MSCs: what’s in a name?

Whether they are "stem" or "stromal", from adult tissues or from umbilical cord blood, MSCs are being used for a lot of clinical trials. Read more

Mopping up immune troublemakers after transplant

Memory CD8+ T cells play an important role in kidney transplant rejection, and they resist drugs that would otherwise improve Read more

Tracking a frameshift through the ribosome

Ribosomal frameshifting, visualized through X-ray Read more

Department of Neurosurgery

An exceptional electrical thrill ride #CNS2018

A recent paper in Neuropsychologia got a lot of attention on Twitter and at the Cognitive Neuroscience Society meeting in Boston over the weekend. It discusses what can happen when the amygdala, a region of the brain known for regulating emotional responses, receives direct electrical stimulation. A thrill ride – but for only one study participant. Two of nine people noticed the electrical stimulation. One individual reported (a video is included in the paper):

“It was, um, it was terrifying, it was just…it was like I was about to get attacked by a dog. Like the moment, like someone unleashes a dog on you, and it’s just like it’s so close…

He also spontaneously reported “this is fun.” He further explained that he could distinguish feelings in his body that would normally be associated with fear recognized and the absence of an actual threat, making the experience “fun”.

But wait, why were Emory neuroscientists Cory Inman, Jon Willie and Stephan Hamann and colleagues doing this? Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Give a zap to Emory brain research for #STATMadness

Next week, we will be asking the Emory research community to support Emory’s entry in a contest. It’s like “Battle of the Bands.” Whoever gets the loudest cheers wins. We have some intriguing neuroscience research. Please help!

STAT Madness is a “March Madness” style bracket competition, but with biomedical research advances as competitors. Universities or research institutes nominate their champions, research that was published the previous year.

Our entry for 2018:

Direct amygdala stimulation can enhance human memory

The findings, from Cory Inman, Jon Willie and colleagues from the Department of Neurosurgery and Joe Manns from Psychology, were the first published example of electrical brain stimulation in humans giving an event-specific boost to memory lasting overnight. The research was conducted with epilepsy patients undergoing an invasive procedure for seizure diagnosis. However, the technology could one day be incorporated into a device aimed at helping those with memory impairments, such as people with traumatic brain injury or neurodegenerative diseases.

Extra note: you may have seen similar neuroscience research in a recent Nature Communications paper, which was described in the New York Times. Cory Inman had some comments below — he and neurosurgeon Robert Gross were co-authors:

The localization to the left lateral temporal cortex was interesting, because it hadn’t been identified as a region that modulates episodic or hippocampus-dependent memory. [The Emory authors stimulated the amygdala.] The more recent paper found a similar size of memory enhancement, with a slightly different and harder memory task of free recall, using “closed-loop” stimulation based on whether the brain is in a ‘bad’ encoding state. It’s possible that closed-loop stimulation could be used with the amygdala as well. 

Emory’s first opponoent is University of California, San Francisco. We are about half way down on the right side of the bracket.

As far as voting, you can fill out a whole bracket or you can just vote for Emory, along with other places you may feel an allegiance to. The contest will go several rounds. The first round begins on February 26. If Emory advances, then people will be able to continue voting for us starting March 2.

At the moment, you can sign up to be reminded to vote with an email address at:
https://signup.statnews.com/stat-madness

Starting Monday, February 26, you can follow the 2018 STAT Madness bracket and vote here:
https://www.statnews.com/feature/stat-madness/bracket/

Please share on social media using the hashtag #statmadness2018.

STAT is a life sciences-focused news site, launched in 2015 by the owner of the Boston Globe. It covers medical research and biotech nationally and internationally. Emory took part in 2017’s contest, with Tab Ansari’s groundbreaking work on SIV remission, a collaboration with Tony Fauci’s lab at NIAID.

 

 

Posted on by Quinn Eastman in Neuro Leave a comment

Five hot projects at Emory in 2017

CRISPR-Cas9 gene editing alleviates Huntington’s in mouse model

— Shi-Hua and Xiao-Jiang Li. This project is progressing, with funding from NCATS and a pig-oriented collaboration with partners in China.

Once activated by cancer immunotherapy drugs, T cells still need fuel (CD28)

— Rafi Ahmed’s lab at Emory Vaccine Center. Also see T cell revival predicts lung cancer outcomes. At Thursday’s Winship symposium on cancer immunotherapy, Rafi said the name of the game is now combinations, with an especially good one being PD-1 inhibitors plus IL2.

Pilot study shows direct amygdala stimulation can enhance human memory

— Cory Inman, Joe Manns, Jon Willie. Effects being optimized, see SFN abstract.

Immune responses of five returning travelers infected by Zika virus

— Lilin Lai, Mark Mulligan. Covered here, Emory Hope Clinic and Baylor have data from more patients.

Frog slime kills flu virus

— Joshy Jacob’s lab at Emory Vaccine Center. A follow-up peptide with a name referencing Star Wars is coming.

Posted on by Quinn Eastman in Uncategorized Leave a comment

Cell therapy clinical trial in stroke

Emory neurosurgeon Robert Gross was recently quoted in a Tennessee newspaper article about a clinical trial of cell therapy for stroke. He used cautionary language to set expectations.

“We’re still in the very early exploratory phases of this type of work,” Gross told the Chattanooga Times Free Press. “In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that.”

A more preliminary study (just 18 patients) using the same approach at Stanford and University of Pittsburgh was published this summer in Stroke, which says it was the “first reported intracerebral stem cell transplant study for stroke in North America.” The San Diego Union Tribune made an effort to be balanced in how the results were described:

Stroke patients who received genetically modified stem cells significantly recovered their mobility… Outcomes varied, but more than a third experienced significant benefit.

The newspaper articles made us curious about what these cells actually are. They’re mesenchymal stromal cells, engineered with an extra modified Notch gene. That extra gene drives them to make more supportive factors for neurons, but it doesn’t turn them into neurons. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Tools for illuminating brain function make their own light

Optogenetics has taken neuroscience by storm in recent years because the technique allows scientists to study the brain conveniently in animals, activating or inhibiting selected groups of neurons at the flip of a switch.  Most often, scientists use a fiber optic cable to deliver light into the brain.

Researchers at Emory and Georgia Tech have developed tools that could allow neuroscientists to put aside the fiber optic cable, and use a glowing protein from coral as the light source instead.

Biomedical engineering student Jack Tung and neurosurgeon/neuroscientist Robert Gross, MD, PhD have dubbed these tools “inhibitory luminopsins” because they inhibit neuronal activity both in response to light and to a chemical supplied from outside.

A demonstration of the luminopsins’ capabilities was published September 24 in the journal Scientific Reports.  The authors show that these tools enabled them to modulate neuronal firing, both in culture and in vivo, and modify the behavior of live animals.

Tung and Gross are now using inhibitory luminopsins to study ways to halt or prevent seizure activity in animals.

“We think that this approach may be particularly useful for modeling treatments for generalized seizures and seizures that involve multiple areas of the brain,” Tung says. “We’re also working on making luminopsins responsive to seizure activity: turning on the light only when it is needed, in a closed-loop feedback controlled fashion.” More here. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

The buzz of consciousness and how seizures disrupt it

These days, it sounds a bit old-fashioned to ask the question: “Where is consciousness located in the brain?” The prevailing thinking is that consciousness lives in the network, rather than in one particular place. Still, neuroscientists sometimes get an intriguing glimpse of a critical link in the network.

A recent paper in the journal Epilepsy & Behavior describes an epilepsy patient who had electrodes implanted within her brain at Emory University Hospital, because neurologists wanted to understand where her seizures were coming from and plan possible surgery. Medication had not controlled her seizures and previous surgery elsewhere had not either.

ElectrodesSmaller

MRI showing electrode placement. Yellow outline indicates the location of the caudate and thalamus. Image from Leeman-Markowsi et al, Epilepsy & Behavior (2015).

During intracranial EEG monitoring, implanted electrodes detected a pattern of signals coming from one part of the thalamus, a central region of the brain. The pattern was present when the patient was conscious, and then stopped as soon as seizure activity made her lose awareness.

The pattern of signals had a characteristic frequency – around 35 times per second – so it helps to think of the signal as an auditory tone. Lead author Beth Leeman-Markowski, director of EUH’s Epilepsy Monitoring Unit at the time when the patient was evaluated, describes the signal as a “buzz.”

“That buzz has something to do with maintenance of consciousness,” she says. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Brain surgery with a light touch

As part of reporting on neurosurgeon Robert Gross’s work with patients who have drug-resistant epilepsy, I interviewed a remarkable woman, Barbara Olds. She had laser ablation surgery for temporal lobe epilepsy in 2012, which drastically reduced her seizures and relieved her epilepsy-associated depression.

Emory Medicine’s editor decided to focus on deep brain stimulation, rather than ablative surgery, so Ms. Olds’ experiences were not part of the magazine feature. Still, talking with her highlighted some interesting questions for me.

Emory neuropsychologist Dan Drane, who probes the effects of epilepsy surgery on memory and language abilities, had identified Olds as a good example of how the more precise stereotactic laser ablation procedure pioneered by Gross can preserve those cognitive functions, in contrast to an open resection. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Without intent, yet malignant

Brain cancer doesn’t have a purpose or intent. It’s just a derangement of molecular biology, cells that keep growing when they’re not supposed to.

But it’s difficult not to think in terms of purpose or intent when looking at what cancers do.  For example, Winship Cancer Institute scientists Abdessamad (Samad) Zerrouqi, Beata Pyrzynska, Dan Brat and Erwin Van Meir have a recent paper in Cancer Research examining how glioblastoma cells regulate the process of blood clotting.*

Blood clots, often in the legs, are a frequent occurrence in patients fighting glioblastoma, the most common and the most aggressive form of brain cancer. Zerrouqi and http://www.gooakley.com/ Van Meir show that a tumor suppressor gene (p14ARF) that is often mutated in glioblastoma stops them from activating blood clotting. Take away the gene and glioblastoma cells activate the clotting process more.

At first glance, a puzzle emerges: why would a cancer “want” to induce blood clots? Cancer cells often send out growth factors that stimulate the growth of new blood vessels (angiogenesis). The cells are growing fast, thus they need their own blood supply. Activating clotting seems contradictory: why build a new highway and then induce a traffic jam?

Thrombosis-necrosis

The two left arrows indicate clots causing necrosis around the vessels. Cells at the edge of the necrotic zone (right arrow) tend to be more proliferative and invasive. Image courtesy of Zerrouqi.

In a way, tumor cells are acting somewhat Nietzschean, blindly managing their own cheap oakley evolution according to the principle “Whatever doesn’t kill me makes me stronger.”

Blood clots lead to both destruction of the healthy and tumor tissue and hypoxia, a shortage of oxygen that drives more aggressiveness in the tumor. The clots create “micro-necroses” at the leading edge of the tumor that over time probably fuse and create a big central necrosis.

“The paradox is that the tumor kills itself and the normal brain, yet the capacity of doing this is the hallmark of the most malignant form of this tumor,” Van Meir says.

“The advantage of tumoral thrombosis will be selection of cells to progress to higher aggressiveness: infiltrative,  resistant to death with conventional Oakley Sunglasses cheap therapies, metabolically adapted to low levels of oxygen and nutrients,” Zerrouqi says. “At this stage, the tumor seems to have a clear deadly intent.”

A fragment of one of the proteins that cancer cells use to exert the clotting effect, called TFPI2, could be used to antagonize blood clotting  therapeutically, they write in Cancer Research. The findings could also have implications for understanding the effects of current medications, such as the angiogenesis inhibitor bevacizumab, also known as Avastin.

*A paper by Van Meir and Dan Brat from 2005 is the top Google link under the search term “glioblastoma clotting.”

Posted on by Quinn Eastman in Cancer Leave a comment

Emory researchers receive grants to further work in pediatric brain tumor research

Dr. Castellino explains his research on medulloblastomas to participants attending the SBTF’s Grant Award Ceremony.

Two Emory researchers are being recognized by the Southeastern Brain Tumor Foundation (SBTF) for their work in pediatric brain tumor research.

Tracey-Ann Read, PhD, assistant professor in the Department of Neurosurgery, Emory University School of Medicine and director of the Pediatric Neuro-Oncology Laboratory at Emory was awarded a $75,000 grant for her work. She is studying the cell of origin that is responsible for the highly malignant pediatric brain tumor known as an Atypical Teratoid Rhabdoid Tumor (AT/RT). She is also developing a mouse model to study this very lethal brain cancer that occurs in early childhood.

Robert Craig Castellino, MD, assistant professor of pediatrics at Emory and pediatric hematologist/oncologist at Children’s Healthcare of Atlanta at Egleston received $50,000 to support his research efforts. He is studying how the childhood brain cancer, known as medulloblastoma, can metastasize from the brain to other sites in the body, specifically the spine. Medulloblastoma is the most common pediatric malignant brain tumor.

SBTF board members and researchers who were awarded grants pose following the April ceremony.

Read and Castellino received the awards at the SBTF’s Grant Awards Ceremony in April at Emory University Hospital Midtown. Two other researchers from Duke University were also presented with grant money for their contributions in brain tumor research in adults.

Emory neurosurgeon Costas Hadjipanayis, MD, PhD, is the president of the Southeastern Brain Tumor Foundation. He says research, from young investigators such as these, is crucial in the race to find a cure for brain tumors. As federal research funding becomes even more difficult to obtain with cuts in funding, private foundation grants, such as from the SBTF, can permit researchers to start important research projects that can provide preliminary data for bigger grant proposals.

The SBTF awards $200,000-300,000 each year to major medical centers throughout the Southeast in support of cutting-edge brain and spinal tumor research.

 

Posted on by Janet Christenbury in Cancer Leave a comment