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Neuroscience, Sleep, Stanford News, Videos

Exploring the history and study of sleep with Stanford’s William Dement

Exploring the history and study of sleep with Stanford's William Dement

The Good Stuff, a playlist-based online show, kicked off a week-long series about sleep with an interview with well-known sleep researcher William Dement, MD, PhD, who many refer to as the “father of sleep medicine.”

It’s surprising how new the field of sleep research is. As host Matt says about the discovery of rapid eye movement during sleep in the 1950s, “We developed the atom bomb before we noticed people’s eyes were moving while they slept?” Dement was the first to find that we sleep during REM sleep as a medical student at the University of Chicago. He later went on to describe the five stages of sleep as well as to study sleep disorders and the effects of sleep deprivation.

Dement is amusing and charming in the interview, and I feel like I got a glimpse into why Dement’s Sleep and Dreams class at Stanford is so popular.

Part two of the series – which addresses the question “Why do we sleep?” and features Dement and Clete Kushida, MD, PhD, medical director of the Stanford Sleep Medicine Center – was posted today, and parts three and four will be posted later this week.

Previously: “Father of Sleep Medicine” talks with CNN about what happens when we don’t sleep well, Stanford doc gives teens a crash course on the dangers of sleep deprivation, William Dement: Stanford Medicine’s “Sandman”, Stanford docs discuss all things sleepThanks, Jerry: Honoring pioneering Stanford sleep research and An afternoon with bedheads and Deadheads

Cancer, Neuroscience, Pediatrics, Research, Stanford News, Videos

How one family’s generosity helped advance research on the deadliest childhood brain tumor

How one family’s generosity helped advance research on the deadliest childhood brain tumor

Back in February 2014, Libby and Tony Kranz found themselves at the center of every parent’s worst nightmare. Their six-year-old daughter Jennifer died just four months after being diagnosed with diffused intrinsic pontine glioma (DIPG), an incurable and fatal brain tumor. At the time, the Kranzes decided to generously donate their daughter’s brain to research in hopes that scientists could hopefully develop more effective treatments for DIPG, which affects 200-400 school-aged children in the United States annually and has a five-year survival rate of less than 1 percent.

As reported in the above Bay Area Proud segment, Michelle Monje, MD, PhD, an assistant professor of neurology and neurological sciences who sees patients at Lucile Packard Children’s Hospital Stanford, and colleagues harvested Jennifer’s tumor and successfully created a line of DIPG stem cells, one of only 16 in existence in the world. More from the story:

Using Jennifer’s stem cell lines and others, Monje and her team tested dozens of existing chemotherapy drugs to see if any were effective against DIPG. One appears to be working.

The drug was able to slow the growth of a DIPG tumor in a laboratory setting. Monje’s hope is that this treatment one day could extend the life of children diagnosed with DIPG by as many as six months.

That would have more than doubled Jennifer’s life expectancy.

“It’s a step in the right direction if we can effectively prolong life and prolong quality of life,” Monje said.

Libby Kranz says that for their family, donating their daughter’s tumor to researchers “just felt right.” She and Tony hope that by aiding the research efforts, parents and families will have more, and better quality time with their sick children.

“It’s incredible and it’s humbling,” she said, “to know my daughter is part of it, and that we’re part of it too.”

Previously: Existing drug shows early promise against deadly childhood brain tumor, Stanford brain tumor research featured on “Bay Area Proud,Emmy nod for film about Stanford brain tumor research – and the little boy who made it possible and Finding hope for rare pediatric brain tumor

Behavioral Science, In the News, Mental Health, Neuroscience, Research, Science

Inside the brain of optogenetics pioneer Karl Deisseroth

Inside the brain of optogenetics pioneer Karl Deisseroth

brain-494152_1280Lighting the brain,” a recent New Yorker profile, offers insight into the brain of Karl Deisseroth, MD, PhD, the well-known innovator of both optogenetics and CLARITY. (Optogenetics is a genetic engineering feat that allows researchers to control neurons in living animals using light. CLARITY is a technique that makes individual neural connections visible.)

Deisseroth, readers of the article learn, is a guy who shows up to his leading scientific laboratory wearing jeans and a t-shirt and who doesn’t let a little fender bender tweak his mood.

Yes, he’s brilliant. His ability to instantly memorize information morphed into a “circus act” of sorts when he was in elementary school. He began medical school at age 20. But, he’s also driven and hard working. When optogenetics encountered early resistance and doubt after its initial publication in 2005, Deisseroth “began working furiously,” the article states. Into work before 6 a.m., Deisseroth slaved over his brainchild often until 1 a.m., his wife, Michelle Monje, MD, PhD, reported.

It took a few more papers — and demonstrations of the applicability of optogenetics to examine real diseases — for the scientific community to catch on. But then, like a contagion of scientific glee, optogenetics rocked the neuroscience community.

Monje realized its popularity at a recent scientific conference:

“People were stopping us at the airport asking to take a picture with him, asking for autographs,” she said. “He can’t walk through the conference hall—there’s a mob. It’s like Beatlemania. I realized, I’m married to a Beatle. The nerdy Beatle.”

For more on the “nerdy Beatle,” and the science behind both optogenetics and CLARITY, check out the article for yourself. It’s well worth your brain power.

Previously: Stanford’s Karl Deisseroth awarded prestigious Albany Prize, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact and New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics
Image by Tumisu

Neuroscience, Research, Stanford News

Stanford neurobiologist takes meandering path to her line of work

Stanford neurobiologist takes meandering path to her line of work

Professor Lisa Giocomo, i Assistant Professor of Neurobiology at the  Stanford University School of Medicine in her lab on Monday, April 27, 2015. ( Norbert von der Groeben/Stanford Health Care )

Why can you stumble, without incident, from your bed to the coffee maker in your kitchen each morning, even though you’re not fully awake? As I write in the latest issue of Inside Stanford Medicine, Lisa Giocomo, PhD, assistant professor of neurobiology, knows why.

Giocomo studies special neurons in your brain called “grid cells” that help us remember our environment. Grid cells keep track of physical locations and can be thought of as the brain’s GPS. From grid cell activity, scientists can chart the path an animal took, such as if it walked in a straight line.

While holding a cup of coffee, Giocomo chatted with me recently about how she became a neurobiologist. Giocomo’s path to the field wasn’t a straight line; it included stops at a small mountain town in Colorado, Baylor University, Boston University, and the Kavli Institute for Systems Neuroscience in Norway. In Norway Giocomo worked with 2014 Nobel laureates Edvard Moser, PhD, and May-Britt Moser, PhD, conducting research on the GPS-like grid cells. (“It was like magic when I talked about my project idea with the Mosers,” she recalled fondly.)

“I started out being interested in biology and then I went into psychology,” she told me. “In the end, I came back to neuroscience and biology.”

Giocomo opened her lab in Stanford’s neurobiology department in 2013. To read more about her journey here, check out the full piece.

Kimberlee D’Ardenne was a writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: Stanford neurobiologist shares insights from working in Nobel-winning lab
Photo by Norbert von der Groeben

Big data, Neuroscience, Videos

Countdown to Big Data in Biomedicine: Mining medical records to identify patterns in public health

Countdown to Big Data in Biomedicine: Mining medical records to identify patterns in public health

video platform video management video solutionsvideo player

The routine information contained in medical records holds the potential to unlock important public-health discoveries. That was the message conveyed at the 2014 Big Data in Biomedicine conference at Stanford by Martin Landray, PhD, a professor of medicine and epidemiology at Oxford University and deputy director of the Big Data Institute within the Li Ka Shing Centre for Health Information and Discovery. In the above video from last year’s event, Landray explains how he and colleagues are working to better understand the determinants of common life-threatening and disabling diseases through the design, conduct and analysis of large-scale epidemiological studies and the widespread dissemination of both the findings and methods used to generate them.

This month, Landray will return to the Big Data in Biomedicine conference and moderate a discussion on neuroimaging. Among the panelists are Michael Greicius, MD, associate professor in the Department of Neurology and Neurological Sciences at Stanford, and Brian Wandell, PhD, founding director of Stanford’s Center for Cognitive and Neurobiological Imaging and deputy director of the Stanford Neurosciences Institute.

Registration for the conference, which will be held May 20-22 at Stanford, is currently open. More details about the program can be found on its website.

Previously: Stanford bioengineer discusses mining social media and smartphone data for biomedical research, Using genetics to answer fundamental questions in biology, medicine and anthropologyBig data used to help identify patients at risk of deadly high-cholesterol disorder, Examining the potential of big data to transform health care and Registration for Big Data in Biomedicine conference now open

Bioengineering, Imaging, Neuroscience, Research, Stanford News, Stem Cells

New way to watch what stem cells transplanted into the brain do once they get there

New way to watch what stem cells transplanted into the brain do once they get there

binocularsStem cell replacement therapy is a promising but problem-plagued medical intervention.

In a recent news release detailing a possible way forward, I wrote:

Many brain disorders, such as Parkinson’s disease, are characterized by defective nerve cells in specific brain regions. This makes disorders such as Parkinson’s excellent candidates for stem cell therapies, in which the defective nerve cells are replaced. But the experiments in which such procedures have been attempted have met with mixed results, and those conducting the experiments are hard put to explain them.

That’s because there’s been no good way to evaluate what those transplanted stems cells are doing once you’ve put them inside a living individual. I mean, you’re not gonna break into someone’s brain every couple of days to take a peek, right? Instead, you have to look for behavioral changes. Is the patient or experimental animal walking better (if you’re trying to treat Parkinson’s), or (if it’s Alzheimer’s) remembering better ? Then, even when you see those changes, you still don’t know whether new nerve cells derived from the newly transplanted cells integrated into the proper brain circuits and are now functioning correctly there, or whether the originally transplanted cells are just sitting around secreting some kind of feel-good factor to pep up ailing cells in the vicinity, juicing their  performance. Or maybe it was a placebo effect.

It’s hard to improve on a procedure when you don’t really know what went wrong – or even what went right – on the last attempt. Optimizing the regimen becomes a matter of guesswork and luck.

But in a new study in NeuroImage, neuroscientist/bioengineer Jin Hyung Lee, PhD, and her colleagues came up with a way to peer deep into the living brain and view the results of a stem-cell transplant procedure. They combined an established brain-imaging technique with a newer but increasingly widespread one, called optogenetics, that lets researchers stimulate specific cells.

The first step in optogenetics is to genetically modify the cells you want to stimulate, so that their surfaces become coated by a photosensitive protein that generates electric current in response to laser light. Lee’s team performed this operation on the stem cells before transplanting them into rats’ brains. This way, they could selectively stimulate nerve cells derived from those stem cells and,  using the brain-imaging technique, see if doing so triggered nerve-cell activity at the site of the transplant as well as other places in the brain with which the new cells had established connections.

In these experiments, the stem-cell-derived nerve cells survived, matured into nerve cells, integrated into targeted brain circuits and, most important, fired on cue and ignited activity in downstream nerve circuits. But had all that not happened, at least the researchers would have been able to pinpoint the weak link in the chain.

In principle, the new approach should be possible to use for all kinds of stem-cell therapies, and in humans as well as animals. As Lee told me when I interviewed her for my release on her new study, “If we can watch the new cells’ behaviors for weeks and months after we’ve transplanted them, we can learn – much more quickly and in a guided way rather than a trial-and-error fashion – what kind of cells to put in, exactly where to put them, and how.”

If this light-driven stem-cell-monitoring technique or some others I’ve reported on hold up, brave explorers may no longer have to poke around in the dark.

Previously: Alchemy: From liposuction fluid to new liver cells, Iron-supplement-slurping stem cells can be transplanted, then tracked to make sure they’re making new knees, You’ve got a lot of nerve! Industrial-scale procedure for generating plenty of personalized nerve cells and Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later
Photo by Nicki Dugan Pogue

AHCJ15, Applied Biotechnology, Imaging, Mental Health, Neuroscience, Technology

Talking about “mouseheimers,” and a call for new neuroscience technologies

Talking about "mouseheimers," and a call for new neuroscience technologies

3723710203_1b8c9d96ed_zOur ability to technologically assess the brain has room for improvement, according to panelists at the recent Association of Health Care Journalism 2015 conference. Amit Etkin, PhD, MD, neuropsychiatrist and psychiatrist at Stanford, summed it up when he said, “We need to develop tools to answer questions we want to ask, rather than ask questions we can answer with the tools we have.”

Etkin asserted that there have been no fundamental advances in psychiatry since 1987; all the medications put out now are basically the same, and the treatments work partially, sometimes, and for only some people. Interdisciplinary work combining psychiatry, neuroscience, and radiology is the frontier: Researchers are just getting a sense of how “interventional neuroscience,” such as that pioneered at the interdisciplinary NeuroCircuit initiative at the Stanford Neurosciences Institute, can identify which brain regions control various processes. This involves looking at brain signatures that are common across disorders, instead of dividing and parsing symptoms, which is the approach of the Diagnostic and Statistical Manual of Mental Disorders.

Researchers are searching for an ideal marker for Alzheimer’s: something predictive (will you get the disease?), diagnostic (do you have the disease?), and dynamic (how severe is your disease right now?)

Michael Greicius, MD, MPH, professor of neurology and neurological sciences at Stanford, researches Alzheimer’s and has a bone to pick with media hype about Alzheimer’s research conducted in mice. What the mice have shouldn’t be considered the same condition, he says, so he’s termed it “mouseheimer’s.” Only 2 percent of the Alzheimer’s population has the dominant, inherited, exceedingly potent genetic form, which is the form used in research on rodents. Further, the mice are double or even triple transgenic. We still use these improbable biological hosts because we need an artificial model: Alzheimer’s is really just a human thing, and even great apes don’t get it. The next best modeling possibility, he suggested, are flies.

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Behavioral Science, In the News, Neuroscience, Research

Embrace your stress: From enemy to friend

Embrace your stress: From enemy to friend

2204059683_09eb09601b_zStress isn’t evil, health psychologist Kelly McGonigal, PhD, emphasized on KQED’s Forum on Friday. “Just a few years ago, that would have sounded like nonsense. But now, thanks in part to several appearances coinciding with the publication of her book, “The Upside of Stress,” McGonigal is making in-roads on the “stress-as-boogeyman” narrative.

By embracing stress, accepting it as your body’s natural response to events, people can live longer and even channel their stress into a productive form, she said.

“One way to think about stress is that it’s energy and you get to decide what the right thing to do with that energy is,” McGonigal said.

Just as top performers and athletes capture the momentum of stress to improve their performance, all of us can learn to relate to stress in a way that leaves us wiser and stronger, she explained.

Stress can also be a catalyst to strengthen relationships: “It’s part of the brain’s  and body’s motivation to help you connect with others and help you strengthen social bonds.”

During rough patches, it can also be immensely helpful to maintain the perspective that life is teaching you a lesson that will leave you stronger, McGonigal told listeners.

Previously: Tend and befriend — helping you helps me, Resolution check-in with a Stanford psychologist, one week into the new year and Exploring the costs and deaths associated with workplace stress
Image by bottled_void

Cancer, Neuroscience, Pediatrics, Research, Stanford News, Videos

Brain tumor growth driven by neuronal activity, Stanford-led study finds

Brain tumor growth driven by neuronal activity, Stanford-led study finds

Nerve activity in the cerebral cortex can drive the growth of deadly brain tumors called high-grade gliomas, new research has found. The finding, from a study of mice with human brain tumors, provides a surprising example of an organ’s function driving the growth of tumors within it, according to Michelle Monje, MD, PhD, the Stanford neuroscientist who led the work. The work appears online today in Cell.

High-grade gliomas include tumors that affect children, teens and adults. They are the most lethal of all brain tumors, and their survival rates have scarcely improved in 30 years. Monje’s team and others around the world are trying to learn how the tumors arise and grow, with the hope that this understanding will enable development of new drugs that specifically attack the tumors’ vulnerabilities.

From our press release about the research:

Monje’s team identified a specific protein, called neuroligin-3, which is largely responsible for the increase in tumor growth associated with neuronal activity in the cerebral cortex. Neuroligin-3 had similar effects across the different types of high-grade gliomas, in spite of the fact that the four cancers have different molecular and genetic characteristics.

“To see a microenvironmental factor that affects all of these very distinct classes of high-grade gliomas was a big surprise,” Monje said.

The identity of the factor was also unexpected. In healthy tissue, neuroligin-3 helps to direct the formation and activity of synapses, playing an important role in the brain’s ability to remodel itself. The new study showed that a secreted form of neuroligin-3 promotes tumor growth.

“This group of tumors hijacks a basic mechanism of neuroplasticity,” Monje said.

Blocking the tumor-stimulating effects of neuroligin-3 might be an effective treatment for high-grade gliomas, Monje added.

In the video above, Monje describes some of the earlier work that led her team to ask whether nerve activity could drive tumor growth. In the healthy brain, it’s important for neuronal activity to be able to modify how the brain grows and develops, she explains – this is how experience changes our brains. But: “The growth-inducing effects of neuronal activity are very robust and it made me wonder if a similar physiology was being hijacked by glioma cells,” she says in the video.

Previously: Emmy nod for film about Stanford brain tumor research — and the little boy who made it possible, Big advance against a vicious pediatric brain tumor and New Stanford trial targets rare brain tumor

Biomed Bites, Imaging, Neuroscience, Research, Science, Videos

Vrrrooom, vrrrooom vesicles: A Stanford researcher’s work on neurotransmission

Vrrrooom, vrrrooom vesicles: A Stanford researcher's work on neurotransmission

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers.

When one neuron wants to communicate with another neuron, it doesn’t talk, make gestures, or perform an interpretive dance. Instead, it ejects a vesicle filled with chemical information. That vesicle travels like an interstellar ship to the next neuron, which sucks it up, receiving the message.

And this isn’t a slow, hmm, maybe-I-should-send-this-out-sometime-today kind of message.

“The process of effusion of synaptic vesicles is very fast,” says Axel Brunger, PhD, in the video above. “It occurs on the order of a millisecond. It’s one of the fastest known biological processes, so we’re trying to understand this process at a molecular level and how it actually works is a big mystery at the moment.”

Brunger, the chair of the Department of Molecular and Cellular Physiology, and his team use a variety of optical imaging methods and high-resolution structural methods to examine the transmission of synaptic vesicles:

We’re now using our [in vitro] system to study the effect of a number of factors, including factors involved in a number of diseases.

What we are hoping from these studies is to obtain a better understanding of how these factors and then secondly and importantly, to develop new strategies or therapeutics to combat these diseases.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: New insights into how the brain stays bright, Revealed: The likely role of Parkinson’s protein in the healthy brain and Examining the potential of creating new synapses in old or damaged brains 

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