Roundup Of Roundups

The following research papers and grants of note were highlighted on the Einstein website in a section called "Research Roundup." You can explore all of the discoveries published in this special section of our website throughout the year by visiting the Research landing page of our website.

Understanding blood-forming stem cells—Hematopoietic stem cells (HSCs) not only renew themselves by dividing but also differentiate to form all of the body’s blood cells. But the mechanisms that keep HSC division and differentiation in balance remain unclear. Keisuke Ito, M.D., Ph.D., has received a five-year, $2.9 million grant to find the factors that determine the fate of HSCs. After transplanting HSCs into a mouse model, Dr. Ito and his colleagues will isolate and analyze individual HSCs to determine which fate they have chosen—division or differentiation—and what cellular factors caused them to make that choice. Findings from this study could, for example, allow scientists to manipulate HSCs so that they differentiate into blood for use in transfusions. Dr. Ito is associate professor of cell biology and of medicine and director of scientific resources at the Gottesman Institute for Stem Cell and Regenerative Medicine Research. (1R01DK115577)

Thursday, December 07, 2017

Reducing Opioid Use Disorder—Eighty percent of people who have opioid use disorder (OUD) don’t get treated. Syringe exchange programs (SEPS) are a great way to reach many of these people, who receive sterile syringes and other health services at those sites. Aaron Fox, M.D., M.S., has received a $3.5 million, five-year NIH grant to conduct a 24-week clinical trial to evaluate the possible benefits of offering OUD treatment at SEPs. Two hundred fifty out-of-treatment opioid users who use SEPs will be randomized into two groups. People in the experimental group will receive on-site buprenorphine maintenance treatment (shown to reduce opioid use and overdose and HIV risk behaviors) and then will be referred to a community health center (CHC) for continued care. People in the control group won’t receive buprenorphine maintenance treatment at SEPS but will be referred directly to a CHC for buprenorphine treatment. The researchers will evaluate whether receiving OUD treatment at SEPS encourages people to remain in treatment and reduces HIV-risk behavior. Dr. Fox is associate professor of medicine at Einstein and attending physician at Montefiore. (1R01DA044878)

Thursday, December 07, 2017

Epigenetic Markers in Pancreatic Cancer—Cancers sometimes start when external influences cause changes in DNA. These so-called epigenetic modifications can alter gene expression—silencing a gene or over-activating it, for example. In a study published on the cover of the November issue of Genome Research, Amit Verma, M.B.B.S., reported that pancreatic cancers have unique epigenetic modifications in a regulatory portion of DNA known as Hydroxymethylcytosine (5-hmC). He and his team found that 5-hmC was abnormally distributed at locations in the genome that regulate the expression of several genes associated with cancer, such as the gene BRD4. Dr. Verma is professor of oncology and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. The study’s first author is Sanchari Bhattacharyya, Ph.D., a research associate in the department of medicine.

Thursday, November 30, 2017

Studying Roundworms to Treat Alzheimer's—Humans are not the only organisms faced with age-related declines in thinking ability and memory. The same problems afflict the roundworm C. elegans. The NIH has awarded Einstein scientists a five-year, $3.7 million grant to seek new Alzheimer’s treatments by combining roundworm and human research. Using tools for studying memory in worms and identifying gene expression changes in worm neurons, the researchers will identify genes that change with age and are risk factors for Alzheimer’s. They’ll combine those results with findings from human genome-wide association studies, which indicate that changes in gene regulation are responsible for cases of heightened genetic risk for Alzheimer’s. This approach will identify gene regulatory networks shared by humans and worms and may provide new targets for Alzheimer’s drugs. The Einstein principal investigator is Yousin Suh, Ph.D., professor in the departments of genetics, of ophthalmology & visual sciences, and of medicine at Einstein. (1RF1AG057341)

Thursday, November 30, 2017

How the brain drives adaptive behavior—When we react to sensory stimuli, our brains tap into a network of neurons that drives behavior. But little is understood about that network’s architecture, the contributions of its individual cells nor how the network changes with learning. Jose Luis Peña, M.D., Ph.D., has been awarded a five-year $3-million NIH BRAIN Initiative grant to investigate how neural networks become fine-tuned to their environment and adapt through exposure to life experiences. The research will involve barn owls, which are keenly attuned to relying on sound for locating prey. Dr. Pena and colleagues from Seattle University, University of California in Davis and San Diego will use high-throughput electrophysiology, electron microscopy, behavior and theory to determine how sound drives the owl's orienting behavior. Dr. Peña is a professor in the Dominick P. Purpura Department of Neuroscience. (1R01NS104911-01)

Tuesday, November 28, 2017

Eating Twice a Day Keeps Fat Away—In a study published online on October 26 in Cell Metabolism, Einstein researchers found that feeding mice just twice a day decreases fat tissue and enhances muscle mass. By contrast, mice allowed to consume the same number of daily calories whenever they wanted did not obtain those benefits. The researchers found the fasting period created by twice-daily feeding activated the cellular cleansing process known as autophagy in liver, fat, brain, and muscle tissues in young and old mice. This lowered glucose and lipid levels without the muscle loss that usually accompanies calorie restriction. The findings suggest that twice-a-day feeding without restricting calories could help prevent obesity and type 2 diabetes as well as the metabolic decline that occurs when autophagy becomes less efficient in old age. Senior author Rajat Singh, M.D., M.B.B.S., is associate professor of medicine and of molecular pharmacology at Einstein.

Monday, November 27, 2017

The Cerebellum -Addiction Connection—Evidence suggests that dysregulation of the cerebellum—a part of the brain well known for motor coordination—contributes to mental health disorders including schizophrenia, autism and addiction. Yet the cerebellum’s impact on cognitive function remains largely unexplored. Kamran Khodakhah, Ph.D., has received a five-year, $3.6 million grant from the National Institute on Drug Abuse to expand on his earlier research linking the cerebellum to the ventral tegmental area (VTA), a brain region involved in addiction and other reward-seeking behaviors. He and his colleagues will use anatomical and physiological approaches to find the neural pathways by which the cerebellum can affect the VTA as well as two other regions associated with addiction: the prefrontal cortex and the nucleus accumbens. Dr. Khodakhah is professor and chair of the Dominick P. Purpura Department of Neuroscience and the Florence and Irving Rubinstein Chair in Neuroscience. (1R01DA044761-01A1)

Tuesday, November 21, 2017

Supporting People with Intellectual and Developmental Disabilities—Einstein has received a five year, $2.75 million grant from the Department of Health and Human Services for the University Center for Excellence in Developmental Disabilities (UCEDD), based at the Rose F. Kennedy Children’s Evaluation and Rehabilitation Center (RFK CERC). The UCEDD promotes an integrated, “disability-informed” approach to caring for children and adults with developmental disabilities. It also advocates on behalf of individuals with developmental disabilities and trains leaders in the field. The project director is Theodore Kastner, M.D., M.S., the Ruth L. Gottesman Chair in Developmental Pediatrics, professor and chief of the division of developmental medicine in the department of pediatrics. The project co-director is Karen Bonuck, Ph.D., professor of family and social medicine. (90DDUC0035-01-00)

Monday, November 20, 2017

Two Grants Focus on Early DementiaJoe Verghese, M.B.B.S., has been awarded two NIH grants totaling $5 million to pursue his research into diagnosing cognitive impairment at an early and potentially treatable stage.
     Cognitive impairment related to dementia is underdiagnosed, even though tests are available for assessing it. The missed diagnoses—especially common among African Americans and Hispanics—cause delays in providing vital support services. One of Dr. Verghese’s two NIH awards is a five-year, $3.8 million grant to develop and validate a low-cost, five-minute cognitive screening test that can be readily administered by non-clinicians after minimal training. The test will be accompanied by a decision tree aimed at helping providers identify and care for multi-ethnic primary care populations at high risk for developing dementia. It will be assessed at Montefiore Medical Group primary care clinics. (1UG3NS105565-01)
     Dr. Verghese’s second NIH award is a five-year, $1.2 million grant to investigate the biological underpinnings of Motoric Cognitive Risk Syndrome (MCR), which Dr. Verghese and a group of international collaborators recently described. People diagnosed with MCR have trouble thinking and walk slowly—an indication that they’re at high risk for developing Alzheimer’s disease and vascular dementia. Previous studies found that certain interventions can counteract the syndrome, suggesting that treating MCR may prevent it from progressing to more serious disease.
     Dr. Verghese’s MCR research involves more than 10,000 older participants divided into eight cohorts based in five countries: the U.S., Canada, France, India, Japan and Australia. He and his colleagues will evaluate likely biomarkers of MCR, including peripheral inflammation and oxidative stress, along with physiological mechanism that drive the condition.
     Dr. Verghese is professor and division chief of geriatrics, department of medicine; and director of the Montefiore Einstein Center for the Aging Brain. (1R56AG057548-01)

Monday, November 20, 2017

Explaining Cerebral Malaria—In cerebral malaria, the Plasmodium falciparum parasite breaks down the blood-brain barrier and causes fatal brain swelling. But how the parasite causes disease in the brain is not well understood. In a study published online on October 26 in Cell Host & Microbe, lead author Anne Kessler, Ph.D., and colleagues describe a possible mechanism for disease pathogenesis. Using data from eye exams, blood work and MRIs of infected children, the researchers found that the parasites were most likely to cause cerebral malaria when infected red blood cells express parasite proteins that bound to host proteins vital for maintaining a healthy blood brain barrier. The severity of cerebral malaria also correlates with low platelet counts suggesting that both parasite proteins and host platelets work together to damage the host. Senior author Kami Kim, M.D., supervised this research while at Einstein and is now at the University of South Florida.

Friday, November 17, 2017

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—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—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—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—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—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—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