Research News & Grants
Section compiled by Carole Walker
Enzyme study focuses on longevity
and stress resistance
The team employed a protein based approach (a.k.a. proteomics) to examine the intra-cellular mechanisms supporting their hypothesis, and found that alterations in kinases protected cells from death and oxidative stress and participated in the resulting extension in longevity. These same pathways may also inhibit some cancers, which was the most common cause of death in their WT mice.
“The results suggest that the sympathetic nervous system in general, and AC5 in particular, are fundamentally important mechanisms for regulating life span and stress resistance,” says Vatner. “What we are trying to accomplish is to develop a treatment that translates basic science to the bedside; translating the mouse data to a novel therapy. If you could take a pill that would allow you to live a third longer, protect your heart against stress, protect your bones against the osteoporosis of old age, and allow you to eat more, but lose weight, would you take this pill?”
The findings complement prior work by Vatner and his colleagues, demonstrating that inhibition of other components of molecular signaling in the sympathetic nervous system have a beneficial effect on heart failure. They hope to find a pharmacological agent that translates these findings into treatment for patients with cardiovascular disease.
These findings, published in the July 27 edition of Cell, were the result of a team effort. Vatner specifically recognizes the participation of Junichi Sadoshima, MD, PhD, and Dorothy Vatner, MD, both professors in his department and both of whom direct a major project on this grant, as well as Lin Yan, PhD, an
assistant professor, who is first author on the Cell paper.
Study focuses on new approach
to chronic diseases
Their goal is to uncover the mechanism behind the regulation of metal ion homeostasis, particularly magnesium homeostasis in vertebrates, through the investigation of the structure and function of channel kinases, also known as chanzymes. Recently discovered bi-functional molecules, they consist of an ion channel fused to a protein kinase. Recent evidence suggests that channel kinases TRPM6 and TRPM7 play a key role in the regulation of metal ion homeostasis in vertebrates.
Magnesium is required for nearly every biological process; hundreds of enzymes need magnesium as an essential co-factor. Part of Ryazanov’s research will focus on TRPM6 and TRPM7, which regulate the ability of cells to absorb magnesium and other trace metal ions. Another part will look at how TRPM7 affects magnesium’s ability to regulate cell growth, an important factor in the potential development of medical interventions to control or cure disease. The research will also investigate how magnesium balance affects kidney function when these channel enzymes are not present.
“What the NIH found so exciting about our work is that we are focusing on the previously overlooked role that magnesium, the second most abundant metal ion in living cells, plays in the development of disease,” says Ryazanov, who is principal investigator of the project. “We recently discovered a novel type of signaling protein that plays a key role in the regulation of magnesium homeostasis in the cells. Understanding how those proteins function could lead us to new treatments for a wide range of conditions, including heart, kidney and neurological diseases.”
Double awards for best paper
and postpartum study
She determined that the use of a minimally trained doula, selected by the mother-to-be, enhances the postpartum well-being of nulliparous mothers and their infants. Overall, doula supported mothers when compared to standard care mothers were more likely to report positive prenatal expectations about childbirth and positive perceptions of their infants, support from others, and self-worth. The research was conducted in collaboration with Marshall Klaus, MD, professor emeritus at the University of California-Southern California and a renowned scholar in the field of maternal-infant attachment.
The first honor — called the Journal of Obstetric, Gynecologic and Neonatal Nursing Writing Award — singled out Campbell as lead author of the article, “A Randomized Control Trial of Continuous Support in Labor by a Lay Doula,” published in the journal’s July/August 2006 issue.
This article reports the results of a randomized, controlled clinical trial conducted to determine whether having a female friend or family member act as “lay doula” helps a woman through labor and improves the childbirth experience. Campbell found that with such support, women had a significantly shorter length of labor, greater cervical dilation at the time of epidural anesthesia, and higher infant Apgar scores at one and five minutes after birth. There were also fewer Cesarean deliveries among women receiving doula support.
Jeffrey R. Backstrand, PhD, a professor at UMDNJ-School of Nursing, is a co-author of the article, along with Marian F. Lake, RNC, MPH, CCRC, and Michele Falk, MSW — both of St. Peter’s University Hospital.
New study looks at periodontitis
This is the first comprehensive study to evaluate these children, who are more likely to suffer from LAP than other populations. The disease occurs 15 to 20 times more frequently in African-American children and 10 times more frequently in Hispanic children than in Caucasians. If untreated, LAP can lead to loss of first molars and incisors. Scientists believe the microorganism Aggregatibacter actinomycetemcomitans (Aa) causes this infection, but definitive evidence from a longitudinal study does not yet exist.
Fine and his colleagues will examine 3,000 Newark children, ages 11 to 16, screening them for periodontal disease and cavities as well as for Aa. Two groups — one with Aa and one without — will be given oral examinations every six months for a minimum of two to three years. During each visit, saliva samples will be collected for later analysis, and participants will receive a cleaning and oral hygiene instructions.
Saliva samples from children who develop the disease will be compared to samples from those who do not, in order to help pinpoint its cause. In addition,
saliva will be used to determine host susceptibility factors in the children who develop disease. Participants diagnosed with LAP will be offered free treatment at the dental school.
The Department of Family Medicine awarded a three year, $587,104 grant from the Health Resources Services Administration to develop a program that improves the ability of young physicians to care for patients with diabetes and other chronic diseases.
“Fostering Successful Aging Through Therapeutic Advances in the Prevention and Management of Herpes Zoster,” an editorial by Thomas A. Cavalieri, DO, interim dean, in Journal of the American Osteopathic Association, Vol. 107, 2007.
Walter Zahorodny, PhD, assistant professor, Pediatrics, awarded a $300,000 grant from the NJ Governor’s Council on Autism for “New Jersey Autism Study: Population-Based Surveillance of Autism.”
The following faculty received grants from the American Heart Association (AHA):
Roman Shirokov, PhD, three year, $196,000, and Eldo Kuzhikandathil, PhD, three-year, $196,000, both from Pharmacology & Physiology; Purnima Bhanot, PhD, Microbiology & Molecular Genetics, four year, $260,000; Peiyong Zhai, PhD, four-year, $260,000; Andreas Ivessa, PhD, four year, $260,000; Diego Fraidenraich, PhD, three year, $196,000, all from Cell Biology & Molecular Medicine. Fraidenraich was also awarded $300,000 from The NJ Commission on Science and Technology to examine how stem cells can be used in the prevention and treatment of heart disease.
Vincent Tsiagbe, PhD, associate professor, Oral Biology, awarded a $271,155 grant from the NIH/National Cancer Institute for “Unraveling Germinal Center B Cell Lymphoma Development.”
“Effect of an essential oil-containing antimicrobial mouth rinse on specific plaque bacteria in vivo” by Daniel Fine, DMD, professor and chair, Oral Biology, and director, Center for Oral Infectious Diseases, and K. Markowitz, D. Furgang, D. Goldsmith, C. Charles, T. Lisante, M. Lynch, in Journal of Clinical Periodontology.
“Susceptibility of staphylococcal biofilms to enzymatic treatments depends on their chemical composition” by P Chaignon, I. Sadovskaya, C. Ragunath, N. Ramsubbu, J. Kaplan, S. Jabbouri, in Appl. Microbiol. Biotechno, 2007, 75:125-132.
David Gorski, MD, PhD, associate professor, Surgery, and surgical oncologist, CINJ, presented with a three-year, $450,000 award for “Metabotropic Glutamate Receptor-1: Validation of a Serendipitously Discovered Molecular Target for Breast Cancer Treatment,” funded by the Breast Cancer Research Foundation through the ASCO Foundation.
William Wadsworth, PhD, professor of pathology and laboratory medicine, awarded a $333,112 individual research grant from the NJ Commission on Spinal Cord Research for “Molecular Mechanisms of UNC-6/Netrin Axon Branching.”
Michael Lewis, PhD, University Distinguished Professor of Pediatrics and Psychiatry, chief, Institute for the Study of Child Development, awarded a four-year, $292,155 grant from the NIMH for “Maltreated Children’s Emotions and Self-Cognitions;” a two-year, $295,821 grant from the NJ Governor’s Council on Autism for “Brain Maturation and Self-Representation in Young Children with Autism Spectrum Disorder;” and is a co-principal investigator on a five-year, $1,754,625 grant from the NIMH for “Emotions and Risk to Psychopathology in Infants and Children.” The PI is Margaret Sullivan, PhD, professor.
The New Jersey Commission on Science and Technology funded the following UMDNJ research projects:
Patrizia Cassacia Bonnefil, MD, PhD, Neuroscience and Cell Biology, $2,518,857 in collaboration with Rutgers for “Bioengineering Human Embryonic Stem Cells.”
Tulin Budak Alpdogan, MD, Medical Oncology/CINJ, $300,000 for “Post Transplant High Dose MTX/ARA c Consolidation: A Drug Resistance Gene Transfer.”
John Langenfeld, MD, Surgery, $300,000 for “Identification of Tumor Stem Cells in Lung Cancer.”
Shaohua Li, MD, Pathology and Laboratory Medicine, $298,246 for “Vasculogenesis from Embryonic Stem Cells.”
Randall McKinnon, PhD, Neurosurgery, $300,000 for “Stem Cell Therapeutics: PDGF Directed Glial Migration.”
Daniel Medina, PhD, CINJ, $300,000 for “Identification and characterization of Mantle Cell Lymphoma Stem Cells.”
Robert Nagele, PhD, Molecular Biology, and NJ Institute for Successful Aging, $297,080 for “Genomic Stability, Chromatin Remodeling and Differentiation Potential of Mesenchymal Stem Cells.”
Sidney Pestka, PhD, chair, Molecular Genetics, Microbiology and Immunology, $300,000 for “Use of Stem Cells for Delivery of Biotherapeutics for the Treatment of Cancers.”
Yufang Shi, PhD, Molecular Genetics, Microbiology and Immunology, $300,000 for “Mechanisms of Mesenchymal Stem Cell Induced Immunosuppression.”
Dale Woodbury, PhD, Neuroscience and Cell Biology, $268,533 for “Plasticity of Amnion Derived Stem Cells in Vitro and In Vivo.”
Megqing Xiang, PhD, $300,000 for “Controlled Differentiation of Inner Retinal Cell Types from Stem Cells.”
“Subcutaneous Unfractionated Heparin vs. Low Molecular Weight Heparin for Acute Thromboembolic Disease: Issues of Efficacy and Cost,” by Jeffrey Carson, MD, the Richard C. Reynolds Professor of Medicine, in Journal of the American Medical Association 2006: 296(8): 991-993.
“Signaling by Transmembrane Proteins Shifts Gears” by Masayori Inouye, PhD, professor and chair, Biochemistry, in Cell 126(5):829- 831.
“SIN1/ MIP1 Maintains Rictor mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity” by first author Estela Jacinto, PhD, assistant professor, Physiology and Biophysics, in Cell 2006:127 (1):125-137.
Glenn Paulson, associate dean, Research, and director of the school's New Jersey Center for Public Health Preparedness, and George DiFerdinando, adjunct professor, Epidemiology, and center coordinator of NJCPHP, to serve on the Health Emergency Preparedness Advisory Council. Paulson will be vice chairman. Jeffrey Hammond, MD, MPH, professor of surgery and chief of trauma/surgical critical care at RWJMS, will serve as chair.