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Detecting Combat Brain Injury with DTI

Detecting Combat Brain Injury with DTI—Neuroimaging identifies traumatic brain injury in combat veterans, but questions have been raised whether differences between veterans and controls might skew results. To address this problem, diffusion tensor imaging (DTI), which shows microscopic changes in white matter, was performed for the first time on veterans matched with controls of very similar backgrounds. Michael L. Lipton, M.D., Ph.D., compared DTI images from 16 blast-exposed combat veterans to images of 18 of the veterans’ siblings and first cousins, who grew up in the same community but were not exposed to combat. Abnormalities consistent with post-traumatic effects in veterans were not seen in the closely matched controls. The findings, published online on August 17 in Neuroradiology, further support the usefulness of DTI to accurately detect brain abnormalities resulting from trauma. Dr. Lipton is professor of radiology and of psychiatry and behavioral sciences at Einstein and medical director of MRI services at Montefiore.

Thursday, September 20, 2018
 
Discovering HIV-1's Infection Pathway

Discovering HIV-1's Infection Pathway—HIV-1, the virus that causes AIDS, invades non-dividing immune cells. The virus persists inside those cells, frustrating efforts to eradicate infections. Until now, HIV’1’s mechanism for infecting non-dividing cells has been a mystery. In a new study published online on July 11 in the  Journal of Virology, Felipe Diaz-Griffero, Ph.D., and colleagues showed that HIV-1 exploits a chain of two repeating amino acids on the surface of white cells to gain entry into the cells. The researchers pinpointed the region on the virus’s outer shell that interacts with the chain. They also identified two HIV-1 inhibitors that prevent the virus from using this entry pathway, which could serve as targets for new drugs to slow infection—especially for patients already resistant to current anti-retroviral treatments. Dr. Diaz-Griffero is professor of microbiology & immunology and the Elsie Wachtel Faculty Scholar at Einstein.

Friday, September 07, 2018
 
New Therapeutic Target for Melanomas

New Therapeutic Target for Melanomas—The invasiveness of cancers can be influenced by methylation and demethylation, epigenetic processes that alter the gene activity of cells without changing the genetic code. In a new study published online on July 25 in JCI Insight, Orsolya Giricz, Ph.D., and Amit K. Verma, M.B.B.S., analyzed a group of melanomas in which demethylation was coupled with overexpression of the CSF-1 receptor (CSF-1R), a protein that influences the activity of immune cells. This combination increased the growth and invasiveness of cancerous cells, especially when mutations involving the BRAF gene were present. Inhibiting the enzyme that activates CSF-1R or decreasing of CSF-1R’s expression slowed the melanomas’ advance. The findings reveal a previously unknown role for CSF-1R and suggest that it may be a good target for future melanoma therapies. 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. Giricz is an associate in Dr. Verma’s lab at Einstein.

Thursday, September 06, 2018
 
Ribosomal Proteins and Rare Diseases

Ribosomal Proteins and Rare Diseases—Ribosomes are the cells’ factories for producing proteins. Diseases such as the genetic blood disorder Diamond-Blackfan Anemia are caused by defects in ribosomal proteins that were thought to impair ribosome function.  But new findings involving fruit flies, published online on August 2 in Developmental Cell by Nicholas E. Baker, Ph.D., and colleagues, indicate that ribosomal protein defects actually activate a previously unknown and destructive signaling pathway. Although it’s unclear just why this pathway exists, Dr. Baker and colleagues speculate that it may help rid the body of damaged cells. The findings may shed light on how damaged cells lead to disease, as well as aspects of Diamond-Blackfan Anemia that might provide new avenues for treatments. Dr. Baker is professor of genetics, of developmental and molecular biology and of ophthalmology and visual sciences and the paper’s corresponding author. Dr. Baker also holds the Harold and Muriel Block Chair in Genetics.

Thursday, August 23, 2018
 
A Major Step in Developing an Effective Ebola Therapy

A Major Step in Developing an Effective Ebola Therapy—In a paper published online on August 9 in Cell, 48 collaborating authors from 23 institutions and companies, including Kartik Chandran, Ph.D., and Jonathan Lai, Ph.D., made significant strides towards understanding how monoclonal antibodies work to defeat Ebola virus. The two new Ebola outbreaks in the Democratic Republic of the Congo this year, including one ongoing, highlight the need for effective treatments and preventive measures against the deadly microbe. Read full story.

Thursday, August 09, 2018
 
Three NIH Grants for Colon Cancer Research

Three NIH Grants for Colon Cancer Research—Among cancers affecting both men and women in the United States, colorectal cancer ranks second only to cancer of the lung and bronchus as the leading cause of cancer-related death. Each year more than 140,000 Americans develop colorectal cancer, and more than 50,000 die from it. Some cases of colorectal cancer result from an inherited genetic susceptibility. But for well over 80 percent of people who develop the disease, studies involving human populations and animals show that diet strongly influences whether colorectal cancer will occur and whether it will progress. Intestinal tissue comes into direct contact with numerous dietary components over many years. The National Institutes of Health has awarded Leonard Augenlicht, Ph.D., professor of medicine and of cell biology at Albert Einstein College of Medicine and director of the Albert Einstein Cancer Center’s Biology of Colon Cancer Program, three new grants totaling $7.1 million to further study how diet influences colon cancer. Read full story.

Monday, July 30, 2018
 
Sleuthing the Cerebellum

Sleuthing the Cerebellum—The brain’s cerebellum is best known for coordinating voluntary movements such as posture, balance and speech. More recently, the cerebellum has also been linked to mental health disorders such as autism spectrum disorders, schizophrenia and addiction, although how it contributes to these problems is poorly understood. The National Institute of Mental Health has awarded Kamran Khodakhah, Ph.D., a five-year, $2.8 million grant to investigate the relationship between the cerebellum and mental health disorders. Dr. Khodakhah has identified two specific pathways by which the cerebellum comes in contact with other parts of the brain to influence social behavior. He and his team will look for defects in those pathways that could reveal how the cerebellum contributes to mental health disorders. Dr. Khodakhah is professor and chair of the Dominick P. Purpura Department of Neuroscience and the Florence and Irving Rubinstein Chair in Neuroscience. (1R01MH115604-01A1)

Friday, July 27, 2018
 
Minimizing Stroke Misdiagnosis

Minimizing Stroke Misdiagnosis—Each year, some 800,0000 stroke patients arrive in the emergency rooms of American hospitals. Up to nine percent of these patients are initially misdiagnosed. One problem is that some stroke patients have non-specific symptoms including headache, yet most emergency room headache cases are benign. The National Institutes of Health has awarded Ava L. Liberman, M.D., a five-year, $1 million grant to quantify the rate of stroke misdiagnosis among patients reporting to emergency rooms with headaches. Dr. Liberman will use information from the emergency department of John Hopkins and the Montefiore Medical Center to identify both patient- and physician-related factors that contribute to stroke misdiagnosis to develop new clinical tools to improve stroke and headache diagnostic accuracy. Dr. Liberman is an assistant professor in the Saul R. Korey Department of Neurology at Einstein and an attending physician at Montefiore Health System and the Stern Stroke Center. (1K23NS107643-01)

Thursday, July 26, 2018
 
Investigating Rett Syndrome

Investigating Rett Syndrome—By disrupting neuronal and brain development, mutations to the MECP2 gene (which codes for the transcription factor MECP2) cause the many symptoms that characterize Rett syndrome, an autism spectrum disorder. However, the molecular mechanisms by which MeCP2 controls neuronal function and development aren’t well understood. Michael Brenowitz, Ph.D., has found that shifts in ion types and levels alters the ability of native and defective versions of MECP2 protein to bind to DNA. The National Institute of General Medical Sciences has awarded Dr. Brenowitz a four-year, $1.3 million grant to study MECP2’s binding properties. He and his colleagues will identify and characterize the DNA sequences and modifications that influence MeCP2’s ability to recognize and attach strongly to binding sites on genes. They will also determine the structure of MeCP2 bound to DNA and analyze how MeCP2 competes with other DNA-binding proteins. The results may lead to strategies for treating Rett syndrome by stabilizing defective MeCP2’s gene interactions. Dr. Brenowitz is professor of biochemistry and of molecular pharmacology at Einstein. The studies that led to this project were supported by awards from Einstein’s Rose F. Kennedy Intellectual and Developmental Disabilities Research Center and Rettsyndrome.org.(1R01GM129350-01)

Tuesday, July 24, 2018
 
Bacteria Lowers PrEP Drugs' Effectiveness

Bacteria Lowers PrEP Drugs' Effectiveness—For the first time, researchers have shown how vaginal bacteria changes the effectiveness of two topical HIV prevention (PrEP) drugs: tenofovir gel and dapivirine ring. In a study published online on July 12 in JCI Insight, Betsy C. Herold, M.D. and colleagues demonstrated that some bacteria alter the ways cells are able to utilize the drugs. Among the finding were that Gardnerella vaginalis blocked the uptake of tenofovir by human cells and Lactobacillus crispatus competed with human cells for drug by actively transporting and metabolizing it. Higher drug levels overcame the negative effects. Importantly, other PrEP drugs were not impacted by microbiota and may be better candidates for future formulations. These findings likely contribute to the disappointing clinical trial results, where only partial protection has been observed, and highlight the importance of preclinical and early clinical evaluation of the impact of the vagina microenvironment on drug pharmacokinetics. Dr. Herold is the Harold and Muriel Block Chair in Pediatrics, director of the Translational Prevention Research Center, professor and chief of the division of pediatric infectious diseases, and vice chair for research in the department of pediatrics.

Thursday, July 19, 2018
 
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