Download Zeroing in on infectious disease

PROFESSOR COLLEEN JONSSON
Zeroing in on
infectious disease
The Center for Predictive Medicine for Biodefense and
Emerging Infectious Diseases at the University of Louisville
is dedicated to conducting basic and translational research
into infectious diseases, with the help of the Regional
Biocontainment Laboratory’s Shared Resources Services
THROUGH ITS IMPORTANT and timely
work, the Center for Predictive Medicine for
Biodefense and Emerging Infectious Diseases
(CPM) aims to improve human health by
developing effective diagnostic biomarkers,
vaccines, antivirals and therapeutics for
emerging, neglected rare infectious diseases.
It also aims to protect national security by
guarding against biothreats. The CPM is well on
its way to meeting these goals thanks to the
innovative work of the researchers it supports.
Colleen Jonsson, PhD, Director of the
CPM, Professor of Microbiology – as
Director of the CPM, Jonsson is in charge
of guiding and working towards the goals
of the Center and its members. In the
laboratory setting, Jonsson’s work uses in
vitro and animal models to address virushost interaction. Her research programme
is focused on the recent 2009 H1N1
influenza virus and hantaviruses.
William E Severson, PhD, Director of the
Regional Biocontainment Laboratory (RBL)’s
Shared Resources Services – the new RBL
is an integral addition to the CPM that has
Biosafety Level 2, Biosafety Level 3 and Select
Agent facilities that are utilised for basic and
applied research concerning the creation of
biomarkers, vaccines, antivirals and therapeutics
for infectious diseases. As the leader of the new
RBL, Severson is directing its dedicated staff to
ensure the lab’s state-of-the-art equipment is a
useful cornerstone in translational partnerships,
both internally and externally.
Donghoon Chung, PhD, Assistant
Professor of Microbiology – Chung’s
laboratory studies the replication
mechanism of alphaviruses, which can be
found across the globe, and infect humans
and equines via mosquitoes. To study the
molecular mechanism in an explicit way,
his lab is using high-throughput screening
techniques to discover small molecules
that probe the biology of alphaviruses.
He is also interested in developing
these molecules into therapeutics for
viral diseases.
Matthew Lawrenz, PhD, Assistant
Professor of Microbiology – Lawrenz’s
laboratory is defining the early events that
occur during plague infection (a re-emerging
disease and potential bioterrorism weapon)
to discover how to better prevent and treat
human plague. Specifically, his lab is studying
how Yersinia pestis, the bacterium that
causes the plague, colonises its human host.
His goal is to use this information to design
better vaccine and therapeutic candidates for
the plague.
Michael Hughes, MD, Director of Pancreas
Transplantation, Assistant Professor of
Surgery – Hughes’ laboratory is focused
on chronic infection with the Hepatitis C
virus (HCV – a leading cause of cirrhosis,
liver failure and liver transplantation
worldwide). Few treatment options have
existed for HCV until recently. With
multiple new agents coming to market to
treat HCV infection, Hughes is working to
characterise viral adaptation, mutation and
evolution during treatment.
Jonathan Warawa, PhD, Assistant Professor of
Microbiology – Warawa’s laboratory is studying
bacterial respiratory pathogens, with a special
focus on the biodefense pathogen Burkholderia
pseudomallei. The pathogen causes a fatal
septicaemic disease. It is intrinsically resistant
to several classes of antibiotics and has been
identified as a Tier 1 Select Agent pathogen
since it is a potential bioweapon. Therefore,
the lab’s research into the respiratory disease
the pathogen causes is significant for treating
the naturally occurring disease and for
biodefense preparedness.
Igor Lukashevich, MD, PhD, Professor of
Pharmacology – Lukashevich’s laboratory
covers two major areas: pathogenesis
of viral haemorrhagic fevers (VHF) and
vaccine research and development. The
lab has achieved great success so far
with the reassortant ML29, a vaccine
candidate against Lassa fever, the most
prevalent VHF in Africa. The ML29 is safe
and effective as a preventive vaccine and a
post-exposure treatment.
Haixun Guo, PhD, Assistant Professor of
Radiology – Guo’s laboratory leads the
radiochemistry and molecular imaging
probe development programme. It focuses
on developing novel positron emission
tomography and single photon emission
computed tomography probes to image
inflammation and infection.
Yousef Abu Kwaik, PhD, Bumgardner
Chair in Molecular Pathogenesis,
Department of Microbiology and
Immunology – Abu Kwaik’s laboratory is
examining cell and molecular biology of
the intracellular infection from Legionella
and Francisella. The research aims to
uncover potential targets for therapy
and prevention of diseases caused by the
two organisms.
Jill Steinbach, PhD, Assistant Professor of
Bioengineering – Steinbach’s programme
is initiating research into designing and
developing drug and gene delivery vehicles
and new nanomaterials that provide more
efficacious prophylactics/therapeutics for
sexually transmitted infections, including acute
and chronic (latent) infections.
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PROFESSOR COLLEEN JONSSON
Decimating
infectious diseases
Researchers based at the Center for Predictive Medicine for Biodefense and Emerging Diseases at
the University of Louisville, Kentucky, are using pioneering methods and shared resources to address
critical research questions surrounding rare, neglected, emerging and re-emerging pathogens
IN THE LAST quarter of the 20th Century,
many of the pathogens underlying previously
eradicated diseases have re-emerged as deadly
foes once more. Even today, they are adapting,
changing and developing a resistance to the drugs
used to treat them. Additionally, new, previously
unidentified pathogens have emerged from the
environment. The Center for Predictive Medicine
for Biodefense and Emerging Diseases (CPM) at
the University of Louisville (UofL) in Kentucky,
USA, is performing cutting-edge research to
reverse and overcome these trends.
The Center’s goal is to engage in exceptional
translational research that will one day lead to
diagnostic biomarkers, vaccines, antivirals and
therapeutics for new and re-emerging pathogens
and biothreats. The CPM’s work, which is directed
by Dr Colleen Jonsson, is not only important
to human health, but also to US national
security, as its scientific experts and facilities
are ready to serve in the event of a pandemic or
bioterrorism emergency.
THE CENTER’S RESEARCH
The faculty who work in the CPM focus
their attention on four different areas:
rare, neglected, emerging and re-emerging
pathogens research. For example, Drs Michael
Hughes and Jill Steinbach are researching
Regional Biocontainment Lab.
36INTERNATIONAL INNOVATION
the mechanisms of pathogen colonisation
and invasion of host cells, while Drs Jonathan
Warawa, Matthew Lawrenz and Yousef
Abu Kwaik are studying the mechanisms of
microbial virulence. Lawrenz is also examining
pathogen replication in host cells, as is Dr
Donghoon Chung. Finally, Jonsson herself is
rolling up her sleeves to pin down the details
of the host immune mechanisms that respond
to and clear infection. The ultimate goal behind
these endeavours is to identify new therapeutic
targets through basic discovery research and
to pair this work with translational research
to develop new drug and vaccine candidates,
whole live animal imaging probes and drug
delivery systems.
CROSSING DISCIPLINES
FOR INNOVATIVE IDEAS
A cross-disciplinary approach is crucial to the
success of the CPM’s novel research. Sometimes
these collaborations are forged solely within
the Center, as the diversity of complementary
expertise in microbiology, virology and radiology
on hand means that the CPM can provide a bridge
to connect multiple disciplines in one forum.
“The cross-disciplinary approach of the CPM has
opened several new avenues of research in my
laboratory,” enthuses Lawrenz, who researches the
plague at the CPM.
“The opportunity to
collaborate with cell
biologists and experts
in
high-throughput
biology within the CPM
has allowed us to take
unique
approaches
to studying hostpathogen interactions
that we had not
previously considered.”
In fact, through his
collaborations, Lawrenz
was able to initiate the
first
genome-wide
screen to identify
host proteins that Yersinia pestis uses to survive
within macrophages.
However, just as often as not, CPM collaborations
are happening not only across disciplines, but also
across state and country borders. For example,
CPM researchers are engaged in collaborations
ranging from the Infectious Disease Department
at the Cincinnati Children’s Hospital to the Pasteur
Institute in Paris.
INTRODUCING THE REGIONAL
BIOCONTAINMENT LABORATORY
A cross-disciplinary and collaborative approach
is also central to the Regional Biocontainment
Laboratory (RBL), which opened under the
umbrella of the CPM in autumn 2010. The
RBL stands as a critical regional, national and
international shared resource for scientists
engaged in translational research with lethal
pathogens requiring Biosafety Level 3 (BSL-3)
containment. The RBL was built as one of 11 BSL-3
facilities that the National Institute for Allergy and
Infectious Diseases commissioned after the 9/11
terrorism attack and anthrax mailings in 2001.
Due to the lethal nature of the pathogens under
examination in the RBL, it has been built to the
most rigorous standards, and it is certified for use
by the Centers for Disease Control and Prevention
and US Department of Agriculture Select Agents.
In addition to being built with safety in mind,
the RBL received recognition for its ‘green
design’. The US Green Building Council awarded
it the silver level from the Leadership in Energy
and Environmental Design programme, which
encourages the energy efficient, environmentally
friendly design of modern buildings.
SHARING RBL RESOURCES
In 2011, the CPM created a Shared Resources
Service Center to support internal and external
users of the RBL. The Shared Resources within
the RBL are under the direction of Dr William
Severson. He works collaboratively with users
from UofL, external academics and commercial
INTELLIGENCE
UofL CPM Regional Biocontainment Laboratory ABSL-3.
CENTER FOR PREDICTIVE MEDICINE
FOR BIODEFENSE AND EMERGING
INFECTIOUS DISEASES
OBJECTIVES
New and re-emerging pathogens and the
diseases they cause pose a continued threat to
humanity, whether they stem from natural or
intentional causes. The mission of the Center
is to support basic and translational research
to advance scientific understanding of these
pathogens; and to promote the development
of countermeasures for emerging and
biothreat pathogens.
PARTNERS
Unites States Army Institute of Infectious
Diseases • Western Kentucky University •
Purdue University • Texas Tech University
• NIH Rocky Mountain Laboratory • NIH
Center for Infectious Disease Imaging,
Harvard University • University of Kansas •
Kansas State University
clients to conduct their translational research
utilising high-tech instruments – the Siemens
PET/SPECT/CT tri-modality scanner, Caliper
Life IVIS Spectrum and Zeiss LSM 710/LIVE 5
confocal microscope. Users have access to these
instruments through five Core services: BioImaging, Immunology, Microbiology, Animal
Models and High Throughput Biology (HTB).
“The Shared Resources, especially the Animal
Models Core, play an important role in the imaging
probe development research. They enable us to
evaluate the imaging probes for BSL-3 pathogens
in vitro and in vivo,” states Dr Haixun Guo, who is
Assistant Professor of Radiology in the UofL School
of Medicine and an avid RBL Shared Resources user.
PROVIDING A SERVICE
Both the equipment and Cores assist its users with
a number of otherwise impossible, timely or costly
tasks. The HTB Core, for example, provides support
for DNA sequencing, a quantitative reverse
transcription polymerase chain reaction (qRTPCR), assay development and implementation
and high-throughput screening of small molecule
chemical and siRNA genome libraries. The BioImaging Core, on the other hand, makes use of
the Siemens PET/SPECT/CT Trimodal to assist
scientists in high-quality molecular imaging and
pharmacokinetic study of radioactive compounds.
With this sort of data, it is then possible to
understand the natural history of infection in
animal models as well as define the biodistribution
and efficacy of small molecules and vaccines.
Staff members that manage and support the
Core facilities are working hard to provide access
to these exceptional services by collaborating
with companies and institutions across the globe.
“There are a number of possible types of usage,”
states Severson. “An investigator may collaborate
with CPM or UofL faculty to submit grants and
contracts or work with the RBL Shared Resources
staff for regulatory support. Moreover, external
investigators may directly access the facility and
publish their findings independently with UofL
regulatory oversight.”
Despite these services having only been around
for a short period, there is already significant
evidence of knowledge sharing and collaboration
taking place with internal and external partners.
“The construction of RBL was the major reason
for relocating my research programme from
University of Maryland to UofL,” explains Dr Igor
Lukashevich, who is a Professor of Pharmacology
in the UofL School of Medicine. “The powerful
live-imaging technology provided as a part of the
Shared Resources is a unique feature of RBL.”
Jonsson is proud of the collaboration opportunities
and improved research quality to which the unique
BSL-3 Shared Resources Service Center has given
way. She states: “We want to bring visibility to
our resources and outreach aims to foster regional
and national partnerships as well as bring external
fee-for-service research to the RBL. The Center is a
benefit for all who use it”.
EXPANDING THE LABORATORY
In 2009, Jonsson petitioned the National Institutes
of Health (NIH) to expand the RBL’s facilities, and
for her efforts, she received US $9.8 million to
do the job. This expansion, which will also be of a
green design, will be completed in summer 2014.
The extension will take the RBL’s state-of-theart biosafety facility to a whole new level. For
example, the changes will facilitate translational
studies in animal models, such as mice and ferrets,
and it will permit preclinical evaluation and realtime data upload of vaccines and antivirals. At
present this is impossible in the facility’s current
configuration. Moreover, the changes to the RBL
will shepherd in many value-adding benefits,
such as hands-on animal BSL-2 clinical procedure
training and enabling full diagnostics of vaccine,
therapeutic and antiviral countermeasures by
supporting clinical chemistry, haematology and
pathology activities.
FUNDING
National Institutes of Health (NIH)
Commercial Partners
CONTACT
Professor Colleen B Jonsson
Director
Clinical & Translational Research Building
Sixth Floor, 505 South Hancock
Louisville, Kentucky 40202
USA
T +1 502 852 5773
E [email protected]
Dr William E Severson
Director, Shared Resources Service Center
T +1 502 852 1546
E [email protected]
http://centerforpredictivemedicine.org
COLLEEN JONSSON joined the University
of Louisville in 2008 as Director of The Center
for Predictive Medicine for Biodefense and
Emerging Diseases (CPM) and Professor of
Microbiology. In addition to recruitment
of faculty to the new Center, she led the
completion of the construction, commissioning
and in autumn 2010 celebrated the opening of
the Regional Biocontainment Laboratory (RBL).
WILLIAM SEVERSON joined the CPM IN 2011
to lead the management of the RBL. Since
opening, Jonsson and Severson have worked
with numerous academic, government and
commercial institutions in the pursuit of new
targets, small molecules and vaccines for
deadly pathogens.
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