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Mapping a Viral Infection Highway

Mapping a Viral Infection Highway—Herpes simplex virus 1 (HSV-1), the virus responsible for oral herpes, infects about half the world’s population. HSV-1 infects neurons of cranial nerves—especially the trigeminal ganglion nerves responsible for facial sensation and motor function. The viruses travel up the axons of these nerves to multiply in their nerve bodies. Newly-made HSV-1 then travel back down the axon to be released into the synapse. HSV-1 is thought to hijack the cell’s microtubule network to travel back and forth in the axon, but how it does so is unclear. The National Institute of Allergy and Infectious Diseases has awarded Duncan W. Wilson, Ph.D., a five-year, $3.5 million grant to study UL36p, an HSV-1 protein that appears to attach the virus to microtubules via the motor proteins kinesin and dynein. Using microscopic imaging and biochemical techniques, Dr. Wilson will explore how UL36p helps HSV-1 move through axons during infection. Dr. Wilson is professor of developmental and molecular biology. (1R01AI125244-01A1)

Wednesday, June 07, 2017
 
Spotlighting Near-Infrared Probes

Spotlighting Near-Infrared Probes—Proteins engineered from natural photoreceptors, which sense light of the near-infrared part of the light spectrum, can be activated through the skin in deep tissues of living animals. This makes them valuable tools for noninvasively imaging, assessing and manipulating biological processes. The National Institute of General Medical Sciences has awarded Vladislav Verkhusha, Ph.D., a five-year, $2 million grant to develop new near-infrared fluorescence proteins, biosensors and optogenetic tools. Using directed molecular evolution, Dr. Verkhusha will first design these genetically encoded probes from bacterial photoreceptors. He will then use those near-infrared optical probes and molecular tools in novel ways for studying molecular interactions, cellular physiology and tissue metabolism in development, cancer, and in neurological and infectious diseases in both humans and animals. Dr. Verkhusha is professor of anatomy and structural biology. (1R35GM122567)

Friday, June 02, 2017
 
Novel Target for Nerve Repair

Novel Target for Nerve Repair—Men with prostate cancer often undergo radical prostatectomy—a surgical procedure that commonly causes erectile dysfunction due to damage to the cavernous nerve (CN). The National Institute of Diabetes and Digestive and Kidney Diseases has awarded a four-year, $2.2 million grant to David Sharp, Ph.D., and Kelvin Davies, Ph.D., to test a novel strategy for repairing CN damage following prostatectomy. The researchers will investigate whether inhibiting expression of the enzyme fidgetin-like 2 (FL2) can speed-up nerve repair after CN injury in rodent models. FL2 interferes with the growth of axons by severing microtubules. Dr. Sharp is professor of physiology & biophysics and of ophthalmology and visual sciences. Dr. Davies is professor of urology and of physiology & biophysics. (1R01DK109314-01A1)

Tuesday, May 30, 2017
 
Helping HAND from Buprenorphine

Helping HAND from Buprenorphine—Thanks to antiretroviral drugs, the neurological symptoms experienced by HIV-infected people have shifted from dementia to milder, lifelong, HIV-associated neurocognitive disorders (HAND). The National Institute on Drug Abuse has awarded Joan W. Berman, Ph.D., a five-year, $3.6 million grant to study whether buprenorphine--an opiate addiction medication that works by binding to the brain’s opioid receptors--can prevent HAND by binding to the opioid receptors of monocytes in the blood. Using a mouse model of HIV-induced HAND, Dr. Berman’s group, and Matias Jaureguiberry-Bravo, a Ph.D. student in her lab, with her collaborator Dr. David Volsky (Mount Sinai Icahn School of Medicine), will study whether buprenorphine can prevent HIV-infected monocytes from crossing the blood-brain barrier, a key event in causing HAND. This strategy may help both opioid abusers (who are at increased risk for HIV infection) and non-drug using HIV-infected people. Dr. Berman is professor of pathology and of microbiology & immunology. (1R01DA041931-01A1)

Wednesday, May 24, 2017
 
Studying Lupus Cell by Cell

Studying Lupus Cell by Cell—Systemiclupus erythematosus (SLE) occurs when a hyperactive immune system attacks the body’s own tissues, resulting in chronic inflammation and organ damage. Inflammation of the kidneys, or lupus nephritis (LN), affects nearly half of SLE patients, leading to potentially fatal kidney failure. Medications now used to treat LN are not always effective. To gain better insight into disease pathways in LN and to develop novel treatment strategies, lead author Evan Der, a Ph.D. student in Einstein’s department of microbiology & immunology, together with senior author Chaim Putterman, M.D., and colleagues at Einstein, Montefiore, NYU, and Rockefeller University, have developed a novel approach to analyze the RNA sequences of individual cells from kidney and skin biopsies of patients by using single-cell RNA-sequencing. The study was published online on May 4 in JCI Insight. Dr. Putterman is professor of medicine and of microbiology & immunology at Einstein and chief of rheumatology at Einstein and Montefiore. 

Friday, May 12, 2017
 
Clocking in for Embryonic Development

Clocking in for Embryonic Development—Early in the course of vertebrate development, the primitive backbone (consisting of a clump of cells) must be sliced into vertebral percursors called somites. This segmentation of somites is controlled by oscillator-mechanism (“clock”) genes belonging to the Hes/Her family of genes. The periodic rises and falls in expression of these genes must be precisely regulated: The smallest errors, due to gene mutations or other causes, can result in birth defects. The National Cancer Institute has awarded Ertugrul Ozbudak, Ph.D., a four-year, $1.3 million grant to study the Hes/Her gene family. This work should shed light on the genetic basis of vertebral defects and possible strategies for preventing them. In addition, aberrant oscillations in the levels of Hes/Her proteins (which control the switch from proliferation to differentiation in various tissues) have been detected in certain cancers. So the research may also lead to anti-cancer therapies. Dr. Ozbudak is associate professor of genetics. (1R01GM122956-01)

Wednesday, May 10, 2017
 
Selectively Targeting Leukemia

Selectively Targeting Leukemia—The National Cancer Institute has awarded Ulrich Steidl, M.D., Ph.D., a five-year, $1.9 million grant to study pre-leukemic stem cells and how they are induced to form leukemia cells. The research could lead to better treatment options against acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), a preleukemic disease. Cure rates over the past 45 years for both conditions have been no better than 20 percent. Dr. Steidl’s group previously showed that PU.1, a transcription factor that regulates the expression of leukemia-related genes, is frequently inactivated in pre-leukemic stem cells and in patients with AML. Using genetic models and novel inhibitors of PU.1, Dr. Steidl hopes to uncover critical pathways that induce pre-leukemic stem cells to produce leukemia cells. These PU.1 inhibitors could potentially be developed into a drug, since they appear to selectively kill leukemia cells. Dr. Steidl is professor of cell biology and of medicine and is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research. (1R01CA217092-01)

Monday, May 08, 2017
 
Purging Persister Bacteria in TB Treatment

Purging Persister Bacteria in TB Treatment—Tuberculosis treatment is hampered by patients’ need to undergo six months of drug treatment—necessary because of the presence of “persister” bacteria that don’t immediately succumb to treatment and may become resistant to it. In a paper published online on April 10 in the Proceedings of the National Academy of Sciences, a team of researchers led by William Jacobs, Jr., Ph.D., looked at whether adding chemicals to current drug regimens could decrease the length of treatment time by targeting persisters. Dr. Jacobs and colleagues found they could prevent persisters from developing by augmenting treatment with N-acetylcysteine, an amino acid derivative previously approved for treating acetaminophen overdose. Dr. Jacobs is a Howard Hughes Medical Institute Investigator and the Leo and Julia Forchheimer Chair in Microbiology & Immunology. 

Friday, April 28, 2017
 
Sugar Modification Essential for Notch Signaling

Sugar Modification Essential for Notch Signaling—Normal development of mammals and other multicellular organisms depend on Notch—a large cell-surface receptor that enables cells to communicate with each other. In a paper published online on April 11 in eLife, researchers led by Pamela Stanley, Ph.D., and Tetsuya Okajima, M.D., Ph.D., of Nagoya University, looked at how glycan modifications of Notch affect its cell-signaling ability. The researchers showed that, in the development of the retina, Notch-regulated signaling depends on the presence of the sugar O-GlcNAc on certain epidermal growth factor-like (EGF) repeats of the extracellular domain of Notch1. Cell-based assays showed that Delta Notch ligands (molecules that bind to and activate receptors) recognize O-GlcNAc on Notch1. The deletion of O-GlcNAc leads to a decrease in signaling that causes defects in perinatal retinal development. Dr. Stanley is professor of cell biology and the Horace W. Goldsmith Foundation Chair.

Wednesday, April 26, 2017
 
Tracing the Origin of Breast Tissue

Tracing the Origin of Breast Tissue—Researchers had long assumed that two of the main types of human mammary tissue--estrogen-receptor positive and estrogen-receptor negative cells—develop from a single type of stem cell. Now, Wenjun Guo, Ph.D., and his group have collaborated with Maja Oktay, M.D., Ph.D., to show that these two cell types are derived from and maintained by two distinct stem cell populations. Their study published online on March 21 in Cell Reports, used genetic techniques to monitor cells over multiple generations in a mouse model of mammary development. These findings have important clinical applications, since breast cancers are classified and treated based on whether they are estrogen-receptor positive or negative. Dr. Guo is assistant professor of cell biology. Dr. Oktay is associate professor of pathology and of anatomy and structural biology.

Monday, April 10, 2017
 
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