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.

Visual Clutter and Impaired Vision—Visual crowding—clutter’s interference with our ability to recognize individual objects—can be a significant problem for people with macular degeneration and other eye diseases. Adam Kohn, Ph.D., has received a five-year, $2.1 million grant from the National Eye Institute to determine the neural underpinnings of visual crowding. In research using monkeys and focusing on the brain’s visual cortex, Dr. Kohn will examine how crowded visual displays affect the ability of nerves to absorb sensory information. His findings may lead to better therapies for the impaired central vision that characterizes macular degeneration. Dr. Kohn is professor in the Dominick P. Purpura Department of Neuroscience and of ophthalmology and visual sciences and systems & computational biology. (1R01EY028626-01)

Friday, March 09, 2018

Insights into Autoimmunity—There are more than 80 types of autoimmune diseases, which occur when immune cells aberrantly attack the body’s own cells or tissues. CD8 T cells strongly contribute to the pathology observed in type 1 diabetes and many other autoimmune diseases. Teresa DiLorenzo, Ph.D., and Steven Almo, Ph.D., have received a five-year, $3.5 million grant from the National Institutes of Health to fill in critical knowledge gaps regarding the protein-protein interactions that occur when CD8 T cells target and damage tissue. CD8 T cells also help eliminate disease-causing microbes and tumors, so knowledge gained from studying autoreactive CD8 T cells should improve understanding of T-cell biology in general. The research may also lead to more effective ways to manipulate and harness the immune system to prevent disease and improve health. Dr. DiLorenzo is professor of microbiology & immunology and of medicine and Diane Belfer, Cypres & Endelson Families Faculty Scholar in Diabetes Research at Einstein. Dr. Almo is professor and chair of biochemistry, professor of physiology & biophysics, and Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology at Einstein. (1R01AI123730-01A1)

Tuesday, March 06, 2018

How Nuclear Pore Traffic Cops Do Their Job—The nuclear envelope of eukaryotic cells must be permeable — messenger RNA molecules must exit the nucleus to be translated into proteins in the cytoplasm, for example, and newly translated chromatin protein must enter the nucleus to help form chromosomes. This two-way traffic passes through gatekeepers known as nuclear pore complexes endowed with the paradoxical ability to transport thousands of molecules both rapidly and very specifically (i.e., allowing some molecules through while blocking others). To discover the secret to the nuclear pore complexes’ success, David Cowburn, Ph.D., and collaborators looked at interactions between transiting molecules and intrinsically disordered proteins (IDPs) that line the pore’s central channel. Surprisingly, in a report published online on January 26 in the Journal of Biological Chemistry,the binding between IDPs and transiting molecules is energetically weak, allowing for rapid interactions. Simultaneously, the many phenylalanine-glycine repeats within the IDPs makes for more frequent contacts between IDPs and transiting molecule, enhancing specificity. In the February 8 online issue of Structure, Dr. Cowburn and colleagues used neutron scattering experiments to gain insights into the conformational changes that IDPs undergo. Dr. Cowburn is a professor of biochemistry and of physiology & biophysics at Einstein. Samuel Sparks, a Ph.D. student in Dr. Cowburn’s lab, was co-first author of the Journal of Biological Chemistry paper and first author of the Structure paper.

Monday, March 05, 2018

Bone Cancers Without Biopsies—In a study involving patients with osteosarcoma, Einstein-Montefiore researchers have shown for the first time that tumor DNA circulating in the blood (ctDNA) can be identified and tracked over time—a potential boon for patients with this common type of bone cancer. Until now, most disease-monitoring technology has focused on radiologic imaging techniques—an approach that is not very sensitive for tracking the tumor. Daniel Weiser, M.D., and colleagues applied a highly sensitive DNA sequencing method to identify non-cancerous DNA and tumor DNA from the blood of seven osteosarcoma patients. The results, published online on January 18 in Oncotarget, showed that ctDNA could potentially be used to monitor disease progression and tumor response to treatment, without the need for invasive biopsies or imaging. Dr. Weiser is an assistant professor of pediatrics and genetics at Einstein and the medical director of the Intra-Abdominal Solid Tumor Program at Children’s Hospital at Montefiore.

Thursday, March 01, 2018

A Genetic Link Between Stroke and Depression—Stroke and depression are major global health problems. Previous epidemiological studies had found a relationship between depressive symptoms and stroke risk, but for the first time a genetic link between the two conditions has been found. A study published in the journal Stroke online on February 8, has found that a genetic risk for Major Depressive Disorder (MMD) is associated with a higher risk of stroke. The study involved nearly 14,000 stroke cases and more than 28,000 controls among people of European and African ancestry. All underwent genetic testing (resulting in a polygenic risk score for MDD) to test whether genetic risk for MMD is associated with stroke risk.  Overall, for both ancestries, a higher risk for MMD was associated with higher risk for ischemic (clot-caused) stroke. In particular, the researchers found that a higher risk for MMD was associated with higher risk for the small vessel occlusion subtype of stroke in both those of European and African ancestry.  The lead author was Einstein’s Sylvia Wassertheil-Smoller, Ph.D., distinguished university professor emerita of epidemiology & population health.

Wednesday, February 28, 2018

Finding How a Natural HIV-1 Blocker Works—The protein SERINC5, found in cell membranes, is known to inhibit HIV-1 from infecting human T cells. But how the protein interfered with HIV-1 was unclear. Now, Felipe Diaz-Griffero, Ph.D., has identified the mechanism. When HIV-1 particles are produced within infected human T cells, SERINC5 becomes incorporated into the membrane of the newly produced viral particles. The presence of SERINC5 in the viral particle changes the shape of the viral envelope, and that change in the envelope’s conformation restricts HIV-1 from invading new T cells. The findings, published online on December 18 in Virology, suggest that a therapeutic version of SERINC5 might be able to inhibit HIV-1 in the bloodstream before the virus can infect T cells. Dr. Diaz-Griffero is associate professor of microbiology & immunology and the Elsie Wachtel Faculty Scholar at Einstein.

Monday, February 26, 2018

Studying How HIV and Herpes Virus Interact—When people are co-infected with HIV and herpes simplex virus type 2 (HSV-2, the primary cause of genital herpes), the combined infection can reactivate latent HIV-1 infection. But the biological mechanisms which contribute to interactions between HIV and HSV-2 are not well understood. The NIH has awarded Betsy Herold, M.D., and colleagues a five-year, $2.49 million grant to investigate those mechanisms. They will test their hypothesis that HSV-2 triggers changes in CD4+ T cells (including reducing intracellular levels of the proinflammatory cytokine interleukin 32) that promote latent HIV-1 to reactivate. Their findings may lead to new strategies for eliminating HIV. Using HSV-2 coinfection as a tool, they will identify pathways and molecules that could be targeted to block HIV reactivation caused by HSV-2. Conversely, the researchers will explore ways to purposely reactivate latent HIV as part of an HIV eradication strategy known as “shock and kill.” Dr. Herold is professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women’s health. (1R01AI134367-01A1)

Thursday, February 22, 2018

Targeting TB EnzymesMyobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), infects a third of the world population and is a leading cause of mortality. However, drug-resistant strains of Mtb continue to hinder TB control efforts. In a study published online on January 30 in the Proceedings of the National Academy of Sciences, Einstein researchers, led by Catherine J. Vilcheze, Ph.D., and William R. Jacobs, Jr., Ph.D., focused on three NADH dehydrogenase enzymes (Ndh, NdhA and Nuo) involved in the electron transport chain. The researchers found that deleting the gene that codes for Ndh reduced Mtb virulence the most and that compounds that could target both Ndh and Nuo would be good candidates for anti-Mtb drugs. Dr. Jacobs is the Leo and Julia Forchheimer Chair in Microbiology and Immunology, a Howard Hughes Medical Institute Investigator and a professor of genetics and microbiology and immunology at Einstein. Dr. Vilcheze is an instructor in microbiology and immunology at Einstein.

Tuesday, February 20, 2018

Imaging the Effects of Hydrocephalus Shunts—Hydrocephalus, a chronic condition in which excess fluid builds up in the brain, is treated with a fluid-draining tube called a shunt. Although shunts do save lives, their long-term effects on the brain are unknown. Mark E. Wagshul, Ph.D., and colleagues at Montefiore used an advanced MRI method called diffusion tensor imaging (DTI) to scan the brain’s white matter tracts (important structures that send electrical signals between parts of the brain)and determine the possible impacts of shunting on 21 hydrocephalus patients and 21 healthy controls. The study, published online on January 19 in Journal of Neurosurgery, found marked impairment of the major white matter tracts even in patients whose hydrocephalus was well-controlled with shunts. The results suggest DTI could be a valuable tool for tailoring treatments or developing new therapies for hydrocephalus. Dr. Wagshul is associate professor of radiology and is an assistant professor of physiology & biophysics at Einstein.

Friday, February 16, 2018

Treating Both MDR-TB and HIV Improves Survival and Cure Rates—Survival odds are stacked against people co-infected with multidrug-resistant tuberculosis (MDR-TB) and HIV. HIV weakens the immune system, and co-infected patients have high mortality. To help guide treatment for these individuals, James Brust, M.D., with colleagues from Emory, the Centers for Disease Control and Prevention, and the University of KwaZulu-Natal, prospectively measured survival and treatment outcomes in MDR-TB/HIV co-infected patients on antiretroviral therapy (ART) compared to outcomes in patients with MDR-TB alone. Read full story.

Friday, February 16, 2018

Uncovering Herpes Simplex Infection Tactic—Understanding how the herpes simplex virus (HSV) invades cells could lead to new strategies for preventing or treating infections. In a study published online on January 2 in PloS Pathogens, Natalia Cheshenko, Ph.D., and Betsy Herold, M.D. showed that HSV activates a membrane enzyme called scramblase, which then “flips” certain lipids from the inner layer of the cell membrane to the outer layer—making it easier for HSV to interact with membrane proteins such as Akt, which are normally found only on the inside. Interactions between HSV and these proteins promote viral entry. Normally, moving those lipids to the membrane’s outer layer would trigger cell death, known as apoptosis. But the infecting viruses prevent apoptosis by causing the lipids to flip back within two hours of infection. The finding suggests that drugs that inhibit scramblase or Akt could prevent or treat HSV infection. Dr. Herold is professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women’s health. Dr. Herold also holds the Harold and Muriel Block Chair in Pediatrics at Einstein. Dr. Cheskenko is an assistant professor of pediatrics at Einstein.

Wednesday, February 14, 2018

Studying the Biology of Embryonic Stem Cells—Embryonic and induced pluripotent stem cells hold great promise for regenerative medicine. Gene expression in stem cells is influenced by epigenetic marks including methyl groups that are added to or removed from DNA. A class of proteins called Tet enzymes aid in removing methyl groups from DNA, thereby activating specific genes in stem cells. Aberrant Tet-mediated regulation of gene activity can lead to abnormal stem cell function and development and lead to diseases such as cancer. Meelad Dawlaty, Ph.D., has received a 5-year, $1.75 million grant from the National Institutes of Health to investigate how Tet proteins regulate embryonic stem cells. Findings from these studies will improve basic understanding of stem cell biology and could help identify new targets for treating diseases. Dr. Dawlaty is an assistant professor of genetics and member of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein. (1R01GM122839)

Monday, February 12, 2018

Mutation Protects Certain Cells—Cell competition can occur when tissues contain both normal and abnormal cells. It may contribute to the early growth or elimination of tumors, for example, and to how many genetic errors accumulate during aging. Nicholas E. Baker, Ph.D., is using fruit flies to study cell competition. In a paper published online on January 8 in Developmental Cell, he and his colleagues looked at competition involving cells with mutated ribosomal proteins. Such proteins are also mutated in human diseases (ribosomopathies) and in cancer. They found that the ribosomal protein S12 was unusual because cells heterozygous for this mutation resisted competition from wild-type cells. The researchers concluded that in the competition between wild-type cells and cells containing mutated ribosomal proteins, the S12 ribosomal protein sends a signal promoting cell competition. 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. The paper’s first author, Abhijit Kale, Ph.D., was a doctoral student in Dr. Baker’s lab.

Tuesday, February 06, 2018

Exploring Dystonia's Genetic Cause—The neurological disorder dystonia causes muscles to contract involuntarily. It is the third most common movement disorder (after Parkinson’s and essential tremor) and affects about 250,000 Americans. Einstein’s Kamran Khodakhah, Ph.D. and colleagues developed a mouse model of DYT1, the most common inherited form of dystonia that replicates the neurological symptoms of patients. Using this mouse model, they determined that dystonia is caused primarily by dysfunction of the brain’s cerebellum. The National Institute of Neurological Disorders and Stroke has awarded Dr. Khodakhah a five-year, $2.3 million grant to use his mouse model to determine at the cellular and molecular level how mutations associated with DYT1 cause dystonia. Dr. Khodakhah is professor and chair of the Dominick P. Purpura Department of Neuroscience and the Florence and Irving Rubinstein Chair in Neuroscience. (1R01NS105470-01)

Friday, February 02, 2018

Investigating Ebola Infection—Viruses must infect host cells so they can replicate. Ebola virus and other filoviruses, which cause fatal hemorrhagic fever in humans, have evolved a highly complex infection and replication process. Kartik Chandran, Ph.D., has already described the key steps, in which filoviruses bind to the host cell’s outer membrane, are taken up by lysosomes (intracellular bags filled with enzymes) and then multiply by propelling their RNA genetic material through the lysosome and into the cell’s cytoplasm. He was recently awarded a four-year, $1.9 million grant from the National Institute of Allergy and Infectious Diseases to conduct further filovirus research. His group aims to define the molecular mechanism by which filoviruses bind to host cells and to find new host factors that could be targeted to prevent filoviruses from infecting cells and multiplying inside them. Dr. Chandran is professor of microbiology & immunology and the Harold and Muriel Block Faculty Scholar in Virology. (1R01AI134824-01)

Wednesday, January 31, 2018

Rapid HIV Tests Underperform in Children—Rapid diagnostic tests (RDTs) to determine the HIV status of children in the African country of Malawi are not always accurate, according to a paper published online on December 6 in the American Journal of Tropical Medicine and Hygiene. The study involved 341 hospitalized children, aged two months to 16 years old, whose two positive RDTs meant they had tested positive for HIV infection according to hospital guidelines; the children were later retested using standard blood tests for detecting viral loads. A significant percentage of children had false-positive results on the RDTs, meaning the tests incorrectly indicated that they were infected with HIV. Such inaccurate test results put children at risk for lifelong misdiagnosis and unnecessary treatment with antiretroviral therapy. The paper’s lead author was Theresa F. Madaline, M.D., assistant professor of medicine at Einstein and Montefiore.

Monday, January 29, 2018

New Data for TB Research—To develop faster and more cost-effective therapies for tuberculosis, researchers need to better understand the biology of Mycobacterium tuberculosis, the bacterium that causes the disease. William R. Jacobs, Jr., Ph.D., has received a five-year, $2.85 million grant from the National Institute of Allergy and Infectious Diseases to systematically delete the coding regions of each of the nearly 4,000 genes of M. tuberculosis and mark each of those mutant variants with an identifying “barcode” DNA sequence. The complete set of barcoded deletion mutants of the bacillus will then be distributed to researchers around the world. Studying how the mutations affect the bacterium’s function and survival may give researchers insights into better strategies for preventing or treating TB infections. Dr. Jacobs is the Leo and Julia Forchheimer Chair in Microbiology and Immunology, a Howard Hughes Medical Institute investigator and a professor of genetics and microbiology and immunology at Einstein. (1R24AI134650-01

Friday, January 26, 2018

Mapping Bone Marrow Nerves—Stem cells in the bone marrow multiply and differentiate to form all the cells of the bloodstream—a process regulated by sympathetic nerves that infiltrate the marrow. With a three-year, $1.25 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, Paul S. Frenette, M.D., will map those nerves to better understand their functions and physiology. In a three-stage experiment, Dr. Frenette and colleagues will define the marrow’s system of nerves, identify how those nerves relay signals and manipulate certain nerves to increase blood cell production (which could help reverse low blood cell counts in patients undergoing marrow-damaging chemotherapy). Dr. Frenette is professor of medicine and of cell biology and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein. (1U01DK116312-01)

Thursday, January 25, 2018