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A P U B L I CAT I O N O F T H E LOV E L AC E R ES P I RATO RY R ES E A RC H I N ST I T U T E FA LL 2010
•
VOLUME 3, NUMBER 2
PICTURING BETTER MEDICINE: Philip Kuehl, Ph.D.
TAKING A SECOND LOOK AT THE EFFECTS OF SECONDHAND SMOKE: Mohan Sopori, Ph.D.
RESEARCHING THE HIGHS AND LOWS OF RADIATION: Bobby Scott, Ph.D.
As the country and our funding
sources struggle financially,
we continue to seek innovative
ways to support our work.
Our acquisition of a national science
staffing and service company, Sandia
Staffing Alliance, LLC., will boost our
yearly income above $125 million dollars.
(See sidebar on page 13.) This acquisition
will buffer the increasing demands for
more support to our scientists who are
leading research efforts in infectious
disease, COPD/emphysema, asthma,
lung cancer, inhalation toxicology,
environmental respiratory health,
and other programs.
Robert W. Rubin, Ph.D.
President and Chief Executive Officer
We continue to advance our close
relationship with the Brigham and
Women’s Hospital at Harvard by the
addition of new adjunct scientists
from Boston and three new major grant
efforts at NIH. We are appreciative of the
collaborations with clinical investigators
at Harvard who are working with us to
fund projects based on our long-standing
clinical cohort of smokers in Albuquerque.
Our bioinformatics and system biology
efforts got a boost this year with the
addition of Dr. Chris Hart, who is a leading
expert in the genetic bioinformatics and
biology of gene expression. Dr. Hart
is a joint appointment (50%) with the
New College of the University of South
Florida, and represents a new path for
LRRI collaborations. We have another nine
scientists at LRRI who work on quantitative
problems in respiratory disease, and
we are discussing with our Scientific
Oversight Committee the development of
a program in this rapidly expanding field.
A new area of study involves the
investigation of the epigenetics of
COPD/emphysema. We know that
smoking causes mutations in lung cells
and secondary modifications to the DNA
that can lead to cancer. We now find other
epigenetic changes to the genes in tissues
exposed to cigarette smoke that may lead
to COPD/emphysema. How important DNA
chemical modification is in causing this
devastating disease will be an important
part of our research effort.
Our drug development programs continue
with numerous new drug entities under
investigation and a wide variety of vaccine
and antibacterial protocols at the BSL2 and 3 levels. We have developed a
new working relationship with the CDC,
which began with the public health crisis
associated with swine flu. We developed
an animal model of flu transmission,
learned to grow the organism and supplied
large quantities for the World Health
Organization test kits during the peak
of the crisis. We continue to be a world
leader in studies of anthrax and plague.
Lastly, we have started to develop unique
animal models of pulmonary fibrosis.
This is a devastating, almost always
fatal disease for which there is no good
animal model to use as a basis for the
development of therapies. This is a new
area and program which I hope to report
upon in upcoming issues of Breathe.
Jackie Lovelace Johnson, Chair, Mission Hills, KS
W. Phelps Anderson, Roswell, NM
Frank Bond, Santa Fe, NM
Patricia Buffler, Ph.D., M.P.H., Berkeley, CA
Sonia Buist, M.D., Portland, OR
Norm Corzine, Albuquerque, NM
Jane L. Delgado, Ph.D., M.S., Washington, DC
Major General John Doesburg, Retired, Livermore, CA
David L. Durgin, Albuquerque, NM
Joe R.G. Fulcher, Sea Island, GA
Judy K. Jones, Albuquerque, NM
Donald E. Kilgore, M.D., Albuquerque, NM
Jack D. McCarthy, M.D., Albuquerque, NM
Pope Moseley, M.D., M.S., Albuquerque, NM
Barbara Rogers, New York, NY
Ernest Romero, Taos, NM
Robert W. Rubin, Ph.D., Albuquerque, NM
Catherine Sellman, Los Angeles, CA
John R. Shelton, Albuquerque, NM
Pam Sullivan, Albuquerque, NM
James A. Swenberg, D.V.M., Ph.D., Chapel Hill, NC
Melvin Twiest, M.D., M.S., Signal Mountain, TN
Robert W. Rubin, Ph.D.
LRRI Board of Directors
Contents
2
Who We Are
The Lovelace Respiratory
Research Institute (LRRI)
is a private, biomedical
research organization
dedicated to improving
public health through
research on the prevention,
treatment and cure of
respiratory disease.
Picturing Better Medicine
Philip Kuehl, Ph.D.
6
Taking a Second Look at the
Effects of Secondhand Smoke
10
Researching the Highs and Lows of Radiation
Mohan Sopori, Ph.D.
Bobby Scott, Ph.D.
Also:
14 Employee Highlights
15 Notes of Distinction
16 Board of Directors: Featured Members
A. Sonia Buist, M.D.
Jonathan M. Samet, M.D.
17 Financial Outlook
On the Cover
Philip Kuehl, Ph.D., Associate
Research Scientist in the
Chemistry and Inhalation
Exposure Program and
Manager of the Analytical
Chemistry Laboratory
Executive Editor
Robert W. Rubin, Ph.D.
Managing Editor
Kyla Thompson
Writer
Megan Fleming
Writing & Creative Services
Contributor
Sandra McKay
Graphic Design
Cisneros Design
Photography
Corrie Photography
Breathe™ Fall 2010
Volume 3, Number 2
A publication of the Lovelace
Respiratory Research Institute.
Subscriptions are free; requests
should be submitted to the address
below. Material may not be
reproduced without permission.
Lovelace Respiratory Research Institute
2425 Ridgecrest Drive SE
Albuquerque, NM 87108-5127
800.700.1016 | 505.348.9400
Fax: 505.348.8567
The FSC mission is to promote
environmentally appropriate, socially
beneficial, and economically viable
management of the world’s forests.
The FSC logo identifies papers
that have been certified in
accordance with the rules of
the Forest Stewardship Council.
The people who work for
LRRI have a broad range
of technical expertise and
cross-purpose capabilities
that produce the most
professionally respected
research in respiratory
disease. Since 1947, LRRI
has been contracted to
work on respiratory health
issues by scientists and
health care experts in
universities, government,
industry, and patient
advocacy groups.
Although noted for
its hallmark research
on inhalation diseases,
LRRI has broadened its
mission over the years
to address the most
current needs in
respiratory research.
We are committed to
curing respiratory
diseases through research
aimed at understanding
their causes and biological
mechanisms; assessing
and eliminating exposures
to respiratory health
hazards; and developing
improved therapeutics,
vaccines, and diagnostics.
Commensurate with
our dedication to research
is the quality and growth
of our people who
continue to advance our
mission to address the
concerns of respiratory
health for all man-kind.
www.LRRI.org
Who We Are ~ 1
2 ~ Picturing Better Medicine
When you take a medicine,
you assume that it goes where
it should in your body to heal your
aches and pains or effectively
treat a medical issue.
BETTER
MEDICINE
But that’s not always the case. A picture
on a laboratory wall at the south campus
in Lovelace Respiratory Research Institute
illustrates the problem. It shows sideby-side silhouettes of two animal torsos
depicting where two different asthma
drugs actually end up in the body. The
red color indicates where the majority of
the drugs accumulate. The silhouette on
the left shows bright blooms of color in
the mouth, throat and lungs, indicating
that much of the drug gets stuck in the
mouth and throat where it does little good.
In the silhouette on the right, the lungs are
filled with a bright red glow confirming that
the majority of the medication reached its
ultimate destination and started to work.
The program that conducts these types
of real life studies is led by Philip Kuehl,
Ph.D., Associate Research Scientist in
the Chemistry and Inhalation Exposure
Program and Manager of the Analytical
Chemistry Laboratory at LRRI. To produce
them, Dr. Kuehl used a high-tech diagnostic
process called scintigraphy, which uses a
gamma camera to produce an image of
radioactive tissues in an animal’s body.
Picturing Better Medicine ~ 3
To get these types of pictures,
Dr. Kuehl first attached a
radioisotope to a drug creating
a radiopharmaceutical agent
that could be administered,
non-invasively, to an animal or
human patient. Then the patient
was placed under the gamma
camera and pictures were taken
of his body. In the images, the
radiopharmaceutical agent lit up
showing different concentrations of
the drug throughout the body; the
more intense the color the greater
the concentration of the drug.
Scintigraphy is one of the main
tools Dr. Kuehl uses in his research
of targeted drug delivery. “We use
imaging to understand how we can
use formulation and devices to
achieve the deposition of drugs
in the body we need,” he explains.
Formulation, critical to effective
administration of a drug, takes into
account the actual size of the drug
molecule and its form—whether
it’s a powder, liquid, or solid.
Formulation is particularly
important in inhaled powdered
drugs used to treat the lungs; the
particle size must fall within a very
narrow window to pass through the
human nose, mouth, and throat
and make it into the lungs.
Deposition refers to where the
drug deposits once it’s inside the
body and how long it stays there.
The targeted drug delivery studies
underway in Dr. Kuehl’s lab address
the deposition of various medicines
from large drug particles that
lodge in the airways to fight cystic
fibrosis, to more widely distributed
drugs that cover cancerous tumors
dispersed throughout the lungs.
In a recent research collaboration
with the University of New Mexico
(UNM) Hospital Center for Isotopes
in Medicine, Dr. Kuehl and a team
of scientists used scintigraphy to
study the formulation and
deposition of two asthma inhalers.
First, the team perfected the
process of adding a radiolabel,
the radioisotope that can be
4 ~ Picturing Better Medicine
detected by the gamma camera, to each
drug without changing the drug’s product
performance. With that complete, the team
repackaged the radiolabeled drugs into the
two original inhalation devices so the drugs
could be tested accurately.
The team recruited human patients who
used the inhalers and then immediately
had their lungs imaged with the
gamma camera to capture the actual
deposition of the drug in their bodies.
Dr. Kuehl says the mechanics of such a
study are challenging. “Inhalation products
are extremely difficult to develop,” he
says. “We are really lucky to have a diverse
group of people—toxicologists, chemical
engineers, mechanical engineers, and
pharmaceutical scientists—working on
this. Because of the project’s complexity,
if we didn’t have all of those skills in
one place it just wouldn’t happen.”
Dr. Kuehl and the scientific team are
currently analyzing the research results.
Their hope is that images and data from the
study could impact the different inhalation
technologies patients use. The results could
also help doctors choose more accurate
prescriptions for their asthma patients.
The drug study on humans is the culmination
of a series of research studies that LRRI is
uniquely qualified to conduct. “We’re one
of the only places in the U.S. — if not the
world—that is set up to image everything
from rodents to humans,” says Dr. Kuehl.
He and his team of researchers have access
to three different machines to conduct their
research. They use a scintigraphy machine
for imaging small animals at UNM’s College
of Pharmacy. LRRI’s own equipment is used
to capture images of larger animals. The
scintigraphy machine at UNM’s Center for
Isotopes in Medicine, which is designed for
human imaging, completes the continuum.
Highlighting the multidisciplinary team
required to conduct these and other studies,
is a recent pharmacokinetic (PK) study that
included evaluation of airway constriction.
This study required scientists with backgrounds
in immunology, formulations, pharmacokinetics,
aerosol science, and asthma research. The PK
portion of this study sought to determine the
fate of a drug once it’s in the body, specifically
how it’s metabolized and excreted. The efficacy
portion of this study evaluated how well the
compound opened up the restricted airways.
For this study, the LRRI team focused on a
new dry powder formulation of albuterol,
a drug used in emergency rooms to treat
patients suffering from acute asthma
attacks. The team conducted animal
studies to compare two formulations
of the drug, a dry powder and a clinical
nebulized formulation, to determine the
blood concentration levels and the affect
on airway restriction. The team found that
the dry powder formulation matched the
marketed nebulized form in both its PK
profile and its effect on airway restriction.
Dr. Kuehl believes that the dry powder may
be tested in future drug safety studies.
Dr. Kuehl says it’s that variety of opportunity
and challenge that makes his career at LRRI,
which started in 2007, so fulfilling. “We’re very
hands on here and my days are never boring.
That speaks to the diversity of our team.”
He adds that LRRI’s mission matches his
professional ideals. “I love the fact that LRRI
has a mission statement that people really
uphold. The projects that we’re working on
focus on respiratory health and how we
effect respiratory health.” With that mission
serving as the foundation of his research,
Dr. Kuehl and the LRRI team continue to
find ways to make the medicines we take
work better and keep us all healthier.
“Inhalation products are extremely difficult to develop. We are really lucky to have a
diverse group of people–toxicologists,
chemical engineers, mechanical engineers and pharmaceutical scientists–working on this.”
Dr. Kuehl
In another area, Dr. Kuehl is just starting
formulation work on a compound used to treat
lung cancer that is currently administered
through injections. “If it’s used for lung cancer,
why aren’t we giving it directly to the lung?”
he asks. He and an LRRI team have generated
preliminary data suggesting that it’s more
effective to do so. Now they’re working on
stabilizing the compound as a dry powder
formulation for future studies and are
seeking funding for additional research
on the topic.
Along with his research using scintigraphy,
Dr. Kuehl also manages LRRI’s Analytical
Chemistry Department, which provides
chemistry support for other research
projects at LRRI.
In addition to managing the lab, conducting
research and analyzing data, Dr. Kuehl also
gets plenty of hands-on time working on the
mechanics of research projects. You can
often find him fixing aerosol generators,
tinkering with medical devices, and testing
different types of tubing for inhalation
tests, skills he laughingly attributes to
being raised on a farm in Minnesota.
Picturing Better Medicine ~ 5
TAKING A
SECOND LOOK
AT THE EFFECTS OF
SECONDHAND SMOKE
Secondhand smoke is a known culprit
in the cause of cancer, asthma, and other
pulmonary diseases. Now researchers at
LRRI are studying the effects of secondhand
smoke at the very earliest stages of life—
in utero. They hope to use their findings
to develop a treatment that would reduce
the risk of asthma in future generations.
In their research, Mohan Sopori, Ph.D.,
Senior Scientist and Program Manager of
the Respiratory Immunology and Asthma
Program at LRRI, and Shashi Singh, Ph.D.,
Associate Research Scientist in LRRI’s
Respiratory Immunology and Asthma
Program, conducted animal studies to
simulate children’s exposure to parental
smoking. They simulated both smoking by a
pregnant woman and the exposure of a nonsmoking pregnant woman to environmental,
or secondhand, cigarette smoke.
The team’s research results suggest that
whether a woman smokes during pregnancy
or is exposed to secondhand smoke—from her
partner or in the workplace—the developing
embryo is very susceptible to the noxious
effects of cigarette smoke. Children exposed
gestationally to cigarette smoke have a
much higher risk of developing allergic
asthma, bronchopulmonary dysplasia (BPD),
or chronic obstructive pulmonary disease
(COPD)-like condition. “The results from
these experiments were quite dramatic,”
says Dr. Sopori. “Compared to control mice,
mice that were exposed to secondhand
cigarette smoke in utero developed extremely
exaggerated allergic asthma and BPD.”
Dr. Sopori and his team also found that
cigarette smoke exposure during pregnancy
essentially blocked the production of airway
mucus and surfactant proteins. The airway
mucus system (mucociliary apparatus) is
important in the clearance of noxious agents,
including pathogens, from the airway and is
the first line of defense against these agents.
Surfactant proteins are critical for maintaining
the proper architecture of the airways
and airsacs, the alveoli, gas-exchanging
compartments where oxygen in the inspired
air is exchanged for carbon dioxide in the
blood. In emphysema, the alveolar walls
(septae) are dissolved reducing the area
for gas exchange in these compartments.
6 ~ Ta k i n g a S e co n d L o o k a t t h e Ef fe c t s o f S e co n d h a n d S m o ke
Mohan Sopori, Ph.D. (center)
with research associates
Sravanthi Gundavarapu (left)
and Jules Rir-sim-ah (right)
Ta k i n g a S e co n d L o o k a t t h e Ef fe c t s o f S e co n d h a n d S m o ke ~ 7
Mohan Sopori, Ph.D. (standing) and
Shashi P. Singh, Ph.D. (seated)
The team also found that exposure to
secondhand cigarette smoke during
pregnancy affected the formation of
these airsacs. To a pathologist, the
decreased number of airsacs in the pups
of gestationally secondhand smoke-exposed
animals would look like emphysema. “What
is really scary is that we have followed these
animals for up to eight months without
observing any improvement in the alveolar
architecture. Thus, these changes are
essentially irreversible,” says Dr. Sopori.
Dr. Sopori and his team have published several
papers on the research and are continuing
their studies with funding from the National
Institutes of Health and the Flight Attendant
Medical Research Institute. “The idea is to
delineate the exact mechanism by which
maternal exposure to cigarette smoke
exacerbates allergic asthma and affects lung
development,” comments Dr. Sopori. “For
example, if we were to establish that these
effects are mediated by nicotine, we could
possibly block the nicotinic receptors and
ameliorate the adverse effects of gestational
secondhand cigarette smoke exposures.”
8 ~ Ta k i n g a S e co n d L o o k a t t h e Ef fe c t s o f S e co n d h a n d S m o ke
Those findings would be the foundation of
a therapeutic treatment, possibly a drug that
a pregnant woman could take so that the
effects of nicotine would not be manifested
in her child.
A second research project involves
collaboration with Julie Wilder, Ph.D.,
Associate Scientist in LRRI’s Respiratory
Immunology and Asthma Program. The
project studies the regulation of mucus
formation in the lung. Mucus is needed
for normal functioning of the mucociliary
apparatus; however, excessive mucus
formation is associated with a number of
chronic lung diseases including asthma,
chronic bronchitis, and cystic fibrosis.
One of their findings is that nicotine
exacerbates mucus production by isolated
normal human bronchial epithelial cells,
and this over-production is associated with
increased expression of gamma-aminobutyric
acid (GABA) receptors on these cells.
Importantly, inhibitors of either nicotinic or
GABA receptors block the mucus stimulating
effects of nicotine. “What that tells us is that
nicotine receptors are extremely important
in mucus formation,” says Dr. Sopori. “The
question is whether in animal models we
can suppress the mucus promoting effects
of cigarette smoke/nicotine by blocking
nicotinic receptors with appropriate drugs.”
research and are working on another
paper about a treatment combination
that may help reverse the effects of sarin.
Ultimately their research could define the
most effective way to treat individuals
exposed to sarin gas in a terrorist attack.
Analyzing How Terrorist Chemicals Work
Since his arrival at LRRI in 1987, Dr. Sopori
has primarily pursued research related to
respiratory and immunological effects of
cigarette smoke/nicotine. “Globally, cigarette
smoke is a major killer and yet billions of
people around the world continue to smoke.
Smoking is a known risk factor for a number
of different diseases, including cardiovascular
disease; cancers of the lung, head, neck, and
prostate; emphysema/COPD; and respiratory
infections,” says Dr. Sopori. “Understanding
how cigarette smoke promotes these diseases
is important for developing appropriate
treatments. At LRRI, we are primarily
interested in delineating the mechanism(s)
by which cigarette smoke affects lung
diseases; understanding the mechanism(s)
is likely to provide rational therapeutic
approaches for these diseases.”
Dr. Sopori’s other research efforts are a
departure from his study of nicotine/cigarette
smoke-related problems in the lung. In a project
funded by the Department of Defense, he’s
analyzing the lethality of the nerve gas sarin.
“The idea behind the research is that once we
know how it kills, we can stop it. We’re making
pretty good progress in understanding the
toxicity of sarin,” says Dr. Sopori.
His team is conducting tests around
the hypothesis that people die from
sarin exposure as a result of severe
bronchoconstriction (collapsed airways)
leading to low oxygen levels in the lung.
“Enriched oxygen seems to improve upon
the lethality of sarin,” he says. He and
his team have published papers on the
Mohan Sopori, Ph.D. (center)
Sravanthi Gundavarapu (left),
research associate, and
Ray Langley, Ph.D. (right)
Ta k i n g a S e co n d L o o k a t t h e Ef fe c t s o f S e co n d h a n d S m o ke ~ 9
Researching
the Highs and Lows
of Radiation
CT scans, heart stress tests and
airport security screenings—people
are being exposed to more lowlevel ionizing radiation from
more devices every year. Ionizing
radiation dislodges electrons from
atoms in a process called ionization.
The increased exposure to ionizing
radiation is causing rising public
concern about its health effects.
10 ~ Researching the Highs and Lows of Radiation
Radiation phobia, the fear of
radiation exposure, has even driven
some people to opt out of CT scans
and X-rays that could provide life
saving medical diagnosis. There’s
even an iPhone App that calculates
how much ionizing radiation a
person would be expected to
receive from various medical
tests, and then assigns a cancer
risk based on the information.
Now the Food and Drug
Administration and National
Institutes of Health are weighing
in and pushing to reduce radiation
exposure and to standardize
recordkeeping of radiation doses.
Bobby Scott, Ph.D., senior scientist in
LRRI’s Aerosol and Respiratory Dosimetry
Program, calls the concern over low-level
radiation exposure to forms of radiation such
as x-rays, gamma rays, and beta radiation
phantom risks. These sparsely–ionizing
forms are called low-linear energy transfer
radiation (low-LET radiation). Dr. Scott is
conducting research that may prove low
doses of low-LET radiation stimulate the
body’s immune system and actually reduce
a person’s risk of developing cancer.
This new research is just the latest in a long
history of radiation research that extends
back to Dr. Scott’s days at Webster High
School in Minden, Louisiana. While there he
won first prize in a regional science fair with
his study of radiation related mutations in the
progeny of irradiated fruit flies. His science
fair win kicked-off a successful career, which
took him from studying physics at Southern
University in Louisiana to postdoctoral work at
Argonne National Laboratory outside Chicago.
In 1977, Dr. Scott came to LRRI, then known
as the Inhalation Toxicology Research Institute
(ITRI), where he’s earned worldwide recognition
for his groundbreaking radiation research.
In 2008, Dr. Scott won the International
Dose-Response Society Award for Outstanding
Leadership in the Field of Dose-Response.
Dr. Scott’s early research at LRRI focused
on the public implications of high-dose
radiation events, such as nuclear accidents.
He analyzed existing abundant high-dose
radiation experimental data to develop
risk models for the potential morbidity and
lethality effects of exposure to radionuclides
taken into the body, including plutonium.
The models were validated with additional
studies at the Institute and by researchers
at Pacific Northwest National Laboratory.
At left: Bobby Scott, Ph.D.
Top: Yong Lin, Ph.D., Molecular
Biology and Lung Cancer Program
(left), Bobby Scott, Ph.D. (right)
Bottom: Bobby Scott, Ph.D.
(left), Julie Wilder, Ph.D. (right),
Respiratory Immunology and
Asthma Program
Scientists around the world have used those
risk models to assess the potential public
health consequences of various radiologic
incidents. Scientists at Sandia National
Laboratories used the models to develop
software that evaluates the health risks
associated with a nuclear power plant accident
or other radiological incident. The International
Atomic Energy Agency used the models
to develop medical response procedures
during a nuclear or radiological emergency.
Researching the Highs and Lows of Radiation ~ 11
Dr. Scott’s risk model for acute lethality
even figured in to an international murder
mystery. In 2006, former Russian KGB officer
Alexander Litvinenko was poisoned with
polonium-210 and died from induced acute
radiation syndrome caused by ingesting a
tiny amount of the toxin. London’s Health
Protection Agency used Dr. Scott’s risk model
to evaluate the lethality of polonium-210
during its investigation into the crime. Dr.
Scott assisted the agency in implementing
his model, which led to a joint publication.
His current research focuses on low-level
radiation exposure, specifically the adaptive
response to low doses of low-LET radiation
in the lung, also called radiation hormesis.
Studies indicate that the process can prevent
cancer by stimulating the body’s natural
defenses. “I have accumulated published
cellular, animal, and epidemiological data
showing that in circumstances where there is
mild low-LET radiation stress, the body can
respond by eliminating aberrant cells,” explains
Dr. Scott. “One response is by increasing
immune function so the immune system works
better in destroying cancer and pre-cancer
cells. A second, and possibly more primitive,
response on the evolutionary scale involves
communications between normal and aberrant
cells, which leads to self-destruction of the
aberrant cells in a process called apoptosis.
We think the self-destruction is regulated
epigenetically. This led to the use of the
term epiapoptosis in place of apoptosis in a
recent paper describing my hormetic relative
risk model for lung cancer induction.”
Both immune system stimulation and
epiapoptosis are part of Dr. Scott’s newest
research, a project funded by a $7.5
million grant from the U. S. Department
of Energy’s Office of Science (BER). He
is leading a team of LRRI scientists and
their supporting staff working on the fiveyear study comprised of four subprojects.
The project started in July 2009.
In Subproject 1, Yong Lin, Ph.D., associate
scientist, Molecular Biology and Lung
Cancer Program at LRRI, and his group
are studying the biological mechanisms
and the genes involved in epiapoptosis as
well as other protective cellular changes in
the lung after low doses of gamma rays.
Animal studies comprise Subproject 2.
Julie Wilder, Ph.D., associate scientist,
Respiratory Immunology and Asthma
12 ~ Researching the Highs and Lows of Radiation
Program at LRRI, and her group are conducting
animal studies to investigate the protective
changes in the immune system that result
from exposure to low doses of gamma rays.
In Subproject 3, Steve Belinsky, Ph.D.,
senior scientist and Director of the Lung
Cancer Program at LRRI, and his group
will be conducting molecular epidemiology
studies of humans exposed to radon. Using
sputum cytology samples from uranium
miners in Colorado, Dr. Belinsky’s group
will study whether high-level exposure to
radon causes adaptive response genes
to be turned off epigenetically allowing
cancer to develop; and whether low-level
exposure to gamma rays from radon progeny
stimulates an adaptive response that protects
individuals from developing cancer.
In Subproject 4, Dr. Scott, along with input
from other participants, will integrate key
findings from the other three subprojects
and results from other research to develop
a systems-biology-based model that better
characterizes lung cancer risks after radiation
exposure. Dr. Scott says the model could
be broadly applicable. “You can take the
learning about these basic mechanisms and
how the stimulation of the immune system
and epiapoptosis suppresses cancer and
apply it to all types of cancer,” he explains.
The model could also be used to debunk the
growing concern about the risks of low-dose
low-LET radiation exposure from medical tests
and airport screenings, those concerns that
Dr. Scott calls phantom risks. “The big issue
in the medical community is the view that any
amount of radiation is harmful,” explains Dr.
Scott. “This is causing great headaches for
doctors because these risks are hypothetical
and lead to radiation phobia.” He points to the
fact that the calculations that people use to
evaluate cancer risks from low-level exposure
are based on straight-line extrapolation of data
from very high radiation exposure from nuclear
weapons deployed in Japan during World War II.
In fact, Dr. Scott’s research may turn the
current debate about low-dose radiation
exposure on its head. “We think the model
we develop will show that the low doses of
low-LET radiation from diagnostic procedures
that people are concerned about actually
suppress lung cancer rather than increase it,”
says Dr. Scott. Those results will be valuable
new tools in the fight against cancer and the
global effort to save lives from the disease.
GROUNDBREAKING RESEARCH
ON WOOD SMOKE
ACQUISITION INCREASES
DEPTH OF LRRI SERVICES
YOHANNES TESFAIGZI’S RESEARCH : LEADING THE NATION
CHERYL DEVAUL AND SANDIA STAFFING ALLIANCE
The nation’s first scientific study on the
effects of wood smoke in smokers was
led by LRRI Senior Scientist Yohannes
Tesfaigzi. The research showed that wood
smoke is associated with chronic obstructive
pulmonary disease (COPD), and has identified
a link that increases the risk for reduced
lung function in cigarette smokers. That
exposure to wood smoke causes COPD was
previously found to be common in women
in developing countries, but has not been
recognized as being a hazard at concentrations
generally found in developed countries.
On April 20, 2010, Lovelace Respiratory
Research Institute announced the acquisition
of Sandia Staffing Alliance (SSA) based in
Albuquerque, NM. SSA provides technical
and professional staff for government research,
which aligns with LRRI’s business competencies.
The acquisition of SSA will increase the
depth of services to their client, and allow
SSA a national platform for a recruiting
base since LRRI already has a national
recruiting business, in addition to established
government relationships.
Lead investigators at LRRI, the only dedicated
respiratory research center in the U.S., in
collaboration with the University of New
Mexico School of Medicine and the University
of Colorado at Denver, conducted the study,
which was financed by the appropriation
from the Tobacco Settlement Fund and from
the National Institutes of Health (NIH).
For the research, a cross sectional study
of 1,827 subjects were drawn from the
Lovelace Smokers’ Cohort, a predominantly
female cohort of smokers that is unique
with its high percentage of Mexican Hispanic
participants. The wood smoke exposure
was self-reported. The research included
measuring air entering and leaving the lungs,
airflow obstruction, and chronic bronchitis.
Also explored were modification of wood
smoke exposure with current cigarette
smokers, ethnicity, sex, and the relationship
with lung cancer-related genes on COPD.
In June 2008, SSA was awarded a contract
from Sandia National Laboratories for a period
of performance of five years with approximately
$50 million a year. SSA has employees in five
states with the majority in Albuquerque.
There are more than 550 employees of SSA.
Led by chief Human Resources Officer Cheryl
DeVaul, LRRI has a solid leadership model
suited for the current economy. SSA came
with a management and administration team
consisting of Ruth Kief, Supplier Manager;
Nicole Reyes, Deputy Supplier Manager and
Recruiter; Stephanie Merkins, Accounts
Payable; Jamie Woodley, Payroll; and
Ruth Chacon, Human Resources Benefits
Administrator. Diane Cannone is the Facility
Security Officer for LRRI and for SSA.
LRRI has grown 150% in revenue over the
past five years. Future growth will be partly
attributed to experienced personnel and
technical resources that expand the Institute’s
expertise in multiple business sectors, including
service staffing contracts.
For information on SSA, refer to their website.
www.sandiastaffingalliance.com
W o o d S m o k e S tNu ed wy Ra en sd e Ia nr cc rh e aR se ev de aSl es r Lv ii nc ke s ~ 1 3
Employee Highlights
Rachel Blea, MBA, joined LRRI
in 2002. She has over 10 years’
experience in the design, development,
and launch of effective information
systems supporting critical business
operations. She has led installation
and training for multiple customers
using her experience in animal care
operations, as well as her detailed
understanding of the functionality
of an in-house developed software,
Animal Management System (AMS).
Her duties also include training all levels
of personnel in database management,
Microsoft applications, file management, and basic use of software and
hardware. She also oversees the
coordination, training, and support
for new and existing customers, as
well as assists in the planning and
deployment of new applications and
enhancements for in-house developed
applications in support of critical
business operations.
Other LRRI positions have included
Network Analyst, where she analyzed
information systems supporting
critical business operations, and
Help Desk Coordinator, which included
providing new user orientation, where
she tailored training to various levels
of computer familiarity.
14 ~ Employee Highlights
Kristy Bruse, Ph.D., became the
LRRI Director of Cardiopulmonary
Safety Pharmacology in 2009.
The Cardiopulmonary Safety
Pharmacology group specializes
in cardiovascular and pulmonary
safety assessment for unique routes
of administrations (e.g., inhalation
and intranasal), BSL-3 infectious disease
exposure, assessment of respiratory
pathological models (e.g., COPD and
fibrosis), and various in vitro and
molecular assays to further understand
the efficacy, mechanism of action,
and/or the pathology behind unknown/
adverse exposure.
Dr. Bruse’s previous positions include
Safety Pharmacology Expert Consultant
with Paracelsus, Inc., and Study Director
for Safety Pharmacology for Covance
Laboratories. She was the Safety
Pharmacology Section Research
Leader at Hoffmann-La Roche and Staff
Pharmacologist for the Department of
Safety Pharmacology at WIL Research.
Dr. Bruse’s awards include the American
Heart Association’s Heartland Affiliate
Fellowship Grant; the Merck Young
Investigators Award from the American
Heart Association’s Council of High
Blood Pressure Research; the Special
Recognition Award, NCDS, from
Hoffman-La Roche, Inc.; and the
D2K Award for Preclinical Research
and Development from HoffmanLa Roche, Inc.
Penny H. Holeman, MPH, MS, MA,
is Director of Biosafety, Training, and
Biosecurity Solutions, where she
manages and directs the Select Agents
and Biosafety programs at LRRI. Ms.
Holeman develops, implements, and
enforces programs that include
laboratory safety, workplace safety
with regard to infectious agents,
security of biological agents, dangerous
goods transportation, incident and
emergency response, and infectious
waste management.
Ms. Holeman has just completed
5 years as Chair of both the Institutional
Biosafety Committee and Infectious
Agents Committee. She currently chairs
LRRI’s Stem Cell Research Oversight
Committee. Ms. Holeman serves as
LRRI’s Biological Safety Officer, where
she is responsible for LRRI’s compliance
with the NIH Guidelines for Research
Involving Recombinant DNA Molecules.
She also serves as LRRI’s Responsible
Official and has the authority to ensure
compliance with the Select Agents and
Toxins regulations.
Previous positions include that of
Worldwide Manager of Biological
Safety for Johnson & Johnson, where
she conducted strategic planning and
leadership to establish and maintain
the worldwide biological safety program
for R&D, manufacturing, and marketing
activities; and served as the corporation’s
expert in biological safety and Biosafety
Level 3 Facilities.
Notes of Distinction
Ray Langley, Ph.D., is an
Associate Research Scientist in the
LRRI Respiratory Immunology and
Asthma Program. Dr. Langley is a
lifelong resident of New Mexico and
originally earned his undergraduate
degree from the University of New
Mexico in Journalism in 1996. In 1999,
after attending a seminar by Dr. Francis
Collins on the Human Genome Project,
Dr. Langley decided to return to UNM to
finish his biology degree and switch his
career to science. Dr. Langley originally
joined LRRI as a research technician.
Two years later, he moved to the UNM
biomedical sciences graduate program
where he earned his Ph.D. in 2007
under the direction of Dr. Mohan Sopori.
At UNM, he studied the chronic effects
of respirable silica sand on Lewis Rats.
After graduation, he went to the
National Center for Genome Resources
as a post-doctoral fellow under the
direction of Dr. Stephen Kingsmore,
president and CEO. At NCGR, Dr.
Langley worked on the Community
Acquired Pneumonia and Sepsis
Outcomes Diagnostic (CAPSOD), where
they developed a diagnostic using a
panel of metabolites that can predict
sepsis death using plasma samples
taken at presentation. The manuscript
and patent are currently under review.
Dr. Langley also worked on an Illumina
GAIIx next-generation sequencing
platform developing sequence libraries
and high throughput library protocol
assays, and bioinformatics for the
service component of the NCGR.
PPD and Lovelace Biomedical and Environmental Research Institute (LBERI)
have entered into a collaboration focused on future service opportunities
for biopharmaceutical and government clients across a range of therapeutic
areas. Under the collaboration, the companies plan to refer to one another’s
potential business opportunities for laboratory, preclinical, and clinical
development services they do not offer to their respective clients. In
addition, the companies will work together to collaborate and jointly bid
on research projects. Dr. Bob Rubin, President and CEO of LRRI, of which
LBERI is a subsidiary, added, “Aligning with one of the world’s leading
CROs allows us to build on its 65-plus year history of discovery research,
public health advancement, and extensive preclinical service offerings.
With PPD, we can expand our already strong laboratory, preclinicals and
clinical development capabilities to meet future health challenges.”
LRRI’s Board of Directors member Sonia Buist, M.D., Professor Emerita of
Medicine, Pulmonary & Critical Care Medicine at Oregon Health and Science
University in Portland, Oregon, has been selected as the recipient of the 2010
Trudeau Medal by the American Thoracic Society. Since 1926, the Trudeau
Medal has been bestowed only on those with lifelong major contributions
to the prevention, diagnosis, and treatment of lung disease. Dr. Buist was
commended for the development of the American Thoracic Society’s Methods
in Epidemiologic, Clinical & Operations Research (MECOR) Program, which has
trained more than 800 pulmonary and critical care researchers in Latin America,
Turkey, Africa, and India; her outstanding contributions to minimizing the
burden of COPD and asthma; and her commitment to improving global health.
Dr. Bobby Scott, LRRI Senior Scientist, Aerosol and Respiratory Dosimetry, was
invited to become a member of the prestigious Editorial and Scientific Committee
of the International Journal of Low Radiation. IJLR is an interdisciplinary Journal
that provides an international forum and refereed authoritative source of
information in the field of Low Radiation and related topics.
LRRI’s scientist Jacob McDonald, Ph.D., has just published in the prestigious
Nature research journals how inhaled carbon nanotubes may suppress
systemic immune functions. The research suggests that with the increasing
production of carbon nanotubes and possible occupational exposures,
immune dysfunction may be a concern for those working in the nanotubes
industry. Dr. McDonald and colleagues report that activation and release
of a molecule from the lung after inhalation of nanotubes has a direct
effect on the immune function of a class of white blood cells in the spleen.
The research, conducted on mice, is significant in the studies of potential
harmful inhalation of carbon nanotubes in humans who work with these
products. It has been suspected that carbon nanotubes with cylindrical
nanostructures may be toxic to those who work in the fields where their
use has furthered the applications of: nanotechnology, electronics, optics,
and other fields of materials science, including architectural fields.
Notes of Distinction ~ 15
Board of Directors: Featured Members
A. Sonia Buist, M.D.
Jonathan M. Samet, M.D.
Portland, OR
Los Angeles, CA
India, Scotland, Canada, and America—Sonia Buist, M.D.,
has lived around the globe and traveled widely. Her
international experience inspired her research and
helped her become a role model for other scientists.
Whether as a research partner or as an advisor,
Jonathan M. Samet, M.D., has been involved with LRRI
for almost 30 years. He is currently on the LRRI Research
Program Oversight Committee. He began collaborating with
the Institute when he was a faculty member at the University
of New Mexico in the early 1980s. “I have a lot of overlapping
interests with LRRI about how the environment affects
lung health, except that my approach is epidemiological
while LRRI’s is laboratory based,” he explains.
Dr. Buist is currently Professor Emerita of Medicine at
the Oregon Health & Science University. Throughout her
career, she’s conducted extensive research on asthma and
chronic obstructive pulmonary disease (COPD) with a focus
on the epidemiology and management of both diseases.
Dr. Buist has helped launch several global initiatives to
address COPD worldwide. She is perhaps best known for the
American Thoracic Society’s Methods in Epidemiological,
Clinical and Operations Research (MECOR) Program, which
she started in 1994. The program has trained more than 800
pulmonary physicians, pediatricians, allergists, and critical
care specialists around the world, in places like Latin America,
Asia, and Africa to conduct epidemiological and clinical
research on respiratory diseases in their area and to come
up with appropriate interventions for their environment.
She generously shares her talent and vision as a member of
numerous federal, international, and private advisory groups,
including LRRI’s Board of Directors. She’s lent her guidance
and expertise to the Board since 2002. “I think that LRRI is a
very interesting model of a research institute with a very
broad range of expertise, which is quite different from the
usual academic model,” says Dr. Buist. “LRRI has established
a very strong niche for itself in the pulmonary research area.”
16 ~ Board of Directors: Featured Members
Today Dr. Samet is Chairman of the Department of
Preventive Medicine at the Keck School of Medicine and
Director of the Institute for Global Health of the University
of Southern California in Los Angeles, California.
Dr. Samet’s research on the environment and health
and focus on policy issues informs his contributions to
the LRRI board. “As a scientist who is concerned with the
regulatory and policy end of things, I try to help LRRI think
about how to have more integrated programs and how to
engage more with populations and clinical researchers.”
“I’m pleased to provide continued input to this organization,”
he says. “LRRI has expertise that isn’t well represented
throughout the country. It’s an important resource and its work
makes a difference in the United States and around the world.”
Financial Outlook
Fiscal Year 2010 Budgeted Revenue $95MM
NIH 36%
DOE 2%
DOD 5%
State 1%
BARDA 4%
LSR 3%
Endowment Contributions 3%
Trade Associations, Other
Commercial Sources, etc. 7%
Pharmaceutical 10%
CDC 1%
EPA 3%
Federal Staffing 25%
0,
00
0
5-Year Analysis of Revenues from Research Activities
$9
0,
50
$100MM
$7
3,
$6
0,
33
7
$60MM
$5
4,
44
6,
12
4
$70MM
90
0,
84
6
$80MM
2,
15
6,
16
3
$90MM
$4
0,
27
$50MM
$40MM
$30MM
$20MM
$10MM
2006
2007
2008
2009
2010 Forecast
Financial Outlook ~ 17
Lovelace Respiratory Research Institute
Non-profit Org.
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2425 Ridgecrest Drive SE
Albuquerque, NM 87108-5127
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fax 505.348.8567
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Albuquerque, NM
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www.LRRI.org
If you would like to donate…
More than 20% of American families suffer
from a respiratory illness. We view that
as an alarming statistic. At times we
are asked by grateful patients and
their families if they can help finance
the research that is so crucial for
respiratory wellness.
Although we do not provide direct
medical treatment to patients, our
research is important to the public’s
health. As an Institute dedicated
to the wellness of mankind and
specifically respiratory health, we
are very grateful for any financial
assistance and can ensure you
that the donations go directly to
research. The Institute is a not-forprofit company and your donation
is tax deductible. If you would like
to donate to LRRI, please visit
our web site www.lrri.org and
click on Donations. Thank you.