Research Roundup

Search Research Roundup

Keywords:   

Looking at the Origins of Leukemia

Looking at the Origins of Leukemia—Myelodysplastic syndromes (MDS) are precancerous blood conditions that frequently progress to acute myeloid leukemia (AML). MDS and AML are both characterized by the presence of blast cells (defective blood-forming stem cells), with higher levels present in AML. Both conditions also originate from clones (i.e., single defective stem cells). In a study published online on December 3 in Nature Medicine, Amit K. Verma, M.B.B.S., and Ulrich Steidl M.D., Ph.D., examined how stem cells evolve into MDS and AML. Jiahao Chen, Ph.D., a researcher in Dr. Steidl’s laboratory, used single-cell sequencing to compare the MDS and AML stem cells of seven patients whose MDS had progressed to AML. The study revealed that stem cell subclones not detectable in MDS blasts became dominant upon progression to AML. These results suggest that the current bulk-cell approach to analyzing cancer-related stem cells may overlook pre-existing rare aberrant stem cells that drive disease progression and the transformation of MDS to AML. Dr. Verma is professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. 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.

Monday, December 10, 2018
 
Targeting Blood Cancers

Targeting Blood Cancers—Myelodysplastic Syndrome (MDS) often progresses to acute myeloid leukemia (AML). Both conditions are triggered by mutations in hematopoietic stem cells (HSCs), which generate all of a person’s blood cells. Mutated HSCs have so far proven resistant to treatment efforts. But in a new study, published online on  September 25 in  the Journal of Clinical Investigation, Aditi Shastri, M.B.B.S., Britta Will, Ph.D., Amit Verma M.B.B.S., Ulrich Steidl, M.D., Ph.D., and colleagues describe a new therapeutic strategy that might work. Dr. Verma and Dr. Steidl’s team had previously found that overexpression of the gene that codes for the transcription factor STAT3 is associated with MDS/AML cases that have a poor prognosis. In the study, they tested the experimental STAT3 inhibitor AZD9150 on MDS/AML stem cells from patients and on MDS/AML mouse models and found that AZD9150 successfully suppressed both STAT3 production and HSC proliferation. These promising preclinical results suggest that AZD9150 may be an effective MDS/AML therapy. Dr. Shastri is an assistant professor of medicine at Einstein and an attending physician in oncology at Montefiore Einstein Center for Cancer Care. Dr. Verma is professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. Dr. Will is an assistant professor of medicine and of cell biology at Einstein. 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 07, 2018
 
New Pathway for Fighting TB

New Pathway for Fighting TB—Drug-resistant strains of Mycobacterium tuberculosis (Mtb)—the bacterium that causes tuberculosis—are on the rise, and better treatments are needed. Previous research has shown that the isoniazid (INH) and vitamin C work by generating Mtb-killing molecules called reactive oxygen species (ROS), but how that happens wasn’t clear. In a study published on August 24 in the Proceedings of the National Academy of Sciences, Einstein researchers, Sangeeta Tiwari, Ph.D., and William R. Jacobs, Jr., Ph.D., found that INH and vitamin C disrupted a previously unsuspected arginine biosynthesis pathway. They found that disruption of the pathway produces ROS, which quickly sterilizes Mtb in vitro and in mice. Compounds that target enzymes in this pathway could be promising candidates for drugs to neutralize Mtb and prevent it from becoming resistant. Dr. Jacobs is the Leo and Julia Forchheimer Chair in Microbiology and Immunology and a professor of genetics and microbiology and immunology at Einstein. Dr. Tiwari is an associate in Dr. Jacobs’ lab at Einstein.

Wednesday, December 05, 2018
 
A Link Between Dietary Restriction and Aging

A Link Between Dietary Restriction and Aging—Findings from animal studies show that dietary restriction extends lifespan by slowing metabolic decline during aging. But how caloric reduction affects metabolites—the chemicals that result from metabolism—isn’t well understood. In a study published online on October 16 in Cell Reports, Derek M. Huffman, Ph.D., identified sarcosine as a chemical that may link dietary restriction and longevity. The researchers found that aging was associated with reduced levels of sarcosine in both rats and humans and that reductions in caloric consumption raised sarcosine levels. In addition, feeding sarcosine to elderly rats raised their sarcosine levels and boosted aspects of cellular to a more youthful state. The findings suggest that high levels of sarcosine may help maintain healthy metabolism and play an important role in extending lifespan. Dr. Huffman is an associate professor of molecular pharmacology and medicine, and is co-director of the Chronobiosis and Energetics/Metabolism of Aging Core (CEAC) at Einstein.

Tuesday, December 04, 2018
 
Cardiovascular Risk & HIV

Cardiovascular Risk & HIV—People living with HIV face an increased risk for cardiovascular disease (CVD). Antiretroviral drugs may contribute to CVD risk by raising cholesterol and triglyceride levels, and emerging evidence suggests that gut microbiota (GMB) may also play a role. The National Heart, Lung, and Blood Institute has awarded Qibin Qi, Ph.D., a five-year, $3.26 million grant to investigate the link between GMB and CVD in patients with HIV. The study focuses on how the GMB contributes to inflammation and immune activation, which are closely involved in CVD development. The findings should advance understanding of the disease mechanism that leads to HIV-related CVD and lead to strategies for preventing and treating CVD in HIV+ individuals. They may also have important public health implications, since it may be possible to reduce the risk for CVD in the general population by altering the GMB. Dr. Qi is an associate professor of epidemiology & population health at Einstein. (1R01HL140976)

Wednesday, November 28, 2018
 
Funding Extends Childhood Development Study

Funding Extends Childhood Development Study—Judy Aschner, M.D., received a five-year, $17 million grant from the National Institutes of Health to continue her Environmental Influences on Child Health Outcomes (ECHO) study, which initially launched in 2016. This new grant will expand the types of assessments and duration of longitudinal follow-up of former preterm infants to determine the factors that influence multiple health outcomes in children. Dr. Aschner’s research focuses on whether exposures to chemicals, metals and stress in the Neonatal Intensive Care Units may contribute to adverse health outcomes during early and middle childhood. Such chemicals include phthalates which are used in plastic medical equipment to make them more flexible and durable. The ECHO study will enroll 50,000 children across the United States and includes researchers from the Icahn School of Medicine at Mount Sinai, New York University, Columbia University, the New York State Psychiatric Institute, and the Feinstein Institute for Medical Research. Dr. Aschner is professor of pediatrics and obstetrics & gynecology and women's health at Einstein. (4UH3OD023320-03)

Wednesday, November 28, 2018
 
Uncovering Autoimmune Triggers

Uncovering Autoimmune Triggers—Dendritic cells, and the MHC II proteins they possess, play a crucial role in the body’s immune response. The MHC II bind peptides that dendritic cells then present to T cells. Depending on whether dendritic cells present “non-self” or “self” peptides, T cells will attack disease-causing microbes or cancer cells—or will cause autoimmune disease by attacking the body’s own tissues. Dendritic cells present different peptides depending on where the cells are located and whether resting or inflammatory conditions prevail. The National Institute of Allergy and Infectious Diseases has awarded Laura Santambrogio, M.D., Ph.D., a five-year, $4.1 million grant  to determine how dendritic cells behave depending on where they originate, and under resting and inflammatory conditions. The study’s goal is to determine how the sets of MHC II-presented peptides presented to T cells maintain tolerance to self or instead lead to autoimmune diseases such as type 1 diabetes. Dr. Santambrogio is professor of pathology and of microbiology & immunology at Einstein. (1R01AI137198-01A1)

Wednesday, November 28, 2018
 
Major Study of Epigenetics in Aging

Major Study of Epigenetics in Aging—The National Institute on Aging has awarded John M. Greally, D.Med., Ph.D., a five-year, $3.6 million grant to conduct the most comprehensive study to date of cellular epigenetic events in aging, focused on understanding why DNA methylation changes with age.  DNA methylation is a modification of DNA associated with changes in gene expression and has consistently been found to change with age, but the mechanism responsible for this epigenetic change remains unknown. Dr. Greally will focus on cellular epigenetic changes to T lymphocytes, which are white blood cells implicated in a number of age-related diseases. He will assess whether age-associated cellular epigenetic changes in T lymphocytes result from events such as reprogramming of cells or from other factors, including chronic exposure to stress hormones. The study will offer insights into how T lymphocytes are involved in age-related diseases. Dr. Greally is professor of genetics, of medicine and of pediatrics and is director of the Center for Epigenomics at Einstein and a clinical geneticist at Montefiore. (1R01AG057422-01A1)

Wednesday, November 28, 2018
 
Combatting Myelodysplastic Syndrome

Combatting Myelodysplastic Syndrome—In the bone marrow disorder Myelodysplastic Syndrome (MDS), hematopoietic (blood-forming) stem cells give rise to poorly formed or defective blood cells. The National Heart, Lung, and Blood Institute has awarded Amit K. Verma, M.B.B.S., and Ulrich G. Steidl, M.D., Ph.D., a five-year, $2.1 million grant to study the role played by the IL8/CXCR2 pathway in causing MDS and to see if  targeting that pathway can prevent the syndrome from developing.  The research could lead to new insights into treating MDS as well as blood cancers such as leukemia. Dr. Verma is a professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. 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. (1R01HL139487)

Wednesday, November 28, 2018
 
Boosting Blood Stem Cell Levels

Boosting Blood Stem Cell Levels—Eltrombopag is used for treating thrombocytopenia (abnormally low platelet levels in blood). The drug stimulates thrombopoietin receptors on immature hematopoietic progenitor cells in the bone marrow, leading to increased platelet production. In a study published online on September 12 in Science Translational Medicine, Britta Will, Ph.D., and Ulrich Steidl, M.D., Ph.D., describe a previously unknown molecular mechanism by which eltrombopag stimulates immature hematopoietic stem cells (HSC) to produce multilineage progenitor cells (i.e., capable of differentiating into many different types of blood cells. The authors found that eltrombopag chelates (binds) iron inside immature HSCs, leading to a transient reduction in intracellular iron levels which, in turn, stimulates stem cell self-renewal. This iron chelation-dependent mechanism of eltrombopag could be clinically important for preserving healthy levels of HSCs under stressful conditions such as chemotherapy or irradiation. Dr. Will is an assistant professor of medicine and of cell biology at Einstein. 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.

Thursday, November 15, 2018
 
First Page | Previous Page | Page of 44 | Next Page | Last Page