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Research, Science, Stanford News

Celebrating 25 years of biomedical innovation at Stanford’s Beckman Center

Celebrating 25 years of biomedical innovation at Stanford's Beckman Center

Beckman dinner - smallInnovation in the Biosphere,” a recent symposium organized to celebrate the 25th anniversary of the Beckman Center for Molecular and Genetic Medicine, attracted a standing-room-only crowd eager to listen to leading researchers in the biosciences. The February 23 gathering was so packed at the Li Ka Shing Center for Learning and Knowledge that live streaming had to be set up to accommodate the many faculty, PhDs and guests that arrived to hear from the impressive list of multidisciplinary presenters.

The symposium was designed to celebrate the concept of information transfer, while acknowledging the many innovations and breakthroughs in immunology, stem cell science, chemical biology, and imaging technology through the years.

The event was conceived by National Medal of Science winner Lucy Shapiro, PhD, the Virginia and D.K. Ludwig Professor of Cancer Research and director of the Beckman Center. “I cannot believe 25 years have gone by,” said Shapiro. “We thought we knew so much.”

Shapiro, the co-organizer of the event, credited Paul Berg, PhD, Nobel Prize-winning professor emeritus in biochemistry, and others with starting the center. The Beckman Center was founded in 1989 “at a time of great expectation” to promote the exchange of ideas across diverse scientific disciplines, based on the notion that innovation transcends traditional academic boundaries. Here’s Shapiro:

What has changed so dramatically is our understanding of how the biological world codes, decodes, and uses information in time and space to create and maintain life on this planet. And almost everything we do comes down to mining information and dealing with not only vast amounts of data but very small molecules and small circuitry.

The bedrock of what it means to be a living entity is an understanding of how a cell or tissue functions as an integrated system. No longer is it enough to study the biochemistry of specific reactions. Or a specific event. Or an overall function that happens when a tissue turns into something else. We now have to understand all these parts as an integrated, logical process.

Investigators from Stanford, UC-Berkeley, UCSF, and other institutions shared their research on the design principles of cellular networks, the manipulation of genetic circuitry to re-engineer life, and the genetic circuitry that establishes the blueprint of a living cell. They explored the deep reading of the genome to mine the information in living things and in creating life from scratch.

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Microbiology, Research, Science, Stanford News

Tiny balloon-like vesicles carry cellular chatter with remarkable specificity, say Stanford researchers

Tiny balloon-like vesicles carry cellular chatter with remarkable specificity, say Stanford researchers

6292985963_bbc06df590_z“BRUSH YOUR TEETH,” I bellowed up the stairs last night at my (seemingly deaf and clueless) children for what seemed like the one-millionth time since their birth. “Surely there has to be a better way,” I pondered, as I trudged up the stairs to deliver my threatening message in person.

The cells in our bodies don’t have the option to, however reluctantly, leave their metaphorical couch and wag their fingers under the noses of their intended recipients. And yet, without a fail-safe method of communication among distant participants, the orderly workings of our bodies would screech to a halt.

Now biologists Masamitsu Kanada, PhD, and Christopher Contag, PhD, have published in the Proceedings of the National Academy of Sciences an interesting and revealing glimpse into one tool cells can use to do the job: tiny balloon-like vesicles capable of delivering a payload of protein or genetic information from one cell to another. As Contag and Kanada explained to me in an email:

Extracellular vesicles are nanosized little containers of information that are produced by most, if not all, cells in the bodies of plants, animals and humans. From many studies it is apparent that adding vesicles from one cell type to another can affect the behavior of the recipient cells, both in a culture dish and in the living body, even across species from plants to animals and presumably humans.

We wanted to assess, under controlled sets of conditions, which biomolecules within vesicles transfer the most information most efficiently. We learned that the process is complex, and that a biomolecule in one type of vesicle is transferred in a way that affects other cells, but the same molecule in another type of vesicle may not affect cell function.

In other words, Contag, who co-directs Stanford’s Molecular Imaging Program, and his colleagues found that not all these vesicles are created equal. Some, whose outer layer was derived from the cell’s external plasma membrane (these are known as micro-vesicles), handily delivered both protein and DNA to recipient cells. Others, with outer layers derived from internal membranes in the cell (known as exosomes), were less capable and didn’t deliver any functional DNA. Interestingly, neither kind was able to deliver RNA, which was instead swiftly degraded.

The distinction between vesicle type and function is important as researchers increasingly rely on them to eavesdrop on cellular conversations or even to deliver particular biomolecules to be used for therapy or imaging. Understanding more about how they work will allow researchers to both better pick the right type for the job at hand and to learn more about how cells talk with one another. As Contag and Kanada said:

How cells communicate across distances is relevant to mobilization of immune cells to attack pathogens, depression of immune responses by tumor cells, signaling of cancer cells to metastasize, modulation of physiological processes in intestinal cells in response to plant-derived diets and to many other biological process. Understanding this form of cell-to-cell communication will bring us closer to controlling how cells talk to one another inside the body.

Now if only I could find the right kind of vesicle to communicate with my recalcitrant children. Perhaps a helium-filled balloon with a pointed message inside could float up the stairs and pop next to their ears? On second thought, that might not be the best choice.

Previously: Researchers develop imaging technologies to detect cancer earlier, faster
Photo by Matthew Faltz

Biomed Bites, Microbiology, Research, Science, Videos

By investigating cells, researchers can “stumble” on the next big thing in medicine

By investigating cells, researchers can "stumble" on the next big thing in medicine

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

Tobias Meyer, PhD, was hooked on biology when he learned humans are made out of cells — 10 trillion distinct little entities, joining together to make a human. (“The way to remember this number is that it is approximately the same as the number of dollars in the American debt,” Meyer suggests in the video above.) He goes on to say:

What fascinated me is that each of these individual cells is really something like a small computer that senses the environment — for example hormones it senses but also pathogens like bacteria or even stress.

Then it processes that information, which makes it do things like secrete, divide, or move. So my lab is particularly interested in this question of how cells integrate all these important signals.

Now chair of the Department of Chemical and Systems Biology at Stanford, Meyer and his team try to decipher how the cells that make up the human body work together:

For example, we recently found a receptor that senses calcium in cells that has not been found before. We were able to show this is important in many different systems like immunology and now many drugs companies are using it to develop drugs they didn’t have before.

For Meyer, the takeaway from his experience in biomedical research is clear: “By doing fundamental research, we often stumble accidentally on a big thing that can have a big impact later in human health.”

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

Research, Science, Stanford News

Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Mochly-RosenFor the first time, Stanford researchers figured out a sneaky way to make an enzyme do something it wouldn’t normally do — imitate another enzyme and digest alcohol properly. Their work suggests a possible preventative mechanism for alcohol-related cancers in an at-risk population and is a promising new route for drug discovery.

Daria Mochly-Rosen, PhD, professor in chemical and systems biology, and Che-Hong Chen, PhD, senior research scientist, conducted the study, which was published online yesterday in Proceedings of the National Academy of Sciences.

Enzymes are notoriously choosy, selectively responding to certain molecules that bind precisely in their active site, but the researchers were able to change the selectivity of an enzyme’s active site by “hijacking” it with a small molecule.

Making an enzyme act like another enzyme isn’t just cool. It can have important health consequences for people who have broken enzymes because of genetic mutations.

I wrote about this enzyme deficiency in a press release on the study:

When most people and animals consume alcohol, the body digests it rapidly, within a few hours. One of the byproducts of alcohol metabolism is a chemical called acetylaldehyde. According to the World Health Organization, acetylaldehyde is a Group-1 carcinogen, which means there is a direct link between exposure and cancer.

For most people, acetylaldehyde is not a major health risk — though it can contribute to hangover symptoms — because an enzyme called ALDH2 quickly converts it to a harmless acid. But for some, acetylaldehyde is a big problem.

These people lack a working version of ALDH2 because of a genetic mutation. ALDH2 deficiency is the most common genetic mutation in humans, affecting about 40 percent of East Asians — some 560 million people, or nearly 8 percent of the world’s population. Without a working enzyme, the body cannot clear the toxic acetylaldehyde quickly.

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Events, Science, Science Policy, Stanford News, Technology

The challenge – and opportunity – of regulating new ideas in science and technology

The challenge – and opportunity – of regulating new ideas in science and technology

running image

Innovation in science and technology holds promise to improve our lives. But disruptive business models, do-it-yourself medical devices, and open platforms also introduce corporate and personal risks. How can the public stay safe from unknown consequences as a company’s product or service matures? In a recent panel co-sponsored by Stanford’s Rock Center for Corporate Governance and Center for Law and the Biosciences, experts in law, business, and ethics discussed what happens when science and technology outrun the law.

Talk of drones, app-based car services, and music-sharing technologies teased out key issues currently disrupting legal paradigms. But biomedical science took center stage. “Health is more regulated than any other [area]” said panelist Hank Greely, JD, the Deane F. and Kate Edelman Johnson Professor of Law and director of the Center for Law and the Biosciences. He characterized the FDA’s processes as useful in slowing innovation in the health space but noted that rigorous pre-market regulation “won’t work in most parts of the economy.”

What happens when regulation is beyond reach? Greely noted that even if the FDA could limit an entrepreneurial company, it couldn’t conquer the DIY market. He referenced a procedure known as transcranial direct current stimulation, which, by applying electrodes to the head, can feel like “Adderall through a wire” or alter a person’s mood according to placement. A transmitting device is so simple to make, Greely said, “the hardest part will be finding an open Radio Shack.”

Moderator Dan Siciliano, JD, faculty director of the Rock Center and professor of the practice of law, asked the panelists which under-regulated technologies they found frightening. Vapor cigarettes, answered Eleanor Lacey, JD, for luring youth through fruit flavors and targeting them through advertising channels prohibited for regular cigarettes. (As previously reported on Scope, the FDA announced last spring that it would regulate the sale, but not marketing, of e-cigarettes.)

Lacey, vice president, general counsel and secretary of SurveyMonkey, discussed regulation issues involving health information that is transmitted on the company’s platform, where users own their data. She pointed to instances of users creating surveys on which respondents shared HIPAA-protected information, admitted suicidal thoughts, or confessed to crimes. The company cooperates with law enforcement in a very narrow set of sensitive situations but also upholds neutrality of the user-owned space and the user right to control the content: “You don’t want us to be able to shut it down,” Lacey said.

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Big data, Genetics, Global Health, Infectious Disease, Research, Science

The benefit of mathematical models in medicine

The benefit of mathematical models in medicine

1024px-Free_range_chicken_flockTheoretical modeling sounds like it has, at best, a distant connection to the day-to-day concerns of medical professionals who care for or research the needs of patients. But when I spoke recently with Noah Rosenberg, PhD, a population geneticist at Stanford and editor of the scientific journal Theoretical Population Biology, he pointed out that modeling can offer distinct benefits to those in medical fields like epidemiology and genetics.

“We see a lot of occasions in public discussions of areas like the spread of epidemics, the demography of aging populations, and big data analysis in genomics where part of the backdrop arises from theoretical population biology work,” Rosenberg said. “We hope to spread the word that there is a place for the kinds of theoretical and mathematical insights that can contribute to those important topics.”

Rosenberg noted that papers in the journal often span the divide between mathematics and biology, but they have a few things in common. In an editorial he published last month in the journal, Rosenberg describes an ideal study for the journal – namely that first, “the mathematical work is motivated by a genuine problem in biology, and there’s a need for theory to resolve the problem,” he said. Secondly, the mathematical work is substantial enough that it uncovers new potential relationships or new explanations for a phenomenon, and lastly, that the advances contribute to our understanding of biology – though some of the best papers in the field can also have a big impact on the field of mathematics, too.

When I asked him to talk about what that would mean for studies that touch on health research, he pointed me to a couple of fascinating papers. One is a paper by Shai Carmi, PhD, and colleagues that explains a new way to look at shared DNA strands between people in order to understand their relatedness and the amount of overlap in their genomes. This has implications for how we think about “the way in which genes descend within families, including genes that may be related to a disease.” It’s one of the journal’s most downloaded papers, Rosenberg told me.

The second is a study by Maciej Boni, PhD, and colleagues that incorporates how decisions that poultry farmers in Southeast Asia make about market conditions might affect the spread of avian influenza in their flocks. When avian flu is identified in a region, poultry flocks are usually culled. It’s an interesting example of how human behavior can affect disease dynamics.

Rosenberg noted that the studies and models that are able to incorporate human behavioral patterns are among the most interesting that he sees. Nailing down how people’s decisions affect the course of an outbreak is notoriously difficult, but like the avian influenza paper demonstrates, mathematical models make it possible to explore the consequences of different assumptions about these decisions.

Rosenberg says that it’s even possible to make mathematical models of cultural practices (like deciding not to immunize your children) and how they spread among groups of people. One public laboratory this interaction is currently playing out in is the measles outbreak that got its start at Disneyland in December. The outbreak topped 100 cases nationwide, mostly among families that refuse to vaccinate their children. “It’s the intersection between human behavior and dynamics of disease,” he said. “Putting those together in a mathematical model to predict what might happen is the kind of work that appears in Theoretical Population Biology.”

Previously: Stanford physician Sanjay Basu on using data to prevent chronic disease in the developing world and Facebook app models how viruses spread through human interaction
Photo by Woodley Wonderworks

Genetics, NIH, Research, Science, Stanford News

Project Roadmap: Mysteries of the epigenome revealed

Project Roadmap: Mysteries of the epigenome revealed

Let’s hear it for large, international collaborations! Hot on the heels of the ENCODE Project (well, in research time anyway) comes the National Institutes of Health’s Roadmap Epigenomics Project, which is geared toward understanding how chemical tags on DNA and its associated proteins determine how each cell uses the information in the genome to develop its own identity. One of the leaders of the massive project was geneticist Anshul Kundaje, PhD, who helped to analyze the huge amounts of data generated by labs around the world as they studied more than 100 adult and fetal human tissues.

The work is published today in Nature in the form of a large package of papers. Kundaje is the first author of the main paper; Nature has also published a nice summary of all the papers in the issue and produced a musical video to explain the project.

From our release:

The problem [of picking and choosing from a genome’s worth of information] is somewhat like being handed a list of all the ingredients available in a well-stocked kitchen without any idea of how to combine them. Tossing a few of them together, willy-nilly, into a baking dish and popping it into the oven isn’t likely to yield anything edible. But with a well-written recipe telling you how much and when to mix together flour, sugar, eggs and butter, you can turn out a perfect cake or fantastic waffles.

The completion of the Human Genome Project gave biologists the list of ingredients to which every cell has access. The Roadmap Epigenomics Project outlines the recipes and shows how cells use these ingredients to generate their own special sauce. By comparing and contrasting these cellular recipes, researchers can begin to draw parallels among cell types and even predict which cells might be involved in specific traits and diseases.

As a proof of principle, Kundaje and others showed in one of the companion papers that, based on the epigenomic maps shared among cells, the immune system is likely to play a larger role in the development of Alzheimer’s disease than previously thought.

Previously: Scientists announce the completion of the ENCODE project, a massive genome encyclopedia , Red light, green light: Simultaneous stop and go signals on stem cells’ genes may enable fast activation, provide “aging clock” and Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using

In the News, Medical Education, Research, Science, Science Policy, Stanford News

A conversation with John Ioannidis, “the superhero poised to save” medical research

A conversation with John Ioannidis, "the superhero poised to save" medical research

ioannidis at deskI always relish a good Q&A. As a writer, I know how hard it is to craft questions that elicit insights into a person — or his or her work. That’s why I jumped at the opportunity to spotlight a recently published Vox interview with John Ioannidis, MD, DSc, director of the Meta-Research Innovation Center at Stanford.

Ioannidis is blunt, and prolific, with his criticisms of science.

Among his concerns: Researchers usually publish only results that show statistical significance, failing to share numerous experiments that didn’t work out, which would also be illustrative. Many studies aren’t reproducible: Sometimes due to a lack of data, other times just due to shoddy procedures. Researchers “spin” data to please their funders.  And in universities, scientists are compelled to publish, a system that favors quantity over quality. Peer review has gaps. And the list goes on and on.

What, then, to do?

Here’s Ioannidis (referred to by the writer as “the superhero poised to save” medical research) in the Q&A:

Maybe what we need is to change the incentive and reward system in a way that would reward the best methods and practices. Currently, we reward the wrong things: people who submit grant proposals and publish papers that make extravagant claims. That’s not what science is about. If we align our incentive and rewards in a way that gives credibility to good methods and science, maybe this is the way to make progress.

One problem is education, he says:

Most scientists in biomedicine and other fields are mostly studying subject matter topics; they learn about the subject matter rather than methods. I think that several institutions are slowly recognizing the need to shift back to methods and how to make a scientist better equipped in study design, understanding biases, in realizing the machinery of research rather than the technical machinery.

There’s much more in the piece, including a glimpse of Ioannidis’ “love numbers” system.

Previously: Shake up research rewards to improve accuracy, says Stanford’s John Ioannidis, John Ioannidis discusses the popularity of his paper examining the reliability of scientific research and “U.S. effect” leads to publication of biased research, says Stanford’s John Ioannidis 
Photo, which originally appeared in STANFORD Magazine, by Robyn Tworney

Research, Science

Love on Scope: A look back

Love on Scope: A look back

heart in sky

Love is in the air. And in honor of the Valentine’s Day holiday, here are some of our favorite love-themed posts of the past.

Love blocks pain, Stanford study shows: According to a 2010 study, intense, passionate feelings of love can block pain in ways similar to painkillers or illicit drugs like cocaine.

Scientist pens love letter to stem cells, calls them “irresistible”: “While you frustrated me to no end, I found you irresistible,” wrote a scientist-turned-blogger about stem cells.

“Love hormone” may mediate wider range of relationships than previously thought: There’s more to oxytocin, the so-called love hormone, than arousal and bonding, said Stanford scientists in 2013.

A study of people’s ability to love: Check out the “love competition” put on by a group of Stanford neuroscientists (with the help of an fMRI machine).

Valentine’s Day advice from “lovestruck scientists”: Looking for some science-based dating tips “that could boost your chances on Valentine’s Day?” This is the post for you.

Photo by Mrs Airwolfhound

Genetics, In the News, Medicine and Society, Research, Science, Technology

A leader in the Human Genome Project shares tale of personalized medicine, from 1980 until today

A leader in the Human Genome Project shares tale of personalized medicine, from 1980 until today

2559447601_005b33ae7d_zEric Lander, PhD, warned the several hundred people who came to hear him speak on the Stanford campus earlier this week that he wasn’t giving a traditional data-packed scientific presentation.

Instead, the founding director of the Broad Institute and veteran of the Human Genome Project — who Google’s Eric Schmidt introduced — promised to tell a story, a yarn about, as he put, the biomedicine of the East Coast meeting the technological innovation of the West Coast. (He couched the statement and admitted that yes, the West Coast does have a bit of biomedicine.)

So here goes:

Once upon a time, 35 years ago, in a land ruled by punk rock and big hair, scientists worked hard to pinpoint the genetic cause of cystic fibrosis, a disease caused by a single mutation. It was slow, hard work, but they persevered and found the gene.

Wouldn’t it be wonderful to know all the human genes, some scientists speculated, buoyed by their preliminary success. Cancer could be vanquished. Genetic disorders a thing of the past. But getting to that point might take as long as 2,000 years.

Enter the Human Genome Project (HGP) in 1990. A collaborative effort of 16 research centers in six countries, the team “industrialized biology,” cranking out a code for the 3 billion base pairs that make up the human genome.

Of equal importance, the HGP was advocating the importance of public access to genetic material. It faced a challenge from a rival private company, Celera, who proposed creating a subscription database with the genetic information.

The HGP also had to contend with hype, Lander said: With a banner-headline, the New York Times had proclaimed in 2000 “Genetic code of human life is cracked by scientists.”

But really, the scientists had little more than a gigantic text — ATCGGCTATATAATCG — that Lander likened to the Rosetta Stone. By comparing it with the genomes of mice, dogs, rats, cats, dolphins and many other critters, scientists worldwide were able to decipher it piece by piece.

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