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Research News & Grants

Genetics of Autism

Linda Brzustowicz, MD, a faculty member in the Department of Psychiatry at UMDNJ-New Jersey Medical School (NJMS), has been awarded a five-year, $3.7 million National Institutes of Health grant to identify gene variants involved in autism.

Linda Brzustowicz became interested in autism after researching the genetics of a disorder called specific language impairment, or SLI. Defined as the failure to develop language normally and without any explanation, such as hearing loss or mental retardation, SLI affects 7 percent of school-age children. Brzustowicz discovered that a region of chromosome 13, associated with autism, is also linked to the susceptibility to develop SLI.

The study will involve the recruitment of families with one or more individuals affected with autism and additional family members with a history of language problems. Researchers will study DNA samples from all family members to see if they can identify specific regions of chromosomes that individuals with autism or language skill difficulty have in common. Although the study will most likely identify only some of the genes involved in autism and language problems, the knowledge will help in the overall understanding of the genetics of autism. The researcher’s next project will focus on the function of any genes they identify.

“Unraveling the genetics of a complex disorder like autism is like solving a jigsaw puzzle; each piece that can be assembled, no matter how small, makes the placement of the next piece that much easier,” explains Brzustowicz.

David Alland, MD, MSc, associate professor of medicine at NJMS, received a $4.1 million grant from the NIH to study “Multiple Detection of Select Agents in Single Well Assays.” The award is for the development of novel biodefense diagnostics.

The emerging threat of bioterrorism has created the need for rapid diagnostic assays of pathogenic bacteria,” says David Alland, who is also division chief of infectious diseases in the Department of Medicine. “To be maximally effective, assays must also be sensitive and specific, and simple enough to be used in local healthcare settings and regional laboratories.”

His lab has had a 13-year collaboration with Fred Kramer, PhD, and Sanjay Tyagi, PhD, both with the Public Health Research Institute (PHRI) at the University’s International Center for Public Health at Science Park. They are the inventors of a new method to monitor polymerase chain reactions (PCR) using fluorescent reporter probes called molecular beacons. Molecular beacons make it possible to differentiate among closely related DNA sequences, and to monitor PCR in “real-time.” Real-time PCR represents a major advance over other PCR techniques because it retains the sensitivity of conventional PCR, but is more specific and much easier to use.

The team will be working on novel approaches to real-time PCR techniques that vastly expand the number of different pathogens that can be detected in a single assay well. They will replace specific molecular beacons with mixtures of molecular beacons that act in concert. Sequences will be identified by detecting “fluorescence signatures” generated by multiple probes that hybridize to DNA sequences in characteristic fashions. The switch from single-probe identification to multi-probe, pattern-based identification will enable them to develop highly multiplexed assays using only a small number of probes or colors.

Among their specific goals are to develop sets of “universal” PCR primers that amplify species-specific DNA sequences from all select bacterial agents and common bacterial pathogens.

Diesel Exhaust & Chemical Sensitivity

Nancy L. Fiedler, PhD, associate professor, and her co-investigator, Robert Laumbach, MD, MPH, assistant professor, both from the Department of Environmental and Community Medicine at UMDNJ-Robert Wood Johnson Medical School (RWJMS), and the Occupational Health Division of the Environmental and Occupational Health Sciences Institute (EOHSI), have been awarded a three-year, $1,519,951 grant from the U.S. Department of the Army for "The effects of diesel exhaust and stress on the acute phase response and symptoms in the chemically intolerant."

Diesel exhaust was one of the exposures reported by the greatest percentage of Gulf War veterans and was associated with increased risk of medically unexplained symptoms, including chemical sensitivity,” Nancy Fiedler explains. “Chemical exposure and stress have both been implicated in the onset of unexplained symptoms among Gulf War veterans.”

The goal of the study is to test an acute model of unexplained Gulf War illness in which healthy human subjects are exposed to environmental concentrations of diesel exhaust and a task known to cause psychologic stress (a speech assignment).

One-hundred and ten healthy men and women, ages 21 to 45, will undergo two one-hour sessions in which they are exposed either to diesel exhaust, or clean air masked with a small amount of diesel exhaust. Half of the subjects will be randomly assigned to the chemical exposure conditions with the speech task, a psychological stressor, while the rest will not perform the task.

Symptoms (e.g., fatigue, mucosal irritation) and markers of immune function in blood will be assessed at a baseline before the onset of exposure, prior to the administration of the psychological stressor, immediately following termination of the stressor, and at six and 24 hours post-exposure. End-tidal CO2, as an indicator of hyperventilation, will be assessed at a baseline before and after exposure. Nasal lavage to assess markers of nasal inflammation will also be performed. Induced sputum will be collected and uestionnaires administered six hours after exposure to assess respiratory inflammation and ymptomatic response.

Transfusion & Hip Repair

Jeffrey L. Carson, MD, Richard C. Reynolds Professor of Medicine and chief of the Division of General Internal Medicine at RWJMS, has been awarded a five-year, $5,820,641 grant from the NIH for “Transfusion therapy trial for functional outcomes in cardiovascular patients undergoing surgical hip fracture repair.”

The purpose of the study is to determine how much blood is needed in patients undergoing surgery for repair of a hip fracture,” says Jeffrey Carson, who is principal investigator and study chairman. “We will determine if transfusing more blood improves the ability to take care of oneself and decreases the risk of complications after surgery.”

His primary aim is to determine if maintaining hemoglobin levels >10 g/dL is associated with improved ability to walk 10 feet across a room without human assistance 60 days after surgical repair of a hip fracture, compared to patients whose hemoglobin levels are allowed to drop to 8 g/dL before receiving a transfusion. Patients will be eligible for the study if their blood count drops below 10 g/dL within the first three days following surgery. At that time they will be randomized into one of the two transfusion groups.

Patients assigned to the 10 g/dL group will receive enough blood to maintain their blood count at or above 10 g/dL. Patients assigned to the symptomatic transfusion group will receive a blood transfusion only in the presence of symptoms from a low blood count, or if their blood count falls below 8 g/dL, at which time transfusion is permitted but is not mandatory. Patients will be telephoned 30 and 60 days after entry into the study to see how they are feeling.

“Healthy people in North America have hemoglobin levels above 12 g/dL. Often this level is much lower in patients after undergoing surgery,” says Carson. “While physicians can increase the blood count by ordering a blood transfusion, they are not sure how high the blood count needs to be for a patient to recover safely and quickly.”

The study is supported by the National Heart, Lung, and Blood Institute and involves 30 medical centers in the U.S. and Canada.

Nutritional Inhibition of Prostate Cancer

Jeffrey D. Laskin, PhD, RWJMS professor of environmental and community medicine, recently received a $1,517,450 grant for five years from the National Cancer Institute for his prostate cancer studies.

The research studies are designed to see if regularly consumed nutrients can prevent the activation of a carcinogen,” he explains. “Many forms of cancer, including cancer of the prostate, seem to require a carcinogen trigger in order to develop. It is well recognized that some dietary nutrients have the capacity to inhibit the development of cancer and we are working on the idea that these same nutrients will prevent carcinogens from inducing cancer of the prostate.”

Laskin plans to use common compounds from plants to test these assumptions using cell culture models. Derivatives of vanillic acid (found in vanilla and used in food and beverage flavorings), ferulic acid (used as a preservative), and epigallocatechins (in green tea, one of the world’s most widely consumed beverages) will be evaluated to understand how these chemopreventative nutrients act on the cells. “It is hoped that the results of these studies will be used to develop clinical trials to delay or prevent the development of prostate cancer,” he explains. A member of the New Jersey Commission on Cancer Research, Laskin is also chief of the toxicology division at the Environmental and Occupational Health Sciences Institute.

Sleep Disturbance & Heart Failure

Nancy Redeker, PhD, RN, CS, professor and associate dean of research, UMDNJ-School of Nursing, and her team of co-investigators are enrolling 400 male and female stable heart failure patients in the $1.6 million, NIH-funded study.

There are approximately 5 million people with heart failure in the U.S. Many of them also suffer from poor sleep. How does disturbed sleep affect fatigue? Does sleep-related fatigue, in turn, influence daily functioning? These are a couple of the questions Nancy Redeker, PhD, RN, CS, professor and associate dean of research, UMDNJ-School of Nursing, is trying to answer. “Our objective is to gather enough data to help us understand these problems so that we can develop an intervention for heart failure patients,” explains Redeker.

What makes this study unique in comparison to previous sleep studies is that patients will be monitored in their own homes. Through the use of polysomnography — converting electrical impulses in the body to graphical representation — many activities will be monitored, including brain waves, eye movements, muscle activity, heartbeat, blood oxygen levels and respiration.

“The ability to monitor in the patient’s home offers great benefits for both the patient and the investigators,” explains Redeker. “Not only is the patient more comfortable but we will be able to more accurately record sleep patterns. It’s often difficult for sleep study patients to obtain a restful sleep away from the comforts of their own home.”

The heart failure patients will wear a wrist actigraph throughout their three days in the study. This device, resembling a wristwatch, will be used to measure daily activity levels and nocturnal sleep. The participants will also answer questions about their mood, fatigue and other symptoms. With the data gathered, Redeker hopes to develop a follow-up study focusing on such solutions as massage therapy or sleeping pills to ease sleep disturbance and improve functional performance and quality of life for these patients.

First U.S. Center for Humanistic Medicine to Open in Newark

Russell Joffe, MD, NJMS dean, will oversee the development of the school’s humanism in medicine curriculum.

A $3.2 million grant from the Healthcare Foundation of New Jersey — the largest in its history — will establish the first center for humanistic medicine in the country at UMDNJ-New Jersey Medical School (NJMS). Named the Healthcare Foundation of New Jersey Center for Humanistic Medicine, it will open in the fall. Training future physicians in communication skills, sensitivity to family issues and compassionate care will be its primary mission.

“This is not just about kindness and compassion,” says Russell Joffe, MD, dean of the medical school. “It is a cultural change in that as medical professionals, we must value people beyond illness and diagnosis.”

Central to this new initiative will be the recruitment of 10 academically talented, service-oriented students, who will be offered full, four-year scholarships. The students are all expected to be from New Jersey, and they will graduate with a medical degree and a special distinction in humanistic medicine. While at NJMS, they will serve as mentors to other students, and will be invited to participate in a humanistic care summer program between their first and second years, as well as community service projects. The medical school has made a commitment of $1.2 million to underwrite the scholarships.

“Ninety-five percent of the complaints hospitals get are not about outcomes. They’re about how the doctor treated the patient. The Center has an opportunity to change the face of medical education,” says Lester Lieberman, chair, Healthcare Foundation of New Jersey.

The center opening will coincide with the introduction of a new medical school curriculum, which will better prepare students to practice medicine in a healthcare environment that is rapidly changing, says Joffe.

RWJMS Grants:

Edward Arnold, PhD, adjunct professor, Molecular Genetics, Microbiology, and Immunology, received a two-year, $466,500 grant from Pfizer for “Crystallographic Studies of a Viral Target.”

Edwin Boudreaux, PhD, assistant professor, Emergency Medicine and Psychiatry, received a five-year, $836,803 grant from the National Institute of Drug Abuse to study “Tobacco Treatment Initiated in the Emergency Department.”

Benjamin Crabtree, PhD, professor, Family Medicine, received a five-year, $416,406 grant from the National Heart, Lung, and Blood Institute Research Supplements for Underrepresented Minorities Program to study “A Trial to Enhance Adherence to Multiple Guidelines.”

Panos Georgopoulos, PhD, associate professor, Environmental and Community Medicine, and director, Computational Chemodynamics Laboratory, received a three-year, $895,577 grant from the American Chemistry Council on “Computational Modeling of Exposures to Volatile Organic Compounds in Both Outdoor and Indoor Settings.”

David Gorski, MD, PhD, assistant professor, Surgery, received a three-year, $466,500 grant from the Department of Defense Breast Cancer Research Program to study “Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene.”

Paul Lioy, PhD, professor, Environmental and Community Medicine, received a three-year, $964,347 grant from the Health Effects Institute for “Assessing Exposure to Air Toxics in Camden, NJ.”
RWJMS Grants:

Margaret Schwarz, MD, assistant professor, Surgery, received a four-year, $1,554,450 grant from the National Heart, Lung, and Blood Institute for “Vasculature is a Determinant of Epithelial Morphogenesis.”

Federico Sesti, PhD, assistant professor, Physiology and Biophysics, received a five-year, $1.5 million grant from the National Institute of General Medical Sciences to study “The Role of KVS and MPS Subunits in Basic Neuronal Function.”

Publications:

“Birth Weight Discordancy and Adverse Perinatal Outcomes Among Twin Gestations in the United States: The Effect of Placental Abruption,” co-authored by Cande Ananth, PhD, MPH, associate professor, Obstetrics, Gynecology, and Reproductive Sciences, Kitaw Demissie, MD, PhD, assistant professor, Environmental and Community Medicine, and Maryellen Hanley, MD, MPH, clinical assistant professor, Obstetrics, Gynecology, and Reproductive Sciences, was in the American Journal of Obstetrics and Gynecology, Vol. 188, 2003.

“Intellectual Impairment in Children with Blood Lead Concentrations Below 10 Micrograms Per Deciliter,” co-authored by Deborah Cory-Slechta, PhD, professor and chair, Environmental and Community Medicine and director, Environmental and Occupational Health Sciences Institute, was in the New England Journal of Medicine, Vol. 348, April 2003.

SPH Grants:

Audrey Gotsch, DrPH, CHES, dean, received a five-year, $1,620,000 grant from NIEHS for HOPE Partnership (Health Observances and Public Education).

Publications:

“Relative Risk of Prostate Cancer for Men with Affected Relatives: Systematic Review and Meta-Analysis,” by Dirk Moore, PhD, associate professor, Biometrics, et al., was in the International Journal of Cancer, Vol. 107, Issue 5, 2003.

NJMS Grants:

Abraham Aviv, MD, professor, Pediatrics, received a five-year, $1,650,000 grant from NIH-NIA for “Telomeres and Vascular Aging.”

Joshua Berlin, PhD, associate professor, Pharmacology and Physiology, received a five-year competitive renewal grant for $1,675,000 from NIH for “Molecular Mechanism of Ion Transport by the Na, K-Pump.”

Nancy Connell, PhD, associate professor and vice chair for research, Microbiology and Molecular Genetics, received a two-year, $633,640 grant from NIH-NIAID for “Nutrient Transfer Mechanisms in Mycobacteria.”

Virendra N. Pandey, PhD, associate professor, Biochemistry and Molecular Biology, received a five-year, $1,749,375 grant from the NIH-NIAID for “Genome Targeted Inhibitors of Retroviruses.”

Samuel Joseph Leibovich, MD, PhD, professor, Cell Biology and Molecular Medicine, received a four-year, $1.3 million grant from NIH-NIGMS for “Toll-Like Receptors, Adenosine and Angiogenesis.”

NJMS Grants:

Muriel Lambert, PhD, professor, Pathology and Laboratory Medicine received a three-year, $885,000 grant from NIH-NHLBI for “Nucleosomes Modulate DNA Interstrand Crosslink Repair.”

Stephen Vatner, MD, professor and chair, Cell Biology and Molecular Medicine, received a five-year, $2,577,000 grant from NIH-NHLBI for “Aging Effects on Cardiovascular Function.”

B.J. Wagner, PhD, professor, Biochemistry and Molecular Biology, received a three-year, $1,166,250 grant from NIH-NEI for “Proteolytic Enzymes and Cataractogenesis.”

Ian Whitehead, PhD, assistant professor, Microbiology and Molecular Genetics, received a five-year, $1,383,950 grant from NIH-NCI for “Novel Pathways for Bcr-Abl Transformation.”

Stacy Zamudio, PhD, assistant professor, Obstetrics, Gynecology and Women’s Health, received a four-year, $1,080,000 grant from NIH for “Altitude-Induced Hypoxia, IUGR and Placental Function.”