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Insights into Autism Spectrum Disorder

Insights into Autism Spectrum Disorder—Noboru Hiroi, Ph.D., has been awarded a five-year, $1.8 million grant from the National Institute on Deafness and Other Communication Disorders to investigate the interplay among genes, early social communication and neonatal maternal care in determining the severity of autism spectrum disorder (ASD). Working with a genetic mouse model of ASD, Dr. Hiroi’s lab has observed that newborn mice display an unusual vocalization or “call,” to communicate with their mothers and that this abnormal call reduces the level of maternal care that newborns receive. The researchers will study whether abnormal newborn-to-mother vocalization is caused by ASD-related gene variants and whether this early experience of social communication gone awry worsens ASD-like behaviors through the epigenetic modification of these gene variants. Dr. Hiroi is professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences. (1R01DC015776-01A1)

Wednesday, September 13, 2017
Studying Brain Functions with Near-Infrared Light

Studying Brain Functions with Near-Infrared Light—Technologies that reveal information about neuronal activity in model animals could provide important information about how the brain functions. The National Institute of Neurological Disorders and Stroke has awarded Vladislav Verkhusha, Ph.D., a three-year, $1.8 million BRAIN Initiative grant to engineer and apply genetically encoded calcium biosensors to neuronal imaging. Dr. Verkhusha and colleagues will develop two new biosensor classes that report on neuronal levels of calcium by emitting light in the near-infrared portion of the light spectrum. This light will pass through the skin to provide images of neuron activity in the brain’s cortex and deeper. The biosensors will also be combined with optogenetic tools that modulate the brain activity. These tools can be activated with the light of the different wavelength, independently of the near-infrared biosensors. The overall approach will increase knowledge of brain function and should lead to new treatments for brain disorders. Dr. Verkhusha is professor of anatomy and structural biology. (1U01NS103573-01)

Monday, September 11, 2017
Preventing Cancer Spread

Preventing Cancer Spread—Using mouse models of metastatic breast and pancreatic cancer, Einstein researchers have found that the drug rebastinib significantly reduces changes in tumors that promote metastasis and dramatically improves the survival of animals with breast tumors. Breast tumor cells invade blood vessels and spread through the body via doorways called Tumor Microenvironment of Metastasis (TMEM) that are found on blood vessels of tumors and consist of three different cell types in direct physical contact: a tumor cell that expresses Mena, a protein that encourages tumor cell invasion; a macrophage; and an endothelial cell. Rebastinib inhibits TMEM function, thereby preventing TMEM-associated tumor cells from invading blood vessels and causing metastasis. The drug specifically blocks a subset of macrophages found in TMEM that express the receptor tyrosine kinase Tie2. Both Tie2-expressing macrophages and TMEM function can become elevated following chemotherapy. Rebastinib may therefore prevent chemotherapy-induced metastasis from occurring. The research, which published August 24 in Molecular Cancer Therapeutics, was led at Einstein by John Condeelis, Ph.D., professor and co-chair of anatomy and structural biology, the Judith and Burton P. Resnick Chair in Translational Research and co-director of the Gruss-Lipper Biophotonics Center and its Integrated Imaging Program, Maja Oktay, M.D., Ph.D., professor of pathology and anatomy and structural biology and the Integrated Imaging program, with co-first authors Allison Harney, Ph.D., and George Karagiannis, D.V.M., Ph.D., bridge postdoctoral fellows in the Integrated Imaging Program at Einstein-Montefiore.

Thursday, September 07, 2017
Focusing on HIV-Related Neurological Problems

Focusing on HIV-Related Neurological Problems—Thanks to antiretroviral drugs, many fewer HIV-infected people experience frank dementia anymore. Nevertheless, more than half of HIV-positive patients treated with antiretrovirals suffer from milder, lifelong HIV-associated neurocognitive disorders, or HAND. Joan W. Berman, Ph.D., professor of pathology and of microbiology & immunology, recently received two NIH grants totaling $7.4 million to study the sequence of events that lead to HAND, examine how certain drugs of abuse increase the risk for HAND, and develop strategies for preventing the disorder. Dr. Berman also holds the Irving D. Karpas M.D. Chair for Excellence in Medical Research.

HAND occurs after HIV-infected white blood cells manage to cross the blood brain barrier, resulting in inflammation, damage to neurons, and persistent reservoirs of virus in the brain. Dr. Berman and Susan Morgello, M.D., of Mount Sinai Icahn School of Medicine, were awarded a five-year, $3.6 million grant from the National Institute of Mental Health to study a particular population of white cells known to be responsible for HAND. The researchers will follow the migration of these cells in HIV-positive patients and study the proteins that regulate the transit of white cells across the blood brain barrier. The research may lead to therapies that block HIV-infected white cells from entering the brain. (1R01MH112391-01A1)

Drugs of abuse and even certain antiretroviral therapies appear to increase the risk for developing HAND. Dr. Berman and Harris Goldstein, M.D., have been awarded a five-year, $3.8 million grant from the National Institute on Drug Abuse (NIDA) to study the interactions among methamphetamines and other drugs of abuse, antiretroviral therapeutics and HIV infection. The researchers hypothesize that methamphetamines and some antiretrovirals weaken the integrity of the blood brain barrier, making it easier for HIV-infected white blood cells to enter the brain. Their research will also use a mouse model of HIV. Dr. Goldstein is professor of pediatrics and of microbiology & immunology and director of the Einstein-Rockefeller-CUNY Center for AIDS Research. He also holds the Charles Michael Chair in Autoimmune Diseases at Einstein. (1R01DA044584-01)

Tuesday, September 05, 2017
Tackling Renal Disease in Lupus Patients

Tackling Renal Disease in Lupus Patients—The autoimmune disease lupus can lead to serious kidney problems in up to 60 percent of patients, with 10-30 percent of patients ultimately developing end-stage renal disease (ESRD). The National Institute of Arthritis and Musculoskeletal and Skin Diseases has awarded Anna Broder, M.D., a five year, $880,000 grant to continue her research on the drug hydroxychloroquine, which  is used to treat lupus but is not widely used after lupus patients develop  ESRD. Dr. Broder will study whether hydroxychloroquine reduces mortality in lupus patients undergoing hemodialysis and kidney transplantation. This will involve analyzing data from a U.S. registry of ESRD patients and studying outcomes in lupus patient with ESRD who are being treated with hydroxychloroquine at Einstein and New York University School of Medicine. Dr. Broder is associate professor of medicine. (1K23AR068441-01A1)

Friday, August 18, 2017
Targeting a Sickle-Cell Problem

Targeting a Sickle-Cell Problem—Sickle cell disease (SCD), a genetic disorder in which red blood cells are misshapen, causes serious complications. One SCD complication is painful leg ulcers, for which there is no approved treatment. Following up on her successful phase 1 study, the U.S. Food and Drug Administration has awarded Caterina Minniti, M.D., a four-year, $1.9 million grant to conduct a phase 2 trial of sodium nitrite cream for treating leg ulcers in SCD patients. When the cream is applied to the wound, sodium nitrite is converted into nitric oxide (NO), which causes blood vessels to dilate and also kills bacteria, stimulates the proliferation of keratinocytes (the main cell type in the skin’s outer layer) and decreases inflammation. These NO- induced changes aid healing. In the phase 1 study, the sodium nitrite cream decreased pain at the wound site and reduced patient’s narcotic use. Dr. Minniti is professor of medicine and of pediatrics at Einstein and director of the Sickle-Cell Center for Adults at Montefiore. (1R01FD005729-01)

Thursday, August 10, 2017
Reducing Radiation Injury

Reducing Radiation Injury—Radiation exposure from nuclear accidents or terrorism can cause mass casualties and poses a serious ongoing threat. Radiation-induced vascular injury (RIVI) is a critical component of the multi-organ failure caused by acute radiation exposure syndrome. RIVI can lead to blood problems such as anemia and thrombocytopenia and damage critical organs, especially intestines and lungs. The National Institutes of Health has awarded Chandan Guha M.B.B.S., Ph.D., a five-year, $2.3 million grant to develop measures to prevent RIVI. In collaboration with Janssen Pharmaceuticals, Inc., Dr. Guha and colleagues will test whether the drug Thrombopoietin Mimetic (TPOm) can protect against vascular injuries caused by radiation. The team will first evaluate TPOm in mice—an effort that will require developing imaging techniques to assess the extent radiation induced normal tissue injury. Dr. Guha is director of the Einstein Institute for Onco-physics, professor and vice chair of radiation oncology, as well as professor of urology and of pathology at Einstein and Montefiore. (1U01AI133608-01)

Friday, August 04, 2017
A One-two TB Knockout Punch

A One-two TB Knockout Punch—Mycobacterium tuberculosis, the bacterium that causes TB, has developed extensive drug resistance so that treatment is often lengthy or ineffective. In a paper published on June 26 in the Proceedings of the National Academy of SciencesMichael Berney, Ph.D.and his graduate student Erik Hasenoehrl, found a way to exploit the bacterium’s oxidative phosphorylation pathway that may lead to better treatments. Dr. Berney’s group, together with collaborators from Singapore, found that resistant TB infections require two terminal oxidases--molecular pumps that TB bacteria rely on to generate energy. Using chemical biology and genetic approaches, Dr. Berney and colleagues showed that simultaneously inactivating both pumps halts TB cell respiration leading to cell death. The researchers shut down both pumps and rapidly cleared M. tuberculosis infection in a TB mouse model by coupling deletion of one oxidase gene with use of a drug. Dr. Berney is an assistant professor of microbiology & immunology.

Thursday, July 13, 2017
Mapping a Viral Infection Highway

Mapping a Viral Infection Highway—Herpes simplex virus 1 (HSV-1), the virus responsible for oral herpes, infects about half the world’s population. HSV-1 infects neurons of cranial nerves—especially the trigeminal ganglion nerves responsible for facial sensation and motor function. The viruses travel up the axons of these nerves to multiply in their nerve bodies. Newly-made HSV-1 then travel back down the axon to be released into the synapse. HSV-1 is thought to hijack the cell’s microtubule network to travel back and forth in the axon, but how it does so is unclear. The National Institute of Allergy and Infectious Diseases has awarded Duncan W. Wilson, Ph.D., a five-year, $3.5 million grant to study UL36p, an HSV-1 protein that appears to attach the virus to microtubules via the motor proteins kinesin and dynein. Using microscopic imaging and biochemical techniques, Dr. Wilson will explore how UL36p helps HSV-1 move through axons during infection. Dr. Wilson is professor of developmental and molecular biology. (1R01AI125244-01A1)

Wednesday, June 07, 2017
Spotlighting Near-Infrared Probes

Spotlighting Near-Infrared Probes—Proteins engineered from natural photoreceptors, which sense light of the near-infrared part of the light spectrum, can be activated through the skin in deep tissues of living animals. This makes them valuable tools for noninvasively imaging, assessing and manipulating biological processes. The National Institute of General Medical Sciences has awarded Vladislav Verkhusha, Ph.D., a five-year, $2 million grant to develop new near-infrared fluorescence proteins, biosensors and optogenetic tools. Using directed molecular evolution, Dr. Verkhusha will first design these genetically encoded probes from bacterial photoreceptors. He will then use those near-infrared optical probes and molecular tools in novel ways for studying molecular interactions, cellular physiology and tissue metabolism in development, cancer, and in neurological and infectious diseases in both humans and animals. Dr. Verkhusha is professor of anatomy and structural biology. (1R35GM122567)

Friday, June 02, 2017
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