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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

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
Discovering How a Parasite Forms Cysts

Discovering How a Parasite Forms Cysts—The single-cell parasite Toxoplasma gondii cause toxoplasmosis, one of the world’s most common parasitic diseases. It’s contracted by ingesting contaminated food or water, and symptoms can range from fever and body aches to serious complications such as brain damage and eye infections. Understanding how the parasite builds a protective cyst wall within its host may reveal how this infection persists causing chronic disease. With a five-year, $2 million grant from the National Institute of Allergy and Infectious Diseases, Louis Weiss, M.D., M.P.H., will use molecular, immunologic and genetic techniques to investigate how the cyst wall forms and develops. He and his colleagues will identify the cyst wall’s components and determine how they interact. The findings may reveal new strategies for suppressing the parasite’s reactivation following infection. Dr. Weiss is professor of pathology and of medicine at Einstein, and co-director of Einstein’s Global Health Center. He is also an attending physician in infectious diseases at Montefiore Health System. (1R01AI134753-01A1)

Friday, July 06, 2018
Immune Evasion in TB Infection

Immune Evasion in TB Infection—Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is notorious for its ability to evade the body’s immune response. John Chan, M.D., Steven Porcelli, M.D., and Michael Berney, Ph.D., have found evidence that M. tuberculosis evades anti-TB immunity by activating an immunosuppressive pathway controlled by the host enzyme indoleamine 2,3-dioxygenase (IDO). The NIH has awarded them a five-year, $4 million grant to study how immunosuppression mediated by IDO activation helps M. tuberculosis circumvent immune defenses. The researchers will use genetic and pharmacologic approaches and mouse TB models for their proposed studies. The results could lead to new interventions for better TB control, including effective vaccines. Dr. Chan is professor of medicine and of microbiology & immunology at Einstein and is an attending physician in infectious diseases at Montefiore Health System. 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. Dr. Berney is an assistant professor of microbiology & immunology at Einstein. (1R01AI137344-01)

Thursday, July 05, 2018
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