Research Roundup

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Dr. Robert Singer was awarded a $1.3 million grant over four years by the National Institutes of Health to study the activity of individual genes, using state-of-the-art microscopy techniques that were pioneered in his laboratory. Using differently colored fluorescent probes that can bind to any gene of interest, Dr. Singer’s laboratory team will observe the rate and frequency of various steps in which the target gene is transcribed, or read, by the cell. The technology is sensitive enough to follow a single gene molecule, which will allow comparisons among different cells and an estimation of the variability in the process of gene transcription. This work will provide insights into the fundamental cellular processes involved in gene transcription, laying the groundwork for understanding what goes wrong in a variety of diseases that have a genetic, or hereditary, component. Dr. Singer is professor and co-chair of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center and professor of neuroscience and of cell biology.

Wednesday, July 31, 2013
 

Mobile Process — Patients with Wiskott-Aldrich Syndrome (WAS), a rare immunodeficiency disorder, are susceptible to chronic infections due to defects in the migratory behavior of immune cells, such as macrophages, in response to chemical cues. In work, published in the January issue of the journal PLoS One, seventh-year M.D.–Ph.D. student Dan Ishihara made a surprising discovery showing that macrophages lacking a functional WAS protein (WASp) retain the ability to detect the chemical warning signs of infection and even respond with an increase in mobility, but are unable to migrate directionally toward the source of infection. Mr. Ishihara’s research further showed that this abnormality in the WASp-deficient macrophages’ mobility is due partly to defects in the cytoskeleton, the internal support structure of all cells. Mr. Ishihara’s research was conducted in the laboratory of his mentor, Dr. Dianne Cox, associate professor of anatomy & structural biology and of developmental & molecular biology.

Wednesday, July 31, 2013
 

Tolerable Improvements — Dr. Sridhar Mani has been awarded a $1.5 million grant over five years from the National Cancer Institute to improve tolerability of the anti-cancer drug CPT-11 (Irinotecan), whose effectiveness is reduced by its dose-limiting side effect, diarrhea.  Building on previous work with collaborators at University of North Carolina, Chapel Hill, identifying promising compounds that have inhibited the effects of gut bacteria-derived metabolites implicated in CPT-11-induced diarrhea, Dr. Mani and his team plan to use in vivo assays and humanized animal models of CPT-11 pharmacokinetics to characterize the effects of these inhibitory compounds on the anti-tumor activity and tolerability of CPT-11.  This work represents a key effort to fine-tune the approach to treating cancer with the proven therapeutic agent, CPT-11.  Dr. Mani is professor of medicine and of genetics,and is the Miriam Mandel Faculty Scholar in Cancer Research.

Wednesday, July 31, 2013
 

Training Tomorrow’s LeadersDr. Robert Marion was awarded a $ 3.9million grant over five years by the Health Resources and Services Administration for an interdisciplinary leadership training program in neurodevelopmental and related disabilities, conditions which affect more than 10% of American preschool- and school-aged children.  The program will consist of a didactic and hands-on curriculum that provides research projects, community-based clinical experiences and administrative and leadership training to at least 50 trainees in various medical and allied health disciplines each year.  The public health goal of this project is to prepare future leaders to provide interdisciplinary services and special healthcare needs to children with developmental disabilities and their families, with an emphasis on educating professionals to work in underserved urban environments.  Dr. Marion, professor of pediatrics and of obstetrics & gynecology and women’s health, is chief of the divisions of developmental medicine and genetics in the department of pediatrics.  He is also director of the Children’s Evaluation and Rehabilitation Center.

Wednesday, July 31, 2013
 

Helpful Interference — Dr. Deborah Palliser has been awarded a $2 million grant over five years from the National Institute of Allergy and Infectious Diseases to investigate RNAi, a recently identified method of silencing specific genes, as a potential microbicide against sexually transmitted infections (STIs), including genital herpes virus and HIV.  Using an animal model of genital herpes infection, Dr. Palliser will evaluate a panel of RNAi molecules for their ability to silence viral and host genes, and she will determine the effect of any associated host immune responses on RNAi-mediated protection. She also will attempt to identify potential RNAi uptake receptor(s) expressed by vaginal cell surface proteins. This work aims to refine the technology and elucidate the mechanism of RNAi-mediated protection against STIs, with the long-term goal of developing a clinical therapy. Dr. Palliser is assistant professor of microbiology & immunology.

Wednesday, July 31, 2013
 

Safe and ProtectedDr. William Jacobs, Jr. has been awarded a $6 million grant over five years from the National Institute of Allergy and Infectious Diseases to develop a novel vaccine for tuberculosis (TB), a bacterial disease whose extensive drug resistance, along with socioeconomic realities, has stymied global control efforts. Using a genetically engineered strain of bacteria called IKEPLUS, which was shown to be safe and to stimulate an enhanced protective immune response in a mouse model, the researchers will evaluate the efficacy of IKEPLUS used both alone and in combination with the traditional BCG vaccine.  Additionally, the laboratory will develop a manufacturing process for a human IKEPLUS vaccine and will establish biomarker assays to determine how well the vaccine protects against TB. This project represents a key effort to develop and optimize a promising vaccine for TB. Dr. Jacobs is professor of microbiology & immunology and of genetics at Einstein, and is a Howard Hughes Medical Institute Investigator.

Wednesday, July 31, 2013
 

Salty Observations — Should the amount of sodium (salt) in food be restricted to prevent cardiovascular disease—or would a low-sodium diet actually aggravate health problems? To help answer that question, Drs. Michael Alderman, and Hillel W. Cohen, carried out a systematic review of nearly 30 observational studies and randomized clinical trials that have looked at dietary sodium’s association with health outcomes. They concluded that the data strongly suggest a “J-shaped” relation of dietary sodium intake to cardiovascular outcomes. This means that adverse outcomes are experienced at the extremes of sodium intake—by people ingesting very little sodium and by those ingesting a great deal of it. Their findings appear in the May 24, 2012 issue of the American Journal of Hypertension. Dr. Alderman is distinguished university professor emeritus of epidemiology & population health and of medicine; Dr. Cohen is  professor of clinical epidemiology & population health.

Wednesday, July 31, 2013
 

Chain of Events — Diabetes causes nerve damage—“diabetic neuropathy”—in the majority of people with this disease. Painful diabetic neuropathy is the most incapacitating neuropathy syndrome.  A paper in the May 13 issue of Nature Medicine describes for the first time the molecular chain of events responsible. Among the paper’s chief authors was Dr. Michael Brownlee, Einstein Diabetes Center’s Associate Director for Biomedical Sciences and the Anita and Jack Saltz Chair in Diabetes Research. The authors found that elevated levels of a toxic by-product of glucose metabolism called methylglyoxal (MG) bind to and change the structure of a sodium channel called Nav 1.8, found only in neurons involved in signaling pain. Consequences of this change in the “pain channel” include an increase in its electrical excitability. These findings may provide new therapeutic options for treating painful diabetic neuropathy.

Wednesday, July 31, 2013
 

Moving Forward — A team of Einstein researchers led by Dr. Hernando Sosa, has been awarded $1.7 million over four years by the National Institute of General Medical Sciences to study the regulation of kinesins, a group of proteins involved in transporting materials between different parts of the cell, as needed.  In contrast to most kinesin regulation research, which has focused on accessory parts of the protein, Dr. Sosa’s laboratory will employ advanced biophysical, microscopical, and computational techniques to study the regulation of its functional core.  Because the kinesins chosen for study play key roles in fundamental cellular processes in a variety of tissues, improved understanding of kinesin functionality will provide a foundation for the development of therapeutics in many human diseases, including motor neuron diseases and Alzheimer’s disease.  Other researchers involved with the grant include Drs. Gary Gerfen, Ao Ma, and David Sharp. Drs. Sosa and Gerfen are associate professors of physiology & biophysics;  Dr. Ma is assistant professor of physiology & biophysics;  and Dr. Sharp is professor of physiology & biophysics.  

Wednesday, July 31, 2013
 

Helping Families — The Health Resources and Services Administration has awarded a grant of nearly $1 million to Drs. Karen Bonuck and Anne Murphy to evaluate a relationship-based parent-child therapy aimed at reducing the potential for child maltreatment among at-risk youngsters from infants through age 3. Dr. Murphy has used this innovative treatment with promising results among more than 100 families during the past five years; it seeks to build secure parent-child relationships in place of the standard parents-only skills training often used to prevent maltreatment. Through the rigorous trial Bonuck-Murphy team has designed, 100 at-risk Bronx families will be randomly assigned to either the new modality or to parent-only classes. A panel of child welfare policy and practice professionals will review their findings to determine whether the therapy may be translated to other treatment settings and geographic locales. Dr. Bonuck is professor of family & social medicine and of obstetrics & gynecology and women’s health. Dr. Murphy is assistant professor of pediatrics.

Wednesday, July 31, 2013
 
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