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Tackling Renal Disease in Lupus Patients

Tackling Renal Disease in Lupus Patients—The autoimmune disease lupus can lead to serious kidney problems in up to 60 percent of patients, with 10-30 percent of patients ultimately developing end-stage renal disease (ESRD). The National Institute of Arthritis and Musculoskeletal and Skin Diseases has awarded Anna Broder, M.D., a five year, $880,000 grant to continue her research on the drug hydroxychloroquine, which  is used to treat lupus but is not widely used after lupus patients develop  ESRD. Dr. Broder will study whether hydroxychloroquine reduces mortality in lupus patients undergoing hemodialysis and kidney transplantation. This will involve analyzing data from a U.S. registry of ESRD patients and studying outcomes in lupus patient with ESRD who are being treated with hydroxychloroquine at Einstein and New York University School of Medicine. Dr. Broder is associate professor of medicine. (1K23AR068441-01A1)

Friday, August 18, 2017
Targeting a Sickle-Cell Problem

Targeting a Sickle-Cell Problem—Sickle cell disease (SCD), a genetic disorder in which red blood cells are misshapen, causes serious complications. One SCD complication is painful leg ulcers, for which there is no approved treatment. Following up on her successful phase 1 study, the U.S. Food and Drug Administration has awarded Caterina Minniti, M.D., a four-year, $1.9 million grant to conduct a phase 2 trial of sodium nitrite cream for treating leg ulcers in SCD patients. When the cream is applied to the wound, sodium nitrite is converted into nitric oxide (NO), which causes blood vessels to dilate and also kills bacteria, stimulates the proliferation of keratinocytes (the main cell type in the skin’s outer layer) and decreases inflammation. These NO- induced changes aid healing. In the phase 1 study, the sodium nitrite cream decreased pain at the wound site and reduced patient’s narcotic use. Dr. Minniti is professor of medicine and of pediatrics at Einstein and director of the Sickle-Cell Center for Adults at Montefiore. (1R01FD005729-01)

Thursday, August 10, 2017
Reducing Radiation Injury

Reducing Radiation Injury—Radiation exposure from nuclear accidents or terrorism can cause mass casualties and poses a serious ongoing threat. Radiation-induced vascular injury (RIVI) is a critical component of the multi-organ failure caused by acute radiation exposure syndrome. RIVI can lead to blood problems such as anemia and thrombocytopenia and damage critical organs, especially intestines and lungs. The National Institutes of Health has awarded Chandan Guha M.B.B.S., Ph.D., a five-year, $2.3 million grant to develop measures to prevent RIVI. In collaboration with Janssen Pharmaceuticals, Inc., Dr. Guha and colleagues will test whether the drug Thrombopoietin Mimetic (TPOm) can protect against vascular injuries caused by radiation. The team will first evaluate TPOm in mice—an effort that will require developing imaging techniques to assess the extent radiation induced normal tissue injury. Dr. Guha is director of the Einstein Institute for Onco-physics, professor and vice chair of radiation oncology, as well as professor of urology and of pathology at Einstein and Montefiore. (1U01AI133608-01)

Friday, August 04, 2017
A One-two TB Knockout Punch

A One-two TB Knockout Punch—Mycobacterium tuberculosis, the bacterium that causes TB, has developed extensive drug resistance so that treatment is often lengthy or ineffective. In a paper published on June 26 in the Proceedings of the National Academy of SciencesMichael Berney, Ph.D.and his graduate student Erik Hasenoehrl, found a way to exploit the bacterium’s oxidative phosphorylation pathway that may lead to better treatments. Dr. Berney’s group, together with collaborators from Singapore, found that resistant TB infections require two terminal oxidases--molecular pumps that TB bacteria rely on to generate energy. Using chemical biology and genetic approaches, Dr. Berney and colleagues showed that simultaneously inactivating both pumps halts TB cell respiration leading to cell death. The researchers shut down both pumps and rapidly cleared M. tuberculosis infection in a TB mouse model by coupling deletion of one oxidase gene with use of a drug. Dr. Berney is an assistant professor of microbiology & immunology.

Thursday, July 13, 2017
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—Systemic Lupus 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
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