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Research, Science, Stanford News

How Bio-X is fueling the #NextGreatDiscovery

How Bio-X is fueling the #NextGreatDiscovery


The videos, images and stories of #NextGreatDiscovery share two things in common: 1) They reveal the lives and motivations of amazing scientists carrying out basic research, and 2) All the scientists are affiliated with Stanford’s pioneering interdisciplinary institute Bio-X.

Almost 15 years ago, Stanford Bio-X was founded to support biomedical research with an interdisciplinary blend of X, which is to say all the fields across the street from Stanford University School of Medicine – engineering, chemistry, physics, biology, math and statistics as well as the professional schools of business, law and education. Bio-X later came to be housed in the Clark Center, located with crosswalks linking those schools and departments.

Two of the scientists featured in #NextGreatDiscovery recently won Nobel prizes in chemistry, and both discuss the importance of Stanford’s collaborative spirit in their research.

From Michael Levitt, PhD:

The university has the medical school and other departments very close to each other. This means that you can mix together all the sciences whether it is engineering and medicine, mathematics and medicine, statistics and medicine. All of these things are really close together so people are able to interact, groups are able to mix. I think it really is a remarkable environment.

From W.E. Moerner, PhD:

One aspect of research today is that our science has become more and more multidisciplinary. Exciting science occurs at the boundaries between conventional disciplines. Here at Stanford we have a spectacular environment for multidisciplinary work. That’s because in a very close proximity we have all of the humanities and sciences departments, the medical school departments and the engineering departments all close together, essentially across the street from one another right here close to my office.

In the series, scientists discuss the importance of funding for the basic sciences, as federal sources become more scarce. Both Levitt and Moerner have received Seed funding through Bio-X, which support new collaborations between scientists bridging disciplines. These grants are critical for promoting interdisciplinary research through funding at a time when federal resources for early stage collaborations are hard to come by, even for scientists whose research receives a nod from Stockholm.

Previously: #NextGreatDiscovery: Exploring the important work of basic scientists, The value of exploring jellyfish eyes: Scientist-penned book supports “curiosity-driven” research, Basic research underlies effort to thwart “greatest threat to face humanity”For third year in row, a Stanford faculty member wins the Nobel Prize in Chemistry and Stanford’s Michael Levitt wins 2013 Nobel Prize in Chemistry
Photo by Peter van Agtmael/Magnum Photos

Research, Science, Stanford News

#NextGreatDiscovery: Exploring the important work of basic scientists

#NextGreatDiscovery: Exploring the important work of basic scientists

Today, Stanford is launching a digital series, called #NextGreatDiscovery, to share the stories of some of the scientists doing groundbreaking basic research here. Through photographs and short videos, followers will get a taste of the work of these grad students, postdocs and professors – in fields ranging from computational structural biology to genetics to immunology – and hear about how important it is that this work continues. After all, basic science not only advances knowledge but has the potential to lead to great biomedical innovations.

Our series comes at a time where national funding for research is critically low, and some investigators are opting to leave academia in favor of industry positions that may not support fundamental research. What would we lose if more of these great minds chose different paths? What would go undiscovered? It’s something to keep in mind as you read this feature story, view our photos on Instagram, and follow #NextGreatDiscovery on Twitter.

Previously: The value of exploring jellyfish eyes: Scientist-penned book supports “curiosity-driven” research, Basic research underlies effort to thwart “greatest threat to face humanity” and Funding basic science leads to clinical discoveries, eventually
Photo by Peter van Agtmael/Magnum Photos

Cancer, Genetics, Research, Science, Stanford News

Combination therapy could fight pancreatic cancer, say Stanford researchers

Combination therapy could fight pancreatic cancer, say Stanford researchers

I’ve mentioned here before my personal connection to pancreatic cancer, which claimed the life of my grandmother. So I was excited to hear from Stanford cancer researcher Julien Sage, PhD, about some developments on the research front. Sage and postdoctoral scholar Pawal Mazur, PhD, collaborated with Alexander Herner, MD and Jens Svieke, MD, at the Technical University Munich to conduct the work, which was published today in Nature Medicine.

In our release on the study, which was done in animal models, Sage explained:

Pancreatic cancer is one of the most deadly of all human cancers, and its incidence is increasing. Nearly always the cause of the disease seems to be a mutation in a gene called KRAS, which makes a protein that is essential for many cellular functions. Although this protein, and others that work with it in the Ras pathway, would appear to be a perfect target for therapy, drugs that block their effect often have severe side effects that limit their effectiveness. So we decided to investigate drugs that affect the DNA rather than the proteins.

Mazur and Herner worked together to test whether drugs that affect the epigenetic status of a cancer cell (that is, the dynamic arrangement of chemical tags on the DNA and its associated proteins that control how and when genes are expressed) could rein in its growth without serious side effects. Many of these tags are what’s called acetyl groups, and they are added to protein complexes called histones that keep the DNA tightly wound in the cell’s nucleus. As I explained in our release:

They started by investigating the effect of a small molecule they called JQ1 on the growth of human pancreatic tumor cells in a laboratory dish. JQ1 inhibits a family of proteins responsible for sensing acetyl groups on histones. The researchers found that the cells treated with JQ1 grew more slowly and displayed fewer cancerous traits. The molecule was also able to significantly shrink established pancreatic tumors in mice with the disease. However, it did not significantly affect the animals’ overall likelihood of survival.

Mazur, who began the work in Siveke’s lab and continued it when he moved to Sage’s lab, next tested whether using JQ1 in combination with any other medications could be more effective:

“It happened that the drug that worked best was another epigenetic drug called vorinostat,” said Sage. “On its own, vorinostat didn’t work very well, but when combined with JQ1 it showed a very strong synergistic effect in both the laboratory mice with pancreatic cancer and in pancreatic cancer cells from people with the disease.”

Vorinostat works by inhibiting a family of proteins that remove the acetyl groups from histones. It has been approved by the FDA for use in people with recurrent or difficult-to-treat cutaneous T cell lymphoma. When human pancreatic cancer cells were treated simultaneously with JQ1 and vorinostat, the cells grew more slowly and were more likely to die.

Mice with established pancreatic cancers treated with both of the drugs showed a marked reduction in tumor size and a significant increase in overall survival time. Their tumors showed no signs of developing a resistance to the treatment, and the mice did not develop any noticeable side effects.

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Cardiovascular Medicine, Chronic Disease, Science, Stanford News, Stem Cells

Patching broken hearts: Stanford researchers regrow lost cells

Patching broken hearts: Stanford researchers regrow lost cells

Design 1_2Most heart attack survivors face a long and progressive course of heart failure due to damage done to the heart muscle. Now, in a study published in the journal Nature, researchers are reporting a method of delivering a missing protein to the lining of the damaged heart that regenerates heart muscle cells — cardiomyocytes — killed off during a heart attack.

The study, which was conducted in animal models, offers hope for future treatments in humans, according to the senior author of the study. “This finding opens the door to a completely revolutionary treatment,” Pilar Ruiz-Lozano, PhD, told me. “There is currently no effective [way] to reverse the scarring in the heart after heart attacks.”

The delivery system that researchers used in this study is a biodesigned tissue-like patch that gets stitched directly onto the damaged portion of the heart. The protein Fstl1 is mixed into the ingredients of the patch, and the patch, made of an acellular collagen, eventually gets absorbed into the heart leaving the protein behind. Our press release explains how the patch came to be:

The researchers discovered that a particular protein, Fstl1, plays a key role in regenerating cardiomyocytes. The protein is normally found in the epicardium — the outermost layer of cells surrounding the heart — but it disappears from there after a heart attack. They next asked what would happen if they were to add Fstl1 back to the heart. To do this, they sutured a collagen patch that mimicked the epicardium to the damaged muscle. When the patch was loaded with Fstl1, it caused new cardiomyocytes to regenerate in the damaged tissue.

In reading over the study, I was particularly interested in what an engineered tissue-like patch applied to a living heart looked like – and how exactly the patch got made. I called one of the study’s first authors and went to see him in his lab.

Vahid Serpooshan, PhD, a postdoctoral scholar in cardiology at Stanford, told me he can make a patch in about 20 minutes. It’s a bit like making Jell-O, he said; collagen and other ingredients get mixed together then poured into a mold. Serpooshan uses molds of various sizes depending on what kind of a heart the patch will be surgically stitched onto.

“The damaged heart tissue has no mechanical integrity,” Serpooshan said. “Adding the patch is like fixing a tire… Once the patch is stitched onto the heart tissue, the cardiac cells start migrating to the patch. They just love the patch area…”

Previously: Stanford physician provides insight on use of aspirin to help keep heart attacks and cancer away, Collagen patch speeds healing after heart attacks in mice and Big data approach identifies new stent drug that could help prevent heart attacks
Image, of a patch stitched to the right side of the heart, by Vahid Serpooshan

Mental Health, Research, Science

Optimizing work breaks for health, job satisfaction and productivity

5187630414_6102463a6c_zThink about the breaks you take during the day. Perhaps you hit pause midday to grab lunch and to run errands. Or maybe you step away from your desk frequently to briefly socialize with co-workers, get coffee or satisfy a sugar craving. Have you ever wondered what might be the optimal length and type of break?

Researchers at Baylor University asked themselves that question and discovered new insights into what constitutes a “better break.” In a study involving employees ages 22 to 67, researchers asked participants to document their breaks from work and analyzed their responses. Psych Central reports that study results suggest not all breaks are created equal, and that the type of breaks we take could potentially affect our health and job satisfaction.

Findings showed a mid-morning break can help boost your concentration, motivation and energy and that doing things you either choose or like to do during a break can help aid in recovery from stress or fatigue. According to the story:

People who take “better breaks” experience better health and increased job satisfaction.

The employee surveys showed that recovery of resources — energy, concentration, and motivation — following a “better break” (earlier in the day, doing things they preferred) led workers to experience less somatic symptoms, including headache, eyestrain, and lower back pain after the break.

These employees also experienced increased job satisfaction and organizational citizenship behavior as well as a decrease in emotional exhaustion (burnout), the study shows.

Longer breaks are good, but it’s beneficial to take frequent short breaks.

While the study was unable to pinpoint an exact length of time for a better workday break (15 minutes, 30 minutes, etc.), the research found that more short breaks were associated with higher resources, suggesting that employees should be encouraged to take more frequent short breaks to facilitate recovery.

Researchers believe breaks are an essential intervention to help a person stay sharp and energized.

“Unlike your cellphone, which popular wisdom tells us should be depleted to zero percent before you charge it fully to 100 percent, people instead need to charge more frequently throughout the day,” [said Emily Hunter, PhD, associate professor of management in Baylor University’s Hankamer School of Business.]

Previously: No time for a vacation? Take a break without leaving the officeHow Stanford and Silicon Valley companies are fostering “work-life integration”, Workplace stress and how it influences health and Stanford class teaches students how to live a happier, healthier life,
Photo by Daniil Kalinin

Evolution, Genetics, Research, Science, Stanford News, Stem Cells

Chimps and humans face-off in Stanford study on inter-species variation

Chimps and humans face-off in Stanford study on inter-species variation

wysocka_illustration (6)Our nearest primate relative, the chimpanzee, shares much of its genome with us. And yet, despite the astounding similarities in our DNA sequences, it’s not difficult to discern the face of one species from the other.

Developmental biologist Joanna Wysocka, PhD, researches, among other things, how human faces are formed during early embryonic development. She and graduate student Sara Prescott compared gene expression patterns between humans and chimpanzees in the hopes of identifying not just what makes us recognizably human, but also how human faces also differ among themselves.

They describe their work, which was published today in Cell, as a kind of “cellular anthropology” that can illuminate important genomic tweaks in our recent evolutionary past. In particular, they found that the critical differences between the two species lie not in the DNA sequence of the genes themselves, but in when and where (and to what levels) the genes are made into proteins during development. These changes have led to important, human-specific adaptations. As Wysocka explained in our release:

We are trying to understand the regulatory changes in our DNA that occurred during recent evolution and make us different from the great apes. In particular, we are interested in craniofacial structures, which have undergone a number of adaptations in head shape, eye placement and facial structure that allow us to house larger brains, walk upright and even use our larynx for complex speech.

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In the News, Media, Medical Education, Medicine and Society, Science

Wikipedia calls for more scientists to participate

Wikipedia calls for more scientists to participate

3204073130_417b9dc56a_z Wikipedia’s volunteer editors hosted the first Wikipedia Science Conference in London last week to urge scientists to participate in editing the massive online encyclopedia. Scientists often view Wikipedia as a “Wild West” because anyone can edit the pages, reports a piece in Nature, but in reality Wikipedia is a community of “ultra-pedants” obsessed by getting the facts right.

Martin Poulter, PhD, the main convener of the conference, is quoted as saying that many posts are already high quality, but professional academics, scientists, and publishers could improve the information in their field of expertise. He refers to a “cultural barrier” that includes a disinclination to participate in the “admittedly petty discussions” that sometimes crop up around Wikipedia edits. Alex Bateman, PhD, another organizer quoted in the article, adds that Wikipedia articles are written organically, sentence by sentence, which is very different than the research paper process. “There have to be changes from both sides. That’s what we’re discussing,” says Poulter.

One proposed project is to improve the Wikipedia biographies of famous scientists, starting with the fellows at The Royal Society, Britain’s pre-eminent scientific institution. The Society has agreed to take on a “Wikipedian in residence” to spearhead these efforts, which are aimed at reassuring scientists about the quality of Wikipedia articles. Another successful partnership is with the European Bioinformatics Institute, which maintains databases on protein and RNA families that have benefitted greatly from Wikipedia contributions. Wikipedia also maintains a page listing articles that need expert scientific attention.

But the benefits go both ways, says Poulter, who thinks academia can benefit from engaging with Wikipedia’s transparent process of knowledge curation. “Wikipedia is an opportunity to recapture some of the academic ethos that has been weakened by the commercial sector,” he is quoted as saying. “If you’re working in the open, you release all your data, your drafts and everything, and you invite comments from the start, rather than only after a process which is hidden away from the public.”

Previously: Science for popular audiences is not just “adding to the noise”Anthropologist discusses Wikipedia’s implications for health information, Is medical information on Wikipedia a public health problem?, How a “culture of permission” prevents doctors from being active in social media and ScienceRoll: What happens when pharma companies edit Wikipedia?
Photo by Johann Dréo

Genetics, In the News, Pregnancy, Research, Science, Women's Health

Maternal-fetal “chimera” cells: What do they actually do?

Maternal-fetal "chimera" cells: What do they actually do?

1292733380_3e6815a6d1_zAfter a woman is pregnant, fetal cells linger in her body long after her baby is brought out into the world. They cross the placenta and congregate in her thyroid, breasts, brain, scars… and elsewhere. The phenomenon is called “fetal microchimerism,” a reference to the hybrid monster of Greek mythology that strikes me as both whimsical and menacing.

But what do these cells do? An entertaining and informative National Geographic blog post highlights a recent review study published in BioEssays that seeks to answer this question. The evidence we have so far is contradictory and messy, not yielding much in the way of patterns: Sometimes cells collect more in diseased tissues, other times in healthy ones. But when viewed through an evolutionary lens, things start to make sense, argue the paper’s authors. These cells allow a baby to inadvertently influence her mother’s body in her own interest, which is sometimes – but not always – in the mother’s interest, too.

Writer Ed Yong explains:

Some of those changes, like faster healing, benefit the mother too. Others may not. For example, foetal cells could stimulate the breast to make more milk, either by releasing certain chemical signals or by transforming into glandular cells themselves. That’s good for the baby but perhaps not for the mother, given that milk takes a lot of energy to make—mothers literally dissolve their own bodies to create it. And if the foetal cells start dividing too rapidly in the breast, they might increase the risk of cancer.

Similarly, the thyroid gland produces hormones that control body temperature. If foetal cells integrate there and start dividing, they could ramp up a mother’s body heat, to a degree that benefits her baby but also drains valuable energy. And again, if they divide uncontrollably, they might increase the risk of cancer. Indeed, thyroid cancer is one of the only types that’s more common in women than men, but is not a reproductive organ like the ovaries or breasts.

Such influences would have developed gradually over hundreds of millions of years in a subtle evolutionary contest between mother and fetus – it is in the mother’s interest for the fetus to do well, but not to monopolize all her resources, so it’s not unlikely that mothers evolved counter-measures. The paper authors don’t have any conclusions yet, but their point is that within this evolutionary framework, it makes sense that fetal cells both help and harm the mother.

Previous research on microchimerism has only asked about such cells’ presence, not their function. The paper’s authors hope to organize a workshop to test some of the hypotheses they proposed, which means gathering microchimeric fetal cells and sequencing their genes, then working out which of the mother’s genes they are activating and whether these correlate with any traits like milk production or temperature. The possibilities for further research are immense:

And then, there’s the matter of cells that travel in the other direction—from the mother to the foetus. What do they do in their new homes? These paths can get even more complicated. It’s possible that the cells from one foetus can travel into its mother, hide out, and then into a sibling during a later pregnancy. “At one point, we started trying to draw family trees, and trying to work out where all the microchimerc cells could be going,” says [co-author Athena Aktipis, PhD]. “It got really messy.”

Previously: How a child’s cells may affect a mother’s long term health
Related: The yin-yang factor
Photo by Simone Tagliaferri

Cancer, Genetics, Imaging, Precision health, Research, Science, Stanford News

You know it when you see it: A precision health approach to diagnosing brain cancer

You know it when you see it: A precision health approach to diagnosing brain cancer

BurlIf you know which virus has made a person ill, as well as whether your patient responds better to drug A or drug B, you’re in a much better position to treat them. In the world of oncology, it’s often the genetic personality of the tumor itself that determines the best treatment protocol. A tumor with one set of gene variants may be susceptible to only one of several treatments. To decide which drug to prescribe, you’ve got to know your tumor.

In some cancers, such as skin cancer, it’s easy to physically examine the tumor and easy to take a biopsy to root out the tumor’s genetic secrets. But for cancers deep in the brain, a biopsy is problematic. And without knowing more about a brain tumor, it’s harder to guess the right treatment.

Now a team of researchers, led by Stanford’s Haruka Itakura, MD, and Olivier Gevaert, PhD, have distinguished three types of brain tumors. Each type is identifiable by their appearance in MRIs and predictably associated with specific molecular characteristics. Itakura and Gevaert report their work in today’s Science Translational Medicine.

Magnetic resonance imaging revealed three distinct kinds of glioblastoma brain tumors, each of which could be associated with a different probability of patient survival and a unique set of molecular signaling pathways. The work paves the way for more precise diagnosis, better targeted therapies and personalized treatment of GBM brain tumors.

Previously: Brain imaging, and the “image management” cells that make it possibleA century of brain imaging and When it comes to brain imaging, there’s nothing simple about it
Photo by Travis

Medicine and Literature, Podcasts, Public Health, Science

Jonas Salk: A life

Jonas Salk: A life

Salk book coverIn 1954, Charlotte DeCroes stood in line with her fellow second graders in Kingsport, Tennessee and received the polio vaccine. Her Tennessee hometown was one of the test sites for what was then the largest and most significant clinical trial in the history of medicine. By the end of 1953, there were 35,968 reported polio cases, and the United States was desperate to solve this devastating illness. A survey at the time ranked fear of polio second only to fear of atomic warfare.

Fast forward to 2015. Charlotte Jacobs, MD, professor of medicine, emerita at Stanford, has written a highly acclaimed biography of the famed researcher/physician Jonas Salk, MD, who developed the polio vaccine. In this 1:2:1 podcast, she told me that her ten-year journey into Salk’s life was instigated partly because she couldn’t find a thorough autobiography on him, something she considered a historical lapse.

Jacobs has written a finely honed and balanced portrait – saluting Salk’s great accomplishment while not flinching from describing a man who was enigmatic, complex and all too human. She conducted more than a hundred personal interviews and spoke to two of his three sons along with his longtime private secretary. The dichotomies of his life are fascinating. While he was loved and lauded by the public and the media, he was a pariah in the scientific community – never appreciated, accepted or awarded. (His scientific colleagues thought he was a press hound, an impression that was fueled by the media’s adoring gaze – covers and feature articles in the most popular media of the time, including Life, Time, Colliers, Consumer Reports, Popular Mechanics and U.S. News and World Report.)

Today, with vaccine wars sweeping certain areas of the country, Jacobs reminds us of a time when a major public-health crisis engulfed the nation and of a hero who made a difference and changed the landscape of medical history. It’s worth remembering.

Previously: Charlotte Jacobs on finding “snippets during every day” to balance careers in medicine and literatureStanford doctor-author brings historic figure Jonas Salk to life and Prescribing a story? Medicine meets literature in “narrative medicine”

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