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Clinical Trials, History, Immunology, Infectious Disease, Research

Stanford scientists strive to solve centuries-old puzzle: Why are young children so vulnerable to disease?

Stanford scientists strive to solve centuries-old puzzle: Why are young children so vulnerable to disease?

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Several months ago, Stanford immunologist Mark Davis, PhD, went for a stroll in Union Cemetery in Redwood City, Calif. (not far from the Stanford campus). Graves there date from the Civil War-era and Davis, who’s currently immersed in a study of childhood immunity, was intrigued.

“In the early years, you see entire families — mom, dad, and then a whole bunch of children’s headstones,” Davis told me. “It really brought home to me how differently we live now that we just take for granted a kid will survive and grow up.”

Vaccines arrived and childhood survival rates soared. Yet young children remain much more vulnerable to infectious diseases than adults. Why?

Davis and his team think vaccines trigger a set of changes that strengthens children’s immune systems — allowing them to ward off diseases they haven’t even heard of before. That’s why the researchers are conducting a group of studies, all focused on revealing new details about the immune system’s response to the flu vaccine. They need participants, particularly young children who have never received a flu vaccine before. They also need older children and twins. All participants will receive a licensed flu vaccine that will help protect from influenza this coming winter.

Davis and colleagues plan to investigate the children’s development of two types of immune cells — memory T and B cells — that are specialized to recognize certain foreign invaders. Interestingly, adults have T cells that spot diseases they’ve never been exposed to, such as HIV, Davis said. Yet newborns lack these specialized cells, leaving them vulnerable to infection.

“Somewhere between birth and adulthood we see the appearance of these memory T cells without having the particular disease,” Davis said. “It’s a real puzzle.”

Davis suspects that routine vaccines and infections may spur the development in children of a broad spectrum of memory T cells, ones that recognize all sorts of diseases. One study plans to follow children for several years, perhaps revealing how, and when, the children develop a full compliment of these memory T cells, Davis told me.

The studies are possible thanks to the development of new analytical techniques, according to virologist and immunologist Harry Greenberg, MD, who is working with Davis on the influenza studies.

“We’ve been studying influenza for half a century, but these new assays developed in the last five years offer hope we can develop better ways of protecting more people,” Greenberg told me.

More information about the flu vaccine studies and the Stanford-LPCH Vaccine Program is available here or (650) 498-7284.

Becky Bach is a proud graduate of the UC Santa Cruz Science Communication Program (go Banana Slugs!) and a science-writing intern at the Office of Communications and Public Affairs.

Previously: Q&A about enterovirus-D68 with Stanford/Packard infectious disease expert, Gut bacteria may influence effectiveness of flu vaccine and Side effects of childhood vaccines are extremely rare, new study finds
Photo by Gabriel Metsu

Applied Biotechnology, Bioengineering, Events, Medical Education, Stanford News, Technology

Stanford physicians and engineers showcase innovative health-care solutions

Stanford physicians and engineers showcase innovative health-care solutions

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A “breathalyzer” that noninvasively determines if patients have unsafe levels of ammonia in their blood. The discovery of a previously approved drug that also fights the Dengue virus. A smartphone-based eye-imaging system that can be used to diagnose vision problems remotely.

These are a few of the 40-plus inventions and clinical solutions presented at the first annual Spectrum Innovation Research Symposium, held last Friday at the Stanford School of Medicine. The event demonstrated the power of bringing together teams of physicians, bioinformaticists and engineers to apply new technologies and ideas to challenging medical problems. Also showcased were budding physician-scientists supported by the Spectrum KL2 and TL1 clinical research training awards. (In the photo above, Colleen Craig, MD, an endocrinology fellow, describes a novel treatment that she’s developing for gastric-bypass patients who suffer from severely low blood sugar.)

The buzz is that it’s going to be a good year for health-care breakthroughs

Spectrum, the recipient of Stanford’s NIH Clinical and Translational Science Award, annually gives up to $50,000 to investigator teams for year-long projects in the areas of drug discovery, medical technologies, predictives/diagnostics, population health sciences and community engagement. This program also provides these teams with training and mentoring to help them move their ideas rapidly from bench to bedside and into the community.

“These modest pilot awards have been immensely successful in stimulating innovative ideas across the spectrum of translational research,” said Spectrum’s director, Harry Greenberg, MD. “They have lead to new inventions that promote individual’s health, new ways of improving the health of the populations and new efforts to assist our surrounding community on health issues.”

As this year’s grantees were rolling up their poster presentations, next year’s scholars were rolling up their sleeves to finish their 2014-15 Spectrum grant proposals, which are due in a few days.

It’s been a pivotal year in medical technology, with the launch of an unprecedented number of game-changing inventions, such as the Mini-ION, a $900 USB-powered DNA sequencer, and Apple HealthKit, a health-and-fitness dashboard and developer kit. In the coming year, these will provide Stanford scholars with amazing technology platforms from which to launch medical solutions that are better, faster and cheaper.

“We are in the middle of amazing biomedical innovation here in Silicon Valley,” said Atul Butte, MD, PhD, and faculty director of the diagnostics/predictives program. “Spectrum enables us to fund the earliest of early technologies, more risky than even the usual angel investments, but with higher potential impacts. In the end, this gets technologies to patients and families that much sooner.”

Because of this, anticipation among the grant-approval committee members at the symposium was high — the buzz is that it’s going to be a good year for health-care breakthroughs.

Previously: Spectrum awards innovation grants to 23 projects, Stanford awarded more than $45 million to spur translational research in medicine, As part of annual tradition, budding physician-scientists display their work, and New class of physician-scientists showcase research
Photo by Kris Newby

Big data, In the News, Patient Care, Pediatrics, Stanford News

Examining the potential of big data to transform health care

Examining the potential of big data to transform health care

Back in 2011, rheumatologist Jennifer Frankovich, MD, and colleagues at Lucile Packard Children’s Hospital Stanford used aggregate patient data from electronic medical records in making a difficult and quick decision in the care of a 13-year-old girl with a rare disease.

Today on San Francisco’s KQED, Frankovich discusses the unusual case and the potential of big data to transform the practice of medicine. Stanford systems-medicine chief Atul Butte, MD, PhD, also weighed in on the topic in the segment by saying, “The idea here is [that] the scientific method itself is growing obsolete.” More from the piece:

Big data is more than medical records and environmental data, Butte says. It could (or already does) include the results of every clinical trial that’s ever been done, every lab test, Google search, tweet. The data from your fitBit.

Eventually, the challenge won’t be finding the data, it’ll be figuring out how to organize it all. “I think the computational side of this is, let’s try to connect everything to everything,” Butte says.

Frankovich agrees with Butte, noting that developing systems to accurately interpret genetic, medical or other health metrics is key if such practices are going to become the standard model of care.

Previously: How efforts to mine electronic health records influence clinical care, NIH Director: “Big Data should inspire us”, Chief technology officer of the United States to speak at Big Data in Biomedicine conference and A new view of patient data: Using electronic medical records to guide treatment

Addiction, In the News, Public Health

Stanford experts skeptical about motives behind e-cigarette health warnings

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Quotes can sometimes make or break a news article. I was skimming a New York Times article on new, harsh health warnings from tobacco companies when a quote from Stanford otolaryngologist Robert Jackler, MD, stopped me in my tracks.

“When I saw it, I nearly fell off my chair,” Jackler told the Times. What made a renowned expert in tobacco advertising fall off his chair? I was hooked (and not on cigarettes, thankfully) and had to keep reading.

It turns out that Jackler had spotted the warning on MarkTen e-cigarette packs, which details many of the deleterious effects of nicotine, calling it “very toxic by inhalation, in contact with the skin, or if swallowed.” The product is not to be used by children, women who are pregnant or breast-feeding, anyone with heart disease or high blood pressure, or those taking medication for depression or asthma. The list goes on.

These warnings are voluntary, explained the Times‘ Matt Richtel, who also wrote:

Experts with years studying tobacco company behavior say they strongly suspect several motives, but, chiefly, that the e-cigarette warnings are a very low-risk way for the companies to insulate themselves from future lawsuits and, even more broadly, to appear responsible, open and frank. By doing so, the experts said, big tobacco curries favor with consumers and regulators, earning a kind of legitimacy that they crave and have sought for decades. Plus, they get to appear more responsible than the smaller e-cigarette companies that seek to unseat them.

The tobacco companies say they are striving to be honest and open. With another choice quote, Stephanie Cordisco, president of the R. J. Reynolds Vapor Company, told the Times: “We’re here to make sure we can put this industry on the right side of history.”

Not so, Stanford science historian Robert Proctor, PhD, responded. He called the voluntary warnings “totally Orwellian.”

“They do everything for legal reasons, otherwise they’d stop making the world’s deadliest consumer products,” Proctor said.

Becky Bach is a former park ranger who now spends her time writing about science and practicing yoga. She is an intern in the Office of Communications and Public Affairs. 

Previously: How e-cigarettes are sparking a new wave of tobacco marketing, E-cigarettes and the FDA: A conversation with a tobacco-marketing researcher and What the experience of Swedish snuff can teach us about e-cigarettes
Photo by Lindsay Fox

CDC, Events, Global Health, Stanford News, Videos

Video of Stanford Ebola panel now available

Video of Stanford Ebola panel now available

Last week, a group of Stanford and CDC experts came together to address the health, governance, security and ethical dimensions of Ebola, the virus that is spreading rapidly in West Africa. Video of the lengthy and timely talk, courtesy of the Freeman Spogli Institute, is now available.

Previously: Ebola panel says 1.4 million cases possible, building trust key to containmentInterdisciplinary campus panel to examine Ebola outbreak from all angles, Expert panel discusses challenges of controlling Ebola in West Africa, Should we worry? Stanford’s global health chief weighs in on Ebola and Biosecurity experts discuss Ebola and related public health concerns and policy implications

Imaging, Research, Science, Stanford News

Stanford researcher details structure of sugar transporter called SWEET

Stanford researcher details structure of sugar transporter called SWEET

SemiSWEETSugar fuels life. But to power our cells, sugar molecules have to slip in and out of cells. And in humans, the sugar sometimes needs to travel deep into tissues such as the intestines or the brain, far removed from the bloodstream.

Thanks to technological advances, scientists are still making new discoveries about these basic processes. And now, a team led by Stanford molecular biologist Liang Feng, PhD, and Carnegie Institution/Stanford biologist Wolf Frommer, PhD,  has unraveled the molecular structure and function of a type of protein that straddles cell membranes, allowing sugar to pass.

The name of the compound — oh, those scientists and their senses of humor — is SWEET, which stands for “Sugars Will Eventually be Exported Transporters.” SWEETs are found in all sorts of creatures, including humans, and plants; bacteria have semiSWEETs that are about half the size of a SWEET.

To determine the structure of these super-small proteins, Feng and his team used powerful X-ray equipment at the Argonne National Laboratory in Illinois and the Stanford Synchrotron Radiation Lightsource on campus. “Before our study, we had no idea what the protein looked like and how it could function,” Feng told me.

As described in a paper published earlier this month in Nature, Feng and his colleagues learned that SWEET actively changes shape to swallow sugar, unlike a fixed channel such as a train tunnel. SWEET swings open jaws like a crocodile, clamps them shut, then shoots the sugar into the cell interior.

SWEETs, and the two other types of sugar transporters found in humans, could play a prominent role in a variety of human diseases, including diabetes, although most research now has been done in plants. The project produced what Feng calls “snapshots” of SWEET transporting sugar. Next, he plans to develop a moving “video” of the protein.

“We need to understand the blueprint of this machinery,” Feng said. “What we learn could be used to improve crop yield or to design drugs that can help with sugar-related diseases such as diabetes.”

Becky Bach is a former park ranger who now spends her time writing about science or on her yoga mat. She is a science-writing intern in the Office of Communications and Public Affairs. 

Previously: Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?, Joyride: Brief post-antibiotic sugar spike gives pathogens a lift, Short and sweet: Three days in a sugar solution, and you’ve got your see-through tissue sample 
Image courtesy of Liang Feng

Grand Roundup

Grand Roundup: Top posts for the week of Sept. 21

The five most-read stories this week on Scope were:

Study: Pregnancy causes surprising changes in how the immune system responds to the flu: New Stanford research shows that immune cells from pregnant women are strongly activated by influenza, which may explain the increased risk of flu complications in pregnancy.

Free online Stanford course examines medical education in the new millennium: At this year’s Stanford Medicine X, executive director Larry Chu, MD, announced the launch of the Medicine X Academy. As part of the academy, a massive open online course (MOOC) course titled “Medical Education in the New Millennium” began this week.

Exercise and your brain: Stanford research highlighted on NIH Director’s blog: In a blog entry, Francis Collins, MD, director of the National Institutes of Health, discussed research by Thomas Rando, MD, PhD, who studies stem cells in muscle and longevity, and Tony Wyss-Coray, PhD, who studies the immune system’s impact on the brain.

Treating an infection to prevent a cancer: H. pylori and stomach cancer: In a Viewpoint piece in the Journal of the American Medical Association, Stanford infectious disease specialist Julie Parsonnet, MD, and her co-authors discuss the link between gastric cancer and chronic infections of Helicobacter pylori.

Discovery may help predict how many days it will take for individual surgery patients to bounce back: Researchers here found that they could predict how well a patient would recover from surgery, based on the activity of a specific set of immune cells. Their work was published in Science Translational Medicine.

And still going strong – the most popular post from the past:

The mystery surrounding lung-transplant survival rates: A 2012 article in the San Francisco Chronicle offered a look at the challenges facing lung transplant patients and explored why a significant number don’t live beyond the five-year mark, despite improvements in survival rates.

Stanford News, Surgery, Videos

The importance of human connection as part of the patient experience

The importance of human connection as part of the patient experience

When I first heard Tim Engberg describe the feeling of intense loneliness and separation from humanity he felt as he was being wheeled on a gurney into surgery, I immediately pictured myself in a hospital bed staring at the ceiling, desperate for the touch of a familiar hand, afraid.  When you’re well, you forget so quickly how lonely and scary it is to be sick, and in Engberg’s case, with enormous pain in his neck, an infection threatening to render him paralyzed, and the enormity of the looming surgery, the sense of aloneness was overwhelming.

Engberg just so happens to be the vice president of Stanford Health Care’s Ambulatory Care. Most of his days he spends as an executive of a hospital, thinking about how to ensure that patients are being taken care of in the best possible way. Like many of us, it took being a patient himself to fully understand what a difference our nurses and doctors make and how they can pull someone back from the brink of despair to full recovery, or as Engberg puts it, “back into the human race.”

Engerb’s story is captured in the video above.

Evolution, In the News, Research, Stanford News

Blond ambition: Delving into the work of Stanford biologist David Kingsley

Blond ambition: Delving into the work of Stanford biologist David Kingsley

Thanks to a tiny fish called the stickleback, Stanford developmental biologist David Kingsley, PhD, and his team uncovered the genetic basis for blond hair earlier this year.

Kingsley’s research caught the eye of the team at HHMI Bulletin, which featured his discovery in their fall issue. As described in the piece, Kingsley and fellow researcher Catherine Guenther, PhD, discovered the change in a single point in the genetic sequence outside the gene itself. The discovery prompted a question because the gene, known as KITLG, is involved in many other key processes in developing organisms. Yet Kingsley found the control for hair color acted alone.

“The genetic mechanism that controls blond hair doesn’t alter the biology of any other part of the body. It’s a trait that’s skin deep, and only skin deep,” Kingsley told HHMI.

The HHMI feature also includes a video of Kingsley – above – that provides glimpses into his lab and reveals the sources of his inspiration (as well as his penchant for purchasing telescopes).

And for a Friday giggle, check out his lab members spelling his name with their bodies here.

Becky Bach is a science-writing intern at the Office of Communications and Public Affairs. 

Previously: It’s a blond thing: Stanford researchers suss out molecular basis of hair color, Something fishy: Threespine stickleback genome published by Stanford researchers and Hey guys, sometimes less is really more

Cancer, Clinical Trials, In the News, NIH, Patient Care, Research

National Cancer Institute looking for “Exceptional Responders”

OLYMPUS DIGITAL CAMERAHope is a powerful force in cancer treatment. For patients and their families, the hope is that, no matter how unlikely, the treatment plan will cure the patient and eradicate the disease. Sadly, this is sometimes a long shot. But sometimes, against all odds, the therapy is unusually successful. Now the National Cancer Institute is trying to learn why.

This week the institute launched a study into the phenomena of “Exceptional Responders” – that is, cancer patients who have a unique response to treatments (primarily chemotherapy) that have not been effective for most other patients. As they describe in a Q&A about the effort:

For this initiative, exceptional responders will be identified among patients enrolled in early-phase clinical trials in which fewer than 10 percent of the patients responded to the treatments being studied; patients who were treated with drugs not found to be generally effective for their disease; patients who were treated in later-phase clinical trials of single agents or combinations; and even patients who were treated with established therapies. In this pilot study, malignant tissue (and normal tissue, when possible) and clinical data will be obtained from a group of exceptional responders and analyzed in detail. The goal is to determine whether certain molecular features of the malignant tissue can predict responses to the same or similar drugs.

The researchers would like to obtain tumor samples, as well as normal tissue, from about 100 exceptional responders. They’ll compare DNA sequences and RNA transcript levels and other molecular measurements to try to understand why these patients were such outliers in their response to treatment. In at least one previous case, an exceptional responder with bladder cancer led researchers to discover a new molecular pathway involved in the development of the disease, and suggested new therapeutic approaches for other similar patients.

Do you know someone who might qualify for the study? More from the Q&A:

Patients who believe they may be exceptional responders should contact their physicians or clinical trialists to see if they can assist in submitting tissue for consideration. [...] Investigators who have tissue from a potential exceptional responder should send an email to NCIExceptionalResponders@mail.nih.gov. The email should include a short description of the case, without patient identifiers; information about whether tissue collected before the exceptional response is available; whether informed consent was given to use tissue for research; and the patient’s vital status.

Photo by pol sifter

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