News & Grants
Learning and Memory in MS
D. Chiaravalloti, PhD, an assistant professor in the Department
of Physical Medicine and Rehabilitation at UMDNJ-New Jersey
Medical School, has received two grants to study cognitive
functioning in individuals with multiple sclerosis (MS). The
first grant for $1,370,000 is funded for five years by the
NIH/National Institute of Child Health and Human Development.
a small randomized clinical study called "Treating New Learning
in Multiple Sclerosis (MS)," Chiaravalloti demonstrated that
individuals with MS who have documented memory impairment
show a significant improvement in their memory performance
following a treatment protocol utilizing imagery and context
to facilitate learning.
in new learning and memory is one of the most common deficits
in individuals with MS, impacting many aspects of everyday
life, including employment status and social functioning.
Chiaravalloti aims to replicate the earlier finding and further
evaluate the impact of the treatment protocol on everyday
functioning; observe the long-term effects of the treatment
six months following its completion; and examine the usefulness
of once-amonth "booster" sessions to maintain the treatment
effects for more than six months.
grant for $428,000, funded by the National Multiple Sclerosis
Society for three years, is for "Working Memory in MS: Using
fMRI to Identify the Deficit." Many MS patients report difficulties
with attention, concentration and memory. Research has shown
that these deficits in their "working memory" may in fact
be the source of some of these cognitive difficulties. The
term working memory refers to the ability to hold and manipulate
information in the mind (adding numbers without writing them
and her team are examining working memory abilities in 60
participants: 20 with MS who have an impairment in working
memory functions, 20 with MS who do not have this impairment,
and 20 healthy controls.
J. Lioy, PhD, (right) a professor and director of the Exposure
Measurement and Assessment Division (EMAD) in the Department
of Environmental and Occupational Medicine at UMDNJ-Robert
Wood Johnson Medical School (RWJMS), and deputy director for
government relations at the Environmental and Occupational
Health Sciences Institute (EOHSI), and Panos A. Georgopoulos,
PhD, (left) a professor in the division and director of the
Computational Chemodynamics Laboratory at EOHSI, have been
awarded a five-year, $2,499,903 renewal grant from the U.S.
Environmental Protection Agency (EPA) for "Human Exposure
Modeling - An Integrated Probabilistic Modeling Environment
for Reducing Uncertainty in Human Health Risk Assessment:
Characterizing Multipathway Human Exposure and Source-to-Dose
completed by this team over the past five years led to the
development of a modeling system for evaluating simple and
complex environmental health problems. "Our approach follows
the release of toxicants from sources and eventually helps
us to estimate the dose received by a person or many persons,"
Modeling Environment for Total Risk Studies (MENTOR) integrates
concepts from environmental science, engineering, medicine,
toxicology and epidemiology. The model improves human exposure
and dose assessments used in evaluating risk. It helps to
determine the interventions needed to characterize, reduce
and eliminate local and national environmental health problems.
system's strength is its ability to incorporate new information
within a very flexible modeling environment rather than build
a new model every time one is needed to address an acute or
chronic environmental health issue," says Georgopoulos.
Flight and the Immune System
Shi, DVM, PhD, University Professor in the Department of Molecular
Genetics, Microbiology and Immunology at UMDNJRobert Wood
Johnson Medical School, has been awarded a $1,747,312 grant
from the National Space Biomedical Research Institute,which
is supported by NASA, for "Apoptosis and Immune Homeostasis
During Hind Limb Unloading." This new project is a continuation
of his current study, "Effects of Antiorthostatic Suspension
on the Immune System."
indicates that astronauts have significantly increased rates
of infection after their flights. Shi is simulating space
flight conditions to study the effect on the immune system
in an animal model. He has demonstrated that lymphocyte numbers
are dramatically reduced and the immune response is significantly
altered under these conditions.
to further investigate the cellular and molecular mechanisms
affecting the immune system during space flights," says Shi.
"Our goal is to elucidate the role of Fas and endogenous opioids
in the modulation of the immune system by hind limb unloading
and determine the effect of hind limb unloading on lymphocyte
dynamics and immune responses."
Neutral Circuitry for Rage & Agression
Siegel, PhD (bottom), professor of neurology and neurosciences
and psychiatry, and Steven S. Zalcman, PhD, assistant professor
of psychiatry, both at UMDNJ-New Jersey Medical School, have
been awarded a five-year, $1,637,188 grant from the NIH/National
Institute on Neurological Disorders and Stroke to identify
the neural circuitry and neurochemical and neurophysiological
mechanisms that underlie the expression and control of rage
and aggressive behavior. The primary focus of this study,
which represents a major new direction in their research program,
is to recognize and characterize the roles of serotonin and
cytokines in the medial hypothalamus in regulating these forms
rationale is based upon our most recent preliminary studies,"
says Siegel. "We provide evidence that, in the medial hypothalamus,
5-HT1A and 5-HT2 receptors and cytokines IL-1R and IL-2 powerfully
modulate defensive rage behavior in our animal model. The
overarching hypothesis is that differential cytokine effects
upon defensive rage and predatory attack are mediated principally
through distinct neurotransmitter receptors of which serotonin
and possibly GABA are primary candidates."
experiments are proposed to test this hypothesis. The first
will utilize immunocytochemical and neuroanatomical methods
to characterize the pathway from midbrain periaqueductal gray
(PAG) to the medial hypothalamus mediating defensive rage
and its relationship to serotonin axons and pre-terminals
in this region. The second will determine the effects of 5-HT1A
and 5-HT2 receptors in the medial hypothalamus on defensive
rage. The third will determine the role of IL-1R in the medial
hypothalamus on defensive rage, its relationship to 5-HT2
receptors, the distribution of IL-1R in this region and its
relationship to serotonin axons and pre-terminals as well
as to c-Fos labeled neurons following the expression of defensive
rage. The fourth experiment will seek to determine the role
of IL-2 in the medial hypothalamus on defensive rage and the
underlying neurotransmitterreceptor mechanism. The fifth will
identify the effects of activation of 5-HT and the above cytokines
on predatory attack behavior.
discovery that cytokines in the brain play a significant role
in defensive rage represents a most significant observation,"
says Zalcman. "It has provided an entirely new direction of
research with a focus that will address how cytokines and
related substances in the brain may play critical roles in
the expression and control of aggression and rage."
Connections in the Nervous System Development
G. Wadsworth, PhD, an associate professor in the Department
of Pathology and Laboratory Medicine at UMDNJRobert Wood Johnson
Medical School, has been awarded a five-year, $1,772,300 grant
from the NIH/National Institute of Neurological Disorders
and Stroke to study "Extracellular Matrix and Axonal Guidance
in C. elegans."
is studying the molecular mechanism by which nerve cells form
intricate networks of connections during nervous system development,"
explains Wadsworth. "Many of these mechanisms are consistent
among all animals and in our studies we use a model organism
called C. elegans.We are able to make genetic mutants and
observe nervous system development in this transparent nematode."
of the work has focused on a molecule named UNC-6, which Wadsworth
co-discovered as a postdoctoral fellow at The John Hopkins
University. UNC-6 is the founding member of the netrin family
of proteins. The netrins help guide the nerve cells to make
correct connections in vertebrate animals, including humans.
Understanding the mechanisms of nervous system development
could aid in developing therapeutic agents to treat nerves
damaged by injuries or disease.
the Fuctional Properties of Proteins
L. Harris, PhD, an associate professor in the Department of
Pharmacology and Physiology at UMDNJ-New Jersey Medical School,
has received a four-year, $1,169,990 grant from the National
Institutes of Health to study channel-forming proteins. His
lab investigates the functional properties of proteins that
form gap junction channels, which are intercellular pores
through which ions and small molecules pass from cell to cell.
In neurons they form electrical synapses. These pores mediate
intercellular electrical and molecular signaling, important
in neurobiology, physiology, development and disease.
channels are oligomers of connexin (Cx) protein, of which
there are at least 20 isoforms," he says, explaining that
channels formed by each isoform seem to have distinct intercellular
signaling functions. "Defects in a single isoform cause a
distinctive phenotype, such as neuronal demyelination (Cx32),
deafness (Cx26), cardiac malformation (Cx43), cataracts (Cx50)
and susceptibility to cancer (Cx32). These connexin-defect
phenotypes arise from disruption of normal molecular movement
through connexin channels. Control of this molecular movement
is the primary focus of our work." The lab uses physiological,
biochemical and genetic approaches to explore channel structure/function.
Connexin channels are studied at macroscopic and single-channel
levels in reconstituted and expression systems. Genetically
altered connexins are used to define permeation and modulation
mechanisms. A particular focus is on the functional contributions
of connexin domains and isoforms to channel function. Connexin
channels are pathways for direct movement of cytoplasmic molecules
between cells. In spite of considerable knowledge about connexin
channels, the character and mechanism of their most salient
property - selective permeability among signaling molecules
- remains largely unknown.Which chemical signals pass through
connexin channels and how selectivity among them is achieved,
are fundamental issues with far-reaching impact.
to define these processes," he says. "The channels formed
by each of the ~20 varieties of connexin differ from one another
with regard to molecular permeability. The importance of this
specificity is demonstrated by the fact that every functional
deletion of a connexin type produces a distinct pathology,
such as neuronal demyelination, deafness, cardiac defects,
cataracts or infertility."
Oral Bacterium That Affects Adolecents
B. Kaplan, PhD, an assistant professor in the Department of
Oral Biology at UMDNJ-New Jersey Dental School, was awarded
a fouryear, $857,151 grant from the NIH/National Institute
of Dental and Craniofacial Research to study an oral bacterium
that causes a form of periodontal disease affecting adolescents.
bacterial species are able to attach to surfaces and form
biofilms, which cause dental caries, periodontal disease,
infective endocarditis and other chronic infections. This
bacterium, known as Actinobacillus actinomycetemcomitans,
or Aa, forms tenacious biofilms in plastic dishes, and is
capable of spreading across the surface of the dish.
interested in studying this spreading phenomenon," says Kaplan,
"and discovered that Aa cells secrete an enzyme that digests
the slime layer and releases bacterial cells from the biofilm,
which enables it to spread."
and his team used genetic engineering to purify large amounts
of this enzyme and found that it causes the detachment of
preformed Aa biofilms from surfaces.
most exciting finding was that this enzyme causes the detachment
of biofilms produced by a wide variety of bacterial species,
suggesting that it may be useful as a broad-spectrum anti-biofilm
agent," he explains.
Mapping to Periodontitis
R. Diehl, PhD, director of the Center for Pharmacogenomics
and Complex Disease Research at UMDNJ-New Jersey Dental School,
has been awarded a five-year, $1,846,563 grant from the NIH/National
Institute of Dental and Craniofacial Research to study "Gene
Mapping of Susceptibility to Periodontitis."
differences among individuals have major effects on the risk
of chronic periodontitis, the focus of this new study. This
disease affects more than 20 % of adults age 40 and is the
major cause of tooth loss in older Americans. Periodontitis
may also increase risk of cardiovascular disease, osteoporosis,
and in women of childbearing age,may be associated with preterm
delivery and low birth weight. Chronic periodontitis is a
"complex disease." Both inherited genetic variation and environmental
factors, such as smoking, hygiene and pathogenic bacteria,
determine individuals' risk. Diehl's previous studies of adult
twins demonstrated that the disease has a heritability of
50 percent, indicating that genes and environment play about
an equal role in determining whether a person is affected.
Diehl's Center incorporates advanced molecular genomics and
bioinformatics techniques for analyses of single nucleotide
polymorphisms (SNPs) and statistical genetic strategies such
as haplotype mapping that greatly increase power to identify
genes' underlying complex traits. A critical component needed
for success in this approach is availability of very large,
high-quality clinical populations. Diehl and his team will
test more than 100 candidate genes for association with periodontitis
in 8,000 subjects recruited in the U.S. Discovery of specific
gene mutations may lead to improved therapies designed to
correct biochemical aberrations caused by the gene defects.
Different therapeutic approaches may be targeted to address
different gene defects rather than a "one size fits all" approach
used today. "It is important to recognize that absence of
a simple one-to-one mapping between disease gene and clinical
phenotype in a complex disease such as periodontitis doesn't
necessarily diminish the value of identifying genes that determine
individual differences in susceptibility," says Diehl. "These
genetic variants still have great potential to explain a substantial
portion of disease risk in the population and to predict risk
Jersey Dental School Publications:
of Direct and Conventional Intraoral Radiographs in Detecting
Alveolar Bone Loss" by Ahmed
Khocht, DDS, MSD, clinical associate professor,
Malvin Janal, PhD, senior research associate,
Lynn Harasty, DMD, clinical associate professor,
and Kuang-min Chang, DMD, PhD,
associate professor, all in Periodontics, was in JADA,
Vol. 134, November 2003.
Responses from Loading of Implants: A Pilot Study" by
Barry Simon, DDS, MSD,
professor, Periodontics, Harry
Zohn, DMD, clinical associate professor, Periodontics,
Neal Lehrman, DMD,
clinical associate professor, Periodontics, Saul
Weiner, DDS, professor, Restorative Dentistry,
and David Ehrenberg, DDS, MS,
assistant professor, Restorative Dentistry, et. al., was in
the International Journal of Oral and Maxillofacial Implants,Vol.
19, No. 1, 2004.
Milles, DDS, professor, Oral & Maxillofacial
Surgery, presented “Alternative Methods of Mandibular
Reconstruction” at the Northern Regional Hospital at
Mustame, Tallinn, Estonia.
Jersey Medical School Grants:
assistant professor, Cell Biology and Molecular Medicine,
received a four-year, $800,000 grant from the NIH/National
Heart, Lung and Blood Institute for “Mechanisms of RasGAP
in Cardiac Cell Growth and Survival.”
S. Johnson, MD, MPH, professor and chair,
Family Medicine, Debbie Salas-Lopez, MD, assistant professor,
Clinical Medicine, and Paulette Stanford, MD, associate professor,
Pediatrics, received a three-year, $988,000 grant from the
Department of Health & Human Services, Health Resources
and Services Administration to establish a Primary Care
Kaushik-Basu, PhD, assistant professor, Biochemistry
and Molecular Biology, received a four-year, $800,000 grant
from the NIH/National Institute of Diabetes, Digestive and
Kidney Disorders for “Molecular Modulators of HCV Replications.”
Ishikawa, PhD, professor, Cell Biology and
Molecular Medicine, received a four-year, $840,000 grant from
the NIH/National Institute of
General and Medical Sciences for “Catalytic Activation
of Adenylyl Cyclase Type V.”
Quigley, MD, assistant professor, Neurology
and Neurosciences, received a threeyear, $760,940 grant from
the Department of Veterans Affairs for “Risk Perception
and the Psychobiological Sequelae of Vaccination.”
Whitehead, PhD, assistant professor, received
a four-year, $800,000 grant from the American Cancer Society
to study "RhoGEFs in Cell Growth and Cancer." These studies
will examine the role of small GTPases in malignant progression
with emphasis on breast cancer.
Review of Prolotherapy for Osteoarthritis, Low Back Pain,
and other Musculoskeletal Conditions: A Physiatric Perspective,"
by Sunny Kim, MD,
resident, Todd Stitik, MD,
associate professor, Patrick
Foye, MD, assistant professor, and Denise
Campagnolo, MD, associate professor, Physical
Medicine and Rehabilitation, was in the American Journal of
Physical Medicine and Rehabilitation, Vol. 83, No. 5.
Economic Burden of Hospitalizations Associated with Child
Abuse and Neglect,” by Sue
Rovi, PhD, assistant professor, Ping-Hsin
Chen, PhD, assistant professor, and Mark
Johnson, MD MPH, was in the American Journal
of Public Health, Vol. 94, No. 4, 2004.
Wood Johnson Medical Scool Publications:
Dynamics of Imprinted X Inactivation During Early Mouse Development,”
an online article, co-authored by Danny
Distinguished University Professor of Biochemistry and Investigator,
Howard Hughes Medical Institute, was in Science, December
Treatment Interruption in Patients with Multidrug-Resistant
Human Immunodeficiency Virus,” by last author and
protocol co-chair, John D. Baxter,
MD, associate professor of medicine, was in
The New England Journal of Medicine, Vol. 349, No. 9, 2003.
Crabtree, PhD, professor, Family Medicine,
received a three-year, $600,000 grant from the Robert Wood
Johnson Foundation for "Prescription for Health: Promoting
Healthy Behaviors in Primary Care Research Networks."
Foty, PhD, assistant professor, Surgery, received
a three-year, $575,127 grant from the U.S. Army to study "Quantifying
Tumor Endothelial Cell Interaction in Organotropic Prostate
Gallo, PhD, professor, Environmental and Occupational
Medicine, received a one-year, $731,000 grant from the U.S.
Environmental Protection Agency to study "Influence of
Environmental Factors in Cancer Causation."
Lobel, PhD, professor, Pharmacology, and resident
member, CABM, received a one-year, $342,354 grant from the
NIH-National Center for Research Resources for the purchase
of a Nanospray Liquid Chromatography Tandem Mass Spectrometry
Millonig, PhD, assistant professor, Neuroscience
and Cell Biology, received a two-year, $399,967 grant from
the New Jersey Commission on Spinal Cord Research for “The
Development of Spinal Cord Therapies Through a Genetic Analysis
of Mouse Spinal Cord Development.”
Montelione, PhD, adjunct professor, Biochemistry,
received a one-year, $760,000 grant from the National Institute
of General Medical Sciences for “Acquisition of
800 MHZ NMR System with Cryogenic Probe.”
Abate-Shen, PhD, resident member, CABM, leader,
Prostate Program, CINJ, professor, Medicine and Neurosciences
and Cell Biology, and chief, Division of Developmental Medicine
and Research, received a five-year, $4,485,615 consortium
grant for "A Mouse Model for Prostate Cancer".
Institute for the Study of Child Development
received its first fMRI
grant, $465,000 for three years, to study “The Relationship
Brain Functioning and Performance.” In collaboration
with the RWJMS Department of Radiology, it will study how
differences in adolescents’ inhibitory behavior is related
to brain activity as a function of prenatal cocaine exposure.
Yang, PhD, associate professor, Pharmacology,
a two-year, $384,863 grant from The National Cancer Institute
“Study the Role of Ubiquitinin in Cancer Progression.”
Zheng, PhD, associate professor, Neuroscience
and Cell Biology, received a two-year, $364,092 grant from
the New Jersey Commission on Spinal Cord Research to study
“Inhibitory Mechanisms of Axonal Growth in Spinal