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Research, Science, Stanford News

They said “Yes”: The attitude that defines Stanford Bio-X

They said "Yes": The attitude that defines Stanford Bio-X

bio-X peopleI write a lot about interdisciplinary research (it’s my job), but it was just recently that I heard the best description of what it is that makes interdisciplinary collaborations possible. It came from Carla Shatz, PhD, who directs Stanford Bio-X — an interdisciplinary institute founded in 1998 that brings together faculty from the schools of medicine, humanities & sciences and engineering. She told me:

You have to be able to walk into someone’s lab and say, “You know, I have this problem in my lab. Would you like to have a cup of coffee and talk about it?” And then that person needs to say, “Yes.”

We were talking about a recent report by the National Research Council of the National Academies. They had put together a workshop and then published a report giving advice and best practices for supporting interdisciplinary research. The report used Bio-X as a success story for the type of innovation that can come out of programs that cross disciplines.

Nowhere in the report is there a subhead reading, “Faculty have to say yes,” but a lot of the other advice is straight out of the Bio-X playbook. The institute needs to be located at the cross section of several schools or departments (check). The institute needs a building that brings people together (check). The institute needs to support students (check). The institute needs to be a financial value add rather than taxing participating departments (check).

This isn’t specifically called out in the report, but Shatz added that a good interdisciplinary institute also needs good food. She pointed out that people come from all over campus to eat at Nexus, located in the middle of the Clark Center that houses Bio-X and serves as a focus for its activities. It turns out scientists are just like the rest of us: offer good food and they will come. And then they will chat, and the next thing you know they’ll be collaborating.

I wrote a Q&A with Shatz based on our conversation. From now on, when I hear the phrase “She said yes” I’ll think of her, and her great description of the attitude that underlies collaboration.

Previously: Bio-X Kids Science Day inspires young scientists, Dinners spark neuroscience conversation, collaboration, Stanford’s Clark Center, home to Bio-X, turns 10 and Pioneers in science
Photo from Bio-X

Research, Science, Stanford News, Stem Cells

Induced pluripotent stem cell mysteries explored by Stanford researchers

Induced pluripotent stem cell mysteries explored by Stanford researchers

Induced pluripotent stem cells, also called iPS cells, made from easily accessible skin or other adult cells, are ideal for disease modeling, drug discovery and, possibly, cell therapy. That’s because they can be generated in large numbers and grown indefinitely in the laboratory. They also reflect the genetic background of the person from whom they were generated. However, some fundamental questions still remain before they’re ready for the full glare of the clinical limelight. Does it matter what type of starting cells scientists use to create the pluripotent stem cells? And what’s the best control to use when studying the effect of a particular, patient-specific mutation?

Now Stanford cardiologist Joseph Wu, MD, PhD, and his colleagues have addressed and answered these questions. Their work was published yesterday in two back-to-back papers in the Journal of the American College of Cardiology. (Each paper is also accompanied by an editorial.) As Wu explained in an e-mail to me:

If your goal is to generate healthy iPS cell derivatives for regenerative therapy, it’s important to know whether the starting material makes a difference. For example, if I’m treating Alzheimer’s disease, is there a benefit to using iPS cell-derived brain cells made from brain cells? Likewise, if I’m treating a skin disorder, is there a benefit to using iPS cell-derived skin cells made from skin cells? As cardiologists, we are asked this quite often and each time, I had to say “I don’t know.” So we decided to do a study comparing the differentiation and functional ability of iPS cell-derived cardiomyocytes generated from two different sources: skin and heart. We also wanted to devise more efficient ways for researchers to quickly and easily create their own “designer” iPS cell lines to study particular mutations.

To answer the first question, the researchers created iPS cells from two types of starter cells: human fetal skin cells and cardiac progenitor cells. Not surprisingly, only the cardiac progenitor cells expressed genes known to be expressed in heart tissue. Wu and his colleagues then exposed the newly created pluripotent stem cells to growing conditions that favor the development of heart muscle cells called cardiomyocytes. They found that, although iPS cells derived from cardiac progenitor cells were more efficient at becoming cardiomyocytes, both types of starting material produced heart muscle cells that functioned similarly after a period of growth in the laboratory. As Wu explained:

These two populations of cells are essentially no different from one another over time. It appears that they lost the memory of their starting material (this memory is stored in the form of chemical tags on the cells’ DNA in a phenomena known as epigenetic marking). This suggests that I could take my own skin cells, make iPS cells and then create specialized brain, heart, liver or kidney cells for cell therapy. This is much easier than biopsying each tissue, and could be a good way to create universal iPS cell lines for research or cell therapy.

In the second paper, Wu and his colleagues devised a way to introduce specific mutations into iPS cells before transforming them into particular tissues. The approach relies on the use of what’s known as “dominant negative” mutations that exert their disruptive effect even when the unmutated gene is still present. This is important because it’s much easier and quicker than previous similar efforts, which required a complicated, time-consuming procedure to snip out and then replace individual genes. The technique also allows researchers to generate two cell lines that are identical except for the mutation under study. That way researchers can be confident that differences between the cell lines are due only to that mutation, which is particularly important when the lines are used to test the effect of therapeutic drugs. Again, from Wu:

Investigators can make their own designer iPS cell lines to study particular mutations with genetically identical controls to use in their experiments. We won’t have to make new iPS cells from each patient, which is laborious and time consuming. Instead we can create standardized lines to study many different mutations alone and in combination. This has the potential to revolutionize the field of disease modeling and drug discovery.

The two papers describe ongoing research in the Wu lab designed to optimize iPS cells for a variety of applications. The group, including graduate student Arun Sharma, recently published research using human iPS cell-derived cardiomyocytes to investigate the effect of various antiviral drugs againse coxsackievirus, a leading cause of an infection of the middle layer of the heart wall in children and the elderly. The research is the first time that iPS cell-derived heart muscle has been used to investigate the mechanisms behind an acquired viral disease.

Previously: A new era for stem cells in cardiac medicine? A simple, effective way to generate patient-specific heart muscle cells, “Clinical trail in a dish” may make common medicines safer, say Stanford scientists and Lab-made heart cells mimic common cardiac disease in Stanford study

Humor, Parenting, Science

A humorous look at how a background in science can help with parenting

A humorous look at how a background in science can help with parenting

Scientist-moms out there might enjoy this playful (tongue-in-cheek) Huffington Post essay on how having a science degree made the writer a better parent. I had to chuckle at Sarah Gilbert’s list of how she’s found uses for the sciences in her day-to-day life:

Physics: Knowing that my house will return to complete disorder immediately after I clean it, because entropy.

Biology: Knowing everything my baby ate by the contents of her diaper, because scat identification.

Neuro-psychology: Knowing that my toddler freaking out over sandwich crusts is just a phase, because frontal lobe development.

Statistics: Knowing that the chance of having a baby brother is 50/50 no matter what my mother-in-law thinks, because mutually exclusive events.

Astronomy: Knowing that the woman judging me by my yogurt-spattered shirt isn’t the only thing in the universe, because cosmology.

In the News, Science, Stanford News

Internships expose local high-schoolers to STEM careers and academic life

Internships expose local high-schoolers to STEM careers and academic life

beakersIt’s summertime: Do you know where your teenagers are? A piece in the Palo Alto Weekly discusses some of the choice science internships available to local high-school students at Stanford and other universities in the region. Shadowing scientists in the lab and even contributing to research, the young interns learn real-world applications for subjects they learn in school. They also gain work experience and exposure to academic careers in STEM fields. And a high-profile internship couldn’t hurt to include on college applications.

From the piece:

Coordinators often have to sift through hundreds of applications from students applying from all over the country and internationally. One of the most sought after is the Stanford Institutes of Medicine Summer Research Program, which alone received about 1,400 applications this year to fill about 70 to 75 openings. Decisions are based on academic grounds to help narrow down the number of prospective candidates — a tough task in a pool of extremely well-educated candidates.

But coordinators also recognize the need to provide opportunities for students who don’t have the chance to join accelerated science programs and express that oftentimes the most important quality of an applicant is a passion for science.

The article notes that internships gained through family and friend connections can be unevenly distributed, and  how programs like Stanford’s Raising Interest in Science and Engineering (RISE) Summer Internship Program have made the experiences more accessible. More from the piece:

“Typically those are kids with very educated parents who speak fluent English and who are comfortable poking around Stanford a little bit … or have a network and know somebody who works in a lab here. The RISE students typically just don’t have family members that can help them in that way,” [Kate Storm] says. “I think it’s important to serve all students, not just the privileged gifted students who are going to thrive and do well no matter what because they’ve got the backing of their school and parents and siblings.”

These types of opportunities are important to start curbing the racial disparities that exist in STEM occupations. Roughly 70 percent of the people in STEM occupations were Caucasian, 14 percent Asian, 6.5 percent Hispanic and 6.4 percent African American, according to an American Community Survey Report from the U.S. Census Bureau in 2011. Since 2008, Storm says about 80 percent of RISE graduates have gone on to major in math, engineering or science in college.

Researchers are also passionate about increasing the number of girls in labs since women are also largely underrepresented in STEM fields. The same 2011 U.S. Census Bureau report stated that roughly 25.8 percent of those in STEM occupations are women, compared to 45.7 percent of all jobs.

Previously: Residential learning program offers undergrads a new approach to scientific inquiry, The “transformative experience” of working in a Stanford stem-cell lab, Image of the Week: CIRM intern Brian Woo’s summer projectImage of the Week: CIRM intern Christina Bui’s summer project and Stanford’s RISE program gives high-schoolers a scientific boost
Photo by Amy

Chronic Disease, Research, Science, Stanford News, Technology

Stanford team develops nanotech-based microchip to diagnose Type 1 diabetes

Stanford team develops nanotech-based microchip to diagnose Type 1 diabetes

Dr. Brian Feldman?s M.D. hold a computer chip that he develop that will benefit diabetic patients at the Stanford School of Medicine,  on Thursday, July 4, 2014.  ( Norbert von der Groeben/ Stanford School of Medicine )

Years ago, when patients showed up at the doctor with excessive thirst, frequent urination and unexplained weight loss – in other words, the classic symptoms of diabetes mellitus – diagnosing them was usually just a matter of checking for high blood sugar. Yes, they needed to be treated for the correct form of the disease, but the two main types were found in different populations. So, in most cases, no lab test was needed to figure out whether someone had Type 1 or Type 2 diabetes; demographic factors were enough to make the distinction.

Of late, there’s been much more cross-over between the two groups. To treat patients correctly, it’s important to diagnose the right form of diabetes, but there’s a problem: The only test that does so is expensive, cumbersome and available only in hospitals.

So it’s great news that Stanford scientists are developing a new Type 1 diabetes test, described in a paper published online this week in Nature Medicine. The new nanotechnology-based microchip, which researcher Brian Feldman, MD, PhD, holds in the photo above, tests patients’ blood for the auto-antibodies that cause Type 1 diabetes. The new test is cheap, portable, and uses much less blood than the older diagnostic test. Unlike the old test, it requires no radioactive reagents and is simple enough to use in low-tech settings.

The test uses a nanotech enhancement (specifically, nano-sized islands of gold; hence the golden glow of the chip that Feldman is holding) to help detect auto-antibodies. In addition to diagnosing new patients, this technology will also enable better research into how Type 1 diabetes develops, as our press release explains:

…[P]eople who are at risk of developing Type 1 diabetes, such patients’ close relatives, also may benefit from the test because it will allow doctors to quickly and cheaply track their auto-antibody levels before they show symptoms. Because it is so inexpensive, the test may also allow the first broad screening for diabetes auto-antibodies in the population at large.

“The auto-antibodies truly are a crystal ball,” Feldman said. “Even if you don’t have [Type 1] diabetes yet, if you have one auto-antibody linked to diabetes in your blood, you are at significant risk; with multiple auto-antibodies, it’s more than 90 percent risk.”

Feldman’s team has started a biotech company to further develop the test and is seeking FDA approval for the new method. In addition, Stanford University and the researchers have filed a patent for the new technique.

Previously: A simple blood test may unearth the earliest signs of heart transplant rejection, Stanford microbiologist’s secret sauce for disease detection and One family’s story on caring for their children with type 1 diabetes
Photo by Norbert von der Groeben

Medicine and Society, Science, Stanford News, Technology

Residential learning program offers undergrads a new approach to scientific inquiry

Residential learning program offers undergrads a new approach to scientific inquiry

SIMILE studentsTwenty-two Stanford freshmen spent the last school year living, studying and socializing immersed in scientific inquiry. In its inaugural year, the residential education program SIMILE: Science in the Making Integrated Learning Environment drew interest from and selected a diverse group representative of the student body, many of whom don’t intend to become physicians or scientists or even plan to major in related fields. SIMILE students take pre-major requisites including writing, rhetoric and breadth requirements focused on the historical, cultural and social contexts of science. They also complete hands-on projects, attend field trips and regularly interact with faculty and guest lecturers in the program. Housed in the all-freshman Burbank House with ITALIC (Immersion in the Arts: Living in Culture), SIMILE students attend lectures and discussion sections in-house and have some shared activities with the new arts-focused residential academic program there.

A recent Stanford Report piece notes:

In the fall, Paula Findlen, [PhD,] a professor of Italian history and director of SIMILE, and Reviel Netz, a professor of classics, team-taught Inventing Science, Technology and Medicine. The class explored how those scientific fields emerged from the human desire to understand nature – empirically, mathematically and philosophically – and to control the environment.

Findlen said the program offered a “big picture view” of how human interactions have changed over the centuries, using history as the lens to understand the invention of science, technology and medicine.

“Fundamentally, SIMILE is a program about the history of knowledge,” she said.

Previously: Exploring global health through historical literatureThoughts on the arts and humanities in shaping a medical career and Intersection of arts and medicine a benefit to both, report finds
Photo by Jeremy Moffett

Cancer, Research, Science, Stanford News, Stem Cells

Radiation therapy may attract circulating cancer cells, according to new Stanford study

Radiation therapy may attract circulating cancer cells, according to new Stanford study

Localized radiation therapy for breast cancer kills cancer cells at the tumor site. But, in a cruel irony, Stanford radiation oncologist Edward Graves, PhD, and research associate Marta Vilalta, PhD, have found that the dying cells in the breast may send out a signal that recruits other cancer cells back to the site of the initial tumor. Their work was published today in Cell Reports. As Graves explained in an e-mail to me:

Cancer spreads by shedding tumor cells into the circulation, where they can travel to distant organs and form secondary lesions.  We’ve demonstrated with this study that cancer radiation therapy may actually attract these circulating tumor cells, or CTCs, back to the primary tumor, which may lead to the regrowth of the tumor after radiation therapy.

The researchers studied mouse and human breast cancer cells growing in a laboratory dish, as well as human breast cancer cells implanted into mice. They found that irradiated cells secreted a molecule called granulocyte macrophage colony stimulating factor, or GM-CSF. Blocking the expression of GM-CSF by the cells inhibited (but didn’t completely block) their ability to recruit other cells to the cancer site. The finding is particularly interesting, since physicians sometimes give cancer patients injections of GM-CSF to enhance the growth of infection-fighting white blood cells that can be damaged during chemotherapy. As Graves explained, “This work has important implications for clinical radiotherapy, and for the use of GM-CSF in treating neutropenia in cancer patients during therapy.”

The researchers say, however, that cancer patients shouldn’t eschew radiation therapy. Rather, the finding may help clinicians devise better ways to fight the disease – perhaps by blocking GM-CSF signaling. Graves concluded:

It should be emphasized that radiation therapy remains one of the most effective treatments for cancer. Our findings will help us to further optimize patient outcomes following this already potent therapy.

Previously: Using 3-D technology to screen for breast cancer, Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers and Common drug class targets breast cancer stem cells, may benefit more patients, says study

In the News, Science

Stanford researcher on elephants: “We should value animals that have the same level of sophistication that we do”

Stanford researcher on elephants: “We should value animals that have the same level of sophistication that we do"

elephantsThe July issue of Smithsonian Magazine has a lengthy feature on the crisis facing elephants in Africa, with writer Joshua Hammer explaining, “Of the 50,000 elephants that roamed Chad 50 years ago, barely 2 percent are left. In the neighboring Central African Republic and Cameroon, the population may be even lower. Poverty, bribery and insecurity are all contributing factors in a region where a single large tusk can sell on the black market for $6,000—ten times the annual salary of a typical worker.”

Quoted in the piece is Stanford’s Caitlin O’Connell-Rodwell, PhD, a consulting assistant professor of otolaryngology, who has done extensive field work with the animals. She describes the connection between elephants and humans and expresses deep concern about the animals’ risk of becoming extinct:

“What is special about elephants is just how similar they are to us—socially and developmentally,” says Caitlin O’Connell-Rodwell, a Stanford ecologist who has written four books based on her Namibian field research on elephants. “If you watch a family group reuniting, their behavior is exactly like ours—the little cousins darting off together, the elaborate greetings of adults. Elephants offer a way of looking into the mirror, for better or worse,” she adds. “If we value human rights, we should also value animals that have the same level of sophistication that we do. We should keep those beings with us here on earth.”

Previously: Listening to elephants, communicating science, and inspiring the next generation of researchers, Elephants chat a bit before departing water hole, new Stanford research shows and Researcher dishes on African elephant soap opera
Photo by Caitlin O’Connell-Rodwell and Timothy Rodwell

Cancer, FDA, Genetics, Research, Science, Stanford News

Another blow to the Hedgehog pathway? New hope for patients with drug-resistant cancers

Another blow to the Hedgehog pathway? New hope for patients with drug-resistant cancers

6825694281_dfb79615d6_zIf you’re a regular reader of this blog, or follow cancer literature, you’ll have heard of a signaling pathway called Hedgehog that is activated in many cancers, including brain, skin and even bladder. It’s a cute name for cellular cascade that can kill when inappropriately activated.

Neurologist Yoon-Jae Cho, MD, treats children with brain tumors called medulloblastomas. He and postdoctoral fellow in his lab, Yujie Tang, PhD, published a study yesterday in Nature Medicine that could one day help some patients whose Hedgehog-driven tumors have become resistant to available therapies.

As Cho explained in an e-mail to me:

Medulloblastomas are the most common malignant brain tumors in children. They are comprised of various subgroups, including one with activation of a strong oncogenic signal called the Hedgehog pathway. Notably, the Hedgehog pathway is also activated in several other cancers including basal cell carcinoma, the most common cancer worldwide. Therefore, pharmaceutical companies and several research groups have developed drugs to target this pathway.

The most common of these drugs targets a downstream protein component of the pathway called Smoothened, including one currently marketed by Genentechcalled vismodegib (trade name Erivedge) and an investigational drug produced by Novartis called LDE225. Blocking the activity of Smoothened stops the chain reaction leading to division of the cancer cells. You can think of it (in simplified terms) as a line of dominoes standing on end, waiting for an eager finger to begin the chain reaction. Removing one domino (nixing Smoothened activity) can sometimes stop the rest of the row from falling and block the cancerous cell from dividing. But, as Cho explained:

Unfortunately, many cancers activate the Hedgehog pathway downstream of Smoothened and are inherently resistant to these therapies. Other cancers that are initially responsive to these drugs develop resistance through activation of downstream Hedgehog pathway components.

Cho and his colleagues have now described a new, novel way to interfere with the Hedgehog pathway. They’ve found that compounds that inhibit a protein called BRD4 can stop the growth of human Hedgehog-driven cancers – even when they’re resistant to drugs blocking Smoothened activity. This is particularly interesting because the BRD family of proteins recognizes and binds to particular chemical tags on chromatin that control whether (and when) a gene is made into a protein. It’s the first time such an epigenetic regulator has been implicated as a target in the Hedgehog pathway. Additionally, it’s a new avenue to explore for patients with Hedgehog-driven medulloblastomas – as many as half of whom will be resistant to Smoothened inhibition, according to a previous study co-authored by Cho and members of the International Cancer Genome Consortium’s Pediatric Brain Tumor Project. Cho concludes, “Our study offers a promising new treatment strategy for patients with Hedgehog-driven cancers that are resistant to the currently used Smoothened antagonists.”

Previously: New skin cancer target identified by Stanford researchers, Humble anti-fungal pill appears to have noble side-effect: treating skin cancer and Studies show new drug may treat and prevent basal cell carcinoma
Photo by Phillip Taylor

Big data, Cancer, Research, Science, Stanford News, Videos

Will hypothesis or data-driven research advance science? A Stanford biochemist weighs in

Will hypothesis or data-driven research advance science? A Stanford biochemist weighs in

The 2014 Big Data in Biomedicine conference was held here last month, and keynote speakers, panelists, moderators and attendees are now available on the Stanford Medicine YouTube channel. To continue the discussion of how big data can be harnessed to benefit human health, we’ll be featuring a selection of the videos this month on Scope.

Julia Salzman, PhD, a Stanford assistant professor of biochemistry, is concerned that significant amount of data is being thrown in the trash “because the data don’t fit our sense of what they should look like.” At Big Data in Biomedicine 2014, she explained how giving her computers a long leash led her down an unexpected path and the discovery of a new, and probably noteworthy, biological entity. My colleague Bruce Goldman highlighted her findings in a news release:

Using computational pattern-recognition software, her team discovered numerous instances in which pieces of RNA that normally are stitched together in a particular linear sequence were, instead, assembled in the “wrong” order (with what’s normally the final piece in the sequence preceding what’s normally the first piece, for example). The anomaly was resolved with the realization that what Salzman and her group were seeing were breakdown products of circular RNA — a novel conformation of the molecule.

In its circular form, she noted, an RNA molecule is much more impervious to degradation by ubiquitous RNA-snipping enzymes, so it is more likely than its linear RNA counterparts to persist in a person’s blood. Every cell in the body produces circular RNA, she said, but it seems to be produced at greater levels in many human cancer cells. While its detailed functions remain to be revealed, these features of circular RNA may position it as an excellent target for a blood test, she said.

In the above Behind the Scenes at Big Data video, Salzman discusses her work and addresses a question asked during the Single Cells to Exacycles panel: In this next era of science, will science advance mainly through hypothesis or data driven research? She comments, “I think that’s a fundamental question moving forward, whether the scientific method is dead or whether it’s still alive and kicking. I think that’s a really important question for us as to answer and deal with as scientists.” Watch the interview to find out the rest of Salzman’s thoughts on the issue.

Previously: Rising to the challenge of harnessing big data to benefit patients, Discussing access and transparency of big data in government and U.S. Chief Technology Officer kicks off Big Data in Biomedicine

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