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Bacteria Lowers PrEP Drugs' Effectiveness

Bacteria Lowers PrEP Drugs' Effectiveness—For the first time, researchers have shown how vaginal bacteria changes the effectiveness of two topical HIV prevention (PrEP) drugs: tenofovir gel and dapivirine ring. In a study published online on July 12 in JCI Insight, Betsy C. Herold, M.D. and colleagues demonstrated that some bacteria alter the ways cells are able to utilize the drugs. Among the finding were that Gardnerella vaginalis blocked the uptake of tenofovir by human cells and Lactobacillus crispatus competed with human cells for drug by actively transporting and metabolizing it. Higher drug levels overcame the negative effects. Importantly, other PrEP drugs were not impacted by microbiota and may be better candidates for future formulations. These findings likely contribute to the disappointing clinical trial results, where only partial protection has been observed, and highlight the importance of preclinical and early clinical evaluation of the impact of the vagina microenvironment on drug pharmacokinetics. 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.

Thursday, July 19, 2018
 
Discovering How a Parasite Forms Cysts

Discovering How a Parasite Forms Cysts—The single-cell parasite Toxoplasma gondii cause toxoplasmosis, one of the world’s most common parasitic diseases. It’s contracted by ingesting contaminated food or water, and symptoms can range from fever and body aches to serious complications such as brain damage and eye infections. Understanding how the parasite builds a protective cyst wall within its host may reveal how this infection persists causing chronic disease. With a five-year, $2 million grant from the National Institute of Allergy and Infectious Diseases, Louis Weiss, M.D., M.P.H., will use molecular, immunologic and genetic techniques to investigate how the cyst wall forms and develops. He and his colleagues will identify the cyst wall’s components and determine how they interact. The findings may reveal new strategies for suppressing the parasite’s reactivation following infection. Dr. Weiss is professor of pathology and of medicine at Einstein, and co-director of Einstein’s Global Health Center. He is also an attending physician in infectious diseases at Montefiore Health System. (1R01AI134753-01A1)

Friday, July 06, 2018
 
Immune Evasion in TB Infection

Immune Evasion in TB Infection—Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is notorious for its ability to evade 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 anti-TB 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 circumvent immune defenses. The researchers will use genetic and pharmacologic approaches and mouse TB models for their proposed studies. The results could lead to new interventions for better TB control, including effective vaccines. Dr. Chan is professor of medicine and of microbiology & immunology at Einstein and is an attending physician in infectious diseases at Montefiore Health System. Dr. Porcelli is professor and chair of microbiology & immunology, professor of medicine and the Murray and Evelyn Weinstock Chair in Microbiology and Immunology at Einstein. Dr. Berney is an assistant professor of microbiology & immunology at Einstein. (1R01AI137344-01)

Thursday, July 05, 2018
 
Tracking Memories via mRNA

Tracking Memories via mRNA—“How do memories form?” is a fundamental unanswered question in biology. Researchers in the lab of Robert Singer, Ph.D., have generated a novel mouse model to address that question. In a study published online on June 20 in Science Advances, Dr. Singer and colleagues describe directly visualizing the dynamics of memory-associated messenger RNA in living neurons in response to neuronal activity in real time. A key finding made by Sulagna Das, Ph.D., a postdoctoral researcher in the lab, was that transcription cycles continue even after the initial neuron stimulation is removed. Use of this model system could change our understanding of how memories form and provide insight into neurodegeneration, stroke and mental illness. Dr. Singer is professor and co-chair of anatomy & structural biology, as well as co-director of the Gruss-Lipper Biophotonics Center and of the Integrated Imaging Program at Einstein. He also is professor in the Dominick P. Purpura Department of Neuroscience and of cell biology and the Harold and Muriel Block Chair in anatomy & structural biology at Einstein.

Wednesday, June 27, 2018
 
Autophagy Governs Circadian Clock and Blood Glucose Levels

Autophagy Governs Circadian Clock and Blood Glucose Levels—Our circadian clocks are centered in the brain and control key physiological processes—sleep, body temperature, organ function, and metabolic activities such as maintaining blood glucose levels. Disrupting the clock can potentially lead to diabetes and other metabolic diseases. Read full story.

Thursday, June 21, 2018
 
Drug Extends Lifespan and Healthspan in Mice

Drug Extends Lifespan and Healthspan in Mice—Throughout the animal kingdom, smaller animals usually live longer than larger ones of the same species. A key reason for this longevity boost is that smaller animals typically have reduced activity of key growth factors, including insulin-like growth factor-1 (IGF-1). Signaling of this pathway is triggered when IGF-1 circulating in blood binds to IGF-1 receptors found on many types of cells in the body, resulting in growth-promoting effects on those cells. Read full story.

Tuesday, June 19, 2018
 
Using Ultrasound to Treat Cancer

Using Ultrasound to Treat Cancer—Tumors evade the immune system by inducing T cell tolerance, a state where T cells don’t recognize tumors as foreign and therefore don’t attack them. Thus, a major challenge for cancer immunotherapy is overcoming T cell tolerance. The National Cancer Institute awarded Fernando Macian-Juan, M.D., Ph.D., and Chandan Guha, M.B.B.S., Ph.D., a five-year, $1.9 million grant to study low-intensity focused ultrasound (LOFU) as a way to activate the immune system to combat tumors.  In previous work involving melanoma, the researchers found that LOFU reverses T cell tolerance and activates anti-tumor T cell responses. The team will test LOFU in a mouse model of melanoma to better understand how LOFU works and to test its effectiveness and safety when combined with immunotherapies. Dr. Macian-Juan is professor of pathology at Einstein. Dr. Guha is professor and vice chair of radiation oncology at Einstein and Montefiore Health System. Dr. Guha is also professor of urology and of pathology at Einstein and is director of Einstein’s Institute for Onco-physics. (1R01CA226861-01)

Monday, June 04, 2018
 
Making Vaccines More Effective

Making Vaccines More Effective—After vaccination or infection, antibody-secreting cells (ASCs) are responsible for maintaining antibody production. Most useful of all are long-lived ASCs, which are found in the bone marrow and churn out antibodies over a person’s lifetime. One way to bolster ASCs’ antibody output would be to increase the number of long-lived ASCs. The NIH has awarded David Fooksman, Ph.D., a five-year, $2 million grant to find ways of increasing levels of long-lived ASCs following Dr. Fooksman and colleagues have shown that cell membranes of long-lasting ASCs express high levels of a proteoglycan called CD138. They believe that those high levels of CD138 give long-lasting ASCs a survival advantage over new ASCs, and they will use the NIH grant to test that theory. The researchers will also explore ways of increasing CD138 levels as a way to enhance the survival of long-lasting ASCs and improve long-term immunity. Dr. Fooksman is an assistant professor of pathology and of microbiology & immunology at Einstein. (1R01HL141491-01)

Thursday, May 31, 2018
 
How a Motor Protein Breaks its Tracks

How a Motor Protein Breaks its Tracks—Kinesins are motor proteins found in eukaryotic cells that walk along microtubules. Members of a subfamily of kinesins, the kinesin-13s, do something different: they shorten microtubules to reshape the cytoskeleton during mitosis and other cellular processes. To identify the mechanism behind this atypical kinesin activity, Hernando Sosa, Ph.D., and his colleagues Mathieu Benoit and Ana Asenjo used cryo-electron microscopy to determine the structure of kinesin-13s bound to microtubules. The findings, published online on April 25 in Nature Communications, reveal for the first time how kinesin 13s are adapted to shorten microtubules rather than walking along them. The findings also suggest targets for modulating kinesin activity and microtubule dynamics that could lead to new anti-cancer drugs. Dr. Sosa is an associate professor of physiology & biophysics at Einstein.

Tuesday, May 29, 2018
 
Near-Infrared Biosensor for Multiplex Imaging

Near-Infrared Biosensor for Multiplex Imaging—A family of enzymes called GTPases regulates cell organization and movement and controls the development of cancer and autoimmune diseases. Visualizing how GTPases function can provide insights into how they influence health and disease. In a study published online on April 23 in Nature Chemical Biology, Louis Hodgson, Ph.D., and Vladislav Verkhusha, Ph.D., engineered a new monomeric near-infrared fluorescent protein that absorbs and emits light in the region of the electromagnetic spectrum in which light can pass through animal tissues. By attaching the near-infrared fluorescent protein to a biological sensing domain that detects GTPase activities, the researchers have engineered the first near-infrared biosensor. The biosensor allowed researchers for the first time to simultaneously visualize multiple GTPase activities using near-infrared light and perform optogenetic activation of GTPases in single cells, providing an unprecedented view of cellular processes. Biosensors based on the near-infrared fluorescent protein could also allow for deep-tissue imaging in living animals. Dr. Hodgson is an associate professor, and Dr. Verkhusha is a professor, both of anatomy and structural biology and the Gruss Lipper Biophotonics Center at Einstein.

Thursday, May 24, 2018
 
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