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Silencing “Selfish DNA”  Transposable elements (TEs) are mobile segments of genomic DNA that are often referred to as “selfish DNA” because they insert copies of themselves into different locations within the genome where they can cause harmful mutations. For this reason, it is important that cells repress TEs. A collaborative study between the laboratories of Drs. Arthur Skoultchi and Dmitry Fyodorov, published in the April 5 issue of Science, has revealed a novel mechanism for TE silencing that appears to protect chromosomes from injury. The current model highlights small RNA interference as the major pathway for TE repression; however, the Einstein team, including first author Dr. Xingwu Lu, discovered a new pathway, which silences TEs by compacting the regions of the genome in which they are located, effectively inactivating the selfish DNA.  The researchers also show that the linker histone H1 specifically recruits a “code-writer” enzyme, Su(var)3-9, which marks the TEs for silencing. Dr. Skoultchi is professor and chair of cell biology, as well as the Judith and Burton P. Resnick Chair in Cell Biology; Dr. Fyodorov is associate professor and Dr. Lu is an associate in the same department.

Wednesday, July 31, 2013
 

Looking at Liver Functions The National Institute of Diabetes and Digestive and Kidney Disorders has awarded Drs. Allan Wolkoff and Ana Maria Cuervo $2.9 million over four years to study two processes, endocytosis and autophagy, which are fundamental to the health of liver cells. Endocytosis (how cells engulf material) and autophagy (how cells eliminate internal toxic products) are related events that involve containment of material within similar internal compartments and play critical roles in protein breakdown. Drs. Wolkoff and Cuervo will study these pathways and how they interact to contribute to the maintenance of optimal health in liver cells. Dysfunction in these two pathways is associated with a variety of human diseases and these studies will provide fundamental knowledge that may suggest therapeutic targets for restoring normal liver function or for slowing decline in related liver diseases. Dr. Wolkoff is professor of medicine and of anatomy and structural biology, director of the Marion Bessin Liver Research Center and chief of the division of gastroenterology and liver diseases in medicine. He also holds the Herman Lopata Chair in Liver Disease Research.  Dr. Cuervo is professor of developmental and molecular biology, of anatomy and structural biology and of medicine, and is co-director of the Einstein Institute for Aging Research. She also is the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases.

Wednesday, July 31, 2013
 

Cellular Cleaning to Fight Aging  The National Institute on Aging has awarded Dr. Ana Maria Cuervo a renewal grant of $2.1 million over five years, to continue studying the contribution of chaperone-mediated autophagy (CMA) to characteristics of aging.  CMA is the process by which specific proteins within cells are targeted and broken downin lysosomes.  Dr. Cuervo has previously found that CMA activity decreases with age and that its restoration in aged rodents both prevents organ deterioration and preserves function.  The grant will support her efforts to better understand why and how CMA fails in aged individuals, as well as the associated consequences in various organs.  CMA is a critical facet of cellular quality control and the knowledge gained from these studies will be used to identify new approaches to correct CMA defects and to treat or delay onset of age-related diseases.  Dr. Cuervo is professor of developmental and molecular biology, of anatomy and structural biology, and of medicine, and is co-director of the Einstein Institute for Aging Research. She also is the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases.

Wednesday, July 31, 2013
 

Spiritual Assist — A study involving more than 92,000 postmenopausal women enrolled in the nationwide Women’s Health Initiative found that women who reported attending weekly religious services in the previous month were less likely to be depressed, more likely to be optimistic and more likely to report overall positive social support compared with women attending services less often. The senior author of the study, which appears in the November issue of the Journal of Religious Health, was Dr. Sylvia Wassertheil-Smoller, professor of epidemiology & population health. The lead author was Dr. Eliezer Schnall, an assistant professor at Yeshiva University.

Wednesday, July 31, 2013
 

Dr. Louis Weiss was awarded a $2.1 million grant over five years by the National Institute of Allergy and Infectious Diseases to study the cyst wall of Toxoplasma gondii, a widespread parasite that usually lies dormant in patients, but can be reactivated when the immune system is stressed, such as in patients with congenital toxoplasmosis or in patients with AIDS. Under these conditions, the dormant bradyzoite stage of Toxoplasma can cause significant brain pathology, as cysts filled with hibernating parasites can reactivate frequently causing localized damageto the central nervous system. The cyst wall surrounding the bradyzoites has been shown to contain many stage-specific proteins; they may hold the key to understanding their biology and what causes them to reactivate in disease-causing forms.  Dr. Weiss plans to use proteomic, immunologic and genetic approaches to identify novel components of the cyst wall, taking advantage of special purification techinques that his laboratory has previously developed for this structure.  Because Toxoplasma can be transmitted through contaminated water and food, these studies will shed light on this parasite, which poses a significant threat to public health. Dr. Weiss is a professor of medicine and pathology.

Wednesday, July 31, 2013
 

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
 
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