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Diagnosing Lung Cancer Noninvasively

Diagnosing Lung Cancer Noninvasively—DNA mutations cause cancer and are signs that genome sequence integrity has been lost. The National Institute of Environmental Health Sciences has awarded Jan Vijg, Ph.D., and Simon Spivack, M.D., M.P.H., a five-year, $3.3 million grant to assess genome integrity in normal human cells. The researchers will use a sequencing-based assay they recently developed for detecting most if not all types of mutations using bulk DNA and single cell-based approaches. They will use the assay to measure the mutagenic effects of tobacco smoke, to see if mutations in blood or buccal (cheek) mucosal cells reflect mutations that are found in lungs of smokers and nonsmokers, and are associated with lung cancer. The work could, for the first time, allow someone’s risk for lung cancer to be assessed noninvasively, using sequencing-based assays on blood or buccal cells. Dr. Vijg is professor and chair of genetics, and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein. Dr. Spivack is professor of medicine, of epidemiology and of genetics at Einstein, and chief of pulmonary medicine at Einstein-Montefiore.

Thursday, November 08, 2018
New Protein Engineering Tool

New Protein Engineering Tool—Split inteins arise from gene sequences embedded and separated within a host gene. Upon protein expression, individual intein fragments associate with each other and facilitate the intact host protein’s assembly in a process called protein splicing. Their efficient protein splicing ability makes inteins useful in protein engineering. In a study published article online on August 29 in the Journal of the American Chemical Society, David Cowburn, Ph.D., in collaboration with the laboratory of professor Tom Muir (Princeton University), describe a new group of atypically split inteins—split internally at an unusual location. To characterize atypical intein assembly and chemistry, they engineered a novel atypical intein with superior robustness and stability, called Cat, and demonstrated that this intein shows association mediated by hydrophobic interactions and distinct host sequence dependence properties. Cat is the fastest atypical split intein to date and should find immediate use in various technical applications. Dr. Cowburn is professor of biochemistry and of physiology and biophysics at Einstein.

Monday, November 05, 2018
Investigating Proteins that Regulate Chromosomes

Investigating Proteins that Regulate Chromosomes—The chromosomes of eukaryotic organisms are made of chromatin, a complex of macromolecules consisting of DNA, RNA and proteins. Dmitry Fyodorov, Ph.D., and Arthur Skoultchi, Ph.D., have received a four-year, $1.5 million grant from the National Institute of General Medical Sciences to study the functions of H1 linker histones, a major family of chromatin proteins. Using the fruit fly Drosophila as a model organism, the researchers will investigate how H1 linker histones regulate the structure and activity of chromosomes. H1 histones are essential for normal development, and mutations in H1 histone genes are associated with several human diseases including cancer. Dr. Skoultchi is professor and chair of cell biology and is the Judith and Burton P. Resnick Chair in Cell Biology at Einstein. Dr. Fyodorov is an associate professor of cell biology at Einstein. (1 R01 GM129244-01)

Monday, October 15, 2018
Interrupting the Formation of Blood Cancers

Interrupting the Formation of Blood Cancers—Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are usually incurable blood cancers that are highly associated with aging. They result from hematopoietic (blood-forming) stem cells (HSCs) that have acquired function-changing molecular alterations. To develop curative therapies, scientists must distinguish between alterations compatible with healthy, aged HSC function and alterations that cause HSCs to turn cancerous. The National Cancer Institute has awarded Britta Will, Ph.D., a five-year, $1.9 million grant to investigate the role played by the aging-related decline of chaperone-mediated autophagy (one of the systems cells use to digest and recycle waste products, particularly under stress conditions) in blood-cancer stem cell formation. Findings from this research could yield fundamentally new therapies for patients with MDS/AML, as well as other stem cell-derived cancers. Dr. Will is an assistant professor of medicine and of cell biology at Einstein. (1 R01 CA230756-01)

Monday, October 08, 2018
HPV and Cervical Cancer in HIV-Positive Women

HPV and Cervical Cancer in HIV-Positive Women—Women who are HIV-positive have a high risk of becoming infected with human papillomavirus (HPV) and later developing cervical cancer. A five-year, $3.2 million National Cancer Institute grant will allow Howard Strickler, M.D., and Robert Burk, M.D., to use sophisticated gene sequencing techniques to study whether the risk of cervical precancer in HIV-positive women is largely due previously acquired sexually transmitted HPV that has become reactivated, which commonly happens in immune suppressed women with HIV. They will also study how the methylation of HPV DNA affects precancer risk and how the cervovaginal microbiome influences HPV methylation and cervical precancer in these women. Dr. Strickler is professor of epidemiology & population health and the Harold and Muriel Block Chair in Epidemiology & Population Health at Einstein. Dr. Burk is professor of pediatrics, of microbiology & immunology, of obstetrics & gynecology and women’s health and of epidemiology & population health at Einstein and an attending physician at Montefiore Health System. (1R01CA230331-01)

Friday, October 05, 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
Teaching Old Brains New Tricks

Teaching Old Brains New Tricks—The brain’s prefrontal cortex not only manages cognition—our ability to think—but influences walking as well. In a study published online on August 13 in the Journal of Gerontology: Medical Sciences, Roee Holtzer, Ph.D., and colleagues showed for the first time that training adults 65 and older to execute cognitive tasks while walking improves prefrontal cortex activation efficiency. Participants walked under two conditions: walking without doing a cognitive task (Single-task-walk) and walking while performing a cognitive task (Dual-task-walk).  During both walking conditions, neural activity in the prefrontal cortex was measured using functional-Near-Infrared Spectroscopy. The researchers found that after just one session dual-task walking performance improved and was coupled with enhanced activation efficiency in the prefrontal cortex. In contrast, performance and neural activity associated with single task walking—which is more automatic and less dependent on the prefrontal cortex—did not change after practice. The findings show that aging brains can be made sharper relatively quickly, which may help in reducing falls and other adverse outcomes among older adults. Dr. Holtzer is a professor in the Saul R. Korey Department of Neurology at Einstein.

Friday, September 28, 2018
Detecting Combat Brain Injury with DTI

Detecting Combat Brain Injury with DTI—Neuroimaging identifies traumatic brain injury in combat veterans, but questions have been raised whether differences between veterans and controls might skew results. To address this problem, diffusion tensor imaging (DTI), which shows microscopic changes in white matter, was performed for the first time on veterans matched with controls of very similar backgrounds. Michael L. Lipton, M.D., Ph.D., compared DTI images from 16 blast-exposed combat veterans to images of 18 of the veterans’ siblings and first cousins, who grew up in the same community but were not exposed to combat. Abnormalities consistent with post-traumatic effects in veterans were not seen in the closely matched controls. The findings, published online on August 17 in Neuroradiology, further support the usefulness of DTI to accurately detect brain abnormalities resulting from trauma. Dr. Lipton is professor of radiology and of psychiatry and behavioral sciences at Einstein and medical director of MRI services at Montefiore.

Thursday, September 20, 2018
Discovering HIV-1's Infection Pathway

Discovering HIV-1's Infection Pathway—HIV-1, the virus that causes AIDS, invades non-dividing immune cells. The virus persists inside those cells, frustrating efforts to eradicate infections. Until now, HIV’1’s mechanism for infecting non-dividing cells has been a mystery. In a new study published online on July 11 in the  Journal of Virology, Felipe Diaz-Griffero, Ph.D., and colleagues showed that HIV-1 exploits a chain of two repeating amino acids on the surface of white cells to gain entry into the cells. The researchers pinpointed the region on the virus’s outer shell that interacts with the chain. They also identified two HIV-1 inhibitors that prevent the virus from using this entry pathway, which could serve as targets for new drugs to slow infection—especially for patients already resistant to current anti-retroviral treatments. Dr. Diaz-Griffero is professor of microbiology & immunology and the Elsie Wachtel Faculty Scholar at Einstein.

Friday, September 07, 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
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