Transformative awards for Mocarski's malleable cells, lung fibrosis

The National Institutes of Health has announced a five-year, $1.9 million Transformative Research Award to Emory virologist Edward Mocarski, PhD for his work on how the mechanisms of programmed cell death can be subverted. Mocarski is Robert W. Woodruff professor of microbiology and immunology at Emory University School of Medicine and Emory Vaccine Center. His research, which originated in probing how cells commit suicide when taken over by viruses, could lead to advances in regenerative medicine and organ transplant. The grant, funded through the National Institute of Allergy and Infectious Diseases, is one of nine “high-risk-, high-reward” Transformative Research Awards (13 recipients) announced by the NIH on October 6. In the same group this year, Thomas Barker in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University received a Transformative Research Award for his research on mechanosensors + pulmonary fibrosis. The Transformative Research Award program supports “exceptionally innovative, unconventional, paradigm-shifting research projects that are inherently risky and untested.” Emory has achieved only one other TRA since the program was established in 2009: Shuming Nie's project on imaging to guide cancer surgery. “This Transformative award was made possible because of the creative and engaged graduate students and postdoctoral fellows I have had working with me at Emory,” Mocarski says. In 2011, Mocarski, working with former graduate student William Kaiser and Emory geneticist Tamara Caspary showed that two complementary forms of programmed cell death, necrosis and apoptosis, can be genetically excised from mice, leaving a viable animal with a functioning immune system. These findings are yielding additional fruit. Mocarski’s research indicates that cells from these genetically altered mice are unexpectedly malleable, in that they are easier to reprogram into induced pluripotent stem cells. Once reprogrammed, induced pluripotent stem cells (iPS cells) can be directed to become cells of almost any tissue, making them promising potential tools for the treatment of many diseases. The genetically altered mice are also less susceptible to deadly inflammation and more readily accept bone marrow transplants. The Transformative project’s aims are to exploit these findings and test the ability of drugs that interfere with programmed cell death to facilitate tissue regeneration, iPS cell reprogramming and transplant.      

Cancer metastasis: isolating invasive cells with a color change

At Winship Cancer Institute, Adam Marcus and Jessica Konen have developed a tool for probing how invasive cells are different, which could lead to new ways to fight cancer metastasis. In the video, check out how they track the behavior of apparently devious "leader cells".

Tools for illuminating brain function make their own light

Hey optogenetics fans, cut (or temporarily put aside) the fiber optic cable. Flexible tools allow the choice between activation by light or an external chemical.

Adaptive mutation mechanism may drive some forms of antibiotic resistance

Evolutionary theory says mutations are blind and occur randomly. But in the controversial phenomenon of adaptive mutation, cells can peek under the blindfold, increasing their mutation rate in response to stress.

Scientists at Winship Cancer Institute, Emory University have observed that an apparent “back channel” for genetic information called retromutagenesis can encourage adaptive mutation to take place in bacteria.

The results were published Tuesday, August 25 in PLOS Genetics.

“This mechanism may explain how bacteria develop resistance to some types of antibiotics under selective pressure, as well as how mutations in cancer cells enable their growth or resistance to chemotherapy drugs,” says senior author Paul Doetsch, PhD.

Doetsch is professor of biochemistry, radiation oncology and hematology and medical oncology at Emory University School of Medicine and associate director of basic research at Winship Cancer Institute. The first author of the paper is Genetics and Molecular Biology graduate student Jordan Morreall, PhD, who defended his thesis in April.

Retromutagenesis resolves the puzzle: if cells aren’t growing because they’re under stress, which means their DNA isn’t being copied, how do the new mutants appear?

The answer: a mutation appears in the RNA first. Read more

Posted on by Quinn Eastman in Cancer, Uncategorized Leave a comment

Anti-aging tricks from dietary supplement seen in mice

Our recent news item on a Cell Reports paper from ShiQin Xiong and Wayne Alexander describes a connection between two important biological molecules: the exercise-induced transcription coactivator PGC1-alpha and the enzyme telomerase, sometimes described as a “fountain of youth” because telomeres protect the ends of chromosomes.

While the Emory researchers did not directly assess the effects of exercise in their experiments, their findings provide molecular clues to how exercise might slow the effects of aging or chronic disease in some cell types.

Xiong and Alexander found that the dietary supplement alpha lipoic acid (ALA) can stimulate telomerase, with positive effects in a mouse model of atherosclerosis. ALA is a sulfur-containing fatty acid used to treat diabetic neuropathy in Germany, and has previously been shown to combat atherosclerosis in animal models. The Emory authors’ main focus was on vascular smooth muscle cells and note that more study of ALA’s effects on other cell types is needed.

Below are four key references that may help you put the Cell Reports paper in context: Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

All the boulders at the same time

Emory is preparing to launch a center devoted to antibiotic resistance. On Wednesday, Arjun Srinivasan, one of the CDC’s point people for antibiotic use and hospital acquired infections, kicked off the preparations with a talk on the multifaceted nature of this problem.

Without attempting to cover everything related to antibiotic resistance (that would take a book — or several), I will note in an upcoming post how Emory and partners such as Children’s Healthcare of Atlanta already have begun assembling many of the necessary tools.

Tackling antibiotic resistance has to take into account the habits of physicians, the expectations of patient, improved surveillance and antibiotic overuse in agriculture, as well as research on new antibiotics and detecting dangerous bacteria. In short, it’s both a science and policy issue — captured well by the documentary Resistance.

At the end of his talk, Srinivasan made a remark that brought this home for me, saying “We just have to push all the boulders up the hill at the same time” in response to a question about balancing effort on science vs policy. Allusions to Sisyphus!

Yet he provided some hope too, highlighting a recent CDC study that models how a coordinated response to antibiotic resistance in health care facilities could substantially cut infections. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Providing the potent part of probiotics

Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria – lactobacilli – activates the same ancient signaling pathway in intestinal cells in both insects and mammals. It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).

Asma Nusrat, MD

A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliver that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.

This idea has advanced experimentally, as demonstrated by two papers from Jones and Neish’s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.

Nusrat told me Friday her team began investigating annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria are activating the same molecular signals. (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)

In a second Journal of Clinical Investigation paper published this February, Nusrat and her colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more

Posted on by Quinn Eastman in Immunology, Uncategorized Leave a comment

Regenerative Engineering & Medicine highlights

Last week on Friday, Lab Land attended the annual Regenerative Engineering & Medicine center get-together to hear about progress in this exciting area.

During his talk, Tony Kim of Georgia Tech mentioned a topic that Rose Eveleth recently explored in The Atlantic: why aren’t doctors using amazing “nanorobots” yet? Or as Kim put it, citing a recent review, “So many papers and so few drugs.”

[A summary: scaling up is difficult, testing pharmacokinetics, toxicity and efficacy is difficult, and so is satisfying the FDA.]

The talks Friday emerged from REM seed grants; many paired an Emory medical researcher with a Georgia Tech biomedical engineer. All of these projects take on challenges in delivering regenerative therapies: getting cells or engineered particles to the right place in the body.

For example, cardiologist W. Robert Taylor discussed the hurdles his team had encountered in scaling up his cells-in-capsules therapies for cardiovascular diseases to pigs, in collaboration with Luke Brewster. The pre-pig phase of this research is discussed in more detail here and here. Read more

Posted on by Quinn Eastman in Heart, Neuro Leave a comment

HIV vaccine news: a glass half full

This week, researchers from Yerkes and Emory Vaccine Center led by Cindy Derdeyn published a paper that I first thought was disturbing. It describes how monkeys vaccinated against HIV’s relative SIV (simian immunodeficiency virus) still become infected when challenged with the virus. Moreover, it’s not clear whether the vaccine-induced antibodies are exerting any selective pressure on the virus that gets through.

But then I realized that this might be an example of “burying the lead,” since we haven’t made a big hoopla about the underlying vaccine studies, conducted by Rama Amara. Some of these studies showed that a majority of monkeys can be protected from repeated viral challenge. The more effective vaccine regimens include adjuvants such as the immune-stimulating molecules GM-CSF or CD40L (links are the papers on the protective effects). Read more

Posted on by Quinn Eastman in Immunology Leave a comment

How white blood cells limit muscle regeneration

A paper from cardiologist Aloke Finn and colleagues (published Wednesday, Aug. 5 in Nature Communications) describes how the protein CD163, produced by macrophages, puts the brakes on muscle repair after ischemic injury in mice. Here’s why we think this paper is interesting.

*Speculatively, there are connections to the recent wave of “young blood cures old body” parabiosis research. Increased CD163 is a marker of aging in humans. Maybe low levels of CD163 are part of how young blood is restorative.

*Translational potential — it wouldn’t be too hard to make an antibody against human CD163. Something that blocks CD163 could possibly be used to treat muscle breakdown, which occurs in response to injury, inactivity and in diseases such as cancer and diabetes.

*Finn says his team was surprised to find that mice lacking CD163, tested in experiments where blood flow is restricted in one leg, showed increased blood vessel and muscle growth in the other leg. It looks like part of CD163’s role is to limit muscle regeneration to the site of injury. Read more

Posted on by Quinn Eastman in Heart Leave a comment

CMV reactivation warps immune system after HSCT

As a followup to yesterday’s post on following troublemaker cells in patients with lupus, we’d like to highlight a recent paper in Blood that takes a similar approach to studying how the immune system comes back after bone marrow/blood stem cell transplant.

Leslie Kean, MD, PhD

The paper’s findings have implications for making this type of transplant safer and preventing graft-versus-host disease. In a bone marrow/blood stem cell transplant, to fight cancer, doctors are essentially clearing out someone’s immune system and then “planting” a new one with the help of a donor. What this paper shows is how much CMV (cytomegalovirus) distorts the new immune system.

CMV is often thought of as harmless — most adults in the United States have been infected with CMV by age 40 and don’t get sick because of it. But in this situation, CMV’s emergence from the shadows forces some of the new T cells to multiply, dominating the immune system so much that it creates gaps in the rest of the T cell repertoire, which can compromise protective immunity. Other seemingly innocuous viruses like BK cause trouble in immunosuppressed patients after kidney transplant.

The senior author, Leslie Kean, moved from Emory to Seattle Children’s Hospital in 2013, and her team began these studies here in 2010 (a host of Emory/Winship hematologists and immunologists are co-authors). This paper is sort of a mirror image of the Nature Immunology paper on lupus because it also uses next-generation sequencing to follow immune cells with DNA rearrangements — in this case, T cells. Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Following lupus troublemaker cells, via DNA barcodes

People with systemic lupus erythematosus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Often the symptoms come and go in episodes called flares. In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.

The immune system can produce many types of antibodies, directed against infectious viruses (good) or against human proteins as in lupus (harmful). Each antibody-secreting cell carries a DNA rearrangement that reflects the makeup of its antibody product. Scientists can use the DNA to identify and track that cell, like reading a bar code on an item in a supermarket.


Iñaki Sanz, MD is a Georgia Research Alliance Eminent Scholar, director of the Lowance Center for Human Immunology and head of the Rheumatology division in the Department of Medicine.

Postdoc Chris Tipton, GRA Eminent Scholar Iñaki Sanz and colleagues at Emory have been using these DNA bar codes to investigate some fundamental questions about lupus: where do the autoantibody-producing cells come from? Are they all the same?

Their findings were published in Nature Immunology in May, and a News and Views commentary on the paper calls it “a quantum advance in the understanding of the origin of the autoreactive B cells.” It’s an example of how next-generation sequencing technology is deepening our understanding of autoimmune diseases.

The Emory team obtained blood samples from eight patients experiencing lupus flares and compared them to eight healthy people who had recently been vaccinated against influenza or tetanus.

When the immune system is responding to something it’s seen before, like when someone receives a booster vaccine, the bar codes of the antibody-producing cells look quite similar to each other. A set of just a few antibody-producing cells multiply and expand, making what looks like clones. In contrast, the researchers found that in lupus, many different cells are producing antibodies. Some of the expanded sets of cells are producing antibodies against infectious agents.

“We expected to see an expansion of the cells that produce autoantibodies, but instead we saw a very broad expansion of cells with all types of specificities,” Tipton says.

To use a Star Wars analogy: a booster vaccine response looks like the Clone Wars (oligoclonal — only a few kinds of monsters), but a lupus flare looks like a visit to Mos Eisley cantina (polyclonal — many monsters). Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Momentum at hypersomnia conference

A visitor might not realize this was a meeting devoted to people who experience excessive daytime sleepiness. The 2015 Hypersomnia Foundation Conference on Saturday was full of energy, with:

*more than 245 attendees, about twice as many people as last year’s conference

*medical experts from France, Wisconsin and Louisiana — in addition to Emory

*data from several recent clinical trials

*some signs of industry interest in hypersomnia

Hypersomnia is a sleep disorder in which individuals feel frequent or constant sleepiness and need to sleep for long portions of the day (more than 70 hours per week). It is distinct from other sleep disorders such as narcolepsy and sleep apnea, but its prevalence is still unclear. Conventional stimulants such as amphetamine or modafinil often can be used to treat the sleepiness, but some with hypersomnia find these drugs ineffective or hard to tolerate.

Previous research at Emory has shown that many individuals with hypersomnia have a substance in their spinal fluid that acts like a sleeping pill, enhancing the action of the neurotransmitter GABA. The identity of this mysterious substance is unknown, but Emory researchers report that they are close to identifying it. That could give hypersomnia a “molecular handle” like what narcolepsy has, with loss of hypocretin-producing neurons.

The terminology is still up in the air — keynote speaker Isabelle Arnulf from the Pitié-Salpêtrière University Hospital in Paris said, “The term ‘idiopathic hypersomnia’ does not mean that you are an idiot.” Rather, she said, it means that even specialists can have trouble distinguishing hypersomnia from other sleep disorders, and “idiopathic” signifies that the detailed cause is still under investigation.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment
  • Feedback

    Let us know what you think.

    You can contact us via the email button below or you can use our online feedback form You can also leave comments directly on individual posts.

buy windows 8 personalization enabler key cheap,buy windows 8 crack key key online,Windows 8 Activator,cheap Windows 7 Ultimate Activation Key buy Windows 8.1 Product Key Finder 2014 key online,buy windows 8 build 9200 activator free download key online,buy Windows 8 Activator key cheap,buy How to Activate Windows 8 For Free key cheap,cheap Windows 8 Professional Activation Key download buy Keyword key online,buy linux server software key cheap,buy windows crack key online,Windows Server 2012 Standard Activation Key buy windows office 2013 professional cheap,cheap ms office 365,ms office 2010 cheap download,download visio,buy office 2013 package cheap,buy office 2013 package cheap buy download office 2013 with product key cheap,2013 office product key,office 2013 for free download cheap download,ms office pro cheap download,microsoftproject free office trial,buy office 2010 access cheap,office 2013 online download cheap download,ms office professional Windows 8 Professional,buy Windows 7 key cheap,Windows 8 Enterprise Activation Key,buy small business server key cheap,cheap windows 8.1 buy Windows 8.1 loader 2013 key cheap,buy Windows 8.1 Permanent Activator free 2013 key cheap,buy Activate Windows 8 PRO and Enterprise Build 9200 key online,cheap Windows 7 Home Basic Activation Key download,cheap Windows 7 Professional SP1 Activation Key download buy windows server upgrade key cheap,buy windows 8 pro build 9200 product key key cheap,buy Download Kms Activator Windows 8 Build 8400 key online,buy windows 8 personalization working key cheap buy office 2010 home & business cheap,office software free cheap download,download of office 2013,is visio part of office 2013,buy windows office 2007 cheap buy office 365 office 2013 cheap,office download 2010,buy windows office professional cheap,office standard 2010,buy office professional plus 2013 cheap office pro 2013 plus cheap download,buy free download office word cheap,buy office home 2013 cheap,cheap latest ms office 2013 free download cheap free download office word 2013,where can i download office 2013,buy office 2013 trial version free download cheap,cheap outlook 2007 office pro 2013 plus cheap download,buy free download office word cheap,buy office home 2013 cheap,cheap latest ms office 2013 free download buy windows server learning key online,upgrade windows server,buy windows server 2008 requirements key online,data center windows 8 pro crack,cheap windows 8 pro download,Windows 7 activator free Download,buy windows 7 activation crack key cheap,buy windows 2003 servers key online,buy windows 2003 servers key online buy windows server 2008 enterprise key online,cheap Windows 7 Ultimate Activation Key download,windows business server,buy Windows 7 Pro & Enterprise 32 bit and 64 bit activator key cheap,buy windows 10 free activator key cheap skype software free download for windows 7 full version,cheap windows 8.1 pro download,windows 2008 r2,Windows 8 Pro & Enterprise 32 bit and 64 bit Activator,windows 7 home buy windows 8 crack key online,cheap Windows Server 2012 Datacenter Activation Keywindows 7,Windows 8.1 Permanent Activator free 2013 buy windows 8 crack key online,cheap Windows Server 2012 Datacenter Activation Keywindows 7,Windows 8.1 Permanent Activator free 2013 buy new windows version key online,buy windows 7 loader free download key online,windows home server 2011 Windows 7 Enterprise SP1 Activation Key,buy windows 7 certification key cheap,buy windows 8 crack download free key online,buy windows 7 activation key free download key cheap,buy server operating systems key online Windows 8.1 Activator Loader,buy windows server services key online,buy windows 8 activator 2014 key cheap,buy win 7 activator 2014 key online