Uncovering Autoimmune Triggers

Dendritic cells and their MHC II proteins influence the body’s immune response. MHC II proteins bind peptides that dendritic cells 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 cause autoimmune disease by attacking the body’s own tissues. Dendritic cells present different peptides based 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. She will study how MHC II-presented peptides maintain immunologic tolerance or instead lead to autoimmune diseases such as type 1 diabetes. Dr. Santambrogio is a professor of pathology and of microbiology & immunology at Einstein.

Immune Evasion in Tuberculosis

The TB bacterium Mycobacterium tuberculosis is notorious for evading the body’s immune response. John Chan, M.D., Steven Porcelli, M.D., and Michael Berney, Ph.D., have found evidence that M. tuberculosis evades antituberculosis immunity by activating an immunosuppressive pathway controlled by the host enzyme indoleamine 2,3-dioxygenase (IDO).

The NIH has awarded them a five-year, $4 million grant to study how immunosuppression mediated by IDO activation helps M. tuberculosis stymie immune defenses in mice. The results could lead to better TB control measures.

Dr. Chan is a professor of medicine and of microbiology & immunology at Einstein and is an attending physician in infectious diseases at Montefiore. Dr. Porcelli is a professor and the chair of microbiology & immunology, a professor of medicine, and the Murray and Evelyne Weinstock Chair in Microbiology & Immunology at Einstein. Dr. Berney is an assistant professor of microbiology & immunology at Einstein.

Major Study of Epigenetics in Aging

The National Institute on Aging has awarded John M. Greally, Ph.D., D. Med., a five-year, $3.6 million grant to conduct the most comprehensive study to date of cellular epigenetic events in aging.

DNA methylation—a DNA modification that alters gene expression—has consistently been found to change with age, but the mechanism responsible for this epigenetic change remains unknown. Dr. Greally will study T lymphocytes, which are implicated in age-related diseases. He will assess whether age-associated epigenetic changes to T lymphocytes result from events such as the 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 a professor of genetics, of medicine, and of pediatrics, and the director of the Center for Epigenomics at Einstein and clinical geneticist at Montefiore.

Insights Into How Cells Target and Damage Tissue

Autoimmune diseases occur when immune cells aberrantly attack the body’s own cells or tissues. CD8 T cells strongly contribute to the pathology observed in type 1 diabetes and many other autoimmune diseases. Teresa DiLorenzo, Ph.D., and Steven Almo, Ph.D., have received a five-year, $3.5 million grant from the NIH to fill in knowledge gaps regarding the protein-protein interactions that occur when CD8 T cells target and damage tissue. The research may lead to more-effective ways to manipulate and harness the immune system to prevent disease and improve health.

Dr. DiLorenzo is a professor of microbiology & immunology and of medicine and the Diane Belfer, Cypres & Endelson Families Faculty Scholar in Diabetes Research at Einstein. Dr. Almo is a professor and the chair of biochemistry, a professor of physiology & biophysics, and the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology at Einstein.

Early Programming of Childhood Obesity

Studies show that children born underweight are at higher risk for obesity, cardiovascular disease, and type 2 diabetes. One cause of obesity may involve changes in the patterns of DNA methylation that influence gene expression.

The Eunice Kennedy Shriver National Institute of Child Health & Human Development has awarded Maureen Charron, Ph.D., and Mamta Fuloria, M.B.B.S., a five-year, $3.4 million grant to study DNA methylation of blood cells of intrauterine growth-restricted infants, who are at high risk for becoming obese.

Drs. Charron and Fuloria will examine the children’s blood at birth and at age 2 to determine how DNA methylation has affected their CD3+ T cells, immune cells that influence the development of obesity. Dr. Charron is a professor of biochemistry, of obstetrics & gynecology and women’s health, and of medicine at Einstein. Dr. Fuloria is an associate professor of pediatrics at Einstein.

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. The assay will measure the mutagenic effects of tobacco smoke on buccal (cheek) mucosal cells. The work could, for the first time, allow people’s lung-cancer risk to be assessed noninvasively.

Dr. Vijg is a professor and the chair of genetics and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein. Dr. Spivack is a professor of medicine, of epidemiology & population health, and of genetics at Einstein, and the chief of pulmonary medicine at Einstein and Montefiore.

Gut Microbiota, Cardiovascular Risk, and HIV

People living with HIV face an increased risk of developing cardiovascular disease (CVD). Emerging evidence suggests that gut microbiota (GMB) may contribute to CVD risk.

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 GMB contribute to inflammation and immune activation, which are closely involved with CVD development.

The findings should advance our understanding of the disease mechanism that leads to HIV-related CVD and also reveal strategies for preventing and treating CVD in HIV-positive individuals. They may also have important public health implications, since it may be possible to reduce the risk of CVD in the general population by altering GMB.

Dr. Qi is an associate professor of epidemiology & population health at Einstein.

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 to previously acquired sexually transmitted HPV that has become reactivated (common among immune-suppressed women with HIV) and whether the methylation of HPV DNA affects precancer risk.

Dr. Strickler is a professor and the division head of epidemiology and the Harold and Muriel Block Chair in Epidemiology & Population Health at Einstein. Dr. Burk is a 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.