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Preventing Pneumonia

Preventing Pneumonia—Pneumococcus is the main bacterial cause of pneumonia globally and in the United States, where it causes more than 50,000 deaths annually. The two licensed vaccines against pneumococcus infection are more effective against infections of the blood or cerebrospinal fluid than against pneumococcal pneumonia. The National Institute of Allergy and Infectious Diseases has awarded a five-year, $2 million grant to Liise-anne Pirofski, M.D., to develop monoclonal antibody therapy for pneumococcal pneumonia. The research will focus on serotype 3 pneumococcus, a strain associated with a higher risk of death than others. The Pirofski group will isolate and characterize individual antibodies from people who receive pneumococcal vaccine and select the most promising antibodies for pre-clinical studies to identify lead candidates for therapy. Dr. Pirofski is professor of medicine and of microbiology & immunology, chief of infectious diseases at Einstein and Montefiore and holds the Selma and Dr. Jacques Mitrani Chair in Biomedical Research. (1R01AI123654-01A1)

Monday, January 09, 2017
A Novel Cell Communication System

A Novel Cell Communication System—Following tissue injury, specialized cell-surface receptors transmit signals to mitochondria--the organelles that generate energy for the cell and contribute to cellular repair, growth and division. But just how these receptors communicate with mitochondria has not been clear. In a letter published in the November 24, 2016 issue of Nature, a group of Einstein researchers including co-lead authors Dario Riascos-Bernal and Lily Cao, working under the supervision of Nicholas Sibinga, M.D., describe a novel molecular signaling mechanism that controls mitochondrial activity. Following blood-vessel injury, a cell-surface receptor called FAT1 is processed and activated to control mitochondrial function and cell growth during vascular repair. Aberrant expression of the FAT1 gene has been linked to several cancers, abnormal renal developmental and neurologic disorders. Dr. Sibinga is professor of medicine and of developmental and molecular biology.

Friday, January 06, 2017
Finding the Mechanism for Viral Infection

Finding the Mechanism for Viral Infection—Alphaviruses include important human pathogens such as encephalitic viruses and Chikungunya virus (CHIKV)—a mosquito-borne alphavirus that recently caused large epidemics worldwide, including in the Americas.  In a study published online on December 15 in PLOS Pathogens, Margaret Kielian, Ph.D., and Maria Gaudalupe Martinez, Ph.D., describe for the first time how alphavirus is transmitted from cell to cell during infection. Long cellular extensions from an infected cell contact uninfected neighboring cells and then release alphavirus particles, effectively shielding viruses from neutralizing host antibodies. Drs. Martinez and Kielian found that the alphavirus structural proteins alone induce host cells to form these extensions, which preferentially target uninfected cells. The findings could influence efforts now underway to develop vaccines against CHIKV. Dr. Kielian is professor of cell biology and the Samuel H. Golding Chair in Microbiology.

Thursday, December 22, 2016
Better Leukemia Drug Targets

Better Leukemia Drug Targets—Each year 19,000 Americans are diagnosed with acute myeloid leukemia (AML)—a cancer with a five-year survival rate of only 24 percent. Better therapeutic targets are urgently needed, and one potential target is the PI3 kinase (PI3K) signaling pathway: Its abnormal activation is important for AML disease progression, yet its role in normal blood development remains unclear. The National Cancer Institute has awarded Kira Gritsman, M.D., Ph.D., a five-year, $2.1 million grant to study the role of PI3K variants and identify which ones are essential for normal adult blood formation and maintenance, and which contribute to AML progression. This research could lead to specific PI3K inhibitors that are more effective and less toxic than current AML treatment options. Dr. Gritsman is an assistant professor of cell biology and medicine. (1R01CA196973-01A1)

Thursday, December 15, 2016
Filtering Out False-positive Drug Allergies

Filtering Out False-positive Drug Allergies—In a study published online on November 23 in the Journal of Allergy and Clinical Immunology: In Practice, senior author Elina Jerschow, M.D., and lead author Melissa Iammatteo, M.D., describe a safe way to determine whether patients are truly allergic to medications. Their study involved 229 Montefiore Drug Allergy Clinic patients with previously reported allergic drug reactions. The most commonly reported allergies were to penicillins (71 percent) and to nonsteroidal anti-inflammatory drugs (18 percent). Each patient received a dose of placebo, followed by a one-tenth dose of the drug they allegedly were allergic to, and then a full dose of same drug. Only four percent of patients had objective allergic reactions during challenges, none of which were life-threatening. Nine percent of patients reacted to the placebos, all of them women with multiple reported drug allergies. Dr. Jerschow is associate professor of medicine and attending physician at Montefiore.

Wednesday, December 14, 2016
Prescribing to Prevent HIV

Prescribing to Prevent HIV—The number of new human immunodeficiency virus (HIV) infections has declined over the past decade in the United States, yet 40,000 new cases are still reported each year. A novel HIV prevention strategy—pre-exposure prophylaxis (PrEP)— can help to further the decline in new HIV infections, but health care providers vastly underuse it. PrEP involves HIV-negative individuals taking antiretroviral medications and attending routine visits with a healthcare provider. In a study published online on October 20 in the Journal of General Internal Medicine, Oni Blackstock, M.D., M.H.S., describes her research showing that the vast majority of primary care physicians are aware of PrEP. However, only a minority of them reported ever referring a patient for PrEP or prescribing it; and those physicians believing that PrEP increases risk behaviors were less likely to adopt it. Dr. Blackstock is assistant professor of medicine.

Monday, December 12, 2016
Fluorescent Biosensors and Optogenetic Tools to Understand Brain Function

Fluorescent Biosensors and Optogenetic Tools to Understand Brain Function—The brain produces electrical signals that translate into perceptual, cognitive, emotional and motor functions. To decipher brain function, scientists until recently scientists recorded those electric signals using injected synthetic voltage-sensitive dyes. Vladislav Verkhusha, Ph.D., was recently awarded a $1.2 million NIH BRAIN Initiative grant to develop fluorescent genetically-encoded voltage indicators (GEVIs) to image neuronal activity noninvasively in deep layers of brain using near-infrared (NIR) light. The researchers will then use these NIR GEVIs to monitor brain functions in mice and simultaneously modulate their neuronal circuits using blue-light absorbing opsin optogenetic tools. This novel technique, combining optogenetic actuators and functional imaging, is called all-optical electrophysiology. It will allow for simultaneous activation and recording of neuronal activities noninvasively in the brain using light of different wavelengths. Dr. Verkhusha is professor of anatomy and structural biology.

Friday, December 09, 2016
MAF1 Function and Metabolic Inefficiency

MAF1 Function and Metabolic Inefficiency—The National Institute of General Medical Sciences has awarded Ian Willis, Ph.D., a four-year, $2.1 million grant to study the MAF1 protein and determine how gene expression and energy expenditure is changed in Maf1 knockout mice. MAF1 is best known as a master regulator of RNA polymerase III, the enzyme responsible for synthesizing ~15% of the RNA in virtually every cell in the body. Maf1 knockout mice are lean, resistant to diet-induced obesity and non-alcoholic fatty liver disease and  have increased energy expenditure along with an extended lifespan—changes that are likely due to increased RNA polymerase III transcription, which requires energetically expensive ribonucleotides. Dr. Willis and his team will examine changes in gene expression in key metabolic tissues of Maf1 knockout mice, determine the metabolic changes underlying their increased energy expenditure and investigate RNA polymerase III’s role in driving this energy expenditure. Dr. Willis is professor of biochemistry and systems & computational biology. (1R01GM120358-01)

Thursday, December 08, 2016
Brain Development in Adverse Situations

Brain Development in Adverse Situations—R. Suzanne Zukin, Ph.D., was awarded a five-year, $1.7 million NIH grant to study how adverse experiences early in life influence N-methyl-D-aspartate (NMDA) receptors (NMDARs) in the brain. These receptors play crucial roles in neural circuitry and in higher cognitive functions. During brain development after birth, NMDARs switch from one type (containing GluN2B-) to another (containing GluN2A). The gene silencing factor REST (Repressor element-1 silencing transcription factor) plays a role in this switch. To discover the mechanisms by which early-life stress may block REST activity and the NMDAR switch, Dr. Zukin’s group will study newborn rats that have been separated from their mothers for several hours a day. Dr. Zukin is a professor in the Dominick P. Purpura Department of Neuroscience, director of the Neuropsychopharmacology Center and holds the F.M. Kirby Chair in Neural Repair and Protection. (1R01HD083828-01A1)

Monday, December 05, 2016
Monitoring Cancer in 9/11 First Responders

Monitoring Cancer in 9/11 First Responders—On 9/11/2001 and over the following months, thousands of first responders and other rescue/recovery workers were exposed to potentially carcinogenic substances at the Twin Towers site. The Centers for Disease Control and Prevention has awarded Charles Hall, Ph.D., a four-year, $1.8 million grant to conduct the largest long-term study to date of these exposed individuals. This study will combine follow-up data from all three cohorts of World Trade Center (WTC) rescue/recovery workers, update estimates of the effect of WTC exposure on cancer incidence, study in detail the latency period between exposure and cancer occurrence, and study the effect of WTC exposure and other factors on the survival of these workers following their cancer diagnosis. Dr. Hall is professor of epidemiology & population health. (1U01Oh011315-01)

Thursday, December 01, 2016
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