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.

Modeling an Immune Response—Tumor necrosis factor (TNF) binds to TNF receptors on cell surfaces, triggering signaling pathways that bolster the immune response. TNF acts to promote inflammation, which can sometimes lead to autoimmune disorders such as rheumatoid arthritis. Most previous studies have looked at the TNF binding process in the lab, which limits the usefulness of their findings. Yinghao Wu, Ph.D., was recently awarded a four-year, $1.3 million grant from the National Institutes of Health to simulate TNF binding to cell-surface receptors in vivo using computational modeling methods. Since drugs for some autoimmune diseases work by blocking TNF, the findings could potentially aid in developing more effective therapies. Dr. Wu is an assistant professor of systems & computational biology at Einstein. (1R01GM122804-01)

Friday, January 12, 2018

CAR T Therapy for Lymphoma Available at Montefiore/Einstein—In results published online on December 10 in The New England Journal of Medicine, a type of immunotherapy called CAR-T cell therapy achieved impressive results in a phase 2 clinical trial involving 101 patients with large B-cell lymphomas that had not responded to other forms of treatment. Symptoms disappeared completely in 54 percent of patients, 82 percent had measurable improvement and more than half of patients survived 18 months after treatment. In CAR-T therapy, T cells are separated from a patient’s blood and are genetically engineered to produce receptors on their surfaces called chimeric antigen receptors, or CARs. These synthetic receptors allow the T cells to recognize and attach to a specific antigen on tumor cells—in this case, the CD19 antigen on B cells from which this type of lymphoma arises. After the modified T cells multiply in the laboratory, they are infused back into the patient to seek out and kill cancer cells bearing the CD19 antigen. Ira Braunschweig, M.D., associate professor of medicine at Einstein and director of the Stem Cell Transplant Program and clinical director of Hematologic Malignancies at Montefiore co-authored the NEJM paper and treated six of the patients in the CAR-T therapy trial. Montefiore is now an approved center of excellence for CART therapy and is one of the few such centers in the US to offer this treatment to patients with lymphoma and leukemia.

Tuesday, January 09, 2018

Following mRNA from Birth to Death—Messenger RNA (mRNA) is crucial for converting genetic information into proteins and for regulating gene expression. The life of an mRNA molecule in cells—including its transcription in the nucleus and translation of its message into a protein—can be followed using the MS2 imaging system, developed by Robert Singer, Ph.D., Evelina Tutucci Ph.D., and Maria Vera Ph.D., at Einstein. In a paper published online on November 13 in Nature Methods, Dr. Singer and colleagues describe re-engineering the MS2 system so that it can now follow mRNAs all the way from birth to degradation. Emerging evidence indicates that this final stage in the life of mRNA molecules is highly regulated: The need for rapid activation and de-activation of specific genes requires that mRNA production and degradation be coordinated so that protein levels can be tightly controlled. Dr. Singer is professor and co-chair of anatomy & structural biology, as well as co-director of the Gruss-Lipper Biophotonics Center and of the Integrated Imaging Program. He also is professor in the Dominick P. Purpura Department of Neuroscience and of cell biology and the Harold and Muriel Block Chair in anatomy & structural biology.

Tuesday, January 02, 2018

New Strategy for Treating Leukemia—Acute myeloid leukemia (AML) is a devastating and hard-to-treat cancer of the blood and bone marrow. Defects in the transcription factor PU.1 are known to play a role in causing AML. But until now, all efforts at targeting AML caused by defective PU.1 have failed. Transcription factors—proteins that regulate gene expression by binding to DNA—have historically been very hard to target pharmacologically. Ulrich G. Steidl, M.D., Ph.D. and colleagues reported last October in the Journal of Clinical Investigation that they inhibited PU.1 through a novel strategy of targeting the minor groove—a part of the DNA double helix to which transcription factors don’t usually bind. The researchers’ first-in-class PU.1 inhibitors successfully halted overactive cell division in blood samples from AML patients, suggesting that targeting PU.1 could be a successful strategy for treating the disease. Dr. Steidl is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research, director of the Stem Cell Isolation and Xenotransplantation Facility and a professor of cell biology and of medicine at Einstein and associate chair for translational research in oncology at Montefiore.

Friday, December 29, 2017

Peripatetic mRNAs—In a study published online on October 24 in the Proceedings of the National Academy of Sciences, Einstein researchers, led by Robert Singer, Ph.D., describe the mechanism by which messenger RNA (mRNA) molecules travel from one cell to another: via extensions called membrane nanotubes that form when cells are in direct contact with each other. mRNA transfer from cell to cell could influence processes such as tissue development and cellular response to stress. Dr. Singer is professor and co-chair of anatomy & structural biology, as well as co-director of the Gruss-Lipper Biophotonics Center and of the Integrated Imaging Program. He also is professor in the Dominick P. Purpura Department of Neuroscience and of cell biology and the Harold and Muriel Block Chair in anatomy & structural biology. Gal Haimovich, the study’s lead author, was a Gruss Lipper Postdoctoral Fellow at Einstein when the research was conducted.

Wednesday, December 27, 2017

Hepatitis C Virus Can Infect Pancreatic Islet Cells—Up to 10 percent of patients with hepatitis C also have type 2 diabetes, but the association between the virus infection and diabetes is not well understood. A pilot study conducted by Yaron Tomer, M.D., and colleagues and published online on December 20 in Virology Journal found that HCV not only infects liver cells but can also infect in vitro pancreatic islet cells, including the cells that secrete insulin. The findings suggest that HCV infection of pancreatic islet cells alters the expression of pro-inflammatory cytokine proteins, which may contribute to the insulin deficiency that can lead to diabetes. Further research is needed to show whether curing hepatitis C can also improve or reverse type 2 diabetes. Dr. Tomer is the Anita and Jack Saltz Chair in Diabetes Research,  professor and chair of  medicine and is professor of microbiology & immunology.

Friday, December 22, 2017

A Window into Cancer's Spread—In a paper published November 28 online in Nature Methods, researchers describe a novel technique for permanently implanting a window into the chest wall of mice. Minimally invasive surgery allows mice to recover from surgery and anesthesia, breathe independently and live with the window for several weeks. Researchers can now repeatedly image the vasculature of the intact lung at single-cell resolution—converting the lung from sealed-off tissue observable only via fixed sections on slides to an accessible living organ. The windows should provide insight into many lung problems including asthma, acute sickle cell crisis and lung cancer. Using this new window the earliest processes involved in metastasis to the lung have been observed for the first time: tumor cells arriving in the lung, exiting from blood vessels (extravasation) and growing within the lung. This capability could revolutionize our understanding of cancer metastasis and its treatment. The study’s senior author is John Condeelis, Ph.D., professor and co-chair of anatomy and structural biology, and co-director of the Gruss Lipper Biophotonics Center and the Integrated Imaging Program. Co-first authors are David Entenberg, M.Sc., senior associate in anatomy & structural biology; and surgery resident Sonia Voiculescu, M.D.

Tuesday, December 19, 2017

Seeking Rejuvenation Factors in Blood—For the last few decades, scientists studying aging have carried out heterochronic parabiosis—surgically creating a circulatory system shared by two animals of different ages. Those studies indicate that the blood of young animals contains rejuvenation factors (known as anti-geronic factors) that restore youthful characteristics to cells and tissues of older animals. Identifying these factors and finding how they exert their effects could lead to drugs for warding off age-associated diseases in people. The National Institute on Aging has awarded Yousin Suh, Ph.D., a four-year, $1.94 million grant to identify circulating anti-geronic factors using cultured cells and animal models of heterochronic parabiosis. Dr. Suh is professor of genetics, of ophthalmology & visual sciences, and of medicine.(1R01AG057433)

Monday, December 18, 2017

Solving a Key Enzyme's Structure—The enzyme cytochrome c oxidase (CcO) plays a key role in enabling the mitochondria in cells to generate energy: It propels protons across the inner mitochondrial membrane so that molecules of ATP can be synthesized. But how CcO performs that function isn’t known. To help answer that question, the National Institute of General Medical Sciences has awarded Denis Rousseau, Ph.D. and Syun-Ru Yeh, Ph.D., a four-year, $2 million grant to determine CcO’s crystal structure. To do so, serial femtosecond crystallography with an X-ray free electron laser will be used, which should for the first time reveal the structure of the enzyme’s catalytic intermediates under near-physiological conditions. The findings could lead to therapies for some of the 40 or so diseases caused by defective mitochondrial function. Drs. Rousseau and Yeh are professors of physiology & biophysics at Einstein and Dr. Rousseau is chair of the department.

Thursday, December 14, 2017

Clues to Alphavirus Exit Strategy—Chikungunya is a mosquito-borne alphavirus that infects millions of people worldwide each year. Understanding how alphaviruses enter and exit the host cells could lead to treatments and vaccines. In a study published November 7 in mBio, Einstein researchers describe a mechanism required for membrane budding, the process by which the virus creates new infectious particles near the membranes of infected cells. They found that a region of the virus’s membrane proteins called the E2 D-loop plays a major role in the interaction of the membrane proteins, E1 and E2. The contact between the E2 D-loop and E1 drives the formation of the membrane structure required for alphavirus budding. The study’s senior author is Margaret Kielian, Ph.D., who holds the Samuel H. Golding Chair in Microbiology and is a professor of cell biology at Einstein; the first author is M.D./Ph.D. student Emily Byrd.

Tuesday, December 12, 2017