Published by
Stanford Medicine

Category

Applied Biotechnology

Applied Biotechnology, Big data, Cancer, Genetics, Research, Science, Stanford News

Peeking into the genome of a deadly cancer pinpoints possible new treatment

Peeking into the genome of a deadly cancer pinpoints possible new treatment

small cell lung cancerSmall cell lung cancer is one of the most deadly kinds of cancers. Typically this aggressive disease is diagnosed fairly late in its course, and the survival rates are so dismal that doctors are reluctant to even subject the patient to surgery to remove the tumor for study. As a result, little is known about the molecular causes of this type of cancer, and no new treatments have been approved by the Food and Drug Administration since 1995.

Now a massive collaboration among researchers around the world, including the University of Cologne in Germany and Stanford, has resulted in the collection of more than 100 human small cell lung cancer tumors. Researchers sequenced the genomes of the tumors and identified some key steps in their development. They also found a potential new weak link for treatment.

The findings were published today in Nature, and Stanford cancer researcher Julien Sage, PhD, one of three co-senior authors of the paper, provided some details in an email:

With this larger number of specimens analyzed, a more detailed picture of the mutations that contribute to the development of small cell lung cancer now emerges. These studies confirmed what was suspected before, that loss of function of the two tumor suppressor genes, Rb and p53, is required for tumor initiation. Importantly, these analyses also identified new therapeutic targets.

The researchers also saw that, in about 25 percent of cases, the Notch protein receptor was also mutated. This protein sits on the surface of a cell; when Notch binds, it initiates a cascade of signaling events within the cell to control its development and growth. As Sage explained:

The mutations in the Notch recepetor were indicative of loss of function, suggesting that Notch normally suppresses small cell lung cancer development. Indeed, when graduate student Jing Lim in my lab activated Notch in mice genetically engineered to develop small cell lung cancer, we found a potent suppression of tumor development. These data identify the Notch signaling pathway as a novel therapeutic target in a cancer type for which new therapies are critically needed.

This is not Sage’s first foray into fighting small cell lung cancer. In 2013, he collaborated with other researchers at Stanford, including oncologist Joel Neal, MD, PhD, to identify a class of antidepressants as a possible therapy for the disease.

Previously: Gene-sequencing rare tumors – and what it means for cancer research and treatment, Listening in on the Ras pathway identifies new target for cancer therapy and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Image by Yale Rosen

Applied Biotechnology, In the News, Research, Stem Cells, Transplants

“Supplying each cell with a scuba tank”: New advances in tissue engineering

"Supplying each cell with a scuba tank": New advances in tissue engineering

membrane-article.jpgResearchers in the U.K. have found a way to make growing synthetic tissue more sustainable. At present, the size of engineered tissues is limited because the cells die from lack of oxygen when the pieces get too big. By adding an oxygen-carrying protein to the stem cells prior to combining them with tissue scaffolding, the researchers overcame this problem.

The study, led by Adam Perriman, PhD, research fellow at the University of Bristol’s Synthetic Biology Research Centre, and Anthony Hollander, PhD, professor of integrative biology at the University of Liverpool, was published yesterday in Nature Communications. The tissue they were fabricating was cartilage, but the process could potentially be applied to other tissues, as well.

Perriman describes the findings in a press release:

We were surprised and delighted to discover that we could deliver the necessary quantity [of oxygen] to the cells to supplement their oxygen requirements. It’s like supplying each cell with its own scuba tank, which it can use to breathe from when there is not enough oxygen in the local environment.

Hollander also comments on the significance of the research:

We have already shown that stem cells can help create parts of the body that can be successfully transplanted into patients, but we have now found a way of making their success even better. Growing large organs remains a huge challenge but with this technology we have overcome one of the major hurdles.

Creating larger pieces of cartilage gives us a possible way of repairing some of the worst damage to human joint tissue, such as the debilitating changes seen in hip or knee osteoarthritis or the severe injuries caused by major trauma, for example in road traffic accidents or war injuries.

Previously: Building bodies, one organ at a time, How Stanford researchers are engineering materials that mimic those found in our own bodies and A brief look at “caring” for engineered tissue
Photo by Warwick Bromley

AHCJ15, Applied Biotechnology, Imaging, Mental Health, Neuroscience, Technology

Talking about “mouseheimers,” and a call for new neuroscience technologies

Talking about "mouseheimers," and a call for new neuroscience technologies

3723710203_1b8c9d96ed_zOur ability to technologically assess the brain has room for improvement, according to panelists at the recent Association of Health Care Journalism 2015 conference. Amit Etkin, PhD, MD, a neuropsychiatrist at Stanford, summed it up when he said, “We need to develop tools to answer questions we want to ask, rather than ask questions we can answer with the tools we have.”

Etkin asserted that there have been no fundamental advances in psychiatry since 1987; all the medications put out now are basically the same, and the treatments work partially, sometimes, and for only some people. Interdisciplinary work combining psychiatry, neuroscience, and radiology is the frontier: Researchers are just getting a sense of how “interventional neuroscience,” such as that pioneered at the interdisciplinary NeuroCircuit initiative at the Stanford Neurosciences Institute, can identify which brain regions control various processes. This involves looking at brain signatures that are common across disorders, instead of dividing and parsing symptoms, which is the approach of the Diagnostic and Statistical Manual of Mental Disorders.

Researchers are searching for an ideal marker for Alzheimer’s: something predictive (will you get the disease?), diagnostic (do you have the disease?), and dynamic (how severe is your disease right now?)

Michael Greicius, MD, MPH, professor of neurology and neurological sciences at Stanford, researches Alzheimer’s and has a bone to pick with media hype about Alzheimer’s research conducted in mice. What the mice have shouldn’t be considered the same condition, he says, so he’s termed it “mouseheimer’s.” Only 2 percent of the Alzheimer’s population has the dominant, inherited, exceedingly potent genetic form, which is the form used in research on rodents. Further, the mice are double or even triple transgenic. We still use these improbable biological hosts because we need an artificial model: Alzheimer’s is really just a human thing, and even great apes don’t get it. The next best modeling possibility, he suggested, are flies.

Continue Reading »

Applied Biotechnology, Bioengineering, Ophthalmology, Research, Science, Technology

New retinal implant could restore sight

New retinal implant could restore sight

2618400441_c19946dff4_zIf your car battery runs out of juice, the car won’t run, but that doesn’t mean it’s time to scrap the car. Similarly (at least slightly), if your photoreceptors are worn out due to a disease such as retinitis pigmentosa or macular degeneration, then you might not be able to see, but your eyes still have a lot of functioning parts.

That’s the principle behind a new retinal implant developed by team of Stanford-led researchers. Unlike previous devices, which require wires and unwieldy surgeries, the new implant is wireless and needs only a minimally invasive surgery to inject a small, photovoltaic chip inside the eye. The team published their results in Nature Medicine.

That chip capitalizes on the remaining capabilities of existing retinal cells known as bipolar and ganglion cells and produces more refined images than existing devices. The chip responds to signals from special glasses worn by the recipient.

“The performance we’re observing at the moment is very encouraging,” Georges Goetz, a lead author of the paper and graduate student in electrical engineering at Stanford, said in our press release. “Based on our current results, we hope that human recipients of this implant will be able to recognize objects and move about.”

The implant has only been used in animal studies, but a clinical trial is planned next year in France.

“Eventually, we hope this technology will restore vision of 20/120,” co-senior author Daniel Palanker, PhD, told me. “And if it works that well, it will become relevant to patients with age-related macular degeneration.”

Previously: Stanford researchers develop solar powered wireless retinal implant, Factors driving prescription decisions for macular degeneration complex — and costly and Tiny size, big impact: Ultrasound powers miniature medical implant 
Photo by Ali T

Applied Biotechnology, Clinical Trials, FDA, Research, Stanford News

An inside look at drug development

An inside look at drug development

B0008664 Assorted pills, tablets and capsules

How are drugs born? If you’re really curious about this, you’d be fascinated by the weekly meetings of industry experts and academic researchers taking part in Stanford’s drug-development training program known as SPARK.

A recently published book, A Practical Guide to Drug Development in Academia, crystallizes the sessions. Even if you’re not a scientist dreaming of curing cancer with your latest discovery, you might find it interesting.

In his recent review of the book for Nature Chemical Biology, industrial medicinal chemist Derek Lowe, PhD, writes:

I would actually welcome it if this book’s intended audience were broadened even more. Younger scientists starting out in the drug industry would benefit from reading it and getting some early exposure to parts of the process that they’ll eventually have to understand. Journalists covering the industry (especially the small startup companies) will find this book a good reality check for many an over-hopeful press release. Even advanced investors who might want to know what really happens in the labs will find information here that might otherwise be difficult to track down in such a concentrated form.

Lowe also wrote about the book last week on his blog, In the Pipeline, where an interesting discussion has begun.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development and Accelerating the translation of biomedical research into clinical applications.
Photograph from Wellcome Images

Aging, Applied Biotechnology, Biomed Bites, Research, Science, Videos

Are your cells stressed out? One Stanford researcher is helping them relax

Are your cells stressed out? One Stanford researcher is helping them relax

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

In her family, Daria Mochly-Rosen, PhD, is the odd woman out: One parent and four of her siblings are architects.

But as the George D. Smith Professor in Translational Medicine at Stanford, Mochly-Rosen brings her family’s focus on space and design to her work as a biomedical researcher. “I’m looking at the cell as a physical space as a room or a building where things need to touch each other in certain ways,” Mochly-Rosen says in the video above.

She applies this lens of the world to address several basic research questions, including learning about how cells deal with stress. For a cell, stress isn’t a bad day at work or a rough commute home. Instead, its prolonged exposure to chemicals or physical forces that build up and impair cellular function.

In healthy cells, there are “lots of little machines” that reduce the stress, Mochly-Rosen said. In her lab, researchers work to enhance the efficacy of these built-in destressors and to capitalize on the cell’s existing machinery. She says:

We are really interested in finding ways to boost them up and to increase their activity so we can deal better with stresses that are associated with disease or even with simple aging.

And what we do there is we try to find small molecules — in other words, drugs — that will boost the system.

For example, Mochly-Rosen and her team have discovered a molecule that helps with the negative effects of alcohol and alcohol-related cancers.

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

Previously: Why drug development is time consuming and expensive (hint: it’s hard), New painkiller could tackle pain, without risk of addiction and Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Applied Biotechnology, Cancer, Evolution, Immunology, Research, Stanford News

Corrective braces adjust cell-surface molecules’ positions, fix defective activities within cells

Corrective braces adjust cell-surface molecules' positions, fix defective activities within cells

bracesStanford molecular and cellular physiologist and structural biologist Chris Garcia, PhD, and his fellow scientists have tweaked together a set of molecular tools that work like braces of varying lengths and torque to fix things several orders of magnitude too small to see with the naked eye.

Like faulty cell-surface receptors, for instance, whose aberrant signaling can cause all kinds of medical problems, including cancer.

Cell-surface receptors transmit naturally occurring signals from outside cells to the insides of cells. Molecular messengers circulating in the blood stumble on receptors for which they’re a good fit, bind to them, and accelerate or diminish particular internal activities of cells, allowing the body to adjust to the needs of the minute.

Things sometimes go wrong. One or another of the body’s various circulating molecular messengers (for example, regulatory proteins called cytokines) may be too abundant or scarce. Alternatively, a genetic mutation may render a particular receptor type overly sluggish, or too efficient. One such mutation causes receptors for erythropoietin – a cytokine that stimulates production of certain blood-cell types – to be in constant overdrive, resulting in myeloproliferative disorders. Existing drugs for this condition sometimes overshoot, bringing the generation of needed blood-cell types to a screeching halt.

Garcia’s team took advantage of the fact that many receptors – erythropoietin receptors, for example – don’t perform solo, but instead work in pairs. In a proof-of-principle study in Cell, Garcia and his colleagues made brace-like molecular tools composed of stitched-together antibody fragments (known in the trade as diabodies). They then showed that these “two-headed beasts” can selectively grab on to two members of a mutated receptor pair and force the amped-up erythropoietin receptors into positions just far enough apart from, and at just the right angles to, one another to slow down their hyperactive signaling and act like normal ones.

That’s a whole new kind of therapeutic approach. Call it “cellular orthopedics.”

Previously: Souped-up super-version of IL-2 offers promise in cancer treatment and Minuscule DNA ring tricks tumors into revealing their presence
Photo by Zoe

Applied Biotechnology, Bioengineering, Medical Education, Stanford News, Videos

An online film festival for medtech inventors

An online film festival for medtech inventors

biodesign-process

The Stanford Biodesign program recently posted 296 short education videos on medical technology innovation. From needs finding through business planning, it offers entrepreneurs hours of useful advice on developing medical products.

This video library, which was launched with the second edition of the Biodesign textbook, is free to all. Its well-designed online interface makes it easy to access the advice that medtech innovators need, when they need it.

To create the video library, Biodesign hired filmmakers from both inside and outside of Stanford to capture the essence of the 2013-14 Biodesign fellowship program. During this ten-month program, multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program’s track record for bringing new medical devices and technologies to patients is impressive: Biodesign fellows have founded more than 30 companies in the last 14 years.

Each three- to four-minute video features interviews with faculty, fellows, CEOs, investors and alumni who have gone on to launch companies. A few of my favorites are:

The Biodesign video library, which was supported by the Walter H. Coulter Foundation, is an extension of the program’s mission — to help train the next generation of leaders in biomedical technology innovation. While the Stanford-based Biodesign program admits only 12 full-time postgraduate fellows a year, now these lessons-learned can be shared with medtech entrepreneurs around the globe. Just B.Y.O.P. (Bring your own popcorn.)

Previously: A medical invention that brings tears to your eyesBiodesign fellows take on night terrors in children, Stanford Biodesign Program releases video series on the FDA systemHeart devices get at mobile makeover
Illustration from Cambridge University Press

Applied Biotechnology, Bioengineering, Cancer, Genetics, Research, Stanford News

Minuscule DNA ring tricks tumors into revealing their presence

Minuscule DNA ring tricks tumors into revealing their presence

cool minicirclesAn animal study just published in Proceedings of the National Academy of Sciences shows how, in the not-distant future, doctors may be able to not only detect tumors early in humans, but also monitor the effectiveness of cancer drugs in real time, guide clinical trials of new drugs, and even screen entire populations of symptom-free people for nascent tumors that could have otherwise slipped under the radar.

The potential is huge. And the principal investigator, Sam Gambhir, MD, PhD, is credible: He chairs Stanford’s radiology department, directs the Canary Center at Stanford for Cancer Early Detection and has authored or co-authored nearly 600 peer-reviewed research publications.

From my news release about the study:

Imagine: You pop a pill into your mouth and swallow it. It dissolves, releasing tiny particles that are absorbed and cause only cancerous cells to secrete a specific protein into your bloodstream. Two days from now, a finger-prick blood sample will expose whether you’ve got cancer and even give a rough idea of its extent. That’s a highly futuristic concept. But its realization may be only years, not decades, away.

The key to early cancer detection lies in finding valid biomarkers: substances whose presence in a person’s blood or urine flags a probable tumor. (High blood levels of the molecule known as PSA, for example, can signify prostate cancer.) But although various tumor types indeed secrete characteristic substances into the blood, these same substances typically are made in healthy tissues, too, albeit usually in smaller amounts. So a positive test result for, say, PSA doesn’t necessarily mean the person has cancer. Contrariwise, a small tumor just may not secrete enough of the trademark substance to be detectable.

Gambhir’s team appears to have found a way to force any of numerous tumor types to produce a biomarker whose presence in the blood unambiguously signifies cancer, because no adult tissues – cancerous or otherwise – would normally be making it. This particular substance is a protein naturally present in human embryos as they’re forming and developing, but absent in adults.

The scientists designed a genetic construct, called a DNA minicircle, that contains a single gene coding for the telltale substance. DNA minicircles are tiny, artificial, single-stranded DNA rings about 4,000 nucleotides in circumference – roughly one-millionth as long as the strand that you’d get if you stretched the DNA in all 23 chromosomes of the human genome end to end.

Gambhir and his colleagues rigged their minicircles so that this sole gene would be “turned on” only inside cancer cells. (For more details on how to do this, please see my release.) They injected the minicircles into mice who had small tumors and mice who didn’t. Within 48 hours, a simple blood test indicated the presence of the biomarker in the blood of mice with tumors, but not in the blood of the tumor-free mice.The bigger the tumor volume, the more of the biomarker in the blood.

The technique will likely apply to a broad range of cancers, and can possibly be modified to help pinpoint budding tumors’ location in the body.

Previously: Nano-hitchhikers ride stem cells into heart, let researchers watch in real time and weeks later, Nanoparticles home in on human tumors growing in mice’s brains, increase accuracy of surgical removal and Nanomedicine moves one step closer to reality
Photo by Jim Strommer

Applied Biotechnology, Stanford News, Technology

Stanford team produces free Braille notetaker app

Stanford team produces free Braille notetaker app

brailleIn 2011, we showed you a video demonstration of an app that enables visually impaired people to type on a touchscreen tablet. Over the past few years, Sohan Dharmaraja, PhD, and Adrian Lew, PhD, completely redesigned the prototype they first developed with New Mexico State University student Adam Duran at Stanford’s Army High-Performance Computing Research Center. Now, their app, called iBrailler Notes, is ready for prime time.

This finished product, as Dharmajara and Lew explain in a recent story in Stanford Report, looks nothing like the original prototype that caught the media’s eye over three years ago. “Creating a prototype is relatively easy when your audience is a handful of fellow classmates. We did it almost as a whim to see if we could do it,” Dharmaraja said. “But creating a real app, that potentially millions might rely upon every day, is a whole other ballgame.”

Redesigning the app was no small feat because the final design had to be intuitive for users that may have little to no experience with touchscreen technology. As Dharmaraja explains, several of their test subjects had never used a tablet before:

Our testers did not know what a tablet computer or a touchscreen was, much less how to use them. We had to teach them how to use a touchscreen before they could tell us how to improve our products.

Dharmajara and Lew patterned their iBrailler Notes app after the traditional eight-keyed Perkins Brailler. What makes iBrailler Notes unique is the app enables the user to type regardless of where they position their fingers on the touchscreen—the user simply places eight to ten fingers on the touchscreen and the app automatically encircles each fingertip with a key. More from the article:

“We constantly pushed ourselves to innovate because being born with a disability shouldn’t mean you get left out of today’s technology revolution,” Dharmaraja said. “When you see the smile of someone doing something that you and I take for granted, it’s motivating.”

Lew added, “We think the time was well-spent to get it right.”

Previously: Developing a touchscreen Braille writerTennis, anyone? New York Times examines tennis for the blindMap of the Carina Nebula for the visually impairedRubik’s Cube for the visually impairedThe blind can see, and The mind maps the visual world with minimal means.
Photo courtesy of Sohan Dharmaraja

Stanford Medicine Resources: