In his undergraduate days, Winship Cancer Institute dermatologist and cancer researcher Jack Arbiser was an organic chemist. That may be why he recognized an organic synthesis reagent based on the metal palladium as a potential anti-cancer drug.
We’re talking about Tris-DBA-palladium. Arbiser and colleagues showed in a 2008 Clinical Cancer Research paper that this deep purple stuff (see photo) is active against melanoma, and since then, against other types of cancer such as pancreatic cancer, multiple myeloma, and CLL leukemia.
Tris-DBA-PD has a deep purple color. The palladium atoms can be seen in the diagram as two blue balls at the center. From Wikipedia.
Since it’s used in organic synthesis, you might expect Tris-DBA-palladium not to be very soluble in water. A new paper in Scientific Reports demonstrates that this issue can be addressed by hooking up the reagent to nanoparticles made of hyaluronic acid, which targets tumor cells. They are effective against melanoma in mice, the paper shows.
“We have already demonstrated that Tris DBA palladium by itself has activity against melanoma in mice,” Arbiser writes (in his VA grant summary). “However, we believe that we can make Tris DBA palladium into an even more powerful drug by adding it to nanoparticles that are guided to the tumor.”
In an email to Lab Land, Arbiser says he arrived at Tris-DBA-palladium by using his chemist’s imagination, in a “your chocolate landed in my peanut butter” kind of way.
“I got the idea for looking at this compound because it is a complex of Pd with a curcumin-like structure, and I figured it might have the characteristics of platinum and curcumin together,” he says. Read more
When studying Crohn’s disease – an inflammatory disorder of the gastrointestinal tract, a challenge is separating out potential causes from the flood of systemic inflammation inherent in the condition. Researchers led by Subra Kugathasan, MD recently published an analysis that digs under signs of inflammation, in an effort to assess possible causes.
Graduate student Hari Somineni, in Kugathasan’s lab, teamed up with Emory and Georgia Tech geneticists for a sophisticated approach that may have found some gold nuggets in the inflammatory gravel. The results were published in the journal Gastroenterology.
In studying Crohn’s disease, Emory + Georgia Tech researchers may have found some gold nuggets in the inflammatory gravel.
The group looked at DNA methylation in blood samples from pediatric patients with Crohn’s disease, both at diagnosis and after treatment and follow-up. The information came from blood samples from 164 children with Crohn’s disease and 74 controls, as part of the RISK study, which is supported by the Crohn’s & Colitis Foundation and Kugathasan leads.
DNA methylation is a dynamic process that can influence molecular phenotypes of complex diseases by turning the gene(s) on or off. The researchers observed that disrupted methylation patterns at the time of diagnosis in pediatric Crohn’s disease patients returned to those resembling controls following treatment of inflammation
“Our study emphasized how important it is to do longitudinal profiling – to look at the patients before and after treatment, rather than just taking a cross section,” Somineni says.
An experimental screening method, developed by Emory and Georgia Tech scientists, aims to detect immune rejection of a transplanted organ earlier and without a biopsy needle.
The technology is based on nanoparticles that detect granzyme B enzymes produced by killer T cells. When the T cells are active, they slice up the nanoparticles, generating a fluorescent signal that is detectable in urine. The results from a mouse skin graft model were published in Nature Biomedical Engineering, from Gabe Kwong’s lab at GT and Andrew Adams’ at Emory. More extensive story here.
Co-first authors Quoc Mac and Dave Mathews
Adams is also developing technologies for imaging transplant rejection via immunoPET, with Georgia Tech’s Phil Santangelo.
Humans are good at deciphering complex images, compared to computers. Until recently, internet users often needed to verify that they were human by completing a CAPTCHA security check. A familiar variety asked the user to check all the boxes that contain a car, or a street sign.
If we asked random people off the street to look at pathology slides and “quick, check all the boxes that contain tumor cells,” what would happen? The accuracy, compared to a trained pathologist, wouldn’t be very good.
Not as easy as labeling which boxes contain street signs!
This challenge of expertise – crowdsourcing and pathology are not immediately compatible – is what Lee Cooper and colleagues sought to overcome in a recent paper published in Bioinformatics. So they put together something they called “structured crowdsourcing.”
“We are interested in describing how the immune system behaves in breast cancers, and so we built an artificial intelligence system to look at pathology slides and identify the tissue components,” Cooper says.
His group was particularly interested in the aggressive form of breast cancer: triple negative. They used pathology slide images from the Cancer Genome Atlas, a National Cancer Institute resource. The goal was to mark up the slides and label which sections contained tumor, stroma, white blood cells, dead cells etc.
They used social media to recruit 25 volunteers — medical students and pathologists from around the world (Egypt, Bangladesh, Saudi Arabia, United Arab Emirates, Syria, USA). Participants underwent training and used Slack to communicate and learn about how to classify images. They collaborated using the Digital Slide Archive, a tool developed at Emory. Read more
When influenza viruses that infect birds and humans meet in the same cell, they can shuffle their genomes and produce new strains that might have pandemic potential. Think of this process, called reassortment, as viruses having sex.
In the last several years, public health officials have been monitoring two varieties of bird flu viruses with alarming properties: H7N9 and H5N8. Scientists at Emory have been probing the factors that limit reassortment between these strains and a well-known strain (H3N2) that has been dominating the last few flu seasons in the United States.
Helen Branswell has an article in STAT this week, explaining that H5N8 actually emerged from reassortment involving much-feared-but-not-damaging-to-humans-so-far H5N1:
Several years ago, these viruses effectively splintered, with some dumping their N1 neuraminidase — a gene that produces a key protein found on the surface of flu viruses — and replacing it with another. The process is called reassortment, and, in this case, it resulted in the emergence of a lot of new pairings over a fairly short period of time.
The most common and most dangerous viruses to emerge — for birds at least — have been H5N6 and H5N8 viruses. Both are highly pathogenic, meaning they kill domestic poultry.
“The H5N1 virus has not gone away. It’s just changed into different versions of itself,” explained influenza expert Malik Peiris, a professor of virology at the University of Hong Kong.
From the Emory study, the good news is that “packaging signals” on the H5 and H7 viral RNA genomes are often incompatible with the H3N2 viruses. That means it could be difficult for segments of the genome from the bird viruses to get wrapped up with the human viruses. But mix and match still occurred at a low level, particularly with H5N8. Read more
Nothing he tried had worked. For Sigurjon Jakobsson, the trip to Atlanta with his family was a last-ditch effort to wake up. He had struggled with sleeping excessively for several years before coming from Iceland to see a visionary neurologist, who might have answers.
In high school, Sigurjon was a decathlete competing as part of Iceland’s national sports team. But at the age of 16, an increasing need for sleep began to encroach upon his life. Sigurjon needed several alarm clocks to get out of bed and was frequently late to school or his job at a construction company. He often slept more than 16 hours in a day.
Sigurjon feeling awake (Atlanta, summer 2018)
When Sigurjon describes his experiences, they sound like depression, although his mood and lack of motivation appear more a consequence of his insatiable desire to sleep. He quit sports. He dropped out of college and became isolated and lost touch with close friends.
“Your will to do things just kinda dies,” he says. “And then you’re always trying and trying again. It just gets worse. You kinda die inside from being tired all the time.”
At the recommendation of a neurologist in Iceland, Sigurjon’s family sought out David Rye, who is known internationally for his research on idiopathic hypersomnia, a poorly understood sleep disorder. Read more
Neuroscientists at Emory University School of Medicine have discovered a focal pathway in the brain that when electrically stimulated causes immediate laughter, followed by a sense of calm and happiness, even during awake brain surgery. The effects of stimulation were observed in an epilepsy patient undergoing diagnostic monitoring for seizure diagnosis. These effects were then harnessed to help her complete a separate awake brain surgery two days later.
The behavioral effects of direct electrical stimulation of the cingulum bundle, a white matter tract in the brain, were confirmed in two other epilepsy patients undergoing diagnostic monitoring. The findings are scheduled for publication in the Journal of Clinical Investigation.
Emory neurosurgeons see the technique as a “potentially transformative” way to calm some patients during awake brain surgery, even those who are not especially anxious. For optimal protection of critical brain functions during surgery, patients may need to be awake and not sedated, so that doctors can talk with them, assess their language skills, and detect impairments that may arise from resection. Read more
Researchers at Emory University School of Medicine have gained insight into a feature of fragile X syndrome, which is also seen in other neurological and neurodevelopmental disorders.
In a mouse model of fragile X syndrome, homeostatic mechanisms that would normally help brain cells adjust to developmental changes don’t work properly. This helps explain why cortical hyperexcitability, which is linked to sensory sensitivity and seizure susceptibility, gradually appears during brain development.
Studying a model of fragile X syndrome, Emory researchers were looking at neurons displaying single spiking and multi-spiking behavior.
These physiological insights could help guide clinical research and efforts at early intervention, the scientists say. The results were published Feb. 5 by Cell Reports (open access).
Fragile X syndrome is the most common inherited form of intellectual disability and a leading single-gene cause of autism. Individuals with fragile X syndrome often display sensory sensitivity and some — about 15 percent— have seizures.
Scientists’ explanation for these phenomena is cortical hyperexcitability, meaning that the response of the cortex (the outer part of the brain) to sensory input is more than typical. Cortical hyperexcitability has also been observed in the broader category of autism spectrum disorder, as well as migraine or after a stroke.
At Emory, graduate student Pernille Bülow forged a collaboration between Peter Wenner, PhD and Gary Bassell, PhD. Wenner, interested in homeostatic plasticity, and Bassell, an expert in fragile X neurobiology, wanted to investigate why a mechanism called homeostatic intrinsic plasticity does not compensate for the changes in the brain brought about in fragile X syndrome. More here.
Neurologist Raul Nogueira’s clinical research on thrombectomy, a life-saving intervention after ischemic stroke, is getting recognition – in non-traditional ways.
A group of Korean neurologists and radiologists recently analyzed the most mentioned neurointervention papers by “altmetrics.” Altmetrics measure the impact a research paper has by looking at online discussion – in international news media, blogs, Wikipedia and social media platforms, as well as attention from post-publication peer-review and patient advocacy groups.
Raul Noguiera, MD
As it turned out, one of Nogueira’s papers was the most mentioned and he was also an author on 12 of the 101 top articles. Nogueira was the first author of a 2018 paper in the New England Journal of Medicine, reporting on results from the DAWN trial. The study was a landmark, extending the time window for thrombectomy to 24 hours. Those treated with thrombectomy in addition to standard care regained significantly more functional independence after 90 days than those who received standard treatment only.
Another recent example that fits within altmetrics: The DAWN study was cited by the American Heart Association as a top research finding in stroke for 2018.
Nogueira is a professor of neurology, neurosurgery and radiology at Emory University School of Medicine and director of endovascular services at Grady Memorial Hospital’s Marcus Stroke & Neuroscience Center. Thrombectomy is the removal of a clot from a blood vessel in the brain – in this case, through a mechanical stent-retriever device.