective and deleterious inflammatory responses, and ultimately to develop interventional strategies that improve patient outcomes.

Laboratory of Jane Yu

lead a research laboratory focusing on investigation of the role of tumor suppressor proteins tuberin (TSC2) and hamartin (TSC1) in steroid action, cell survival, cellular metabolism, tumorigenesis and metastasis, and signaling transduction pathways. My laboratory also develops animal models to test the efficacy of FDA approved drugs on the progression and metastasis of mTORC1 hyperactive cells, lung inflammation and injury.

Current studies include determining the role of estrogen in the progression of lymphangioleiomyomatosis (LAM), a female predominant rare lung disease, from the alteration of signalingpathways, to the integrity of alveolar epithelium and microenvironment inthe lung, and to the pulmonary functions. We are also investigating the potential application of using bloodbased biomarkers in LAM.

Laboratory of Kristin Hudock

We seek to understand how an individual’s innate immune response contributes to the pathogenesis of cystic fibrosis (CF), acute respiratory distress syndrome (ARDS) and pneumonia. To accomplish this goal, we combine basic and translational approaches to discover what regulates the balance between host defense and tissue injury in human lung and inflammatory diseases.

Laboratory of Bruce C. Trapnell

Clinical:

• Pulmonary alveolar proteinosis
• Cystic fibrosis
• Alpha-1 antitrypsin deficiency
• Other rare lung disorders

Research

Alveolar macrophage function; molecular techniques using gene knockout, transgenic and conditional gene expression mouse models and non-human primates, in vitro and in vivo viral gene transfer, and bone marrow transplantation

Clinical Research

The Division has over 30 active clinical research trials, both investigator-initiated and industry supported. Clinical trial studies include pulmonary arterial hypertension, cystic fibrosis, emphysema, asthma, pulmonary fibrosis, interstitial lung disease, pulmonary alveolar proteinosis, and lymphangioleiomyomatosis (LAM).

Rare Lung Disease Consortium
The Rare Lung Disease Consortium is a NIH sponsored, Cincinnati-based network of institutions which perform cooperative trials in rare lung disease. Diseases that are currently under study by the RLDC include:

• Lymphangioleiomyomatosis
• Pulmonary alveolar proteinosis
• Hermansky Pudluk Syndrome
• Pulmonary alveolar microlithiasis
• Cystic lung diseases including Birt Hogg Dube and Pulmonary Langerhans cell histiocytosis

Cystic fibrosis -- Patricia Joseph and M.Veronica Indihar
The Cincinnati CF Center is one of 18 Therapeutic Development Network sites for the Cystic Fibrosis Foundation. Our cystic fibrosis physicians are investigators on multiple TDN and non-TDN studies.

Rare lung diseases -- Nishant Gupta
My clinical research program focuses on interstitial and rare lung diseases, especially diffuse cystic lung diseases such as lymphangioleiomyomatosis (LAM), Birt-Hogg-Dube syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), and Sjögren syndrome associated lung disease.

Pulmonary Arterial Hypertension (PAH) -- Jean Elwing
I am the principal investigator for several clinical trials in the Division of Pulmonary, Critical Care and Sleep Medicine, evaluating existing and novel therapies for pulmonary arterial hypertension (PAH). Currently, there are 10-12 ongoing phase II and III clinical trials or registries available to PAH patients, with the main focus of examining therapeutics and treatment regimens in hopes to determine the optimal strategies. The UC PH program follows a large cohort of patients affected by PAH. All patients seen in clinic are evaluated for possible participation in clinical trials or registries; the goal is to offer every patient an opportunity to participate in clinical research.

Patient quality improvement -- Ahsan Zafar
My research interests are in improving patient outcomes by designing better care delivery systems using improvement science methodologies. My projects have led to reduced COPD readmissions, improved care of COPD patients in emergency department during acute exacerbation and reduced hospital acquired infections in the intensive care units.