Last year, NJDS and Access One were able to make significant improvements in access to oral healthcare for HIV-positive individuals living in Atlantic, Burlington, Camden, Cape May, Cumberland, Gloucester and Salem Counties. In addition, 11 dental students participated in the service learning experience; three dental students completed the summer Externship Program, involving direct care or scientific inquiry; and four community healthcare professionals participated in the HIV/AIDS Clinical Training Preceptorship. One hundred and twenty medical students from UMDNJ-School of Osteopathic Medicine completed an oral/dental healthcare rotation at the sites, and 70 NJDS faculty and staff participated in the continuing education program.
The special strengths of the partnership between NJDS and Access One include: a strong commitment to provide HIV oral healthcare; convenient sites of three dental centers; established programs with a strong client base; providing faculty and staff at the facilities; the school’s support for required clinical and didactic training rotation of students; a continuing education program for NJDS faculty and staff; and well-established relationships with regional Early Intervention Centers and AIDS Service Organizations.
A contract with Auracom International, a translation service, also makes it possible to communicate with patients in almost any language. Other strengths of the program include bilingual faculty, staff and students; and collaborative initiatives with the UMDNJ-Center for Continuing and Outreach Education, New Jersey Access Initiative’s Division of Addiction Service, the UMDNJ-School of Public Health’s Tobacco Dependence Program, and MANNA, which provides a dietician at the dental centers to provide nutrition education and counseling.
$2 Million for Parkinsonís Disease Studies
"We discovered that the ROS quenching ability of DJ-1 is inadequate to account for its robust neuroprotective potential,” Mouradian explains. “And, we also discovered a new function for DJ-1, whereby it potently blocks a specific cell death signaling cascade that involves activation of a kinase called Apoptosis Signal Regulating Kinase 1 (ASK1).”
Her team’s studies indicated that DJ-1 binds to the death promoting protein Daxx in the nucleus of cells, prevents its translocation to the cytoplasm and therefore prevents the interaction of Daxx with its effector kinase ASK1 that normally takes place in the cytoplasm. This molecular interaction between DJ-1 and Daxx inhibits ASK1 from becoming activated and from proceeding to cause cell death.
“Our efforts are focused on investigating how various mutations in DJ-1 influence this apoptotic mechanism using cellular models and on elucidating this pathway in the brains of Parkinson’s disease patients and DJ-1 deficient mice,” she says, adding that the project investigates the ability of DJ-1 to modulate the transcription of genes that are key to the survival of dopaminergic neurons.
Their ultimate objective is to identify potential targets for therapeutic interventions by either blocking ASK1 mediated death signaling pathway or boosting the neuroprotective activity of DJ-1 in order to slow down or block the neurodegenerative process.
The second project is funded by a three-year, $399,003 grant for “Anti-apoptotic Function of DJ-1 in Parkinson's Disease.”
“It aims to test the in vivo validity of our hypotheses generated from cellular model studies that point to the ability of DJ-1 to protect neurons by blocking the Daxx/ASK1 cell death pathway,” she explains. “As expected from human DJ-1 linked Parkinson’s disease, mice that lack DJ-1 are more susceptible to a toxin that specifically kills dopaminergic neurons and causes severe Parkinsonism in humans.”
Since the team’s findings indicate that DJ-1 protects neurons by preventing ASK1 activation, mice that lack DJ-1 would be expected to have their ASK1 unchecked. The researchers would also expect that if they delete both ASK1 and DJ-1 genes, mice would be relatively protected against the dopaminergic toxin compared to mice that lack only DJ-1. The team has engineered these double “knock-out” mice and is analyzing how they fare after exposure to this toxin.
$3.1 Million for HIV Studies
Progress toward an HIV-1 vaccine has been stymied by the inability to induce a protective humoral response. Well-characterized neutralization epitopes are either poorly immunogenic or effectively masked on the majority of primary isolates. However, evidence suggests that even highly masked isolates possess sensitive neutralization targets that are frequently recognized by autologous patient sera and occasionally by heterologous sera.
Pinter says this suggests that mapping the epitopes involved may identify novel targets that are capable of inducing broadly neutralizing activities. He and his group have identified patient sera that possess broadly neutralizing activities for primary isolates, and are applying methods for localizing the target epitopes. They are also isolating monoclonal antibodies from B cells obtained from these patients, as another means of identifying sensitive sites and characterizing their properties. Information derived from these studies will be used to generate candidate vaccines, which will then be tested in rabbits for immunogenicity and ability to induce neutralizing antibodies.
Their laboratory’s work is also supported by a second five-year award from NIH for $2.4 million for “Characterization of the Antigenic Properties of the V1V2 Domain of HIV-1 gp120.” The group has found that the V1V2 domain can mask sensitive neutralization targets in HIV Env, and is a major determinant of the sensitivity of a virus strain to neutralization. They have also shown that the V1V2 region of certain isolates contains sites that are recognized by antibodies, and that these antibodies possess very strong neutralizing activities for those viruses. Unfortunately, those sites are not highly conserved.
He says, “The goals of this project are to learn more about the mechanism of masking by the V1V2 domain, to better understand the structure and function of this region, and to identify conserved targets in the V1V2 region that could be incorporated into vaccines. A better understanding of the factors that make most HIV isolates difficult to neutralize would help us design a vaccine that works.”
Differentiating Between Generally and Partner Only Violent Sub-Groups: Lifetime Anti-social Behavior, Family of Origin Violence, and Impulsivity” by co-author Douglas Boyle, PhD, JD, senior research administrator, in Journal of Family Violence, 23(1), 47 55, 2008.
David Mwangi, PhD candidate, Molecular Pathology and Immunology, and high school teacher, appointed to the American Association of Immunologists / J.H. Wallace High School Teachers Program.
Evan Jacobs, PhD candidate, Molecular Pathology and Immunology, won the Alexander Nakeff Young Investigators Award at the Great Lakes International Imaging and Flow Cytometry Association’s 17th annual meeting.
Junichi Sadoshima, MD, PhD, professor, Cell Biology & Molecular Medicine, and director, Center for Molecular Biology, awarded a five-year, $2,750,128 grant from NIH/National Heart Lung and Blood Institute for “Cardioprotection Effects of Thioredoxin 1.”
Hreday Sapru, PhD, professor, Neurological Surgery, awarded a five-year, $1,947,200 grant from NIH-National Heart, Lung and Blood Institute for “Central Cardiovascular Regulation: Role of Urocortin III.”
Walter Duran, PhD, professor, Pharmacology & Physiology, awarded a five-year $1,937,680 grant from the NIH-National Heart, Lung and Blood Institute for “Inactivation of Hyperpermeability After Ischemia-Reperfusion Induced Inflammation.”
Debkumar Pain, PhD, associate professor, Pharmacology & Physiology, awarded a five-year, $1,597,689 grant from the NIH-National Institute of Aging for "Mitochondrial Aconitase: FeS Cluster Biogenesis and Interaction with mtDNA."
Roman Shirokov, PhD, assistant professor, Pharmacology & Physiology, awarded a five-year, $1,557,000 grant from the NIH-National Institute of Mental Health for "Gating/permeation Coupling in Calcium Channels."
Bin Tian, PhD, assistant professor, Biochemistry & Molecular Biology, awarded a five-year, $1,521,000 grant from the NIH-National Institute of General Medical Sciences for "Analysis of mRNA Polyadenylation Across Species
Jiang H. Ye, MD, associate professor, Anesthesiology, awarded a four-year, $1,410,874 grant from the NIH-National Institute of Alcohol Abuse and Alcoholism for "Alcohol and Mesolimbic Glutamatergic Transmissions."
Ian Whitehead, PhD, associate professor, Microbiology & Molecular Genetics, awarded a five-year, $1,396,440 grant from the NIH-National Cancer Institute for "Novel Pathways for Bcr-Abl Transformation."
Arkady Mustaev, PhD, assistant professor, Public Health Research Institute, awarded a four-year, $1,368,900 grant from the NIH-National Institute of General Medical Sciences for “Structure and Function of RNA Polymerases in E. coli.”
“A Redox-Dependent Pathway for Regulating Class II HDACs and Cardiac Hypertrophy” by Tetsuro Ago, Cell Biology and Molecular Medicine; Tong Liu, Biochemistry and Molecular Biology; Peiyong Zhai, Cell Biology and Molecular Medicine; Wei Chen and Hong Li, Biochemistry and Molecular Biology; Jeffery Molkentin; Stephen Vatner, MD, professor and chair, and Junichi Sadoshima, MD, professor, Cell Biology and Molecular Medicine, in Cell.
Mel Kantor, DDS, professor, Diagnostic Sciences, awarded a $369,000 grant from Health Resources and Services Administration for Ryan White HIV/AIDS Treatment Modernization Act-Part A. He also received a $537,617 Department of Health and Human Services Care and Treatment Grant.
Jeanette DeCastro, director, Academic Advisement and Student Support; Cecile Feldman, DMD, dean and professor, Community Health; Kim Fenesy, DMD,
“Women’s Health Issues and the Oral & Maxillofacial Surgeon” by Meredith Blitz-Goldstein, DDS, assistant clinical professor and director, Anesthesia, Oral & Maxillofacial Surgery, and HD Ephros, in Journal of Oral and Maxillofacial Surgery, 65 2007: No. 9, Pg. 97.
“Microsurgery Repair of Trigeminal Nerve Injuries” by Vince Ziccardi, DDS, MD, chair, Oral & Maxillofacial Surgery, in Journal of Oral and Maxillofacial Surgery, 65 2007: No.9, Pg 101, Suppl 2.
“A Screen for Leukotoxin Mutants in Aggregatibacter actinomycetemcomitans: Genes of the Phosphotransferase System are Required for Leukotoxin Biosynthesis” by Jeffrey Kaplan, PhD, associate professor, and Scott Kachlany, PhD, assistant professor, both in Oral Biology, in Infection and Immunity, 76: 3561-3568.
“Aggregatibacter actinomycetemcomitans and its Relationship to Initiation of Localized Aggressive Periodontitis: A Longitudinal Cohort Study of Initially Healthy Adolescents” by Daniel Fine, DDS, chair, and Kenneth Markowitz, DDS, assistant professor, both in Oral Biology; D. Furgang; K. Fairlie; J. Ferrandiz; C. Nasri; M. McKiernan; and J. Gunsolley; in Journal of Clinical Microbiology, 47: 3959-3869.
Junfeng Zhang, PhD, MS, professor and acting chair, Environmental & Occupational Health; Scott Diehl, PhD, professor, Oral Biology at NJDS; Howard Kipen, MD, MPH, professor, Clinical Research & Occupational Medicine at RWJMS; Shou-En Lu, PhD, and Pamela Ohman Strickland, PhD, associate professors, Biostatistics; and David Rich, ScD, MPH, assistant professor, Epidemiology, awarded a three-year, $1,178,867 grant from NIH-National Institute of Environmental Health Sciences for “Response to Drastic Changes in Air Pollution: Reversibility and Susceptibility.”
“Neighborhoods and Disability in Later Life” by Vicki Freedman, PhD, professor, and Irina Grafova, PhD, assistant professor, both in Health Systems and Policy;
Ronald Ellis, PhD, associate professor, Molecular Biology, awarded a five-year, $1.4 million NIH grant for "Evolution of Developmental Regulatory Pathways.”
Elyse Perweiler, RN, MPP, associate professor, Medicine, awarded a three-year, $901,705 grant from HRSA for “Model State-Supported Area Health Education Centers.”
“What’s Your Diagnosis? Sharpen Your Physical Diagnostic Skills,” by Carman Ciervo, DO, associate professor and chair, Joshua Coren, DO, MBA, assistant professor, Family Medicine, and David Mason, DO, acting chair, Osteopathic Medicine and associate professor, Primary Care, in Consultant for Pediatricians, Vol. 7, 2008.
“Patient Education Using Relaxation and Guided Imagery to Lower Anxiety Associated with Multiple Sclerosis and Injections,” by Donald Barone, DO, Internal Medicine, and Kathleen Barone, RN, MSCN, Medicine, and M. Franco, in International Journal of MS Care, Vol. 10, 2008.
“Girls Who Disclose Sexual Abuse: Urogenital Symptoms and Signs After Genital Contact” by Esther Deblinger, PhD, clinical director, The Center for Children's Support, and Martin Finkel, DO, director, CARES Institute; C. DeLago and C. Schroeder, in Pediatrics, Vol. 122, 2008.
“Androgen Deficiency in the Aging Male: The Beginning, the Middle and the Ongoing” by Terrie Ginsberg, DO, assistant professor, New Jersey Institute for Successful Aging, and Thomas Cavalieri, DO, dean, in Clinical Geriatrics, Vol. 16:2008.
“Stability and Change in Patient Preferences and Spouse Substituted Judgments Regarding Dialysis Continuation” by Rachel Pruchno, PhD, professor, Medicine, Francine Cartwright, New Jersey Institute for Successful Aging, M.J. Rovine, and M. Wilson-Genderson, in Journal of Gerontology: Social Sciences,
Raymond Habas, PhD, assistant professor, Biochemistry, awarded a five-year, $1,355,465 grant from the NIH for “Non-canonical Wnt Signaling and Cell Motility.”
Michael Reiss, MD, professor, Medicine, awarded a five-year, $1,496,306 grant from the NIH for “Targeting Transforming Growth Factor in Metastatic Breast Cancer.”
Loren Runnels, PhD, assistant professor, Pharmacology, awarded a five-year, $1,481,842 grant for “Functional Analysis of the Bi-functional Ion Channel and Kinase TRPM7.”
Kathleen Scotto, PhD, professor, Pharmacology, senior associate dean, Research, and UMDNJ vice president for research, awarded a five-year, $1,333,658 grant for “Caffeine Regulates Splicing of Cancer-Related Genes: Dissecting the Mechanism.”
“Surfing on Calcium Waves” by Janet Alder, PhD, assistant professor, and James Zheng, PhD, professor, both in Neuroscience & Cell Biology, in Neuron, 2007:54(4):502-505.
“Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer” by co-author Bruce Haffty, MD, professor and chair, Radiation Oncology, in Journal of Clinical Oncology 2006:24(36):5652–5657.