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Live and Let Die  In a recent issue of the Proceedings of the National Academy of Sciences, Dr. Richard Kitsis demonstrated that the two kinds of cell death – apoptosis, a process by which cells are intentionally deleted and promptly cleaned up, and necrosis, wherein dying cells and their deteriorating contents leak out and cause bystander damage – may actually share a “unified death machinery,” despite being markedly different processes.  Dr. Kitsis’ laboratory genetically manipulated the Bax protein to show that in addition to its appreciated role in apoptosis, Bax also is a key regulator of necrosis.  These insights lead the way to a better understanding of complex pathological processes such as heart attacks and strokes that involve both forms of a cell death. They also suggest potential new therapeutic strategies for cancer, where augmented tumor cell death is the goal.  Dr. Kitsis is professor of medicine and of cell biology, director of Einstein’s Wilf Family Cardiovascular Research Institute, and holds the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease. 

Wednesday, July 31, 2013
 

An Essential Factor  In a recent issue of the journal Blood, Drs. Sanjeev Gupta and Antonia Follenzi successfully challenge the long-held view that bone marrow transplantation is of little value in the treatment of hemophilia A, the more common form of this rare bleeding disorder. Their research found that, following transplantation therapy, an essential clotting factor (FVIII) appeared in the blood of hemophiliac mice, protecting these mice from bleeding challenges. The authors also traced the source of FVIII to circulating and liver-resident macrophages, a kind of white blood cell, as well as to stem cells within the bone marrow. The study thus illuminates potential new treatment avenues for hemophilia A. The College of Medicine has filed a patent application related to this research that is available for licensing to partners interested in further testing and developing this treatment. Dr. Gupta is professor of medicine and of pathology, and holds the Eleazar & Feige Reicher Chair in Translational Medicine; Dr. Follenzi is visiting assistant professor of pathology.

Wednesday, July 31, 2013
 

In Living Color ­­ Fluorescent proteins (FPs) have revolutionized optical microscopy by allowing studies of living cells and tissues. In the June 16 online issue of Nature Methods, Dr. Vladislav Verkhusha and research fellow Dr. Daria Shcherbakova describe four new near-infrared FPs they’ve developed that allow for multicolor imaging of tissues deep within humans and other mammals. Such FPs are ideal for in vivo imaging because wavelengths in the near-infrared portion of the electromagnetic spectrum (650 nm to 900 nm) pass right through hemoglobin, melanin and water. The scientists derived the new FPs from photoreceptors called phytochromes that bacteria use to detect light. To test the performance of the four new FPs, the researchers took mouse breast cancer cells that expressed each FP and injected those cells into the mammary glands of mice, where the cancer cells grew into tumors. The FPs proved to be highly sensitive probes, allowing the tumors to be detected at very early stages. The near-infrared FPs could open up new possibilities for simultaneously labeling two or more tissues and for tracking several cell populations in a living animal. Dr. Verkhusha is professor of anatomy and structural biology.

Wednesday, July 31, 2013
 

Virus Entry & Exit  The National Institute of General Medical Sciences has awarded $1.5 million over four years to Dr. Margaret Kielian for her investigation into the methods used by viruses to infect hosts. In order to function, viruses must find a way to enter host cells so they can reproduce. Viruses within the cell must then find a way to exit so the cycle can repeat. Using biochemical and imaging techniques, Dr. Kielian’s study will identify the human molecules that interact with the virus during these steps. She will then examine the ways that viruses use those interactions to promote their own survival. By revealing the interplay between a virus and its host cell, this study may uncover new ways of understanding viral infections and developing anti-viral therapies. Dr. Kielian is a professor of cell biology.

Wednesday, July 31, 2013
 

Tough to Stomach —  Dr. Anne Muesch has been awarded $2.5 million over five years by the National Cancer Institute to study how a bacterium that colonizes the gastric mucosa, known as Helicobacter pylori, causes gastritis and increases the risk of stomach cancer. Gastric carcinoma is the second leading cause of cancer-related deaths and the fourth most common cancer in the world. A gene expressed in particularly virulent strains of H. pylori, called cytotoxin-associated gene A (CagA) induces loss of polarity (organization of cell shape and structures), increased migration and destruction of gastric epithelial cells, in part by inhibiting a conserved cell polarity determinant, the serine/threonine kinase Par1. Dr. Muesch’s group has identified 76 putative epithelial Par1 substrates in an unbiased screen that they will evaluate for their involvement in the disruption of epithelial polarity upon CagA expression and H. pylori infection. She is associate professor of developmental & molecular biology.

Wednesday, July 31, 2013
 

Signaling Obesity — Dr. Young-Hwan Jo has been awarded $1.8 million over five years by the National Institute of Diabetes and Digestive and Kidney Diseases to support his research of physiological interactions between two distinct types of neurons located within the hypothalamus, and their relation to obesity resulting from a surplus of energy known as a positive energy balance. Dr. Jo will attempt to determine how the exchanges between different populations of neurons contribute to the control of hypothalamic neurophysiology and the regulation of energy homeostasis in relation to obesity. Dr. Jo is assistant professor of medicine and of molecular pharmacology.

Wednesday, July 31, 2013
 

Training Support — The National Institute of Diabetes and Digestive and Kidney Diseases has renewed Dr. Frederick Kaskel’s Developmental Nephrology T32 training grant with an additional five-year reward of $1.32 million. The grant, which will have been active for more than four decades through this renewal, trains new pediatric nephrology physician-scientists in the latest advances in basic and translational research. The goal is to generate well-trained investigators who can address and solve the major questions regarding pediatric kidney diseases and translate this knowledge into clinical practice. Trainees supported by this grant are researching congenital and developmental disorders, inflammatory diseases, acute injury, and end-stage disease of the kidney. Dr. Kaskel is professor and vice chair of pediatrics and director of pediatric nephrology.

Wednesday, July 31, 2013
 

Complex Research — Dr. Arne Gennerich has been awarded $1.5 million over five years by the National Institute of General Medical Sciences to examine the molecular mechanism of the cytoplasmic dynein-dynactin motor complex in order to define the molecular bases of dynein-related diseases in humans. Cytoplasmic dynein is a protein vital to various cellular activities, and mutations in dynactin (a large protein complex required for most cytoplasmic dynein activity) are known to cause neurodegeneration, leading to diseases such as distal spinal and bulbar muscular atrophy and Perry syndrome. Dr. Gennerich will study the molecular mechanisms that underlie the function and dysfunction of the dynein-dynactin complex. Dr. Gennerich is assistant professor of anatomy and structural biology.

Wednesday, July 31, 2013
 

In“valv”uable Insights  Dr. Bin Zhou has been awarded $2.4 million over four years by the National Heart, Lung, and Blood Institute in order to study the genetic pathways that regulate aortic valve biology and that mediate calcific aortic valve stenosis (CAVS). A complex syndrome involving multiple cellular processes, CAVS is the most common disease to require surgical valve replacement. Using mouse models to study CAVS and its cellular and molecular mechanisms, Dr. Zhou is seeking critical information concerning the origins and effects of CAVS, with the goal of developing new therapeutic and preventive strategies for this devastating form of heart disease. Dr. Zhou is associate professor of genetics, of pediatrics and of medicine (cardiology). Drs. Bingruo Wu (genetics), Deyou Zheng (neurology), and Richard Kitsis (medicine) are co-investigators on this project.

Wednesday, July 31, 2013
 

Therapeutic InvestigationDr. Alain Litwin has been awarded $3.7 million over five years from the National Institute on Drug Abuse to study models of care for injection drug users infected with hepatitis C virus (HCV), a potentially lethal virus that infects the liver and is spread by blood-to-blood contact. While HCV treatment leading to a sustained viral response is associated with improved survival, injection drug users have classically had poor access to care and limited success following such regimens. Dr. Litwin will conduct a randomized control trial of three models of care that incorporate new HCV therapies -- on-site primary care, substance abuse treatment, and psychiatric care within drug treatment clinics -- to determine which model is best and most cost-effective for successfully treating HCV-infected injection drug users. Dr. Litwin is associate professor of clinical medicine and of clinical psychiatry and behavioral sciences.

Wednesday, July 31, 2013
 
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