Major NIH Research Awards
Einstein investigators received $148 million in research funding from the National Institutes of Health (NIH) during the federal fiscal year 2015. Below are highlights of grants received between July 1, 2015 and December 31, 2015.
Monitoring the Placenta
The placenta’s health is crucial to the health of both fetus and mother. Abnormalities in placental structure or function cause pregnancy complications, including preterm birth, miscarriage, stillbirth and preeclampsia. S. Zev Williams, M.D., Ph.D., has received a five-year, $3.8 million grant to develop methods for noninvasively monitoring placental function so that problems can be detected early and treated.
The research is premised on the fact that changes in the expression of coding and noncoding genes reflect the functional state of an organ, and those changes in gene expression can be detected by assessing that organ’s transcriptome (the identity and concentration of all its RNA molecules—mRNA as well as noncoding types, including tRNA, rRNA and microRNA).
Dr. Williams’ laboratory, in collaboration with Thomas Tuschl, Ph.D., at Rockefeller University and the Howard Hughes Medical Institute, has developed an RNA sequencing method for profiling placental microRNAs found in the mother’s blood. His project will advance this technology to permit noninvasive monitoring of the placental transcriptome using both maternal blood and urine. Ideally, this work will result in a noninvasive tool for gaining insights into the processes underlying pregnancy-related diseases and indicate when therapeutic interventions are needed. Dr. Williams is an assistant professor of obstetrics & gynecology and women’s health and of genetics and director of the Program for Early and Recurrent Pregnancy Loss at Einstein and Montefiore.
Testing a New Autism Therapy
Up to 90 percent of children with autism spectrum disorders (ASD) have “sensitivity issues”—they’re too sensitive or not sensitive enough to their environment, or are not able to integrate sensory information in an orderly way. Such problems impair ASD children’s school performance and social opportunities as well as their long-term outcomes. Sophie Molholm, Ph.D., and her research partners have been awarded a five-year, $3.18 million NIH grant to better understand the brain processes responsible for these sensitivity issues and to test the effectiveness of Sensory Integration Treatment (SIT), a noninvasive intervention for treating sensory symptoms in ASD. The testing will involve 180 children ages 6 to 8-1/2 who have ASD and sensory issues. They will be randomized to receive either 10 weeks of SIT, 10 weeks of a commonly used behavioral intervention (Discrete Trial Training) or no treatment. Outcome assessment will involve behavioral and electrophysiological measures taken at baseline, immediately after treatment and at 12 weeks following treatment. The team will evaluate SIT’s impact on functional skills and autism severity and look for possible neurological mechanisms through which this intervention may work. Dr. Molholm is an associate professor in the department of pediatrics and in the Dominick P. Purpura Department of Neuroscience, the Muriel and Harold Block Faculty Scholar in Mental Illness, director of the Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory and associate director of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center.
Opioid Use and HIV
The dramatic increase in misuse, addiction and overdose of prescription opioid (PO) analgesics stems largely from providers prescribing POs for chronic pain. That puts people living with HIV at particular risk for PO misuse, since they suffer disproportionately from chronic pain and from substance use and mental health disorders. Joanna L. Starrels, M.D., M.S., has been awarded a four-year, $2.3 million grant to study how PO use influences the health outcomes of people living with HIV and chronic pain, 250 of whom will be followed over a 12-month period. The main goals of her research are to gather evidence that can help guide the clinical management of patients living with HIV and chronic pain and to improve the health of these patients. Dr. Starrels is an associate professor of medicine at Einstein and an attending physician in internal medicine at Montefiore.
Over the past several decades, patients suffering from end-stage organ failure have greatly benefited from donated kidneys, hearts and other organs. Unfortunately, graft vascular disease (GVD) limits the long-term effectiveness of almost all donated organs—even when immunosuppressant drugs are used. In GVD, lesions consisting of smooth muscle cells and extracellular matrix develop within the intima (innermost layer) of vessels of the donated organ. No therapies have yet proven effective in preventing or reversing GVD. As they accumulate, GVD lesions restrict blood flow and lead to organ failure. Nicholas E. S. Sibinga, M.D., has been awarded a four-year, $2.1 million grant to study the role that a cellular growth factor called colony stimulating factor-1 (CSF-1) plays in GVD. In previous studies involving mice, Dr. Sibinga, in collaboration with E. Richard Stanley, Ph.D., a professor of developmental and molecular biology at Einstein, has shown that the absence of CSF-1 either in tissue recipients or in donor tissue significantly limits the size of GVD lesions. Now he will investigate whether inhibiting CSF-1 could be a treatment strategy for minimizing GVD and prolonging the function of transplanted organs. Dr. Sibinga is an associate professor of medicine and of developmental and molecular biology and an attending physician at the Montefiore Einstein Center for Heart and Vascular Care.
Lab-Made Donor Blood
People with sickle cell disease and other chronic anemia conditions typically receive transfusion therapy over many years. But for patients of Asian and African backgrounds, finding compatible donors can be difficult: The high degree of genetic diversity in their blood-group antigens means they tend to have rare blood groups, yet most blood donors are whites and of European ancestry whose blood-group antigens are much less diverse. Over time, the difficulty of finding well-matched donors for these patients causes a high incidence of alloimmunization (unwanted immune response following transfusion of genetically different blood cells). Eric E. Bouhassira, Ph.D., has received a four-year, $2 million grant to develop methods for the laboratory production of red blood cells that people with rare blood groups can use safely. One part of the project involves a panel of six donors with rare blood types. From skin cells of these individuals, Dr. Bouhassira and his colleagues at the New York Blood Center will generate induced pluripotent stem cells that will be made to differentiate into hematopoietic stem cells and then into red cells that lack the antigens responsible for causing immune reactions. The goal is to produce “universally safe” red cells in sufficient quantity for use in the production of reagent red blood cells and eventually for lifesaving transfusion therapy. The first people to receive such cells would be patients with sickle cell disease who have no other treatment options. Dr. Bouhassira is a professor of cell biology and of medicine and the Ingeborg and Ira Leon Rennert Professor of Stem Cell Biology and Regenerative Medicine.
Exploring the Interactome
For any organism, the network of molecular interactions that occur intracellularly, intercellularly and between its cells and their external environment is known as its interactome. Little is known about interactions involving the one-third of proteins that human cells secrete or that are present on their surfaces (e.g., cell-surface receptors). These proteins detect environmental and other cues critical to both normal physiology and disease, including autoimmune disease, infectious diseases and cancer. Steven C. Almo, Ph.D., has been awarded a three-year, $1.9 million grant to map the “ecto-interactome”—the entire set of interactions involving secreted and cell-surface proteins—using two high-throughput platforms now being optimized. This mapping effort could both increase our understanding of basic biology and lead to novel strategies for treating a wide range of human diseases. Dr. Almo is a professor and chair of biochemistry, a professor of physiology & biophysics, the Wollowick Family Foundation Chair and director of the Einstein Macromolecular Therapeutics Development Facility.
The Doors of Visual Perception
Elyse S. Sussman, Ph.D., and Adam Kohn, Ph.D., have been awarded a three-year, $1.7 million grant to study how visual adaptation contributes to visual perception. Visual adaptation is a widespread process in which recent visual inputs dramatically influence brain activity and perception. However, adaptation’s function in vision is poorly understood. Based on preliminary data, the researchers hypothesize that adaptation may be a form of predictive coding that “educates” perception by taking special notice of new or unexpected events while discounting expected ones. They will test this hypothesis by conducting research involving human electroencephalography (monitoring and recording electrical activity in the brain), monkey neurophysiology and computer modeling. These studies may reveal how the visual circuits of the brain influence perception—knowledge needed for treating people with visual-processing deficits and for developing prosthetic devices for aiding vision. Dr. Sussman is a professor of neuroscience and of otorhinolaryngology–head & neck surgery. Dr. Kohn is an associate professor of neuroscience and of ophthalmology and visual sciences.
Treating Infections in Children
The U.S. Department of Health and Human Services’ Agency for Healthcare Research and Quality recently awarded Michael L. Rinke, M.D., Ph.D., a three-year, $1.3 million grant to study healthcare-associated infections (HAIs) in children receiving ambulatory care. Information on HAIs among children in ambulatory settings is scarcer than similar information for children treated in hospitals. Dr. Rinke will use the New York City Clinical Data Research Network—a comprehensive repository of healthcare data from five pediatric healthcare systems—to identify incidence rates, risk factors, patient outcomes and costs for three pediatric ambulatory HAIs, along with ways to track them using computerized data. The three HAIs he will track are central-line–associated bloodstream infections, catheter-associated urinary tract infections and surgical site infections in ambulatory pediatric patients. The project’s goals are to focus attention on the safety of pediatric ambulatory patients and reduce HAIs among young patients. Dr. Rinke is an assistant professor of pediatrics at Einstein, and the medical director of pediatric quality and a hospitalist at the Children’s Hospital at Montefiore.
Halting HIV Assembly
More than 35 million individuals worldwide are living with HIV, and drug resistance to various available treatments is prevalent because of the virus’ extremely high mutation rate. The National Institute of General Medical Sciences has awarded Ganjam V. Kalpana, Ph.D., nearly $1.3 million over four years to study potential drug targets for HIV and develop inhibitors for these targets. More specifically, she and her laboratory team are focused on inhibiting the early stages of HIV virus assembly, which is the process by which the viral components are assembled together inside the cell to form infectious virus particles. The researchers have found that disrupting the interaction between the HIV protein integrase and the host protein integrase interactor 1 (INI1) can vastly reduce the ability of HIV to assemble its viral machinery, thereby preventing HIV replication inside human cells. Dr. Kalpana and her team plan to build on these findings to shed new light on the mechanisms involved in early virus particle formation. Dr. Kalpana is a professor of genetics and of microbiology & immunology and the Mark Trauner Faculty Scholar in Neuro-oncology.