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.
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.
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.
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.
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.
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.