Breathe Easy: Researchers relentlessly pursue solutions to lung disease to help people breathe easier and live longer

By Sandra Sarr

There is no yesterday in your lungs 
there is no tomorrow either 
there is only now 
there is only inhale  
there is only exhale 
there is only this moment 
—excerpted with permission from a poem by John Roedel

 

 

 

 

 

 

 

 

The function of lungs is a subject most take for granted since breathing does not require thought. Our lungs usually do their job effortlessly and reliably. When they don’t or can’t, medical intervention becomes necessary. Breath is essential to life. And when available medical interventions do not offer sufficient relief, new discoveries become a lifeline.

At the Center for Lung Biology and Disease (CLBD), a Center of Biomedical Research Excellence (COBRE) at LSU School of Veterinary Medicine, some of the best and brightest minds are taking aim at all manner of life-threatening respiratory diseases, including bacterial and viral lung infections, asthma, and acute lung injury. Backed by more than $11.5 million in funding from the National Institutes of Health, the CLBD has proven itself a true center of excellence where discoveries are in progress to alleviate human suffering.

Lung diseases are an increasing problem, especially in babies, the immunocompromised and the elderly. Louisiana is among the top five states most affected by pulmonary diseases. The overarching goal of the CLBD is to gain new insights into the pathogenesis of devastating lung diseases that will guide improved strategies to treat and prevent lung diseases in humans.

 
A powerful contributor to LSU Vet Med’s discover mission, the CLBD augments research on campus in the molecular and cellular immunological mechanisms of pulmonary and pulmonary-related heart diseases.

Research powerhouse

One measure of success is LSU Vet Med’s exponential growth in federally funded research programs. LSU Vet Med now ranks 8th in NIH funding among all U.S. veterinary schools, with NIH funding increasing by 55 percent within the last five years. The CLBD is a key contributor to this growth.  

CLBD researchers have earned 14 NIH-funded grants and pursued projects spanning numerous aspects of lung biology and disease, including three of the main pillars of research at LSU Vet Med: 1) infectious diseases, 2) immunology, and 3) inhalation toxicology.  

“The goal of the CLBD aligns with LSU Vet Med’s overarching strategic plan, which advocates for research Centers of Excellence (COE) that highlight existing and future faculty research strengths and also emphasizes biomedical research aimed at improving the health and wellbeing of Louisiana’s citizens,” according to Dr. Tammy Dugas, co-principal investigator, Everett D. Besch Professor, Associate Dean for Research and Graduate Education.

“Many of the CLBD investigators focus on multiple aspects of lung research, including the COVID-19 pandemic. Research findings of the CLBD investigators will improve the understanding of the human body’s defenses in order to develop effective therapeutics and vaccines against devastating lung diseases that can cause acute lung injury and its severe form, acute respiratory distress syndrome, which is the primary complication in COVID-19 infection in humans,” according to Dr. Samithamby (“Jey”) Jeyaseelan, co-principal investigator, Dr. William L. Jenkins Professor in Veterinary Medicine and Professor in the Department of Pathobiological Sciences.  

Expanding discoveries

Funding comes from the NIH Centers of Biomedical Research Excellence, or COBRE program, which seeks to promote the initiation and development or expansion of unique, innovative, state-of-the-art biomedical and behavioral research centers at institutions in states that historically have received low levels of support from NIH, including Louisiana.

“The COBRE grant has succeeded in its purpose, allowing us to recruit young investigators, support their research, and position them to obtain their own federal funding for their projects. Already, our individual investigators have generated 14 external grants amounting to $23,511,328 in federal dollars in addition to the initial COBRE grant, which amplifies their research output and productivity,” Dr. Dugas said.

According to the NIH, COBRE support comes in three sequential five-year phases: Phase I focuses on developing research infrastructure and providing junior investigators with formal mentoring and research project funding to help them acquire preliminary data and successfully compete for independent research grant support. Phase II seeks to strengthen each center through further improvements in research infrastructure and continuing development and support of a critical mass of investigators with shared scientific interests.  

In addition to the $11.5 million for its initial five years, the grant is renewable for two additional five-year terms for a total of more than $32 million. After five years of Phase I support, centers are expected to be able to compete successfully for other sources of research funding, such as program project or center grants from other NIH institutes and centers or other funding sources.  

Phase III transitional centers provide support for maintaining COBRE research cores developed during Phases I and II, and sustain a collaborative, multidisciplinary research environment with pilot project programs and mentoring and training components.  

“This grant focuses on lung disease, which is an ongoing area of breakthrough research done by the investigators at the LSU Vet Med,” Dr. Jeyaseelan said. “This is an outstanding opportunity for a group of new and early-stage investigators to get their research programs off the ground and to flourish. It sets essential milestones in research that they must fulfill and includes the remarkable value of personalized mentoring. It is indeed an awesome program.”

“The team of young investigators inspire each other. Synergies between them help propel their research. They are positioned to build their own federally funded research programs at LSU to further their research,” Dr. Dugas said.  

Co-principal investigators, Drs. Jeyaseelan and Dugas have assembled a team of outstanding investigators with advanced knowledge and research expertise across different colleges on LSU campus to address immunological mechanisms contributing to numerous infectious and non-infectious pulmonary diseases.  

“Working together, they can tackle research problems that they may not have tried on their own,” Dr. Dugas said.

Breath work  

Meet the CLBD project investigators  and their discoveries-in-progress:

Weishan Huang, PhD (project investigator, LSU Vet Med)

Dr. Huang investigates the influence of genetics and environment on how lung diseases progress and explores new therapies for respiratory viral infections such as flu and COVID-19. She studies host-virus interactions, immune responses to infections and vaccinations, mechanisms of immunopathology, and strategies for preventing and treating respiratory viral infections. Dr. Huang’s research utilizes the interdisciplinary team expertise at the LSU Vet Med and CLBD including immunology, virology, pathology, molecular and cellular biology, bioengineering, and bioinformatics.

Yogesh Saini, DVM, PhD (project investigator, LSU Vet Med)

Dr. Saini’s interdisciplinary research deals with the cellular and molecular mechanisms associated with allergic asthma, ozone-induced airway disease, and secondhand smoke-induced COPD. Patients with asthma develop pulmonary exacerbations due to heightened immune responses. Current treatments, such as corticosteroids, aim to suppress immune responses and thus put these patients in the immunocompromised health status. He looks at the role of macrophages (virus-fighting front-responder cells in the airways of lungs) in asthma outcomes.  

Alexandra Noël, PhD (project investigator, LSU Vet Med)

More than 13 million Americans engage in vaping or use of an electronic nicotine delivery system (ENDS). Dr. Noël researches how vaping affects health outcomes. There are few reports concerning vaping during pregnancy and no studies on asthma in prenatally JUUL (e-cigarette)-exposed offspring. Dr. Noël is testing the hypothesis that in utero JUUL exposure causes unfavorable birth outcomes and lasting pulmonary health effects. Research shows that inhalation of JUUL aerosols during pregnancy affects the intrauterine environment, impairs lung development, and heightens the effects of allergic airway responses later in life.

Xing Fu (project investigator, LSU AgCenter)

Fibrosis is common in diseases and injuries of tissues and organs, including heart failure-induced cardiac fibrosis and pulmonary fibrosis. Fibrosis is a disease that results when tissue becomes damaged or scarred. In regenerative tissue, such as skeletal muscle and lung, acute injury-induced fibrosis is usually temporary and resolves spontaneously when regeneration is accomplished. The fate and function of fibroblasts in chronic fibrosis are not very clear. Dr. Fu’s research delineates the mechanisms by which fibroblast proliferation and differentiation activities impact the development of left ventricular heart failure-induced cardiac fibrosis and pulmonary fibrosis.

Chen Chen (project investigator, LSU College of Science)

Staphylococcus aureus-associated pneumonia accounts for about 50,000 infections per year in the U.S. and is one of the leading agents of ventilator-associated pneumonia. S. aureus pneumonia has a high rate of mortality due to antibiotic resistance and lack of an effective vaccine. During pulmonary infection, the neutrophil influx is a double-edged sword: neutrophils clear the invading pathogens, or overzealous neutrophils may cause tissue damage leading to pneumonia. Hence, understanding the mechanisms by which S. aureus keeps lung neutrophils at rest is crucial to decipher how S. aureus maintains its silent colonization state and when/how its presence becomes pathogenic. Dr. Chen’s research focuses on revealing a potential new therapy to treat pneumonia associated with massive neutrophil migration.

Mariano Carossino, DVM, PhD, Dipl. ACVM, Dipl. ACVP (project investigator, LSU Vet Med)

Dr. Carossino studies virus-host interactions during respiratory and persistent viral infections. Obesity and type 2 diabetes affect a large proportion of the U.S. population. Those with these metabolic diseases are at least three times more likely to develop severe COVID-19 or influenza infections necessitating intensive care. Dr. Carossino is focused on dissecting the cellular mechanisms influencing the pathogenicity of viral respiratory infections and driving this increased susceptibility in this at-risk population.  

Basel Abuaita, PhD (project investigator, LSU Vet Med)

Antibiotic-resistant Staphylococcus aureus infection is a major public health threat in the lung and extrapulmonary organs.  It is unclear whether stress responses aid or impede pulmonary immunity. Dr. Abuaita’s research explores mechanisms by which cellular stress responses in innate immune cells aid in bacterial clearance in the infected lung. Discoveries may reveal new approaches for treating respiratory infections caused by antibiotic-resistant bacteria.  The goals are to define how these stress pathways control the function of innate immune cells of the lung and to test whether modulators of these cellular stresses can help to defend the lung against infection. 

William Beavers, PhD (project investigator, LSU Vet Med)

Staphylococcus aureus, the leading cause of skin and soft tissue infections, causes over 900,000 severe infections annually in the U.S. It is increasingly resistant to commonly used antibiotics. We define how the host kills S. aureus and how S. aureus avoids killing by the host at the molecular level, focusing on antimicrobial protein post-translational modifications. Taking an interdisciplinary approach, combining analytical chemistry, bacteriology, bacterial pathogenesis, and chemical biology, both in vitro and in vivo, we identify and validate S. aureus therapeutic weaknesses for targeting by the next generation of antimicrobials that will enhance our ability to treat S. aureus infections. 
“The lung COBRE grant is working as it was intended. The first generation of lung COBRE scientists are now joining the team as leaders, and they will go on to mentor others,” Dr. Dugas said of a program that, each moment, builds toward discoveries to help people breathe easier. 

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