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Fate of fats and stem cells — Dr. Keisuke Ito has received $1.6 million from the National Institute of Diabetes and Digestive and Kidney Disease to study the role of lipid metabolism in the maintenance of hematopoietic stem cells (HSCs). HSCs have the potential to become all types of blood cells and are therefore important in maintaining the blood cell population throughout the lifespan of an organism. Understanding the mechanisms that determine the fate of HSCs will allow investigators to harness the potential of stem cells for clinical applications. The researchers will investigate how a key gene involved in lipid metabolism, PPARdelta, determines the fate and maintenance of this stem cell population, with a goal of identifying therapeutic approaches for manipulating the function of HSCs and clinical potential for enhancing and extending the health and well-being of patients. Dr. Ito is assistant professor of medicine and of cell biology, and director of Scientific Resources of the Stem Cell Institute.

Wednesday, July 31, 2013
 

Fateful Regulator — Researchers led by postdoctoral fellow Dr. Britta Will and her mentor, Dr. Ulrich Steidl, have identified a new critical regulator of hematopoietic stem cell (HSC) fate called Satb1, a protein that has been linked to several types of cancer. HSCs are precursor blood cells that have the ability to mature into specialized cell types. They are guided by various factors within the cell to either commit to a particular cell lineage (differentiation commitment) or to maintain their immature form (self-renewal).  Although individual molecular mechanisms underlying each of these two opposing cell fates are understood, until recently, how they are coordinated has remained elusive. By studying stem cells lacking Satb1, the research team was able to show that the protein indeed coordinates the two processes:  Satb1 regulates self-renewal by simultaneously promoting quiescence (halting cell division) and by repressing differentiation commitment. The findings appear in the April 7 issue of Nature Immunology. Dr. Steidl is assistant professor of cell biology and of medicine (oncology).

Wednesday, July 31, 2013
 

“Leuk”ing for a Cure — Dr. Ulrich G. Steidl had received an award of $1.8 million from The National Cancer Institute to study the role of a specific gene, HLX, in causing acute myeloid leukemia (AML), a cancer of white blood cells characterized by abnormal, rapid growth that interferes with the cells’ normal functions.  The HLX gene encodes a protein that activates other genes (transcription factor); Dr. Steidl previously found that excessive amounts of HLX is associated with AML in both mouse models and in human patients.  With this funding, he will study the mechanisms by which high amounts of HLX initiate AML; the genes that HLX targets for activation, which may work in concert to cause disease; and how HLX might be manipulated to identify possible therapeutic approaches.  Dr. Steidl is assistant professor of cell biology and of medicine and is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research.

Wednesday, July 31, 2013
 

Pompe’s Circumstance  Dr. Jeffrey Pessin has been awarded $2.5 million from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to study the mechanism of Pompe’s disease.  Resulting from deficiency in an enzyme that breaks down glycogen, a storage form of glucose in the liver and muscle that is the major source of energy for cells, Pompe’s disease can cause fatal heart and lung failure in infants.  The process by which cells degrade damaged or unused components and molecules is called macroautophagy and late events in this pathway are damaged in this disease.  The grant will aid Dr. Pessin’s research into the mechanism of muscle degradation in Pompe’s disease and how defects in macroautophagy contribute to this process.  Ultimately, Dr. Pessin aims to design nutritional, exercise, and drug therapies that may help restore proper function in this pathway, which also might be used to treat related diseases.  Dr. Pessin is professor of medicine and of molecular pharmacology, director of the Diabetes Research Center, and the Judy R. and Alfred A. Rosenberg Professorial Chair in Diabetes Research.

Wednesday, July 31, 2013
 

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
 
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