Plasma cells, antibody factories

Alterations in DNA methylation patterns when B cells turn into plasma cells. From Barwick Nature Immunology et al (2016) Read more

Are you experienced?

Part of a package on sepsis we've been working on for Emory Medicine magazine. This focuses on Read more

Aging, CVD risk factors and progenitor cells

Teasing apart the effects of time and CVD risk factors on cells that regenerate blood vessels. From Emory Clinical Cardiovascular Research Read more

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

Optic nerve reaching out

Congratulations to Ying Li, MD, PhD, 3rd place winner of the Best Image contest held as part of the Emory Postdoctoral Research Symposium, which takes place next week (Thursday, May 19). Li is in Eldon Geisert’s lab, and provided Lab Land this description:

“Like a benevolent overseer of the cosmos, the epicenter of the optic nerve appears to extend a axon reassuringly to the small, seemingly lowly single ganglion cell, reminding us that every cell matters.”i-6FBNVsV-X3

Posted on by Quinn Eastman in Neuro Leave a comment

Focal adhesions in Technicolor

i-QMq63rH-S

Mouse embryonic fibroblasts forming focal adhesions

Congratulations to Alejandra Valdivia, PhD, winner of the Best Image contest held as part of the Emory Postdoctoral Research Symposium, which takes place next week (Thursday, May 19). She is in Alejandra San Martin’s lab, studying NADPH oxidase enzymes and how they regulate cell migration.

Valdivia submitted this image of mouse embryonic fibroblasts forming focal adhesions, points of contact of the cell with the extracellular matrix. Focal adhesions allow the cells to adhere and migrate.

Explanation: Red is for paxillin, a protein concentrated in focal adhesions. Green is phalloidin, a toxin from mushrooms that binds one type of the cytoskeletal protein actin, seen here as stress fibers. Blue is DNA, showing the cells’ nuclei.

 

Posted on by Quinn Eastman in Heart Leave a comment

Rep. Tom Price discusses research funding

Rep. Tom Price (R-GA) expressed support for strong federal funding of scientific and biomedical research in a town-hall-type meeting Wednesday with Emory faculty and students, organized by the graduate student group Emory Science Advocacy Network.

Price tied a major expansion of federal funding for scientific research to reform of entitlements such as Medicare and Social Security (like this). Asked whether he could envision a large increase in the National Institutes of Health budget, comparable to the doubling in funding that occurred in the 1990s, Price replied: “In the near term, I don’t see it.”

However, a “smaller bump,” more along the lines of the $2 billion increase in NIH funding passed by Congress in December, could be more possible, he said.

thumbnail_IMG_7329-1

Price with Emory Science Advocacy Network officers/members

Price also advocated streamlining the Food and Drug Administration’s approval processes for new antibiotics and medical devices, and giving scientists more discretion in how federal research dollars are allocated.

In a question-and-answer session, Emory ethnobotanist Cassandra Quave urged Price to have Congress give increased attention to the problem of antibiotic resistance, in which some bacterial infections are becoming difficult to treat.

“Yes, we need more resources going into this,” Price said, going on to support a “dual track” approval process for new antibiotics.

Price expressed concerns that the United States’ role as a leader in medical innovation was waning, because of regulatory constraints that drive devices such as heart valves to be tested elsewhere first.

“We’re already losing bright minds,” he said, citing how colleagues from other surgical specialties were visiting other countries to learn new techniques.

Price, who represents parts of Cobb, Dekalb and Fulton counties, was appointed chairman of the House Budget Committee at the end of 2014, replacing Rep. Paul Ryan (R-WI).

Before his election to Congress in 2004, Price was an orthopedic surgeon. He grew up and went to medical school in Michigan, and came to Georgia for his orthopedic surgery residency at Emory. He was an assistant professor at Emory and medical director of the Orthopedic Clinic at Grady Memorial Hospital, while he was a member of the State Senate. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Malaria vaccine development: chimeric protein, no myth

Third in a series on malaria immunology from graduate student Taryn McLaughlin. Sorry for the delay last week, caused by technical blog glitches.

It’s easy for me to find reasons to brag when it comes to research here at Emory. However, even an unbiased person should be excited about the malaria vaccine platform being developed by Alberto Moreno at the Emory Vaccine Center.

His vaccine is based on a chimeric protein (a protein that is a combination of bits and pieces of multiple proteins, a la the creature from Greek mythology) that should get your immune system to target multiple stages of the Plasmodium vivax life cycle. Part of it targets the infectious sporozoite, part of it targets the blood stage merozoite, and part of it will even target the transmitted gamete in future versions. This seems like a no brainer. Of course we should be targeting multiple stages! 
Read more

Posted on by Quinn Eastman in Immunology Leave a comment