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Confirming Age-Related Mutations

Confirming Age-Related Mutations—Mutations that accumulate with age in somatic (non-reproductive) cells are thought to contribute to aging and cancer. But testing whether somatic mutations do increase with age has been difficult, since mutations differ from cell to cell. In a study published online on April 16 in Proceedings of the National Academy of Sciences, Jan Vijg, Ph.D., Lei Zhang, Ph.D., and Xiao Dong, Ph.D., looked for somatic mutations in human B lymphocytes across a wide age span—from newborns to centenarians. They used a recently developed method for sequencing the entire genomes of single cells. B lymphocytes play key roles in the immune response, and immune deficiency is a well-known hallmark of aging. The number of mutations--many in the functional part of the B cell genome--increased from hundreds in newborns to more than 3,000 in centenarians. The study is the first to show that the number of mutations accumulating in normal human somatic cells is high enough to cause adverse effects. Dr. Vijg is professor and chair of genetics, and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein. Drs. Zhang and Dong are postdoctoral research fellows in the Vijg lab.

Tuesday, May 21, 2019
Targeting Aging to Prevent Alzheimer's

Targeting Aging to Prevent Alzheimer's—When somatotropic signaling (i.e., signaling that stimulates body growth) is diminished, the result is delayed aging and longer lifespans in both model organisms and people. Centenarians, in fact, have several mutations that weaken somatotropic signaling. Sofiya Milman, M.D., has received a five-year, $4 million grant from the National Institute on Aging to identify genes and gene functions that inhibit growth-related signaling. Dr. Milman and her colleagues will study participants in Einstein’s LonGenity study—a cohort of 1,400 older adults, half of whom are the offspring of centenarians. The researchers will investigate the role that somatotropic signaling plays in the brains of aging humans. They hope to identify mechanisms that confer cognitive resilience by delaying aging—findings that could lead to therapies that protect against Alzheimer’s and other diseases associated with aging. Dr. Milman is an associate professor of medicine and of genetics at Einstein and an attending physician in medicine at Montefiore. (1R01AG061155-01A1)

Friday, May 17, 2019
Preventing HIV Infection Among High-Risk Women

Preventing HIV Infection Among High-Risk Women—Imbalances among microbes in the vagina, collectively known as the vaginal microbiome, can increase a woman’s risk for contracting HIV and may affect how well pre-exposure prophylaxis (PrEP) works. The Eunice Kennedy Shriver National Institute of Child Health & Human Development has awarded a five-year, $2.6 million grant to Betsy C. Herold, M.D., to study how the vaginal microbiome affects PrEP efficacy. The findings could help in developing better preventive measures for young women at high risk for HIV infection. The study will identify which of several new PrEP formulas remain effective when used by women with different microbiomes under real-world conditions. Dr. Herold is the Harold and Muriel Block Chair in Pediatrics, director of the Translational Prevention Research Center, professor and chief of the division of pediatric infectious diseases, and vice chair for research in the department of pediatrics. Her co-investigators are Marla J. Keller, M.D., Tao Wang, M.D., Ph.D. (both at Einstein) and Greg Buck, Ph.D., of Virginia Commonwealth University School of Medicine. (1R01HD098977-01)

Wednesday, May 15, 2019
Finding a New Viral Cause of Cervical Cancer

Finding a New Viral Cause of Cervical Cancer—Virtually all cases of cervical cancer are caused by high-risk types of human papillomavirus (HPV).  In a study published online on April 9 in International Journal of Cancer, Ana Gradissimo, Ph.D., and Robert D. Burk, M.D., provide the first molecular evidence showing that HPV73—now classified as “possibly oncogenic”—definitely can cause cervical cancer. The findings are a matter of public health concern for two key reasons: HPV screening tests aimed at preventing cervical cancer don’t test for HPV73; and since current HPV vaccines don’t include HPV73, they won’t be able to prevent HPV73--related cervical disease.  The researchers recommend that the International Agency for Research on Cancer upgrade HVP73’s classification from possibly carcinogenic to carcinogenic and that public health officials monitor of HPV73’s prevalence in cervical cancer across populations.  Dr. Burk is professor of pediatrics, of microbiology & immunology, of epidemiology & public health, of obstetrics & gynecology and women’s health, and an attending physician at Montefiore. Dr. Gradissimo is a postdoctoral research fellow at Einstein.

Thursday, May 09, 2019
Metabolomics and Diabetes

Metabolomics and Diabetes—Type 2 diabetes (T2D) is a major public health challenge, but its causes still aren’t fully understood. Analysis of metabolites (metabolomics) in the blood can reveal subtle changes in metabolic pathways that that may precede T2D’s onset. Qibin Qi, Ph.D., has received a 4-year, $2.2 million grant from National Institute of Diabetes and Digestive and Kidney Diseases to conduct a large-scale study linking plasma metabolites with diet, lifestyle, and gut microbiota in relation to T2D in both Hispanics and non-Hispanics. The research, involving both individuals with T2D and matched controls, may provide new insight into the role of diet, lifestyle, and gut microbiota in the development of T2D and could help identify novel modifiable factors to prevent the development of T2D. Dr. Qi is associate professor and associate director of the Center for Population Cohorts in the department of epidemiology & population health at Einstein. (1R01DK119268-01)

Tuesday, May 07, 2019
Finding the Root Causes of Blood Cancers

Finding the Root Causes of Blood Cancers—The enzyme TET2 play a key role in causing blood cancers, but how it become activated wasn’t known. In a study published online on April 3 in Cancer Discovery, co-senior authors Amit K. Verma, M.B.B.S., and Amittha Wickrema, Ph.D., of the University of Chicago report that the enzyme kinase JAK2 activates TET2 through phosphorylation. The researchers also discovered that JAK2V617F, a JAK2 mutation seen in blood cancers, is associated with increased TET2 activity, increased hydroxymethylation (an epigenetic alteration commonly found in blood cancers) and the overexpression of oncogenic genes.  These findings indicate that the phosphorylation and consequent activation of TET2, mediated byJAK2V617F, leads to epigenetic and oncogenic changes that may underlie the development of blood cancers. 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.

Wednesday, May 01, 2019
Visualizing How Neurons Develop in the Fruit Fly Eye

Visualizing How Neurons Develop in the Fruit Fly Eye—Proneural bHLH proteins are transcription factors that regulate the development of key nerve cells needed for vision (including rod and cone photoreceptors and corneal nerves) and for maintaining the health of the eye. It is known that the ability of bHLH transcription factors to bind to DNA is antagonized by other proteins known as the ID-class of HLH proteins. Nicholas Baker, Ph.D., has received a four-year, $1.3 million grant from the National Institutes of Health to better understand the function of this network of interacting proteins. The research is expected to reveal new regulators of neural development that are important in the eye. It may also lead to new strategies for maintaining and regenerating healthy eye function. Dr. Baker is professor of genetics, of developmental & molecular biology and of ophthalmology & visual sciences and is also the Harold and Muriel Block Chair in Genetics and director of the division of molecular genetics at Einstein. (1R01EY028990-01A1)

Tuesday, April 23, 2019
Treating Hepatitis C-Infected Injection Drug Users

Treating Hepatitis C-Infected Injection Drug Users—Hepatitis C virus (HCV) leads to more than 15,000 deaths annually in the U.S. Antiviral drugs capable of curing HCV infection were introduced several years ago. Yet people who inject drugs—who are at the heart of the country’s HCV epidemic—are rarely offered anti-HCV therapy, due to concerns over poor medication adherence. In a study evaluating whether intensive treatment interventions improves adherence researchers including first author, Matthew Akiyama, M.D., M.Sc., and senior author and principal investigator Alain Litwin, M.D., M.P.H., of Clemson University and Prisma Health randomly assigned 150 HCV-positive people participating in an opioid treatment program to one of three antiviral treatment models: medication administered in directly observed therapy (DOT); medication in a group-therapy (GT) setting, or self-administered individual treatment (SIT), the control group. The findings were published online on April 9 in the Annals of Internal Medicine. High HCV cure rates were observed in all three groups: 98% for DOT patients, 94% for GT patients, and 90% for SIT patients. The findings indicate that HCV therapy should not be withheld for injection drug users, particularly those undergoing treatment for opioid use disorder.  Dr. Akiyama is an assistant professor of medicine at Einstein and attending physician in infectious diseases and in internal medicine at Montefiore.

Friday, April 19, 2019
Unraveling the B-Cell Response Against TB

Unraveling the B-Cell Response Against TB—The bacterial species Mycobacterium tuberculosis (Mtb) caused 1.3 million tuberculosis (TB)-related deaths in 2017. Infection triggers a well-studied T-cell response against Mtb, but the B-cell immune response leading to antibody production is not clearly  understood. John Chan, M.D., received a five-year, $3.5 million grant from the National Institute of Allergy and Infectious Diseases to investigate the role of IgM antibodies in the host immune response to Mtb. Dr. Chan and colleagues will use mouse and ex vivo macaque TB models to better understand the role, importance, and regulation of IgM in immune regulation during the early and chronic stages of TB.  Findings from this study may lead to novel therapies against TB infection. Dr. Chan is professor of medicine and of microbiology & immunology at Einstein and an attending physician in infectious diseases at Montefiore. (1R01AI139297-01A1)

Monday, April 08, 2019
Severing the Brain Injury-Epilepsy Link

Severing the Brain Injury-Epilepsy Link—Traumatic brain injury (TBI) can cause epilepsy, which involves recurring seizures. The more severe the TBI, the greater the chance that epilepsy will develop. Two years ago, Solomon Moshé, M.D., and Aristea Galanopoulou, M.D., Ph.D., received a NIH major grant to develop better ways to prevent epilepsy following TBI. They have now co-edited a supplement to the March 2019 issue of Neurobiology of Disease on preventing TBI-caused epilepsy, including findings from their research. The supplement describes the scope of the TBI/epilepsy problem; steps to identify biomarkers in humans and in animal models; and how to use those biomarkers to design preventive treatments in the laboratory that might work in humans. Drs. Moshé and Galanopoulou are both professors in the Saul R. Korey Department of Neurology, and the Dominick P. Purpura Department of Neuroscience. Dr. Moshé is also the director of the Isabelle Rapin division of child neurology and clinical neurophysiology at Einstein and Montefiore.

Tuesday, March 26, 2019
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