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Health Risks of Diesel Exhaust
Junfeng (Jim) Zhang, PhD, MS, associate professor, Environmental and Occupational Health, UMDNJ-School of Public Health, and a member of the Environmental and Occupational Health Sciences Institute (EOHSI), received a three-year, $572,497 grant from the U.S. Environmental Protection Agency (EPA) for “Validation of Diesel Exhaust Biomarkers.” Zhang’s team is studying the health risks associated with diesel exhaust (DE), which has been a concern of the EPA and other agencies for more than 30 years. It is still poorly characterized, partly due to the lack of DE-specific markers or biomarkers of exposure.
Urinary 1-hydroxypyrene, a major metabolite of pyrene, has been used as a DE biomarker in occupational settings, but pyrene has numerous environmental sources. Nitro-PAHs (polynuclear aromatic hydrocarbons) are emitted specifically by diesel engines; and their urinary metabolites, amino-PAHs, have been measured in DE exposed workers in a recent occupational study.
“Based on this data and our preliminary study of seven adults exposed to diesel-powered city bus exhaust, we propose to piggyback the proposed study onto a current DE health effects study to validate novel biomarkers of DE exposure to effectively quantify environmentally relevant exposures and to explore the effects of a range of demographic and health variables on urinary biomarker levels,” explains Zhang.
Testing will include 50 healthy and nonsmoking men and women during two one-hour controlled exposure sessions to DE at 300 micro-grams per cubic meter PM10 (particles with size smaller than 10 microns in diameter).
“We expect the validated biomarkers to have a large potential for use in DE health risk assessment because the sensitivity and specificity of these biomarkers are adequate to identify not only individuals who are occupationally exposed, but also those who are exposed to elevated environmental levels of DE,” he says.
International Studies on TB
Jerrold J. Ellner, MD, professor and chair, Department of Medicine, UMDNJ-New Jersey Medical School (NJMS), received a $2.5 million grant from the National Institute of Allergy and Infectious Diseases to fund a “U.S.-Brazil Collaboration on Strain Variation in Tuberculosis.”
This program creates collaboration among leading
epidemiologists, immunologists, molecular biologists and microbiologists in the U.S. and Brazil, and uses an
innovative epidemiologic study design that enables them to explore crucial aspects of TB biology and immunology in human populations. It also signals recognition of the excellence of international research in infectious diseases and emerging pathogens at the medical school.
Ellner is the principal investigator on this project, which is funded through the prestigious International Collaborations in Infectious Diseases Research network. The main foreign collaborator is Reynaldo Dietze, MD, director of the Nucleo de Doencas Infecciosas in Vitoria, Brazil. Key investigators at NJMS are David Alland, MD, associate professor, David Hom, MS, assistant professor, Edward Jones, MD, assistant professor, and Padmini Salgame, PhD, professor, all from the Department of Medicine.
HIV/AIDS Research & Training
Linda Podhurst, PhD, acting director of the François-Xavier Bagnoud Center (FXBC) at UMDNJ, is the principal investigator for recent awards from the Health Services and Resources Administration. She received a five-year, $4.88 million grant for the AIDS Education and Training Centers (AETC) National Resource Center (NRC), which provides an online resource library of training materials and coordinates workgroups among the 11 regional AETCs to facilitate collaboration in the development of HIV/AIDS healthcare provider training materials to meet emerging needs.
She is principal investigator for a three-year cooperative agreement ($210,000 year 1) for the HIV/AIDS NRC for Title IV, which coordinates the work groups for the U.S. Public Health Service perinatal and pediatric HIV management guidelines. It also conducts research and provides nationwide communication and coordination services related to HIV clinical care for the Ryan White CARE Act (RWCA) Title IV
program, which serves women, including pregnant women, children and
adolescents living with HIV infection.
She also received a five-year, $825,000 grant for the NRC National Quality Improvement/Management Center to coordinate national expert participation in quality improvement work groups. Other HIV/AIDS NRC Awards for 2005 include a $227,000 grant from John Snow, Inc., for the development of a Web-based curriculum for healthcare providers managing adolescents infected with or at risk for HIV infection.
Studying RNAP Structure & Function
William T. McAllister, PhD, professor and chair, Cell Biology, UMDNJ-School of Osteopathic Medicine, received a four-year, $2,030,429 grant from the NIH for the “Structure and Function of T7 RNA Polymerase.”
The first step in gene expression is the transcription of genetic information found in the DNA genome into messenger RNA. McAllister’s laboratory is focusing on how the enzyme that is responsible for this activity (RNA polymerase) works. As a model system, he and his team have chosen the RNA polymerase (RNAP) that is encoded by bacteriophage T7. This enzyme consists of a single subunit, yet it carries out all the steps in the transcription process in a similar manner as the multi-subunit RNAPs found in prokaryotic and eukaryotic cells. “Our approach is to characterize functional aspects of RNA synthesis using biochemical and genetic methods,” he says. “A number of structures of T7 RNAP have been solved, including free RNAP, RNAP bound to the promoter, an early
initiation complex, and recently, the structure of an elongation complex.”
These structures, together with structures of bacterial and yeast RNAPs, have provided a wealth of information concerning common features of the transcription machinery with important insights into the transcription process. Nevertheless, important gaps remain in knowledge of the various stages of transcription, most importantly with regard to the transition that leads from an unstable initiation complex (IC) to a stable elongation complex (EC), and with regard to the process of termination.
In addition to their utility in studies of transcription, phage RNAPs have a number of practical applications, including high level expression systems. Recently, we have initiated experiments to explore the use of T7 RNAP as an information-dependent molecular motor to move and position molecules along a DNA template. We believe that these studies may have important implications in nanotechnology and information sciences.
New Environmental Bioinformatics Center
William J. Welsh, PhD, the Norman H. Edelman Professor in Bioinformatics and Pharmacology, UMDNJ-Robert Wood Johnson Medical School (RWJMS), and director of the UMDNJ Informatics Institute (right), received a five-year, $5 million grant from the U.S. Environmental Protection Agency (EPA) to establish the nation's first and only National Center of Excellence for Environmental Bioinformatics and Computational Toxicology. UMDNJ will be the lead university, and will partner with Rutgers University, Princeton University and the U.S. Food and Drug Administration’s National Center for Toxicological Research for Toxicoinformatics to establish the “Research Center of Excellence for Environmental Bioinformatics and Computational Toxicology.”
Welsh and Panos Georgopoulos, PhD, professor, Environmental and Occupational Medicine, RWJMS, and director of the Computational Chemodynamics Laboratory and co-director of the Center for Exposure and Risk Modeling, EOHSI, will serve as the Center’s director and associate
The Center will bring together a team of computational scientists with diverse backgrounds in bioinformatics, chemoinformatics and enviroinformatics from the participating organizations to develop and deploy advanced
computational tools for the identification and characterization of potentially
environmentally hazardous substances such as metals and common chemicals. Public outreach and training activities will constitute essential elements of the Center and will be tightly interwoven with the research activities.
Monica Roth, PhD, professor, Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, received a four-year, $921,434 grant from the National Institute of General Medical Sciences to study “Integration of Murine Retroviral Vectors.” Roth has been studying the integration of murine leukemia virus (MuLV), the most common retroviral vector used in gene therapy protocols. Integration is a critical step in the viral life cycle that results in the stable insertion of the viral genome throughout the host DNA. There is no mechanism of excision of an integrated provirus and integration can lead to the disruption and/or activation of cellular genes.
Our proposal utilizes biochemical and genetic approaches to define the interactions which orchestrate the assembly of protein-DNA integrative complex,” she says, explaining that the three specific areas, which examine individual components of the integration complex, will be studied.
The first focuses on the viral Integrase (IN) protein and aims to define the domains of the protein required to assemble a synaptic complex with the viral and target DNAs. The second specific aim will define the structural and/or sequence requirements of the viral DNA at its ends. The third specific aim modifies the MuLV IN protein to include sequences found to direct integration to heterochromatin, considered to be transcriptionally inactive.
“This approach will adapt the mechanism identified for the yeast Ty5 system to the retroviral particles,” says Roth. “The potential of the Ty5 tag or related systems to target retroviral integration will be examined and this can limit the potential of viral integration to activate host genes.”
These studies examine critical aspects of the protein-DNA recognition needed to identify a stable complex for structural and functional analysis. This knowledge of
retroviral integration is necessary for further manipulation to target and/or inhibit this requisite step in the viral life cycle.
Nancy Connell, PhD, professor and vice chair of Research, Medicine, and director, Center for Biodefense, Grant Gallagher, PhD, Oral Biology, New Jersey Dental School, David Alland, MD, assistant professor, Medicine, Kevin Fennelly, MD, associate professor, Medicine, clinical director, Clinical Research Group, Center for Emerging and Reemerging Pathogens, and Elizabeth Raveche, PhD, professor, Pathology, received a
one-year, $996,000 grant from the Joint Vaccine Acquisition Program of the Department of Defense to continue their research into the host response to aerosol infection by M. tuberculosis and other agents.
Yoshihiro Ishikawa, MD, PhD, professor, Biochemistry and Molecular Biology, received a three-year, $1,049,625 grant from the National Institutes of Health for “Pathophysiological Role of Adenylyl Cyclase Isoforms.”
Ashwani Malhotra, PhD,
associate professor, Medicine, Division of Nephrology, received a four-year, $1.4 million grant from the National Institutes of Health-NHLBI for “High Glucose Promotes Myocyte Apoptosis by PKC Pathways.”
Junichi Sadoshima, MD, PhD, professor, Cell Biology and Molecular Medicine, and associate director, Cardiovascular Research Institute, received a five-year, $1,360,625 grant from the NIH to study “Regulation of Myocardial Growth and Death by Akt/GSK3.”
Dorothy Vatner, MD, Ledyard H. Pfund Professor, Cell Biology and Molecular Medicine, received a five-year, $1,574,440 grant from the NIH to study “Age and Gender Differences in Apoptosis and Stem Cells.”
Hua Zhu, PhD, assistant
professor, Microbiology and Molecular Genetics, received a five-year, $1,473,475 grant from the National Institute of Allergy and Infectious Diseases for “Identification of Human Cytomegalovirus Pathogen Genes.”
Robert Heary, MD, associate
professor, Neurological Surgery and director, Spine Center, The University Hospital, received the New Jersey Organ and Tissue Sharing Network’s “Advancing the Science of Donation” award.
Joseph Aisner, MD, professor, Medicine, received a six-year, $1.5 million grant from the NIH-NCI for “Participation in the Eastern Cooperative Oncology Group.”
Michael Lewis, PhD, Distinguished Professor of Pediatrics and Psychiatry, and Margaret Bendersky, PhD, adjunct professor, Pediatrics, are principal investigator and co-investigator for a $5 million grant from the National Institute on Drug Abuse for “Developmental Effects of Prenatal Cocaine Exposure.”
“Anemia and Clinical Outcomes,” by Mercy Kuriyan, MD, MHA, professor, Pathology, and Jeffrey Carson, MD, Richard C. Reynolds Professor of Medicine and chief, Division of General Internal Medicine, was in Anesthesiology Clinics of North America,
Vol. 23, 2005.
“Cutaneous Anthrax: Conservation or Surgical Treatment?” by Janusz Godyn, MD, professor, Pathology and Laboratory Medicine, and Molecular Genetics, Microbiology and Immunology, Richard Siderits, MD, assistant professor, and Anup Hazra, MD, assistant professor, Pathology and Laboratory Medicine, was in Advances in Skin and Wound Care, Vol. 18, No. 3.
“Protein-Protein Recognition: Juxtaposition on Domain and Interface Cores in Immunoglobulins and Other Sandwich-Like Proteins,”
co-authored by Alexander Kister, PhD, assistant professor, Health Informatics, was in the Journal of Molecular Biology, Vol. 342, 2004.
Gloria McNeal, PhD, APRN, BC, associate professor and assistant dean, was named a 2005 Fellow of the American Association of Colleges of Nursing and was appointed chair of the Public Relations Committee of the Association of Black Nursing
Faculty in Higher Education.
Drew Harris, DPM, MPH,
executive director, Special Projects, Office of Academic Affairs, and Glenn Paulson, PhD, ScD, professor, Environmental and Occupational Health, and acting associate dean, Research, presented “The U.S. CDC Centers for Public Health Preparedness: Building a Nationwide Exemplar Network,” at the 28th Annual Arctic and Marine Oilspill Technical Seminar, Calgary, Canada.
Howard M. Kipen, MD, MPH, professor, Environmental and Occupational Health Division, and professor and acting chair, Environmental and Community Medicine, Robert Wood Johnson Medical School, presented “Overview of Human Exposure Experimentation Directed Environmental Issues: Air Pollution and Ethics of Human Experiments” at the American Occupational Health Conference in Washington, DC.
“Nontransformed Cells Can Normalize Gap Junctional Communication With Transformed Cells,” co-authored by Gary Goldberg, PhD,
associate professor, Molecular Biology, was in Biophysical Research Communication, July 2005.
“The Mcm467 Complex of Saccharomyces Cerevisiae is Preferentially Activated by the Autonomously Replicating DNA Sequences,” by Subhasis Biswas, PhD, professor, Molecular Biology, was in Biochemistry, March 2005.
William McAllister, PhD, chair, Cell Biology, presented “RNA Polymerase as a Molecular Machine” at Penn State University, State College, the University of Wyoming, Laramie, and the University of Massachusetts Medical Center, Worcester.
Meredith Shalick, JD, director, Policy and Development, NJ Cares Institute, received the 2005 Jepson Alumni Achievement Award from the University of Richmond, given annually to an alumnus whose achievements reflect the
mission of the school.