Jefferson University Hospitals

Jane & Leonard Korman Respiratory Institute

Research & Clinical Trials

Research is a critical part of our mission at The Jane and Leonard Korman Respiratory Institute — Jefferson Health and National Jewish Health. We work closely with the Center for Translational Medicine (CTM) and Jefferson Coordinating Center for Clinical Research (JCCCR) to advance our understanding of lung disease. As part of our collaboration with National Jewish Health, you have access to some of the most advanced clinical trials in in the country.

Clinical Trials  

By participating in clinical research, you might provide important scientific information for developing new disease treatments and further medical knowledge. Ask your provider if you're eligible to participate in one of our clinical trials.

For more information on pulmonary clinical trials, contact Tamra Perez at Tamra.Perez@jefferson.edu

909908830

Jefferson Research

The following are current Jefferson research activities. Additional projects will be updated as they become available.

Deepak A. Desphande, PhD

Dr. Desphande’s Laboratory studies intracellular signaling regulating contraction, relaxation and proliferation of airway smooth muscle (ASM) cells with particular emphasis on G-protein coupled receptor mediated signaling. Asthma is an inflammatory disease of airways and clinically manifested as severe airflow obstruction. ASM is the principle contractile component of airways, and contraction and relaxation of ASM regulate airway diameter. Any alteration in ASM function results in bronchoconstriction and difficulty in breathing. Therefore, ASM acts as a primary therapeutic target in obstructive airway diseases such as asthma and COPD. Delineating novel receptors and signaling mechanisms that regulate ASM function would provide basis for developing newer and better drugs to treat asthma.

Current projects include understanding age-dependent changes in airway smooth muscle function (funded by NIA/NIH) and bitter taste receptor signaling in airway smooth muscle (funded by American Asthma Foundation). Changes in lung functions during aging are widely appreciated in clinical studies; however, the cellular and molecular mechanism underlying age-dependent changes in respiratory functions are not. The studies in this project aim at delineating aging effects on ASM functions.

Ajay Nayak, PhD

The major focus of Dr. Nayak's research is to elucidate the underlying mechanisms contributing to allergic responses to Cannabis sativa (marijuana). Exposure to Cannabis components results in aberrant respiratory function including exacerbation of asthma. Furthermore, direct contact with the plant may also result in urticarial rash and angioedema. With increasing legalization of marijuana for medicinal and recreational use more individuals are likely to demonstrate allergic reactions in the near future. We are specifically interested in identifying the major allergens of marijuana and developing standardized tools for clinical diagnostics.

Additional research interests include GPCR signaling, regulation and function (in vitro, ex vivo and in vivo) in the context of lung disease, as well as the pathobiology and treatment of fibrotic lung disease.  

Raymond Penn, PhD

The major focus of Dr. Penn’s research is to identify cellular and molecular mechanisms by which G protein-coupled receptors (GPCRs) mediate important functions in airway cells. GPCR signaling regulates contractile function, synthesis and release of autocrine factors, and cell growth/survival in various airway cells, including airway smooth muscle (ASM), airway epithelium, lung fibroblasts, and T lymphocytes.

Aberrant GPCR signaling or exaggerated presentation of GPCR stimuli can promote ASM hyper contractility, airway remodeling, and ASM hyperplasia/hypertrophy, all of which contribute to the pathogenesis of asthma and COPD. GPCRs appear to mediate important mitogenic and survival signaling pathways in cells comprising the tumor microenvironment- including epithelia, fibroblasts, stem cells, and inflammatory cells- rendering them potentially important therapeutic targets in the treatment of cancer. Many GPCR genes possess mutations that alter their expression or function. Researchers here are particularly interested in characterizing such altered function and its contribution to disease state or disease therapy.

Tonio Pera, PhD

The work in Dr. Pera’s laboratory combines expertise in physiology and pharmacology with GPCR biology and biochemistry with the goal of identifying GPCR ligands, which exploit novel signaling mechanisms to manage smooth muscle function and thereby treat cardiovascular and lung diseases. Drug development for cardiovascular and lung diseases has focused largely on refinement within the existing classes of drugs and on the use of combinations of these drugs. This strategy has led to improvements in disease management. As various classes of drugs have reached their full potential this strategy will yield diminishing returns. The concept of biased agonism that has emerged recently indicates that certain ligands of GPCRs may not only turn receptors on or off but also induce qualitatively distinct signaling by the receptors. The research aims to utilize this novel concept of biased agonism to fine-tune receptor signaling to eliminate detrimental, and promote beneficial, signaling in the pulmonary and vascular systems.

Research Projects

  • Applying novel GPCR biology and pharmacology to diseases involving smooth muscle dysfunction 
  • Identifying arrestin-biased muscarinic ligands and delineating muscarinic arrestin signaling in airway smooth muscle with the goals of treating asthma and COPD
  • Targeting specific eicosanoid receptors (EP prostaglandin, cysteinyl leukotriene) with novel subtype selective or biased ligands to manage excessive vascular smooth muscle growth that contributes to hypertension, heart attacks, and stroke

Maria Isabel Ramirez, PhD

Dr. Ramirez's laboratory is studying novel genetic and epigenetic mechanisms of gene regulation that drive the differentiation of distinct epithelial cell lineages during lung development, and the potential alteration of these mechanisms in lung disease. During embryo development, these mechanisms control the precise spatial and temporal patterns of gene expression that are critical for organogenesis of a functional lung ready for the first breath at birth. In adults, patterns of gene expression also have to be maintained to preserve a healthy lung. Understanding these basic mechanisms in development will, in the long-term, provide the basis to find improvements of fetal lung maturation and to understand altered cell phenotypes in lung disease.

Research Projects

  • Function of Novel Long Non-coding RNAs in Lung Epithelial Cell Differentiation
  • Epigenetic Control of Lung Epithelial Cell Differentiation Through Lifespan and Disease
  • Transcription Factor Networks in Lung Epithelial Cell Differentiation

For more information, visit the Ramirez Laboratory page.

Jesse Roman, MD

The Roman lab focuses on evaluating the mechanisms regulating lung tissue remodeling and their role in acute and chronic lung disorders.  A key aspect of tissue remodeling relates to alterations in the expression, assembly, and turnover of extracellular matrices like fibronectin and collagen. These processes are regulated during lung development and during lung injury and repair, and are aberrant in disorders ranging from emphysema and asthma to pulmonary fibrosis and lung cancer.

Alterations in the extracellular matrix of the lung affect cell function as cells recognize these molecules through integrin receptors capable of signal transduction. Consequently, alterations in extracellular matrix composition or recognition will lead to abnormal lung development or disrepair after injury.

Considering the importance of these mechanisms of action, Dr. Roman’s team is exploring how environmental and host factors control extracellular matrix expression in lung, and how these events affect lung injury and disrepair. This work has led to discoveries related to oxidative stress (with implications to lung injury and aging), nicotine (with implications for tobacco-related disorders like COPD), alcohol (which is relevant to acute lung injury and infection), and lung cancer.

Dr. Roman is also engaged in clinical and translational studies evaluating new interventions in idiopathic pulmonary fibrosis.

Freddy Jose Romero, PhD

The Romero laboratory focuses on understanding the molecular mechanism by which cells maintain the proteostasis network and how aging and environmental factors can significantly impact the proteome and trigger fibrotic disorders. Romero and his team are particularly interested in the protein quality control mechanism that operate in the cytosol, mitochondria, and endoplasmic reticulum (ER) and how they affect cellular function and viability during stress and aging. They utilize genetic, biochemical, cellular, and physiological experimental approach and employ systems that include epithelial cell line, mice and human tissue. The goal is discovery novel therapeutics approach to pharmacologically restore the proteostasis network to control or delay progression of fibrotic disorders. 

Research Projects

  • Role of the SCF (FBXO42) complex ubiquitin ligase in HPS pulmonary fibrosis
  • Cross-talk between mitochondria and the ubiquitin-proteasome system (UPS) in pulmonary fibrosis
  • Role of mitochondrial unfolded protein response (UPR (mt))in cellular senescence

Ross Summer, MD, PhD

The Summer laboratory is a basic science laboratory whose overarching goal is to develop novel treatments for patients with various lung disease including Acute Respiratory Distress Syndrome and Pulmonary Fibrosis.

Research Projects

  • Elucidate the mechanisms by which obesity promotes the development of ARDS.
  • Elucidate the mechanisms by which chronic alcohol exposure promotes the development of inflammatory lung diseases.
  • Determine how metabolic disturbances in the lung epithelium contribute to the pathogenesis of pulmonary fibrosis.  

For more in formation, visit the Summer Laboratory page

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Your donations play a critical role in our research. By supporting the Jane & Leonard Korman Respiratory Institute, you assist in the development of the latest treatments that affect the lives of patients who walk through our doors every day.