The Oklahoma State University (OSU) Center for Veterinary Health Sciences (CVHS) this year received a grant of almost $11.3 million from the National Institutes of Health (NIH) to establish the Oklahoma Center for Respiratory and Infectious

Diseases. Firstly, congratulations! Could you discuss the significance of this award for you?

This award is aimed at helping us to build infrastructure in the State. Respiratory disease has been a focus area here for several decades; first, largely dealing with respiratory disease in cattle, a major economic driver in the State. There has been a lot of excellent work done here by individuals, beginning in the 1960s with Drs Roger Panciera, Richard Corstvet and Harold Rinker. Later, there was work on vaccines against the main pathogens thought to be responsible for the disease. More recently, Drs Anthony Confer and Robert Fulton have performed exciting research on the pathogenesis of the disease and the host-pathogen interactions; the ultimate goal is to develop protective vaccines. Drs Douglas Step and Jared Taylor have been working to characterise the pathogens implicated in the disease to understand what changes may be occurring in the sick versus healthy animals.

As the recipient of the first Center of Biomedical Research Excellence (COBRE) grant in Oklahoma State’s history, what does this award mean both for CVHS, and in a broader context, for Oklahoma?

Oklahoma as a state has been pretty successful over the years in competing for these awards. There are many benefits to show for this effort. Strategically, it is to our advantage to collaborate and help one another across the institutions. This award gives us the opportunity to showcase our contributions to the larger biomedical sciences effort in the State. I believe our biomedical science community here considers the veterinary college an important asset and resource, and we now have a stage to show what we can do, providing leadership and building teams.

Who are the grant’s main investigators?

The Principal Investigator is Dr Lin Liu. He has brought together a team of senior investigators

Dr Jerry Malayer and colleagues shed light on their work towards investigating respiratory disease in animals and humans, and their reaction to winning a grant of more than US $11 million to establish a new programme

All creatures great and small

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THE POSSIBLE APPLICATIONS of a better understanding of veterinary medicine are often underestimated. As well as obvious advances in the treatment of companion animals and numerous agricultural applications, research into veterinary medicine also has the power to bring about improvements in human health. Zoonotic diseases, for example, which include leptospirosis and rabies, are afflictions equally applicable to animals and humankind; parasites, similarly, can often cause health problems for both groups. In the environment, anthropogenic changes to habitats and altered land use will produce effects felt first in animal populations, and worldwide the transport of animals and animal products by humans is changing the way animal diseases behave. The link between human and animal health is not widely appreciated, even in the wake of public health threats such as avian and swine influenza.

In the US, bovine respiratory disease (BRD) is the most costly disease affecting the beef cattle industry. It is estimated that it takes an annual toll of US $800 million on a $4.6 billion business. Part of BRD is the action of respiratory viruses, some of which are related to critical viruses affecting humans, including coronaviruses resembling the virus responsible for SARS, and bovine respiratory syncytial virus (RSV), a virus that is closely related to human RSV. In humans, RSV is responsible for the deaths of more than 100,000 children annually – and infects almost every person on the planet at one time in their life. Another problematic lung disease for humans is chronic obstructive pulmonary disease, the fourth leading cause of death in the US; one approach to the study of this disease is observing its effects in animal models.

A CHRONIC SHORTAGE

Despite the great need for veterinary science as part of effective medical research to resolve these issues, the 50 US states are home to only 28 veterinary colleges; questions specific to veterinary medicine are, in general, under-researched. In an effort to try to redress this issue, the Center for Veterinary Health Sciences (CVHS) at Oklahoma State University (OSU) conducts extensive comparative research into respiratory diseases, and has also recently won an $11.3 million grant to establish a new centre: the Oklahoma Center for Respiratory and Infectious Diseases (OCRID). Although a relatively small institution, its focus on collaboration and a mix of applied and basic research have allowed it to achieve successes that belie its select team.

In addition to these commitments, the CVHS also performs a vital role serving as Oklahoma’s only veterinary college. Historically, and continuing into the present day, Oklahoma’s state economy has been largely based on agriculture, with cattle being a particularly important economic driver. The CVHS not only supplies the state with a steady stream of trained veterinarians, but also provides critical advances in the understanding of disease processes important to the industry.

CREATURE COMFORTS

The story of CVHS’ success begins with its interest in livestock, and especially BRD; in fact, researchers at OSU have been pursuing this disease for decades. Collaborators Dr Jared Taylor and Dr Douglas Step of the CVHS have brought veterinary science closer to an understanding

Veteran veterinariansThe Center for Veterinary Health Sciences at Oklahoma State University is home to a number of research teams working on a variety of pressing health issues. Following a Centers of Biomedical Research Excellence grant, the remit of their work is set to expand

to mentor the younger scientists. We currently have four specific research projects that are central to the grant, each led by one of these younger scientists. There is additional funding for smaller competitive grants for which people across the State may apply. The goal is for these younger scientists, through the funding and mentoring, to establish themselves as independent investigators.

According to a World Health Organization (WHO) report, in 2004 respiratory infection had a greater global burden of disease than any other condition. Has the situation since improved? What role has CVHS played?

This remains true, and makes respiratory disease such a critically important area for research. Whether in people or animals, the respiratory tract is pretty vulnerable to external insult. We can reduce the damage we do to ourselves by reducing smoking, promoting clean air, safe workplace practices, and so forth. Humans, animals and animal products now move rapidly around the world, and pathogens are adapting, finding new niches and jumping across species into new hosts, often through the respiratory tract. Co-mingling, whether it’s cattle or people, often results in increased incidence of respiratory disease. I think comparative approaches to understanding these diseases have considerable value.

Can you briefly describe what your roles at the veterinary Center entail? Are your duties set to change following the establishment of the Oklahoma Center for Respiratory and Infectious Diseases?

I serve as Associate Dean for Research and Graduate Education in the Center for Veterinary Health Sciences at Oklahoma State University, where I have been on the faculty since 1994; I am a Professor in the Department of Physiological Sciences and Adjunct Professor in the Department of Biochemistry and Molecular Biology. In addition to promoting our faculty and programmes, I have responsibility for research development in CVHS, including strategic planning, project management and partnerships. I interact with university administration on regulatory compliance, grants and contracts management, intellectual property management, and university-industry relations. The grant will not affect my duties, but Dr Liu will have greater administrative responsibility than before.

NIH recognises the excellence of the research into infectious diseases being conducted in Oklahoma. To what can CVHS’s award be attributed specifically?

The excellent science is certainly an important part of this, but equally important is the quality of the interactions across the institutions, the mentoring environment that has been created, and the network and partnerships we have formed.

Dr Lin Liu is Principal Investigator on the Center of

Biomedical Research Excellence grant and leads the Respiratory

Disease Center.

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of BRD through their research – which has most recently been concerned with genetically characterising two bacteria known to commonly be associated with the disease: Mannheimia haemolytica and Pasteurella multocida. The main objective in this endeavour is to determine what role these two species play in the development of BRD; although they contribute to the disease, their presence in the nose or lungs of cattle does not provide a definitive indicator of infection – and the OSU researchers want to know why.

Step has more than 25 years’ experience as a practicing veterinarian, and he uses the opportunity this work provides to collect samples which Taylor then processes. As part of their investigations, the pair utilises a four-point scale of severity for BRD, and the criteria they have developed for identifying cattle suffering from the disease have been so efficient that they are now used in many parts of the industry. OSU’s work concerning BRD has led to practical solutions to minimise the incidence of the disease in their herds – an achievement in line with their goal of providing practicable approaches to help owners and cattle.

A WEALTH OF EXPERTISE

Although this work is in many ways the fundament of the CVHS’ research, a diversity of projects are in progress, and the grant for the new OCRID is a result of the overall impact of the research programme on Oklahoma. Dr Tom Oomens, for example, has been focusing on the treatment of RSV, building up information about the disease in the hopes of eventually producing a vaccine. Dr Lin Liu’s team, which focuses on chronic obstructive pulmonary disease, among other aspects, was responsible for securing the grant; the group has been investigating the disease for some time, and has recently conducted experiments on rodent models to investigate the possibility of combating the affliction with adult stem cells.

FUNDING THE FUTURE

The new grant includes four primary projects. The first of these is led by Oomens, and focuses on continuing his work with RSV – which could contribute to the development of a safe and

effective vaccine for the disease. He has developed a novel system to study the role of the RSV M protein in virion assembly and production. Another project will rely on the tissue engineering expertise of Dr Heather Gappa-Fahlenkamp, in OSU’s School of Chemical Engineering. The objective of this endeavor is to develop a tissue-equivalent respiratory model for infectious diseases research.

The third project comes from the Department of Pharmaceutical Sciences at the University of Oklahoma. Dr Shanjana Awasthi has developed a novel surfactant protein-A-based immunomodulatory peptide, and her project aims to test whether this peptide can be used to alleviate lung inflammation and infection. Finally, Dr Telugu Narasaraju will investigate the contribution of neutrophils to influenza virus pneumonia, and test a combined drug therapy for treatment of this condition. This project may result in more effective treatment of influenza infections.

SECONDARY OBJECTIVES

A fundamental goal of the grant from the CVHS’ point of view is the development of additional scientific expertise in the state; as such, an integral part of the work will be to develop a mentoring programme to guide junior investigators. The goal is to have the young scientists develop independently-funded programmes after two or three years, making room for more recruits; within five years, the Center hopes to have graduated between five and eight new researchers. Both external and internal advisory committees will provide additional advice to the younger faculty members, as well as monitoring their progress.

A second important objective of the grant project is to expand the research infrastructure to support these new researchers and the new center; this will be done through the establishment of scientific research cores. Further, it is hoped that the new center will be a hub for increased collaborative efforts within the state – and the grant recipients will take measures to ensure that this happens. After five years, there is a possibility that the grant could be renewed for another five-year period if it has proved successful; this will allow the already ambitious programme to continue to expand for the next decade. This would be a development hugely beneficial to the human residents of Oklahoma – as well as its animals.

OKLAHOMA CENTER FOR RESPIRATORY AND INFECTIOUS DISEASES

OBJECTIVES

Comparative research on diseases of the respiratory tract, whether caused by environmental stressors or pathogens; including pathogenesis, therapeutics, molecular mechanisms and bioengineering.

KEY COLLABORATORS

Center for Veterinary Health Sciences (CVHS), Oklahoma, USA:

Professor Lin Liu

Dr Antonius Oomens

Dr Heather Fahlenkamp

Professor Douglas Step

Dr Jared Taylor

Professor Robert W Fulton

Professor Anthony W Confer

Professor Michael Davis

FUNDING

The National Institutes of Health (NIH) • The US Department of Defense • The US Department of Agriculture • The Animal Health Pharmaceutical Industry • The State of Oklahoma • The Samuel Roberts Noble Foundation • The Animal Health Pharmaceutical Industry

CONTACT

Professor Jerry R Malayer, PhD Associate Dean, Research and Graduate Education

Oklahoma State University (OSU) Center for Veterinary Health Sciences 222 McElroy Hall Stillwater, Oklahoma 74078 USA

T +1 405 744 8085 F +1 405 744 0430 E jerry.malayer@okstate.edu

www.cvhs.okstate.edu

DR JERRY R MALAYER is Professor and Associate Dean for Research and Graduate Education in the CVHS at OSU. His research focuses on mechanisms of inter- and intracellular communication, the role of steroid receptors in the control of gene expression and molecular approaches in the development of diagnostic technologies.

Dr Robert Fulton leads critical research on bovine viral diarrhoea, an important contributing component of bovine respiratory disease.

Dr Michael Davis carries out groundbreaking work on responses to extreme exercise including effects on the respiratory tract.

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