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Visualizing How Neurons Develop in the Fruit Fly Eye

Visualizing How Neurons Develop in the Fruit Fly Eye—Proneural bHLH proteins are transcription factors that regulate the development of key nerve cells needed for vision (including rod and cone photoreceptors and corneal nerves) and for maintaining the health of the eye. It is known that the ability of bHLH transcription factors to bind to DNA is antagonized by other proteins known as the ID-class of HLH proteins. Nicholas Baker, Ph.D., has received a four-year, $1.3 million grant from the National Institutes of Health to better understand the function of this network of interacting proteins. The research is expected to reveal new regulators of neural development that are important in the eye. It may also lead to new strategies for maintaining and regenerating healthy eye function. Dr. Baker is professor of genetics, of developmental & molecular biology and of ophthalmology & visual sciences and is also the Harold and Muriel Block Chair in Genetics and director of the division of molecular genetics at Einstein. (1R01EY028990-01A1)

Tuesday, April 23, 2019
 
Treating Hepatitis C-Infected Injection Drug Users

Treating Hepatitis C-Infected Injection Drug Users—Hepatitis C virus (HCV) leads to more than 15,000 deaths annually in the U.S. Antiviral drugs capable of curing HCV infection were introduced several years ago. Yet people who inject drugs—who are at the heart of the country’s HCV epidemic—are rarely offered anti-HCV therapy, due to concerns over poor medication adherence. In a study evaluating whether intensive treatment interventions improves adherence researchers including first author, Matthew Akiyama, M.D., M.Sc., and senior author and principal investigator Alain Litwin, M.D., M.P.H., of Clemson University and Prisma Health randomly assigned 150 HCV-positive people participating in an opioid treatment program to one of three antiviral treatment models: medication administered in directly observed therapy (DOT); medication in a group-therapy (GT) setting, or self-administered individual treatment (SIT), the control group. The findings were published online on April 9 in the Annals of Internal Medicine. High HCV cure rates were observed in all three groups: 98% for DOT patients, 94% for GT patients, and 90% for SIT patients. The findings indicate that HCV therapy should not be withheld for injection drug users, particularly those undergoing treatment for opioid use disorder.  Dr. Akiyama is an assistant professor of medicine at Einstein and attending physician in infectious diseases and in internal medicine at Montefiore.

Friday, April 19, 2019
 
Unraveling the B-Cell Response Against TB

Unraveling the B-Cell Response Against TB—The bacterial species Mycobacterium tuberculosis (Mtb) caused 1.3 million tuberculosis (TB)-related deaths in 2017. Infection triggers a well-studied T-cell response against Mtb, but the B-cell immune response leading to antibody production is not clearly  understood. John Chan, M.D., received a five-year, $3.5 million grant from the National Institute of Allergy and Infectious Diseases to investigate the role of IgM antibodies in the host immune response to Mtb. Dr. Chan and colleagues will use mouse and ex vivo macaque TB models to better understand the role, importance, and regulation of IgM in immune regulation during the early and chronic stages of TB.  Findings from this study may lead to novel therapies against TB infection. Dr. Chan is professor of medicine and of microbiology & immunology at Einstein and an attending physician in infectious diseases at Montefiore. (1R01AI139297-01A1)

Monday, April 08, 2019
 
Severing the Brain Injury-Epilepsy Link

Severing the Brain Injury-Epilepsy Link—Traumatic brain injury (TBI) can cause epilepsy, which involves recurring seizures. The more severe the TBI, the greater the chance that epilepsy will develop. Two years ago, Solomon Moshé, M.D., and Aristea Galanopoulou, M.D., Ph.D., received a NIH major grant to develop better ways to prevent epilepsy following TBI. They have now co-edited a supplement to the March 2019 issue of Neurobiology of Disease on preventing TBI-caused epilepsy, including findings from their research. The supplement describes the scope of the TBI/epilepsy problem; steps to identify biomarkers in humans and in animal models; and how to use those biomarkers to design preventive treatments in the laboratory that might work in humans. Drs. Moshé and Galanopoulou are both professors in the Saul R. Korey Department of Neurology, and the Dominick P. Purpura Department of Neuroscience. Dr. Moshé is also the director of the Isabelle Rapin division of child neurology and clinical neurophysiology at Einstein and Montefiore.

Tuesday, March 26, 2019
 
Investigating the Effects of Social Support on Aging

Investigating the Effects of Social Support on Aging—Strong social support can protect older adults from cognitive and physical decline. The neural underpinnings of social support’s cognition boost, however, are not well understood. In a study published on February 28 in The Journals of Gerontology: Series B, Helena Blumen, Ph.D., and colleagues identified neural networks associated with social support. The researchers used a computational approach to identify neural networks in elderly study participants and linked those networks to the degree of participants’ social support as measured by the Medical Outcomes Study Social Support Survey. Having broad social support was associated with neural networks involving the prefrontal cortex, hippocampus, cingulate cortex, and thalamus— brain regions known to be involved in memory and executive function. These findings suggest that strengthening social support among elderly people may reduce cognitive decline and dementia. Dr. Blumen is assistant professor of medicine and in the Saul R. Korey Department of Neurology at Einstein.

Monday, March 25, 2019
 
Brain Imaging and Walking

Brain Imaging and Walking—Studies in older adults have found a link between walking speed and executive function (mental skills that help people plan, organize and complete tasks). The brain’s frontal cortex is known to control gait in older adults. In a study published online on January 30 in NeuroImage, Mark Wagshul, Ph.D.,Roee Holtzer, Ph.D.,and colleagues investigated whether changes in frontal-cortex structure influence its activation during walking. In a study of healthy older adults using MRI and functional near-infrared spectroscopy (a technique that can measure blood flow in the brain during walking), they found a clear link between increased brain activation during walking (a known risk for falls) and structural changes in the brain. During complex walking tasks, individuals with smaller frontal cortices required greater activation compared with individuals with larger frontal cortices, possibly an indication of inefficient brain utilization.  The researchers hope to use similar measures to predict the risk of falling in older adults. Dr. Wagshul is an associate professor of radiology and is an assistant professor of physiology & biophysics at Einstein. Dr. Holtzer is a professor in the Saul R. Korey Department of Neurology at Einstein.

Monday, March 25, 2019
 
Insight Into HIV-associated Cardiovascular Disease

Insight Into HIV-associated Cardiovascular Disease—Cardiovascular disease (CVD) is a major health problem for people living with HIV. Antiretroviral drugs, viral load, immune-cell activation and inflammation all contribute to HIV-associated CVD. Biomarkers are needed for predicting CVD risk among these individuals. In a study published online on February 14 in Circulation, Qibin Qi, Ph.D., and Wei Zhao, M.S., found that levels of ceramides (a class of circulating blood lipids) correlate with the risk of developing carotid artery plaque (indicating greater likelihood of CVD events) during the course of HIV-infection and use of antiretroviral drugs. The findings suggest that targeting ceramides among people living with HIV might help to treat CVD or prevent its onset.  Dr. Qi is an associate professor of epidemiology & population health Einstein. Wei Zhao is a medical student at Einstein.

Friday, March 22, 2019
 
Understanding Kidney Cancer Progression

Understanding Kidney Cancer Progression—Clear cell renal cell carcinoma (CCRCC) is the most common type of kidney cancer. In a study published online on January 31 in the Journal of Clinical Investigation, Niraj Shenoy, MD., M.S., Amit K. Verma, M.B.B.S., and colleagues describe a new prognostic biomarker for this type of cancer called 5-hydroxymethylcytosine (5hmC). As kidney cancer advances, tumor levels of 5hmc progressively decrease. The researchers found that loss of 5hmC occurs because an aberrant metabolic intermediate inhibits enzymes called TET (Ten-eleven Translocation). Furthermore, the presence of ascorbic acid (Vitamin C) prevents the aberrant intermediate from affecting TET and restores 5hmC levels. High-dose intravenous ascorbic acid inhibited kidney cancer growth in a mouse model and increased 5hmc within the tumors. These findings have led to an ongoing multicenter randomized phase 2 clinical trial of vitamin C as an adjunct to standard of care treatment for metastatic and unresectable CCRCC. Dr. Verma is professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. Dr. Shenoy is an assistant professor of medicine at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care.

Thursday, March 21, 2019
 
A Recipe for Making Therapeutic Liver Cells

A Recipe for Making Therapeutic Liver Cells—So-called pluripotent stem cells can develop into any type of cell in the body—cells that could especially help in treating human diseases in which tissue loss has occurred. However, the signals that direct pluripotent stem cells to develop into desired cell types aren’t well understood. In a new study published online on January 28 in Differentiation, Sanjeev Gupta, M.D., and colleagues showed that human pluripotent stem cells differentiate into hepatocytes (liver cells) when cultured in a medium in which fetal hepatocytes had been grown. Surprisingly, the signals triggering differentiation were identified as small metabolomics products rather than proteins made by fetal hepatocytes. When the hepatocytes resulting from stem cells were transplanted into mice with acute liver failure, they promoted tissue repair and liver regeneration in the mice, indicating that hepatocytes derived in this way possess therapeutic potential. The U.S. Patent and Trademark Office has allowed claims for a patent to Einstein for Dr. Gupta’s differentiation method. Dr. Gupta is professor of medicine and of pathology and is the Eleazar and Feige Reicher Chair in Translational Medicine at Einstein and is an attending physician and hepatologist at Montefiore.

Wednesday, March 13, 2019
 
New Triple-Negative Breast Cancer Target

New Triple-Negative Breast Cancer Target—Up to 20 percent of breast cancers aretriple negative breast cancer (TNBC), an aggressive form of the disease with few treatment options. In looking for genes that promote TNBC metastasis and might be knocked out as a treatment strategy, Harry Ostrer, M.D., and colleagues from Einstein and Montefiore identified Otoconin 90 (OC90)—a gene normally expressed in the ear’s cochlea to form the little calcium stones that help to control equilibrium. But the gene has been repurposed and over-expressed in TNBC as well as prostate and lung cancers to serve a novel and pernicious function. In a cohort of TNBC patients, the researchers found that the altered expression of three genes associated with OC90 overexpression —HMGA2, POLE2 and TRIB3—predicts a greater likelihood that the patients will die from the disease. The findings were published online on February 14 in PLOS ONE. Dr. Ostrer is professor of pathology and of pediatrics at Einstein.

Wednesday, February 27, 2019
 
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