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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

Events, Research, Science, Technology

At TEDMED 2015: Thinking about “breaking through” the valley of death in science

At TEDMED 2015: Thinking about "breaking through" the valley of death in science

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here. 

“I am #BreakingThrough the ‘valley of death.’”

That’s what I wore on my nametag last week at TEDMED. The theme of this year’s conference was “Breaking Through,” and every delegate was asked to write a brief statement that illustrates an area of health care that they’re most passionate about.

The “valley of death” refers to the vast gap in the landscape of biomedical therapeutic development between academia and industry. Traditionally, an academic institution and industry have played two separate but equally important roles in the lengthy and expensive process of bringing new medical innovations to the patient. Academic researchers investigate new mechanisms, pathways and methods, making discoveries that yield promise. Industry then takes these experimental innovations and conducts product development, safety profiling, clinical trials, and manufacturing and distribution, ensuring that extensively tested, safe and efficacious products are widely made available.

However, this transition between academia and industry is not always a smooth one. The pharmaceutical industry is notorious for its extreme risk aversion with new products – and with an average cost of $1B, a 10-year path to FDA approval, and a failure rate north of 95 percent, who can blame them? Meanwhile, most academic labs are neither equipped to nor interested in spending the resources to conduct important yet labor-intensive preclinical work (which, quite frankly, won’t help a scientist graduate, secure tenure, or win a Nobel Prize). And so, because of this, potentially beneficial therapeutics are liable to languish in the valley of death between discovery and human trials.

On Thursday, Stanford professor Daria Mochly-Rosen, PhD, took the TEDMED stage to describe her own experience crossing that valley on the TED stage. In the early 2000s her lab had discovered a novel class of compounds for reducing cardiac injury after heart attack. After receiving universal rejections from pharma companies that they hoped would license the compounds, Mochly-Rosen and one of her graduate students reluctantly took matters into their own hands, left the university, and started KAI Therapeutics to bring their compounds into clinical trials. Long story short, they were eventually wildly successful and acquired by Amgen after demonstrating efficacy in Phase II clinical trials. The experience drove Mochly-Rosen to start the Stanford’s SPARK program, which offers a variety of resources – including classes, industry mentors and grants – to help scientists here survive their own journeys through the valley of death.

As a scientist developing new potential tools for diagnosis and therapy, and as someone who works frequently with early-stage life science companies, I spend a disturbing amount of time thinking about the valley of death. But to me, the valley is much deeper and wider than what it means for pharmaceutical development. It spans similar challenges in medical devices, diagnostics, and even digital health solutions.

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Events, Genetics, Research, Science

At TEDMED 2015: How microbiome studies could improve the future of humanity

At TEDMED 2015:  How microbiome studies could improve the future of humanity

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here. 

TEDMED scholarsOne of the highlights at TEDMED for me was meeting and hearing from Chris Mason, PhD, a Weill Cornell Medical College researcher in epigenetics. This is my field of study, so I was excited to talk to someone deeply involved in the world of genomics. Mason was an engaging and fast talking speaker, with a great sense of humor. And I soon discovered that, while he was doing the same sort of work and analysis that I was doing, his samples are incredibly unique.

While I work on primary cell types across the human body, Mason has interesting questions about the microbiome surrounding our body. The cells that make up the microbiome actually outnumber human cells ten times over – and scientists are increasingly gaining an understanding of how the microbiome, individual and personal to each and every person, can have a unique impact on human health and wellness. Mason, knowing this, began to look for interesting and unique ones that could tell us about how these microbiomes could be enhanced and utilized for improving our human lives.

Mason sequenced microbial cells that were gathered from subway riders around the world, and he discovered that about half of the cells discovered were not known microbial species. Literally under our feet, as Mason puts it, there is a world of diversity to explore and the possibility of discovering new antibiotics and cures to disease. But then Mason also went in the other direction – up! – and collected samples from astronauts in space. Now he has access to more than 8,000 samples of astronaut samples (let your imagination wander on what they saved) for a study of the human body in extreme environments.

During Mason’s talk on the last day of the conference, provocatively described by TEDMED organizers as a discussion of how his work is being done “in the interest of humanity’s interplanetary survival,” he touched on the subway experiments as well as the astronaut work, and then tied it all together by talking about the future of humanity. For Mason, an understanding of biology, both microbial and human, is the natural next step in humans’ progress to the stars and beyond. Genetic engineering is already here and will continue to grow as a technology, and he suggested we use it to extend our reach to the moon and beyond. The microbiome could be altered to protect us from UV radiation in space or to help us adapt to new planets, for example. Think of it as an astronaut suit, but biological, he suggested.

Mason’s thoughts may be controversial, depending on what you think about genetics, but he has clearly thought very hard about what new biological technologies mean for humanity’s future. It’s unknown whether the future will develop as Mason has envisioned it, but his work will likely be influential nonetheless.

Daniel Kim is a fifth-year MD/PhD student at Stanford. He studies biomedical informatics and genomics and is interested in all things data-related.

Photo of the author (second from left) and three other TEDMED scholars, from Lichy Han

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

Health and Fitness, In the News, Orthopedics

Walking tall: The challenge of correcting your gait

Walking tall: The challenge of correcting your gait


Thanks to a bum knee, in elementary school I had to choose between two styles of special Oxford shoes to help correct my gait; I hated those ugly shoes. Luckily these days I have many cute options, along with custom orthotics.

Despite good shoes though, my plantar fasciitis recently sent me back to my physical therapist. Of course the first thing she had me do is walk back and forth across the room, a common sight at any physical therapy office.


Now, everyone from doctors and physical therapists to yoga instructors are teaching people how to walk properly.

A recent story in Vogue chronicles one woman’s efforts to correct her bad habits at two walking and gait clinics — with a physical therapist in Santa Monica and with a yoga teacher in Brooklyn. Author Marisa Meltzer also checked in with Jessica Rose, MD, a professor of orthopedic surgery at Stanford University and director of the Motion & Gait Analysis Laboratory at Lucile Packard Children’s Hospital.

Meltzer received immediate feedback from the physical therapist, displeased with the uneven wear of her shoes. As Melzter describes:

Finally, she instructs me to walk back and forth across the room. Her diagnosis: I’m constantly leaning back like a Looney Tunes character approaching oncoming traffic.

Similarly, Melzter visits a well-known yoga teacher, learning to straighten her upper body, rotate her pelvis, and swing her arms as she walks. She describes her new gait near the end of the article: “It feels unnatural, yet when I catch my reflection in the mirror I see I’m moving elegantly and with confidence.”

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

Previously: Walking-and-texting impairs posture – and walking, and texting, Walking and aging: A historical perspective and Global survey highlights the need for people to keep track of walking distance
Photo by sean_hickin

Behavioral Science, Neuroscience, Podcasts

Advice for changing health behavior: “Think like a designer”

Advice for changing health behavior: "Think like a designer"

When listening to our latest 1:2:1 podcast, featuring a conversation with Kyra Bobinet, MD, MPH, two things jumped out at me. First, Bobinet, an expert in design thinking and behavioral change who says she “leads by my curiosity,” has a very cool personal story, and second: We shouldn’t be so hard on ourselves when we struggle to make positive health changes. In short, it’s not us – it’s a design flaw.

The interests of Bobinet, CEO and founder of a design firm using neuroscience to change behavior, can be traced back to medical school, when she was exposed to a program that taught health education in juvenile hall. “I became fascinated by the behavioral patterns of gang members who had violent pasts and came in and out of the system,” she says. These gang members vowed to stay out of jail when they were released but yet “two days later they were immersed” in their old lives and back in trouble. “Why is that happening? And how is that different than me saying I don’t want to eat french fries during Lent but then doing so the second day?” she wonders aloud.

Not long after, an experience with a patient wound up changing the trajectory of her career. During residency she saw a man with gout who had taken meth just three days prior. Bobinet had only ten minutes in clinic with him, and he only mentioned the drug use during the tail end of their conversation, before she had a chance to probe into it. “He changed my life,” she says. “I was so interested in the behavior that led to the medical condition – I [realized I] didn’t want to write prescriptions for the condition anymore, I wanted to focus on the behavior.” She went on to public health school from there.

In the podcast, Bobinet, who also teaches courses on patient engagement and empowerment in the Stanford AIM Lab with Larry Chu, MD, goes on to talk a lot more about behavior and what she has learned through extensive research of patients and caregivers. She talks about her new book, Well Designed Life, which lays the groundwork for those looking to design the changes they want to see in their life, and she offers more advice and words of encouragement for people who are struggling to, say, stay on a diet or quit smoking. “Think like a designer,” she says. Your failed attempt at making positive change “was just a version, just a protoptype… That was something that didn’t work – but it’s not you, it’s the design… And you have to redesign what will grab your attention now.”

Previously: Designing behavior for better health

Cancer, Complementary Medicine, In the News, Research

“We need a breakthrough”: Cancer researchers call for more effective, lower cost therapies

"We need a breakthrough": Cancer researchers call for more effective, lower cost therapies

1024px-Tripterygium_regelii_1Cancer is wily. Although drug developers are continually crafting hard-hitting drugs, a variety of factors, such as a tumor’s genetic heterogeneity, mean that cancer usually comes out on top.

Something else is needed.

And that something, writes a panel of 180 researchers in a special issue of Seminars in Cancer Biology, is an array of treatments that bombard a series of targets. These treatments can be based on substances found in nature that are lower in cost and toxicity than many current treatments, the researchers write. Some of these compounds stem from plants, such as the Chinese herb Tripterygium wilfordii (although that herb, like many treatments is not without a downside: it also suppresses the immune system).

The team identified 74 molecular targets deserving of investigation and set up a framework for researchers to pitch in. And the time is now, researchers Anupam Bishayee, PhD, and Keith Block, MD, write in the introductory paper: “We have a long way to go before oncology can offer true comfort to most patients.”

Stanford oncologist Dean Felsher, MD, PhD, was part of the project. “This is an area that merits considerable attention and where interdisciplinary and international collaboration is needed,” he said in a statement.  “Our approaches to therapy are improving, but we need a breakthrough that can helps us address the problem of relapse.”

Previously: Researchers develop molecular target for brain cancer, Kidney cancer secrets revealed by Stanford researchers and Tool to identify the origin of certain types of cancer could be a “boon to doctors prescribing therapies”
Photo by Qwert1234

Anesthesiology, Medical Education, Sports

How to combine anesthesiology, internal medicine and rock climbing

How to combine anesthesiology, internal medicine and rock climbing

Michael Lin, M.D. at the Stanford Hospital and Clinics on Wednesday, September 23, 2015.

I’ll admit it: I’m in awe of, and a little intimidated by, medical residents. Between the early call times, long hours, and flurry of patients and cases, I often find myself wondering how these doctors-in-training manage to do it all.

So I was amazed to learn about Michael Lin, a fourth-year resident in Stanford’s combined internal medicine-anesthesia residency program. While most residents focus on just one field – like dermatology or surgery — Lin spends his time training in both anesthesia and internal medicine. He’s equally at home in the operating room prepping patients for surgery and in the internal medicine clinic treating outpatients.

But Lin also manages to squeeze in rock climbing outings to the gym and to meccas such as Yosemite National Park.

During a recent interview, I had the chance to speak with Lin about his dual interests, his experience at Stanford, and why doctors make great rock climbing partners. Here’s an excerpt from our Q&A:

What initially drew you to both fields?

When I was a medical student, I was interested in critical care and I was trying to decide which training route I wanted to take during my residency. I met with a lot of anesthesiologists and pulmonary critical care doctors who said that you get certain, specific skill sets from the medicine training and the anesthesia training. I realized that I didn’t want to choose. I wanted both skill sets.

One thing that has really drawn residents into this program is the critical care component. The ICU is really the intersection of medicine and anesthesia. You’re encountering critically ill patients with severe pathologies, so you need skills in acute resuscitation and advanced medical support that anesthesiologists are accustomed to providing in the OR, but you also need to treat the underlying pathology that landed them there in the first place, which is more aligned with the work of internal medicine physicians.

And as for why doctors make the best rock climbers? Lin has a simple response: “They’re detailed oriented and stay calm under stress, and you can trust them with your life.”

The only downside, he says, is that they always seem to be on call.

Previously: Stanford Internal Medicine Residency program to host Google+ Hangout, My couple’s match: Applying for medical residency as a duo and “We are a team”: Advice for new residents from chief residents, in their own words
Photo by Norbert von der Groeben

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

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