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New Approaches Against Zika Infection

New Approaches Against Zika Infection—The number of mosquito-borne Zika virus infections in humans are expected to increase, and drugs for protecting people are urgently needed.  In a study published online on March 23 in Virology, Felipe Diaz-Griffero, Ph.D., describes a family of therapeutic agents that halts the virus’ entry into cells. Theorizing that Zika requires a cellular protein called AXL to attach to cells, Dr. Diaz-Griffero found that cells in which the gene for AXL was deleted were resistant to infection. The drugs may also thwart Zika infection through a second mechanism: by neutralizing acidic compartments within the cells. This group of drugs could potentially treat people infected with Zika and thereby help prevent the well-established neurological problems associated with Zika. Dr. Diaz-Griffero is professor of microbiology & immunology and the Elsie Wachtel Faculty Scholar at Einstein.

Wednesday, April 18, 2018
 
Boosting T Cells’ Attack

Boosting T Cells’ Attack—Cell-membrane molecules called glycolipids help cells recognize one another and play an important part in launching immune responses. One class of glycolipids, called alpha-galactosylceramides, have been used as a drug to activate a portion of the immune system’s T cells and effectively treat cancers in laboratory mice, although so far this has been difficult to achieve in people with cancer. Steven Porcelli, M.D. and colleagues have found that simultaneously making two different chemical changes to the structure of alpha-galactosylceramides renders them more effective at stimulating T cells to attack cancers, especially in experiments that more accurately replicate cancer in humans. Their approach, described online on March 22 in Cell Chemical Biology, is a step toward improving current drugs and creating new immunotherapies for cancer. Dr. Porcelli is professor and chair of microbiology & immunology, professor of medicine and the Murray and Evelyn Weinstock Chair in Microbiology and Immunology at Einstein.

Monday, April 16, 2018
 
Preventing Diabetes in Men

Preventing Diabetes in Men—Men of color in low-income urban neighborhoods face a high risk for developing type 2 diabetes but are less likely to participate in diabetes prevention programs. To better engage them, Elizabeth Walker, Ph.D., R.N., and colleagues launched the first NIH-funded pilot study of a modified diabetes prevention program tailored to these men with prediabetes. In the 16-week “Power Up for Health” program, based on the National Diabetes Prevention Program, 29 middle-aged men agreed to attend weekly sessions with male lifestyle coaches at five New York City recreation centers. The coaches offered the men support, guidance and motivation for choosing healthier diets and increasing exercise, and researchers monitored their weight loss, lifestyle activities and signs of depression. The findings--published online on March 15 in the American Journal of Men’s Health, alongwith two additional reports (report 1 and report 2) of analyses of the program’s design and participants’ feedback--showed that the 23 men who completed the program lost an average of 9.7 pounds and saw improvements in depressive symptoms, diet and exercise. Dr. Walker and colleagues concluded that “Power Up for Health” shows promise for delaying or preventing type 2 diabetes among men at risk for the disease and that further research is needed with a larger sample size of men. Dr. Walker is professor of medicine and of epidemiology & population health, and is director for the pilot and feasibility program of the New York Regional Center for Diabetes Translation Research (CDTR) at Einstein.

Friday, April 13, 2018
 
Turning Back the Clock

Turning Back the Clock—Aging is usually accompanied by cellular and organ deterioration, due in part to key cellular maintenance pathways that no longer work properly. One such pathway is chaperone-mediate autophagy (CMA), responsible for selectively degrading used proteins so they don’t impair cell function. Ana Maria Cuervo, M.D., Ph.D., has received a five-year, $2.2 million NIH grant to study CMA activity in different organs to better understand why CMA efficiency degradation tails off in elderly people. Interventions that could rev up CMA could potentially slow down the aging process and delay the onset of age-related problems such as neurodegeneration, metabolic disorders and muscle weakness. Dr. Cuervo is professor of developmental and molecular biology, of anatomy and structural biology, and of medicine. She is co-director of the Institute for Aging Research and holds the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases at Einstein. (4R37AG021904-17)

Thursday, April 12, 2018
 
Insights Into Antibody Creation and Cancer

Insights Into Antibody Creation and Cancer—The immune system relies on mutations in genes that code for antibodies to produce the wide variety of antibodies that protect us against pathogens. The enzyme causing these mutations, activation-induced deaminase (AID), sometimes mutates other genes as well, leading to B-cell lymphoma and other cancers. Matthew Scharff, M.D., and Thomas MacCarthy, Ph.D., from Stony Brook University, were awarded a five-year, $2.9 million National Institute of Allergy and Infectious Diseases Multiple Principle Investigator grant to determine how AID targets specific regions within antibody genes. Using computational modeling of antibody gene sequences and biological experiments, the team will identify DNA signatures within antibody-coding genes that attract AID activity. Learning more about the mechanisms underlying antibody diversification could lead to strategies for producing protective antibodies in patients. In addition, understanding how AID induces gene mutations could help to identify factors that put people at risk for cancer. Dr. Scharff is a distinguished professor of cell biology and of medicine and holds the Harry Eagle Chair in Cancer Research/National Women’s Division. Dr. MacCarthy is assistant professor of applied mathematics and statistics at Stony Brook University, who did his postdoctoral training with Dr. Aviv Bergman at Einstein. (1R01AI132507-01A1)

Monday, March 26, 2018
 
Strategies to Tackle the Opioid Epidemic

Strategies to Tackle the Opioid Epidemic—Widespread use and misuse of prescription opioids has led to a nationwide opioid epidemic. Better public health policies and strategies are needed to address the crisis. Joanna Starrels, M.D., M.S., treats and studies both chronic pain and addiction. Dr. Starrels has received a five-year, $943,000 NIH grant to mentor junior investigators to conduct research that will improve patient care and public policy approaches to curb the opioid epidemic. For example, she will study how best to reduce opioid doses for patients with chronic pain who are treated in primary care or HIV treatment settings. Dr. Starrels is associate professor of medicine and attending physician at Montefiore Health System. (1K24DA046309-01)

Thursday, March 22, 2018
 
Mechanisms in Diabetic Bone Loss

Mechanisms in Diabetic Bone Loss —Diabetes affects the way sensory fibers in bones receive mechanical and neural signals. That means bone mass doesn’t increase as it normally does in response to mechanical stimulation. With a five-year, $2.1 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Mia M. Thi, Ph.D., and Sylvia O. Suadicani, Ph.D.,  will build on previous research suggesting that the protein complex Panx1-P2X7R influences bones’ ability to receive and respond to signals. They will examine whether diabetes affects the bones’ sensory fibers; if regulating Panx1-P2X7R is essential for bone adaptation; and if dysfunction of this protein complex triggers inflammation that impairs bone growth. Using animal models of type 1 diabetes, they will investigate new treatments for stemming diabetic bone loss. Dr. Thi is an assistant professor of orthopaedic surgery and an instructor in the Dominick P. Purpura Department of Neuroscience. Dr. Suadicani is associate professor of urology and is an assistant professor in the Dominick P. Purpura Department of Neuroscience. (1R01AR073475-01)

Tuesday, March 20, 2018
 
Visual Clutter and Impaired Vision

Visual Clutter and Impaired Vision—Visual crowding—clutter’s interference with our ability to recognize individual objects—can be a significant problem for people with macular degeneration and other eye diseases. Adam Kohn, Ph.D., has received a five-year, $2.1 million grant from the National Eye Institute to determine the neural underpinnings of visual crowding. In research using monkeys and focusing on the brain’s visual cortex, Dr. Kohn will examine how crowded visual displays affect the ability of nerves to absorb sensory information. His findings may lead to better therapies for the impaired central vision that characterizes macular degeneration. Dr. Kohn is professor in the Dominick P. Purpura Department of Neuroscience and of ophthalmology and visual sciences and systems & computational biology. (1R01EY028626-01)

Friday, March 09, 2018
 
Insights into Autoimmunity

Insights into Autoimmunity—There are more than 80 types of autoimmune diseases, which occur when immune cells aberrantly attack the body’s own cells or tissues. CD8 T cells strongly contribute to the pathology observed in type 1 diabetes and many other autoimmune diseases. Teresa DiLorenzo, Ph.D., and Steven Almo, Ph.D., have received a five-year, $3.5 million grant from the National Institutes of Health to fill in critical knowledge gaps regarding the protein-protein interactions that occur when CD8 T cells target and damage tissue. CD8 T cells also help eliminate disease-causing microbes and tumors, so knowledge gained from studying autoreactive CD8 T cells should improve understanding of T-cell biology in general. The research may also lead to more effective ways to manipulate and harness the immune system to prevent disease and improve health. Dr. DiLorenzo is professor of microbiology & immunology and of medicine and Diane Belfer, Cypres & Endelson Families Faculty Scholar in Diabetes Research at Einstein. Dr. Almo is professor and chair of biochemistry, professor of physiology & biophysics, and Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology at Einstein. (1R01AI123730-01A1)

Tuesday, March 06, 2018
 
How Nuclear Pore Traffic Cops Do Their Job

How Nuclear Pore Traffic Cops Do Their Job—The nuclear envelope of eukaryotic cells must be permeable — messenger RNA molecules must exit the nucleus to be translated into proteins in the cytoplasm, for example, and newly translated chromatin protein must enter the nucleus to help form chromosomes. This two-way traffic passes through gatekeepers known as nuclear pore complexes endowed with the paradoxical ability to transport thousands of molecules both rapidly and very specifically (i.e., allowing some molecules through while blocking others). To discover the secret to the nuclear pore complexes’ success, David Cowburn, Ph.D., and collaborators looked at interactions between transiting molecules and intrinsically disordered proteins (IDPs) that line the pore’s central channel. Surprisingly, in a report published online on January 26 in the Journal of Biological Chemistry,the binding between IDPs and transiting molecules is energetically weak, allowing for rapid interactions. Simultaneously, the many phenylalanine-glycine repeats within the IDPs makes for more frequent contacts between IDPs and transiting molecule, enhancing specificity. In the February 8 online issue of Structure, Dr. Cowburn and colleagues used neutron scattering experiments to gain insights into the conformational changes that IDPs undergo. Dr. Cowburn is a professor of biochemistry and of physiology & biophysics at Einstein. Samuel Sparks, a Ph.D. student in Dr. Cowburn’s lab, was co-first author of the Journal of Biological Chemistry paper and first author of the Structure paper.

Monday, March 05, 2018
 
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