Research Roundup

Displaying results for "verma"Clear results

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
 
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
 
New Mutations Found in Rare Lymphoma/Leukemias

New Mutations Found in Rare Lymphoma/Leukemias—Adult T-cell leukemia/lymphoma (ATLL) is a rare but lethal cancer involving CD4 T-cells. ATLL is diagnosed most often in Japan and in the Caribbean, where the prognosis is worse for reasons that have been unclear. In a study published online on August 13 in Blood, Murali Janakiram, M.D., Amit K. Verma, M.B.B.S., B. Hilda Ye, Ph.D., and colleagues sequenced the genomes of cells from 30 Caribbean-American ATLL patients. Compared to Japanese patients, the Caribbean-American ATLL patients had a distinct genomic profile and a significantly higher frequency of epigenetic mutations, which is associated with a worse prognosis. The findings support a clinical trial testing whether Caribbean-American ATLL patients can benefit from DNA methyltransferase (DNMT) inhibitors, which can “correct” epigenetic mutations. Dr. Janakiram is an assistant professor of medicine. 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. Ye is an associate professor of cell biology at Einstein.

Wednesday, October 03, 2018
 
New Therapeutic Target for Melanomas

New Therapeutic Target for Melanomas—The invasiveness of cancers can be influenced by methylation and demethylation, epigenetic processes that alter the gene activity of cells without changing the genetic code. In a new study published online on July 25 in JCI Insight, Orsolya Giricz, Ph.D., and Amit K. Verma, M.B.B.S., analyzed a group of melanomas in which demethylation was coupled with overexpression of the CSF-1 receptor (CSF-1R), a protein that influences the activity of immune cells. This combination increased the growth and invasiveness of cancerous cells, especially when mutations involving the BRAF gene were present. Inhibiting the enzyme that activates CSF-1R or decreasing of CSF-1R’s expression slowed the melanomas’ advance. The findings reveal a previously unknown role for CSF-1R and suggest that it may be a good target for future melanoma therapies. 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. Giricz is an associate in Dr. Verma’s lab at Einstein.

Thursday, September 06, 2018
 
Epigenetic Markers in Pancreatic Cancer

Epigenetic Markers in Pancreatic Cancer—Cancers sometimes start when external influences cause changes in DNA. These so-called epigenetic modifications can alter gene expression—silencing a gene or over-activating it, for example. In a study featured on the cover of the November issue of Genome Research, Amit Verma, M.B.B.S., reported that pancreatic cancers have unique epigenetic modifications in a regulatory portion of DNA known as Hydroxymethylcytosine (5-hmC). He and his team found that 5-hmC was abnormally distributed at locations in the genome that regulate the expression of several genes associated with cancer, such as the gene BRD4. Dr. Verma is professor of oncology and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. The study’s first author is Sanchari Bhattacharyya, Ph.D., a research associate in the department of medicine.

Friday, December 22, 2017
 
Investigating the Cause of Myelodysplastic Syndrome

Investigating the Cause of Myelodysplastic Syndrome—Within the bone marrow, hematopoietic stem cells (HSCs) occupy niches that include stromal and mesenchymal cells. In myelodysplastic syndromes (MDS), which precede acute myeloid leukemia, HSCs behave abnormally, either because of genetic aberrations or epigenetic alterations to DNA that influence whether genes are expressed or not. In a study published online on July 6 in Cancer Research, collaborators found that novel epigenetic alterations in the bone marrow microenvironment are critically important in causing MDS to progress. More specifically, the presence of an abnormally high number of methyl groups (hypermethylation) in stromal cells activated the Wnt/β-catenin signaling pathway in MDS stem cells, stimulating their progression to leukemia. The findings suggest that drugs that inhibit DNA methyltransferases (DNMTs) that are used to treat MDS can exert their beneficial actions via influencing the surrounding cells of the bone marrow. Senior author, Amit Verma, M.B.B.S., is professor of medicine and of developmental and molecular biology. First author Tushar Bhagat, Ph.D., is a postdoctoral fellow in Dr. Verma’s lab at Einstein.

Tuesday, September 26, 2017
 
9/11 Firefighters and Early Cancer Detection

9/11 Firefighters and Early Cancer Detection—9/11 firefighters were exposed to known and suspected carcinogens in the dusts and gases at the World Trade Center site. An Einstein study of exposed firefighters found an increased incidence of certain cancers in those firefighters compared with non-exposed firefighters. Now, the Einstein researchers have received a three-year, $1.49 million grant from the Centers for Disease Control and Prevention to conduct an extensive follow-up study of 9/11 firefighters to look for blood cancers, which were among those cancers found to be more common among exposed firefighters. The researchers will check specifically for multiple myeloma, chronic lymphocytic leukemia, myelodysplastic syndromes, and their associated precursor conditions. Early detection of these cancers could prove crucial for successfully treating any cases found. The research team is led by Amit Verma, M.D., professor of medicine and of developmental and molecular biology at Einstein; David Prezant, M.D., professor of medicine at Einstein and attending physician at Montefiore; and Ola Landgren, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center. (1U01OH011475-01)

Friday, September 15, 2017
 
Insights into Blood Cancers

Insights into Blood Cancers—Myelodysplastic syndromes (MDS) are a spectrum of blood disorders that often progress to acute myeloid leukemia (AML). MDS and AML can prove fatal, and better treatment options are needed for both of them. The two conditions interfere with normal blood cell function in part by increasing inflammatory signals. One signal overexpressed in patients with MDS/AML triggers increased levels of the inflammatory cytokine Angiopoietin-1 (Angpt-1). Amit Verma M.D.. and colleagues have discovered a new inhibitor of the receptor Tie-2, which is the receptor on the surface of blood cells to which Angpt-1 binds. Using patient samples from the MDS Center of Excellence clinic at Montefiore, the researchers showed that inhibiting Tie-2 using the novel drug pexmetinib restricts leukemic cells from dividing and allows for normal blood cell differentiation, which typically doesn’t occur in MDS/AML. This drug is now being tested in clinical trials in MDS. The researchers report their results in the June issue of Cancer Research. Dr. Verma is professor of medicine and of developmental and molecular biology.

Thursday, July 21, 2016
 
Improving Ability to Diagnose Blood Cancers

Improving Ability to Diagnose Blood Cancers—The low blood counts that characterize the preleukemic disorder, myelodysplastic syndromes (MDS), occur because hematopoietic stem cells don’t fully differentiate into mature red cells but give rise to misshapen “dysplastic” cells. About 10 percent of MDS cases are caused by deletions in a region of chromosome 7 called 7q. In a study published in the November 2 issue of the Proceedings of the National Academy of Sciences, three research groups  led by Amit Verma, M.B.B.S.,  found that one of the missing 7q genes—DOCK4—is essential for forming the actin skeleton that maintains cell shape in healthy developing red blood cells. Reduced levels of DOCK4 lead to abnormally shaped red cells similar to those seen in MDS patients, the researchers found. Using multispectral flow cytometry, they developed a highly sensitive method for quantifying the extent of actin skeleton disruption. Their method can potentially diagnose MDS much sooner than the current diagnostic method in which pathologists examine cells removed via bone marrow biopsy. Dr. Verma is professor of medicine and of developmental & molecular biology. Other Einstein collaborators included Ulrich Steidl, M.D., Ph.D., professor of cell biology and of medicine, as well as graduate student Matthias Bartenstein and postdoc Tushar Bhagat, Ph.D.

Wednesday, November 18, 2015
 
First Page | Previous Page | Page of 2 | Next Page | Last Page