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Regulating Breast Cancer Metastasis

Regulating Breast Cancer Metastasis—Cancer cells produce protrusions called invadopodia that weaken the surrounding extracellular matrix and help the cancer cells spread. The signaling mechanisms that control invadopodia functioning are not fully known. In a study published online on October 23 in The Journal of Cell Biology, Louis Hodgson, Ph.D., and colleagues studied the role of the protein-coding gene Rac3 in a mouse model of breast cancer. They found that Rac3 protein is part of a signaling pathway that regulates breast cancer metastasis by controlling the invadopodia’s ability to stick to and degrade the extracellular matrix. Rac3-dependent signaling helps balance matrix breakdown with cell adhesion to optimize invasion and metastasis by breast cancer cells. Dr. Hodgson is associate professor of anatomy and structural biology and in the Gruss-Lipper Biophotonics Center.

Wednesday, November 15, 2017
Better Assays for Aging Rodents

Better Assays for Aging Rodents—Rodents are useful for studying aging and longevity, but they’re often housed under artificial conditions that differ greatly from the actual challenges faced by people as they age. Now, the National Institute on Aging has awarded Derek M. Huffman, Ph.D., a five-year, $1.7 million grant to develop a quick and simple battery of tests to measure rodents’ response to age-related conditions such as elective surgery, radiation exposure and infections. For researchers who use rodents to study aging, Dr. Huffman’s work should help them better gauge whether their findings accurately reflect healthy aging in humans. Dr. Huffman is an assistant professor of medicine and molecular pharmacology, and is co-director of the Chronobiosis and Energetics/Metabolism of Aging Core (CEAC) at Einstein. (1R01AG057429-01)

Monday, November 13, 2017
Getting Ahead of Metastasis

Getting Ahead of Metastasis—Ninety percent of breast cancer-related deaths occur because the cancer has metastasized, or spread, to other parts of the body. Einstein researchers have identified a biomarker for metastasis called “Tumor Microenvironment of Metastasis,” or TMEM, consisting of three different types of cells found together in a tumor. In a paper published on November 8 online in npj Breast Cancer, the researchers assessed TMEM scores for women with hormone receptor-positive, HER2-negative early stage breast cancer. They found that high “TMEM scores” (many TMEM sites per volume of tissue) predicted that the cancer was likely to spread.  The ability to predict metastasis could lead to more effective treatments for patients. The study’s first author is Joseph Sparano, M.D., professor of medicine and of obstetrics & gynecology and women's health.

Thursday, November 09, 2017
Investigating Poor Cancer Outcomes in Hispanics

Investigating Poor Cancer Outcomes in Hispanics—Using national and local patient cohorts, Einstein-Montefiore researchers in the Division of Hemato-Oncology compared white and Hispanic patients diagnosed with acute myeloid leukemia (AML) and found that Hispanics present with AML at younger ages and have shorter survival than whites. In addition, Hispanic AML patients had an increased frequency of high-risk cancer mutations compared with whites. The findings, published online on October 26 in Blood Advances, suggest that the greater frequency of high-risk mutations among Hispanics may explain their worse AML outcomes compared with whites. The study’s senior author is Ioannis Mantzaris, M.D., M.S., assistant professor of medicine and attending physician at Montefiore Medical Center.

Wednesday, November 01, 2017
A Cellular Cocktail for Growth

A Cellular Cocktail for Growth—The mix of nutrients and growth factors used to maintain cell cultures are crucial for proper cell growth and proliferation. Yet researchers know surprisingly little about how the composition of cell culture media can affect certain cell processes. In a study published online on September 18 in PLOS ONE, John Murray, Ph.D., and colleagues report that culture medium solutes including potassium and sodium are vital for maintaining proper trafficking of subcellular compartments. Using time lapse multi-channel fluorescent imaging, Dr. Murray’s team showed that briefly exposing cells to culture media depleted of those solutes strongly inhibited the activity of intracellular motor proteins. The role played by each culture component in maintaining processes that depend on motor proteins may need to be re-evaluated, the researchers conclude. Dr. Murray is instructor anatomy and structural biology.

Monday, October 30, 2017
Decoding the Molecular Basis of Dyskeratosis Congenita

Decoding the Molecular Basis of Dyskeratosis Congenita—Dyskeratosis congenita (DC) is a rare inherited disease that leaves bone marrow unable to produce sufficient blood cells, often leading to premature death. The National Heart, Lung, and Blood Institute awarded U. Thomas Meier, Ph.D., a four-year, $2.38 million grant to investigate the cellular impact of DC. The researchers will focus on mutations in the gene coding for the enzyme NAP57/dyskerin; these mutations are associated with about half of all DC cases. The research may lead to therapies for DC. Dr. Meier is professor of anatomy and structural biology. (1R01HL136662-01)

Friday, October 20, 2017
Unlocking Another Key to Aging

Unlocking Another Key to Aging—Transposons, also known as “jumping genes,” are DNA sequences that move from one location in the genome to another. Transposons are thought to contribute to aging, but their actual role remains to be clarified. The National Institute on Aging has awarded Julie Secombe, Ph.D., a five-year, $1.69 million grant to study whether transposons influence aging. So far, research on transposons and aging has been limited by available techniques. Dr. Secombe and her team will use novel methods to analyze the genomes of single cells. They will also focus on the role of Myc, a transcription factor (i.e., a protein regulating gene expression) known to affect aging in model organisms. By determining interconnections among Myc transposons that contribute to aging, the team may develop strategies for suppressing this activity and, ultimately, improve human longevity. Dr. Secombe is associate professor of genetics and is associate professor in the Dominick P. Purpura Department of Neuroscience. (1R01AG053269-01A1)

Wednesday, October 18, 2017
Investigating Chronic Fatigue Syndrome

Investigating Chronic Fatigue Syndrome—The NIH has established four new centers for mylagic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which affects more than one million Americans. There is no treatment and no laboratory test to diagnose the disease, which is characterized by profound fatigue that does not improve with rest and may include cognitive dysfunction and pain. Now, John Greally, M.B., B.Ch., Ph.D., has been awarded a five-year, $2.17 million grant from the National Institute of Allergy and Infectious Diseases to lead a subproject core at the center based at Columbia’s Mailman School for Public Health. The Einstein lab has access to blood samples from newly diagnosed and existing ME/CFS patients and will look for transcriptional changes in peripheral blood mononuclear cells—a type of immune cell shown by previous studies to function abnormally in ME/CFS patients. Dr. Greally is a clinical geneticist at Montefiore and professor of genetics, of medicine and of pediatrics and is director of the Center for Epigenomics at Einstein. (1U54AI138370)

Tuesday, October 10, 2017
Curbing Appetite with Oxytocin

Curbing Appetite with Oxytocin—The rare neurodevelopmental genetic disorder Prader-Willi Syndrome (PWS) is characterized by compulsive eating (hyperphagia). The resulting obesity is the leading cause of deaths for people with PWS. Signaling by the hormone oxytocin—which normally acts on brain receptors to inhibit people from eating—is inadequate in PWS, and giving supplemental oxytocin to mouse models of the disorder is known to reduce food intake and body weight. Eric Hollander, M.D., has received a three-year, $1.49 million grant from the U.S. Food and Drug Administration to study whether oxytocin can be safely and effectively given intranasally PWS patients to reduce hyperphagia. Dr. Hollander is professor of psychiatry and behavioral sciences at Einstein and director of the Autism and Obsessive Compulsive Spectrum Program at Montefiore Health System and Einstein. (1R01FD005106-01A3)

Wednesday, October 04, 2017
New Niemann-Pick Treatment Shows Promise

New Niemann-Pick Treatment Shows Promise—In the genetic disorder Niemann-Pick disease type C1 (NPC1), abnormally high levels of lipids accumulate in cells and damage organs including the liver, spleen and brain. NPC1 is usually diagnosed when children develop neurological symptoms such as clumsiness or learning difficulties. Symptoms progressively worsen and patients usually die 10 to 15 years following diagnosis. No FDA-approved treatment exists. Steven Walkley, D.V.M., Ph.D., has co-authored a study in the August 10 issue of The Lancet showing that the drug 2-hydroxypropyl-β-cyclodextrin (HPβCD) can safely slow NPC1’s progression. Patients received monthly or bi-weekly spinal injections of the drug for 18 months. Following the treatment period, biochemical and neurological tests showed that, compared with historical data for patients the same age, patients treated with the drug experienced significantly less cognitive dysfunction, with minimal side effects. Dr. Walkley is director of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center and professor in the Dominick P. Purpura Department of Neuroscience, in the department of pathology, and in the Saul R. Korey Department of Neurology at Einstein.

Monday, October 02, 2017
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