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Events, Medical Education, Stanford News

TEDMED, in pictures

TEDMED, in pictures

A group of MD and PhD students represented Stanford at TEDMED 2015, which was held last week. Several students have written about their experiences on Scope, and here now are some of their photos from the two-and-a-half-day event.

More photos of Stanford Medicine events, people and places can be found on Instagram.

Photos by Eric Trac, Afaaf Shakir, Chao Long, Lichy Han and Thomas Chew

Big data, Cancer, Genetics, NIH, Precision health, Research, Stanford News

“Housekeeping” RNAs have important, and unsuspected, role in cancer prevention, study shows

"Housekeeping" RNAs have important, and unsuspected, role in cancer prevention, study shows

BroomsNot every character in a novel is a princess, a knight or a king. It’s the same for our cellular cast of characters. Most molecules spend their time completing the thousands of mundane tasks necessary to keep our cells humming smoothly. Many of these are referred to as “housekeeping” genes or proteins, and biologists tend to focus their attentions on other, more flashy players.

Now dermatologists Paul Khavari, MD, PhD, and Zurab Siprashvili, PhD, have found that a pair of housekeeping RNA molecules play an important role in cancer prevention. They published their findings yesterday in Nature Genetics.

As I explain in our release:

[The researchers] compared 5,473 tumor genomes with the genomes obtained from surrounding normal tissue in 21 different types of cancer. In many ways, cancer cells represent biology’s wild west. These cells divide rampantly in the absence of normal biological checkpoints, and, as a result, they mutate or even lose genes at much higher rate than normal. As errors accumulate in the genome, things go ever more haywire.

The researchers found that a pair of snoRNAs called SNORD50A/B had been deleted in 10 to 40 percent of tumors in 12 common human cancers, including skin, breast, ovarian, liver and lung. They also noted that breast cancer patients whose tumors had deleted SNORD50A/B, and skin cancer patients whose tumors made lower levels of the RNAs than normal tissue, were less likely than other similar patients to survive their disease.

The researchers used data from the National Institutes of Health’s The Cancer Genome Atlas to find that the RNAs are frequently deleted in tumor tissue. They further went on to show that the RNAs bind an important cancer-associated protein called KRAS and keep it from associating with an activating molecule.

“This is really last thing we would have expected,” said Khavari. “It was particularly surprising because my lab has been studying KRAS intensively for more than a decade, so it was quite a coincidence.”

The researchers believe that understanding more about how the RNAs inhibit KRAS activation could point to possible new therapies for many types of human cancers.

Previously: Listening in on the Ras pathway identifies new target for cancer therapySmoking gun or hit-and-run? How oncogenes make good cells go bad  and Linking cancer gene expression with survival rates, Stanford researchers bring “big data” into the clinic 
Photo by Rob Shenk

Science, Stanford News

A musician amongst the scientists

A musician amongst the scientists

Julie Saiki in her lab - 560

I remember the anxiety I felt during my first college chemistry course. The other students seemed so prepared and confident while I worried about asking an obviously stupid question.

I wonder how much scarier it would have been if I hadn’t taken a full load of science classes in high school? Or if instead of being surrounded by incoming freshman, my classmates included biology, chemistry and engineering graduate students?

This was the situation that Julie Saiki faced when she enrolled in a Stanford’s chemical and systems biology course in drug design and development several years ago. Saiki, a musicology PhD student, had spent her high-school years practicing and performing the violin and viola. After college she lived in Austria for a year, researching 19th and 20th century Austrian chamber music on a Fulbright scholarship. But her career trajectory took a turn. As I wrote in a recent profile article:

Saiki’s plans for a doctorate in musicology were knocked off course after she was diagnosed with ulcerative colitis, a disabling inflammation of the colon. It wasn’t the disease but the cure that sent her in a new academic direction. An herbal remedy put her symptoms into remission, and she went looking for a way to make it available to others. Despite having no science background, she enrolled in a course on drug development; successfully pitched her idea to SPARK, Stanford’s drug development training program; and received approval from the U.S. Food and Drug Administration to begin a clinical trial. Each step brought her cure closer to patients, but the experience, and her success, caused her to re-evaluate her career.

I also describe in the piece the initial thoughts of Daria Mochly-Rosen, PhD, director of SPARK:

Saiki, Mochly-Rosen observed, was a quiet student but whenever she was directly questioned about her group’s progress or approach, her answers were clear and confident. Saiki admits that initially the science lectures were over her head, but her group’s project — a probiotic treatment for Clostridium difficile infections — included market research and how to satisfy regulatory requirements, things Saiki found she could contribute to. She set about to master the individual parts of the process, similar to how she would approach a new piece of music. “You pick things up once you start putting the pieces together,” she said.

Another aspect about Saiki that impressed her mentors at SPARK were her presentation skills. When I talked to her undergraduate violin instructor, Colgate University professor Laura Klugherz, she commented that part of a musician’s training is learning to calm their nerves to the point that they are capable of taking the stage to perform their music beautifully and flawlessly.

I suspect that after playing solo recitals, a room full of scientists isn’t quite so intimidating.

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a former writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development, Ask Stanford Med: Pediatric gastroenterologist taking questions on inflammatory bowel diseases and Stanford Medicine Music Network brings together healers, musicians and music lovers
Photo of Julie Saiki by Norbert von der Groeben

Evolution, Fertility, Pregnancy, Research, Science, Stanford News, Stem Cells, Videos

Viral RNA essential for human development, say Stanford researchers

Viral RNA essential for human development, say Stanford researchers

Viruses are tricky, but we humans may be trickier still. Stanford stem cell biologists Vittorio Sebastiano, PhD, and Jens Durruthy-Durruthy, PhD, published a study today in Nature Genetics indicating that the genetic remnants of ancient viral infections that still linger in our genome are essential to early human embryonic development.

As Sebastiano explained in our release:

We’re starting to accumulate evidence that these viral sequences, which originally may have threatened the survival of our species, were co-opted by our genomes for their own benefit. In this manner, they may even have contributed species-specific characteristics and fundamental cell processes, even in humans.

The researchers, who talk about their work in the video above, relied on a new RNA sequencing technique to investigate the expression of what are called long-intergenic noncoding, or lincRNAs. These molecules don’t contain protein-making instructions, but instead affect the expression of other genes. They’ve been implicated in many important biological processes, including the acquisition of a developmental state called pluripotency that is necessary for a fertilized egg to develop into the cells and tissues of a growing fetus.

More from our release:

They identified more than 2,000 previously unknown RNA sequences, and found that 146 are specifically expressed in embryonic stem cells. They homed in on the 23 most highly expressed sequences, which they termed HPAT1-23, for further study. Thirteen of these, they found, were made up almost entirely of genetic material left behind after an eons-ago infection by a virus called HERV-H.

[…] After identifying HPAT1-23 in embryonic stem cells, Sebastiano and his colleagues studied their expression in human blastocysts — the hollow clump of cells that arises from the egg in the first days after fertilization. They found that HPAT2, HPAT3 and HPAT5 were expressed only in the inner cell mass of the blastocyst, which becomes the developing fetus. Blocking their expression in one cell of a two-celled embryo stopped the affected cell from contributing to the embryo’s inner cell mass. Further studies showed that the expression of the three genes is also required for efficient reprogramming of adult cells into induced pluripotent stem cells.

I can’t stop marveling at the close ties we have with viruses. It makes me think of the words of Michael Corleone in The Godfather: “Keep your friends close, and your enemies closer.” As Durruthy-Durruthy told me, “It’s fascinating to imagine how, during the course of evolution, primates began to recycle these viral leftovers into something that’s beneficial and necessary to our development.”

Previously: My baby, my… virus? Stanford researchers find viral proteins in human embryonic cellsMastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled  and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Video by Christopher Vaughan/Stanford Institute for Stem Cell Biology and Regenerative Medicine

Cancer, Pediatrics, Research, Stanford News

A cure is not enough for young cancer survivors

flower-887443_1920I survived Hodgkin’s lymphoma as a young adult about twenty years ago, thanks to the chemotherapy and radiotherapy that I received at Stanford Hospital as part of a clinical trial.

Even back then, the focus of the research was on fine-tuning my cancer treatment to maintain an excellent likelihood of survival, while minimizing the long-term health problems due to therapy. I knew Hodgkin’s was unlikely to kill me, so I had to worry instead about future health issues caused by my radiation and chemotherapy.

People that survive cancer at a young age are expected to live many decades after diagnosis and treatment, so they are the most vulnerable population to long-term damaging effects from cancer therapy. Stanford’s Karen Effinger, MD, MS, and Michael Link, MD, explore this issue in an editorial published today in JAMA Oncology.

The editorial explains that it is critical to directly study the late effects in young adult cancer survivors, rather than the common practice of extrapolating from studies of children and middle-aged adults.

In particular, they discuss a new study by Katherine Rugbjerg, PhD, and Jorgen Olsen, MD, DMSc, from the Danish Cancer Society Research Center, which used the national Danish registries to compare the long-term risk of hospitalization in almost 34,000 5-year survivors of adolescent and young adult cancers with that of more than 228,000 age- and sex-matched population controls. Reported in the latest issue of JAMA Oncology, Rugbjerg and Olsen found that adolescent and young adult cancer survivors had significant health issues due to their treatment; however, these treatment effects were different than survivors of childhood cancers.

The editorial also discusses the late effects of pediatric cancer treatment on survivors’ neurocognitive development, which impacts education, employment and quality of life. Effinger and Link specifically describe a new study reported in JAMA Oncology by Kevin Krull, PhD, and colleagues from the St. Jude Children’s Research Hospital, which compared the neurocognitive outcomes in 80 adult 25-year survivors of a pediatric cancer with 39 controls. Krull concluded that the risk of neurocognitive impairment from cancer treatment was related to the development of chronic health conditions — rather than directly from exposure to high-doses of chemotherapy, as expected — but longitudinal studies are needed to sort out possible modifying factors.

The editorial authors conclude:

Going forward, we must apply our knowledge of late effects to improve monitoring and interventions for patients. While the progress made in the management of cancer in children and young adults has been gratifying, we must remember the words of Giulio D’Angio, who reminds us that “cure is not enough.”

Jennifer Huber, PhD, is a science writer with extensive technical communications experience as an academic research scientist, freelance science journalist, and writing instructor.

Previously: Study highlights childhood cancer survivors’ increased risk of future health problems, Questioning whether physicians are equipped to care for childhood cancer survivors and A cancer survivor discusses the importance of considering fertility preservation prior to treatment
Photo by klimkin

Palliative Care, Patient Care, Research, Science, Stanford News

Desire for quality end-of-life care crosses ethnic groups

Desire for quality end-of-life care crosses ethnic groups

VJ in officeEthnic minorities want quality end-of-life care, including in-depth conversations with their physicians about how to achieve this, but they often face barriers to getting the care they desire. That’s according to a study published today in the Journal of Palliative Care.

In a press release I wrote about the study, lead author VJ Periyakoil, MD, a Stanford expert in end-of-life care, explained why she decided it was important to conduct a study with the goal of reaching out to traditionally hard-to-reach ethnic groups within the communities where they live:

There is so much generalization and stereotyping by physicians about how ethnic minorities want everything done, irrespective of how effective these treatments might be at the end of life. I decided that we needed to go into their communities and ask them what they want.

Periyakoil and her colleagues conducted a series of in-person interviews at a scattering of community-based senior centers around the San Francisco Bay Area accompanied by interpreters. The populations are particularly hard to reach because of a number of issues, including language barriers, immigration status, and poverty levels, Periyakoil said. In addition to English, interviews were conducted in Spanish and five Asian languages — Burmese, Hindi, Mandarin, Tagalog and Vietnamese. As I described in the release:

The researchers… found that all participants valued high-quality end-of-life care. A majority, 61 percent, said there were barriers to receiving high-quality care for members of their ethnic group.

The 191 participants who reported barriers to getting quality end-of-life care were asked to describe the biggest barriers, which were, in order of how often they were cited: finances and health insurance; physician behavior; communication problems with doctors; family beliefs; health system barriers; and cultural/religious barriers.

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Chronic Disease, Clinical Trials, Mental Health, Research, Stanford News

Treating insulin resistance may speed recovery from major depression

Treating insulin resistance may speed recovery from major depression

depressionIn a randomized, placebo-controlled clinical trial detailed in this study in Psychiatry Research, pioglitazone – a generically available drug that’s approved for type 2 diabetes – helped to relieve symptoms of major depression in patients whose blues had withstood an assault by standard therapeutic regimens for six months or longer.

But this beneficial effect was seen only in depressed patients who were also insulin-resistant.

Depression is remarkably common. Stanford psychiatric researcher Natalie Rasgon, MD, PhD, the study’s senior author, told me that close to one in five Americans are diagnosed with depressive illness at some point in their lives.

Insulin resistance, a stepping stone on the path to type 2 diabetes (not to mention cardiovascular disease and probably Alzheimer’s), is even more common: About one in three otherwise healthy Americans – and an even greater share of people with depression – are insulin-resistant. Especially prevalent among overweight people, insulin resistance also occurs more often than one might expect even among thinner folks, a lot of whom don’t have the faintest idea that’s the case.

Insulin, released by the pancreas in response to food intake, alerts cells throughout the body to the presence of glucose, the body’s primary energy source, in the blood. Insulin-resistant people’s cells fail to take up glucose adequately, leaving high residual blood levels of the sugar to wreak havoc on the body’s tissues. Because the brain is a glucose glutton – it soaks up about 20 percent of all glucose consumption in a healthy, active person – it’s easy to imagine that lousy glucose uptake in the brain would have all kinds of deleterious effects, including effects on mood. Food for thought, anyway.

Here’s how my news release described the study:

[R]esearchers were blinded as to which patients were receiving pioglitazone versus a placebo. The patients didn’t know which they were getting, either. … All the patients had been experiencing episodes of depression lasting, on average, more than one year. Their symptoms had failed to remit under standard treatment regimens. They remained on these regimens for the duration of the Stanford study and, in addition, were given either pioglitazone or a placebo. … The patients were tested for depression severity and insulin resistance at the study’s outset and then roughly every two weeks from the beginning of the trial to the end.

A total of 37 patients – 29 women and eight men – completed the 12-week study. The insulin-sensitive subjects did about as well on the drug as they did on placebo. But among the insulin-resistant group, those given pioglitazone showed a much greater improvement than those who got a placebo. They also showed more improvement than insulin-sensitive patients did.

The more insulin-resistant a participant was at the beginning of the study, the better the drug’s antidepressant effect. Possible, but not proven, explanation: It could be that for some patients standard antidepressant therapies can kick into gear only once these patients’ insulin resistance is reduced. Hungry brains gotta eat.

Previously: Survey shows nearly a quarter of U.S. workers have been diagnosed with depression in their lifetime, Revealed: the brain’s molecular mechanism behind why we get the blues, and International led by Stanford researchers identifies gene linked to insulin resistance
Photo by S.Hart Photography

Addiction, Ask Stanford Med, Health Policy, Public Health, Stanford News

Is a proposed ban on smoking in public housing fair?

Is a proposed ban on smoking in public housing fair?

smoking ban sign - 560

Cigarette smoking kills nearly half a million Americans each year, making it the leading preventable cause of death in the United States.

So the Department of Housing and Urban Development thinks it’s time to ban cigarette smoking from some 1.2 million subsidized households across the nation.

HUD Secretary Julián Castro unveiled a proposal last week intended to protect residents from secondhand smoke in their homes, common areas and administrative offices on public housing property.

“We have a responsibility to protect public housing residents from the harmful effects of secondhand smoke, especially the elderly and children who suffer from asthma and other respiratory diseases,” Castro said, adding the proposed rule would help public housing agencies save $153 million every year in health-care, repairs and preventable fires.

Stanford Law School professor Michelle Mello, PhD, JD, who is a core faculty member with Stanford Health Policy, has researched and written about this issue extensively, including in a 2010 article in The New England Journal of Medicine.

In a piece published yesterday, I asked Mello about her views on the federal smoking ban proposal. A sampling of the Q&A:

What would be the greatest benefit to banning smoking in public housing?

There are lots of benefits, but to me the greatest benefit is to the 760,000 children living in public housing. Although everyone knows that secondhand smoke exposure is extremely toxic, not everyone knows how much children in multiunit housing are exposed — even when no one in their household smokes. Research shows that smoke travels along ducts, hallways, elevator shafts, and other passages, undercutting parents’ efforts to maintain smoke-free homes. Also, chemicals from cigarette smoke linger in carpets and curtains, creating hazardous “third-hand smoke” exposure that especially affects babies and small children.

Beth Duff-Brown is communications manager for Stanford Health Policy.

Photo by Getty Images iStock

Research, Stanford News, Surgery

Immune cell linked to surgery recovery time, Stanford scientists find

Immune cell linked to surgery recovery time, Stanford scientists find

surgery shotWe don’t think about doctors getting sick, or about them feeling just as lousy and miserable as the rest of us when they’re recovering. But it happens.

“In medical school I had a chest surgery and had a horrible recovery — in the hospital 10 days, and exhausted for about two months,” recalled Dan Sessler, MD, professor and chair of the Department of Outcomes Research at the Cleveland Clinic, when I spoke with him recently. “I was so tired I couldn’t pick up a remote and turn on the television.”

Sessler did recover — his was a successful surgery — but going into the operation neither he nor his doctor had any inkling that Sessler wouldn’t experience the normal two-week recovery.

Now, research published online in the journal Anesthesiology could lead to an “immune stress test” where blood taken from a patient prior to surgery could help predict when the patients would be back on their feet. The investigators, including co-senior authors/Stanford physicians Garry Nolan, PhD, and Martin Angst, MD, collected blood from 25 hip replacement patients and exposed the blood to chemicals to mimic how the immune system would respond to a traumatic event like surgery. They found the behavior of a white blood cell called a monocyte was related to how quickly patients recovered.

The researchers are working to replicate the findings in a larger study of 80 patients, and they plan to adapt their findings into a test that can run on standard hospital lab machines. As I wrote in our press release about the practical benefits of such a test:

Knowing the likely recuperation times will help patients plan better for their return to work and other post-surgery commitments. For patients at risk for longer recovery times, doctors could schedule additional physical therapy or special care, or the surgery could be postponed while exercise, dietary changes and stress-release techniques are implemented.

As for Sessler, who was not involved in this study, he said he sees great value in adapting the paper’s results into a test. Predicting a patient’s recovery is “clinically important, and we don’t do a good job” of it, he said.

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a former writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: Discovery may help predict how many days it will take for individual surgery patients to bounce back, New device identifies immune cells at an unprecedented level of detail, inside and out and The importance of human connection as part of the patient experience
Photo by ChaNaWiT

Humor, Medical Education, Stanford News, Videos

“Dear Future Doctor, here’s a few things you’ll need to know”: Med students release parody video

"Dear Future Doctor, here's a few things you'll need to know": Med students release parody video

Ready for the first-ever musical parody produced by Stanford medical students? Filmed on campus last month and released this afternoon, Dear Future Doctor features a group of mostly first-years singing and dancing to the tune of one of Meghan Trainor’s recent hits. Featuring characters like the Late Doctor, the Greedy Doctor and the Celebrity Doctor, the song also – in the words of producer/writer/editor/first-year student Gun Ho Lee – aims to teach a lesson “on what the future doctor is NOT to do.”

The song “is meant to be a satire of the 21st century American medical system,” director/writer/ second-year student Joshua Wortzel elaborates. “In her song, Meghan Trainor pokes fun at some of the unfortunate aspects of modern courtship and gender norms” – and Dear Future Doctor, in turn, pokes fun at some of the things that “we medical students learn about becoming doctors.”


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