HD monkeys display full spectrum of symptoms seen in humans

Transgenic Huntington’s disease monkeys developed at Yerkes display a full spectrum of symptoms resembling the human disease, strengthening the case that they could be used to evaluate emerging treatments before launching human clinical Read more

The cure word, as applied to HIV

HIV researchers are becoming increasingly bold about using the "cure" word in reference to HIV/AIDS, even though nobody has been cured besides the "Berlin patient," Timothy Brown, who had a fortuitous combination of hematopoetic stem cell transplant from a genetically HIV-resistant donor. Sometimes researchers use the term "functional cure," meaning under control without drugs, to be distinct from "sterilizing cure" or "eradication," meaning the virus is gone from the body. A substantial obstacle is that HIV Read more

A sweet brain preserver: trehalose

The natural sugar trehalose is used in the food industry as a preservative and flavor enhancer. Medical researchers keep running into it when they’re looking for ways to fight neurodegenerative diseases. This paper includes patient-derived iPS cells, thanks to Emory's Laboratory for Translational Cell Read more

HD monkeys display full spectrum of symptoms seen in humans

Transgenic Huntington’s disease monkeys display a full spectrum of symptoms resembling the human disease, ranging from motor problems and neurodegeneration to emotional dysregulation and immune system changes, scientists at Yerkes National Primate Research Center, Emory University report.

The results, published online in the journal Brain, Behavior and Immunity, strengthen the case that transgenic Huntington’s disease monkeys could be used to evaluate emerging treatments (such as this) before launching human clinical trials.

“Identifying emotional and immune symptoms in the HD monkeys, along with previous studies demonstrating their cognitive deficits and fine motor problems, suggest the HD monkey model embodies the full array of symptoms similar to human patients with the disease,” says Yerkes research associate Jessica Raper, PhD, lead author of the paper. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

The cure word, as applied to HIV

HIV researchers are becoming increasingly bold about using the “cure” word in reference to HIV/AIDS, even though nobody has been cured besides the “Berlin patient,” Timothy Brown, who had a fortuitous combination of hematopoetic stem cell transplant from a genetically HIV-resistant donor. Sometimes researchers use the term “functional cure,” meaning under control without drugs, to be distinct from “sterilizing cure” or “eradication,” meaning the virus is gone from the body. A substantial obstacle is that HIV integrates into the DNA of some white blood cells.

HIV cure research is part of the $35.6 million, five-year grant recently awarded by the National Institutes of Health to Yerkes/Emory Vaccine Center/Emory Center for AIDS Research. Using the “shock and kill” approach during antiviral drug therapy, researchers will force HIV (or its stand-in in non-human primate research, SIV) to come out of hiding from its reservoirs in the body. The team plans to test novel “latency reversing agents” and then combine the best one with immunotherapeutic drugs, such as PD-1 blockers, and therapeutic vaccines.

The NIH also recently announced a cluster of six HIV cure-oriented grants, named for activist Martin Delaney, to teams led from George Washington University, University of California, San Francisco, Fred Hutchinson Cancer Research Center, Wistar Institute, Philadelphia, Beth Israel Deaconess Medical Center and University of North Carolina. Skimming through the other teams’ research plans, it’s interesting to see the varying degrees of emphasis on “shock and kill”/HIV latency, enhancing the immune response, hematopoetic stem cell transplant/adoptive transfer and gene editing weaponry vs HIV itself.

Posted on by Quinn Eastman in Immunology Leave a comment

A sweet brain preserver: trehalose

It’s sweet, it’s safe, and it looks like it could save neurons. What is it? Trehalose.

Trehalose molecule

Trehalose is a natural sugar.

This natural sugar is used in the food industry as a preservative and flavor enhancer (it’s in Taco Bell’s meat filling). And curiously, medical researchers keep running into trehalose when they’re looking for ways to fight neurodegenerative diseases.

A recent example from Emory’s Department of Pharmacology: Chris Holler, Thomas Kukar and colleagues were looking for drugs that might boost human cells’ production of progranulin (PGRN), a growth factor that keeps neurons healthy. Mutations in the progranulin gene are a common cause of frontotemporal dementia.

The Emory scientists discovered two leads: a class of compounds called mTOR inhibitors — the transplant drug rapamycin is one — and trehalose. The team decided to concentrate on trehalose because it increased PGRN levels in neuronal and non-neuronal cell types, unlike the mTOR inhibitors. Their results were published at the end of June in Molecular Neurodegeneration.

The team confirmed their findings by examining the effects of trehalose on cells derived from patients with progranulin mutations. This paper is the first to include results from Emory’s Laboratory of Translational Cell Biology, which was established in 2012 to facilitate this type of “disease in a dish” approach. Cell biologists Charles Easley, Wilfried Rossoll and Gary Bassell from the LTCB, and neurologists Chad Hales and William Hu from the Center for Neurodegenerative Disease are co-authors.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Outcomes in minimally invasive lung cancer surgery

To accompany our recent article on minimally invasive lung surgery for Winship magazine, please find a video featuring thoracic surgeon Manu Sancheti, MD.

As Sancheti explains, an advantage of minimally invasive approaches (sometimes called VATS for video-assisted thoracic surgery) is that surgeons do not open the patient’s chest, avoiding pain and potential complications and reducing length of stay in the hospital.

Among thoracic surgeons, the shift to this type of approach has taken place in the last few years — unevenly. Here’s a graph froLung surgery graphm one recent publication from Felix Fernandez, MD and colleagues, showing the percent of stage I lung cancer surgeries — compiled for individual surgeons in the Society of Thoracic Surgeons  — that are minimally invasive from 2011-2014. The average is about 63 percent, but it varies widely.

Attention medical journalists: if you want to ask questions like “Are these minimally invasive lung surgery approaches really good for long term patient outcomes?”, Fernandez is your guy. As the numbers come in, he is leading a team that is analyzing them. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Challenging long-held dogmas in cardiology

IGF1_heart

The growth factor IGF-1 (red) peaks roughly two days after an artificial heart attack in mice. But its levels are limited by an enzyme called chymase produced by mast cells. What if the influence of chymase could be curtailed?

Alert to science journalists looking for active debate: Emory cardiology researchers Nawazish Naqvi and Ahsan Husain are not afraid of controversy in their field.

In a 2014 Cell paper, they challenged the long-held assumption that after birth, cardiac muscle cells do not divide, showing a dramatic burst of thyroid hormone-driven cell division in the hearts of preadolescent mice. This finding has implications for regenerative medicine if it can be harnessed, but also stimulated a cluster of papers aiming to refute their findings in Cell the following year (and more are coming).

A second assumption that they’ve challenged more recently is that hours after a heart attack, endangered cardiac muscle cells can’t be rescued. Husain and Naqvi’s paper, published this week in PNAS, shows that the enzyme chymase — produced by a type of immune cell called mast cells — limits the heart’s ability to heal itself. Critically, differences in the extent of damage seen in mice lacking chymase and controls show up days after an artificial heart attack. More here.

Posted on by Quinn Eastman in Uncategorized Leave a comment

How Zika infects the placenta

Zika virus can infect and replicate in immune cells from the placenta, without killing them, scientists have discovered. The finding may explain how the virus can pass through the placenta of a pregnant woman, on its way to infect developing brain cells in her fetus.

Zika_in_vitro_smaller

Infected placental macrophages. Zika antigens visible in red. From Quicke et al (2016).

The results were published in Cell Host & Microbe.

“Our results substantiate the limited evidence from pathology case reports,” says senior author Mehul Suthar, PhD, assistant professor of pediatrics at Emory University School of Medicine. “It was known that the virus was getting into the placenta. But little was known about where the virus was replicating and in what cell type.”

Scientists led by Suthar and Emory pediatric infectious disease specialist Rana Chakraborty, MD, found that Zika virus could infect placental macrophages, called Hofbauer cells, in cell culture. The virus could also infect another type of placental cell, called cytotrophoblasts, but only after a couple days delay and not as readily. Other researchers recently reported that syncytiotrophoblasts, a more differentiated type of placental cell than cytotrophoblasts, are resistant to Zika infection.

The cells for the experiments were derived from full-term placentae, obtained from healthy volunteers who delivered by Cesarean section. The level of viral replication varied markedly from donor to donor, which hints that some women’s placentae may be more susceptible to viral infection than others. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Four take-home thoughts on NGLY1

Please check out our feature in Emory Medicine magazine about two sisters with NGLY1 deficiency. This rare genetic disorder was identified only a few years ago, and now a surge of research is directed toward uncovering its mysteries.

  1. The Stinchcombs are amazing. Seth Mnookin’s July 2014 piece in the New Yorker, and especially, his comments at the end of an interview with The Open Notebook drove me to contact them. “The father cares for the two girls with this disease full time. The mother is working insane hours. And while all this is going on, they’re the most good-natured … I don’t know, they just seem like they’re happy.”
  1. Several research teams around the world are investigating NGLY1 deficiency and potential remedies. For the magazine article, I talked with Emory geneticist Michael Gambello, Hudson Freeze at Sanford Burnham and Lynne Wolfe at the NIH Undiagnosed Diseases Program. Even more: the Grace Science Foundation, established by the Wilsey family, is supporting research at Retrophin/Notre Dame and Gladstone/UCSF. The independent Perlstein lab is investigating NGLY1 deficiency in fruit flies (reminiscent of Emory research from a decade ago on Fragile X syndrome).
  1. There’s a long road ahead for rare genetic disorders such as NGLY1 deficiency. That’s why the title that EM editor Mary Loftus came up with, “In time to help Jessie,” is so poignant. When I read Abby Goodnough’s New York Times piece on RCDP, which is a rare inherited bone disease that also involves seizures, I thought: “That could be NGLY1 in ten years.” Still, progress is possible, as demonstrated by this recent NEJM report on exome sequencing and neurometabolic disorders from British Columbia.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment

FDA approves Emory-developed cancer imaging probe

A cancer imaging agent that was originally developed at Emory was approved on Friday, May 27 by the U.S. Food and Drug Administration.

Axumin, a PET (positron emission tomography) imaging agent, is indicated for diagnosis of recurrent prostate cancer in men who have elevated PSA levels after previous treatment. Axumin, now being commercialized by UK-based Blue Earth Diagnostics, is also known as 18F-fluciclovine or FACBC (an abbreviation for anti-1-amino-3-[18F]fluorocyclobutane-1- carboxylic acid).

goodman-schuster

Mark Goodman, PhD (left) and David Schuster, MD (right)

Imaging using axumin/fluciclovine is expected to help doctors detect and localize recurrent prostate cancer, and could guide biopsy or the planning of additional treatment. Fluciclovine was originally developed at Emory by Mark Goodman and Timothy Shoup, who is now at Massachusetts General Hospital.

The earliest research on fluciclovine in the 1990s was on its use for imaging brain tumors, and it received a FDA “orphan drug” designation for the diagnosis of glioma in 2015. About a decade ago, Emory researchers stumbled upon fluciclovine’s utility with prostate cancer, while investigating its activity in a patient who appeared to have renal cancer, according to radiologist David Schuster, who has led several clinical studies testing fluciclovine.

“This led us to see if this radiotracer would be good for looking at prostate cancer, specifically because of its low native urinary excretion,” Schuster is quoted as saying in the radiology newsletter Aunt Minnie. “If you look at the history of medical science, it is taking advantage of the unexpected.”

Early research on the probe was supported by Nihon Mediphysics, and later support for clinical research on FACBC/fluciclovine came from the National Cancer Institute, the Georgia Research Alliance and the Georgia Cancer Coalition. [Both Emory and Goodman are eligible to receive royalties from its commercialization]. Additional information here.

References for two completed studies on fluciclovine in recurrent prostate cancer

Odewole OA et al. Comparison with CT imaging (2016) 

Schuster DM et al. Head to head comparison with ProstaScint (2014). Read more

Posted on by Quinn Eastman in Cancer Leave a comment

A distinguished flu vaccine researcher

Congratulations to Richard Compans, PhD, who delivered the Dean’s Distinguished Faculty Lecture on May 12, joining a select group of Emory researchers who have received this award. After Dean Chris Larsen presented the award, Compans also received a Catalyst award from the Georgia Research Alliance, presented by GRA President and CEO Mike Cassidy.compans115a-2

At Emory, Compans has led research on ways to improve influenza vaccination, such as vaccines based on non-infectious virus-like particles and microneedle patches for delivery (now being tested clinically). The 2009 H1N1 flu epidemic, as well as concern about pandemic avian flu, have meant that Compans’ work has received considerable attention in the last several years. In his talk, he also discussed his early work on the structure of influenza virus, the virus’s complex ecology, and the limitations of current flu vaccines.

Compans was recruited to Emory from UAB in 1992 and was chair of Emory’s microbiology and immunology department for more than a decade. He was also instrumental in recruiting Rafi Ahmed to establish and lead the Emory Vaccine Center. He is now co-principal investigator of the Emory-UGA Center of Excellence for Influenza Research and Surveillance.

Some recent papers that illustrate the extent of Compans’ influence: Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Fooling the test: antibiotic resistant bacteria that look susceptible

A diagnostic test used by hospitals says a recently isolated strain of bacteria is susceptible to the “last resort” antibiotic colistin. But the strain actually ignores treatment with colistin, causing lethal infections in animals.

Through heteroresistance, a genetically identical subpopulation of antibiotic-resistant bacteria can lurk within a crowd of antibiotic-susceptible bacteria. The phenomenon could be causing unexplained treatment failures in the clinic and highlights the need for more sensitive diagnostic tests, researchers say.

In Nature Microbiology (published online Monday, May 9), scientists led by David Weiss, PhD, describe colistin-heteroresistant strains of Enterobacter cloacae, a type of bacteria that has been causing an increasing number of infections in hospitals around the world.

“Heteroresistance has been observed previously and its clinical relevance debated,” Weiss says. “We were able to show that it makes a difference in an animal model of infection, and is likely to contribute to antibiotic treatment failures in humans.”

Weiss is director of the Emory Antibiotic Resistance Center and associate professor of medicine (infectious diseases) at Emory University School of Medicine and Emory Vaccine Center. His laboratory is based at Yerkes National Primate Research Center. The co-first authors of the paper are graduate students Victor Band and Emily Crispell.

Read more

Posted on by Quinn Eastman in Immunology Leave a comment
1 2 3 4 5 6 7 8 9 10 ... 67 68   Next »