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Precision health, Research, Science, Transplants

Study: Treatment plans for kidney failure should consider cause and circumstances of disease

Study: Treatment plans for kidney failure should consider cause and circumstances of disease

3349943474_0e1bc4236b_zOne size seldom fits all, so it’s not surprising that one treatment regimen may not suit all patients with the same condition. Now, a new study of end-stage kidney failure shows the importance of taking factors like cause and circumstances of a patient’s disease into account when designing a treatment plan.

The study (subscription required) began when Stanford nephrology fellow Michelle O’Shaughnessy, MD, noted that patients with end-stage kidney-failure usually received the same generic treatment plan (dialysis or a kidney transplant), even though there are different causes of the disease and a patient’s condition can progress to kidney failure via many different routes.

As described in our press release, kidney disease is often caused by diabetes or hypertension, but it can also be caused by glomerular disease, a condition with many distinct subtypes. And:

[E]ach of the many glomerular disease subtypes is unique. In certain subtypes, the immune system attacks the kidneys; in others, it damages the blood vessels.

As a result, the various subtypes are treated using different methods before the kidneys begin to fail. The treatments may include steroids or stronger immunosuppressant medications. The resulting side effects can range from severe infections to diabetes to cancer.

For their work, O’Shaughnessy and her colleagues examined data collected from 84,301 patients with end-stage kidney disease caused by one of six major subtypes of glomerular disease. The results showed that the type of glomerular disease significantly affected how long the patient lived after they developed kidney failure; mortality ranged from 4 percent per year for one type of patient to 16 percent per year for another.

“It’s important to know why one kidney patient does well and another does poorly,” concluded O’Shaughnessy. “If physicians take into consideration what caused the kidneys to fail in the first place and what types of treatments patients received prior to kidney failure, it could possibly improve the patients’ quality of life or increase their life span.”

Previously: Keeping kidney failure patients out of the hospitalStudy shows higher Medicaid coverage leads to lower kidney failure ratesStudy shows higher rates of untreated kidney failure among older adults and Geography may determine kidney failure treatment level
Photo by scribbletaylor

Evolution, Genetics, Research, Science, Stanford News

Kennewick Man’s origins revealed by genetic study

Kennewick Man's origins revealed by genetic study

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One day in 1996, on the banks of the Columbia River near Kennewick, Washington, two men found a human skull about ten feet from shore. Eventually, the nearly complete skeleton of an adult man was unearthed and found to be nearly 9,000 years old.

Since that find, controversy has swirled as to whether the man was an ancestor of Native American tribes living in the area, or was more closely related to other population groups around the Pacific Rim. A study published in 2014, based in part on anatomical measurements, concluded that the skeleton, known as the Kennewick Man, was more likely related to indigenous Japanese or Polynesian peoples.

Now Stanford geneticists Morten Rasmussen, PhD, and Carlos Bustamante, PhD, working with Eske Willerslev, PhD, and others at the University of Copenhagen’s Centre for GeoGenetics have studied tiny snippets of ancient DNA isolated from a hand bone. They’ve compared these DNA sequences with those of modern humans and concluded that the Kennewick Man (known to many Native Americans as the Ancient One) is more closely related to Native American groups than to any other population in the world.

The findings are published today online in Nature, and they’re likely to reignite an ongoing controversy as to the skeleton’s origins and to whom the remains belong.

As Rasmussen said in our press release:

Due to the massive controversy surrounding the origins of this sample, the ability to address this will be of interest to both scientists and tribal members. […]

Although the exterior preservation of the skeleton was pristine, the DNA in the sample was highly degraded and dominated by DNA from soil bacteria and other environmental sources. With the little material we had available, we applied the newest methods to squeeze every piece of information out of the bone.

Increasingly, such methods of isolating and sequencing ancient DNA are being used to solve millennia-old mysteries, including those surrounding Otzi the Iceman and a young child known as the Anzick boy buried more than 12,000 years ago in Montana.

Bustamante explained in the release:

Advances in DNA sequencing technology have given us important new tools for studying the great human diasporas and the history of indigenous populations. Now we are seeing its adoption in new areas, including forensics and archeology. The case of Kennewick Man is particularly interesting given the debates surrounding the origins of Native American populations. Morten’s work aligns beautifully with the oral history of native peoples and lends strong support for their claims. I believe that ancient DNA analysis could become standard practice in these types of cases since it can provide objective means of assessing both genetic ancestry and relatedness to living individuals and present-day populations.

Previously: Caribbean skeletons hold slave trade secrets,  Melting pot or mosaic? International collaboration studies genomic diversity in Mexico and  On the hunt for ancient DNA, Stanford researchers improve the odds
Photo, of bust showing how Kennewick Man may have looked, by Brittany Tatchell/Smithsonian (bust by StudioEIS; forensic facial reconstruction by sculptor Amanda Danning)

Biomed Bites, Evolution, Genetics, Research, Science, Videos

One mutation, two people and two (or more) outcomes: What gives?

One mutation, two people and two (or more) outcomes: What gives?

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

Tweak a piano string and you’ve created a different note. Tweak a gene and no one knows exactly what might happen. Perhaps the resultant protein is completely defective. Perhaps the same change does nothing in me but turns your world upside down. Who knows?

One Stanford researcher is working to demystify some of that variability, an endeavor that could lead to big changes in the development of therapies for diseases such as cancer. Daniel Jarosz, PhD, assistant professor of chemical and systems biology and of developmental biology, describes his work in the video above:

We all know there are many mutations associated with disease, for example, that give rise to that disease in some patients, yet there are other patients that have the same mutations and don’t have any effects. We’d really like to understand that…

The clinical benefits of this work are potentially very large.

For example, Jarosz said he and his team study why some tumor genes are able to evolve rapidly to evade chemotherapy. With a greater understanding of what conditions cause rapid evolution — and drug resistance — they can more easily evaluate new therapies.

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

Previously: From finches to cancer: A Stanford researcher explores the role of evolution in disease, Computing our evolution and Whole genome sequencing: The known knowns and the unknown unknowns

In the News, Medicine and Society, Science

Nature issues reminder that “equality in science is a battle still far from won”

Nature issues reminder that "equality in science is a battle still far from won"

9447775248_4337abac3b_zIn light of recent widely covered events (and entertaining reactions on Twitter), Nature published an editorial yesterday titled, simply, “Sexism has no place in science.” It was published as a “reminder that equality in science is a battle still far from won,” and it outlines the problems of sexism and gender basis and some of the ways they can be tackled. I thought it was worth highlighting a few of their ideas here:

  • Recognize and address unconscious bias. Graduate students given grants by the US National Institutes of Health are required to undergo ethics training. Gender-bias training for scientists, for example, would be a powerful way to help turn the tide.
  • Encourage universities and research institutions to extend the deadlines for tenure or project completion for scientists (women and men) who take parental leave, and do not penalize these researchers by excluding them from annual salary rises. Many workplaces are happy to consider and agree to such extension requests when they are made. The policy should simply be adopted across the board.
  • Events organizers and others must invite female scientists to lecture, review, talk and write articles. And if the woman asked says no — for whatever reason — then ask others. This is about more than mere visibility. It can boost female participation too. Anecdotal reports suggest that women are more likely to ask questions in sessions chaired by women. After acknowledging our own bias towards male contributors, Nature, for example, is engaged in a continued effort to commission more women in our pages.
  • Do not use vocabulary and imagery that support one gender more than another. Words matter. It is not ‘political-correctness-gone-mad’ to avoid defaulting to the pronouns ‘him’ and ‘he’, or to ensure that photographs and illustrations feature women.

The piece ends on a hopeful note – “The lot of the female scientist in most developed countries is better than it was a few decades ago” – but reminds readers “that it is essential that all involved strive for better.” Hear, hear!

Previously: What’s holding women in the sciences back?She’s a Barbie girl, living in a Barbie world (that discourages careers in science), Molly Carnes: Gender bias persists in academia and Pioneers in science
Photo by World Bank Photo Collection

Chronic Disease, In the News, Pain, Research, Science, Stanford News

Scientific discovery could lead to treatments for chronic pancreatitis

Scientific discovery could lead to treatments for chronic pancreatitis

Pancreatitis is one of the most common gastrointestinal hospital admissions-related illness. Patients with the acute form of the disease show up at hospitals doubled over with severe abdominal pain, a swollen belly that’s tender to the touch, nausea, and vomiting.

For some patients the disease flares up then disappears. For others, it develops into an ongoing, chronic form of the disease with no known cure. Not only is it extremely painful, it also causes malnutrition and carries with it a high risk of leading to pancreatic cancer. Treatment options are pretty much limited to prescription pain killers.

This has great implication in a disease that has no active therapy with no known agents that can alter its natural devastating course

It’s known that chronic pancreatitis is marked by the uncontrolled growth of scar tissue in the pancreas known as fibrosis, which slowly destroys the organ’s ability to function. Since the pancreas is in charge of excreting enzymes to digest food, patients begin to suffer malnutrition. It’s also known that excessive alcohol consumption is the leading cause of pancreatitis but just what is happening at a molecular level to cause the fibrosis is less clear.

Now, Stanford researcher and gastroenterologist Aida Habtezion, MD, and colleagues here and at Cedars-Sinai Medical Center have published research that sheds light on what exactly is happening and could lead to treatments for the severe disease. In a story I wrote on the study, Habtezion discusses their discovery of a new molecular pathway that when blocked by an experimental pharmacological drug can slow the progression of pancreatitis in animal models and in human cells.

As Habtezion told me, her lab’s research into just how the immune cells of the pancreas behave when inflamed with pancreatitis unveiled the new pathway:

“For the first time we can show that macrophages interact with pancreatic stellate cells via a particular immune pathway, and by targeting this pathway we show a decrease in chronic pancreatitis/fibrosis progression,” she said. “This has great implication in a disease that has no active therapy with no known agents that can alter its natural devastating course.”

The hope is that researchers will now be able to develop a form of the experimental pharmacological agent used in the study to block the molecular pathway that can be given to humans. Blocking the pathway will block the scar tissue growth, and hopefully either slow the progression of the disease or reverse it altogether.

Events, Medical Education, Medical Schools, Science, Stanford News

Stanford Medicine grads urged to break out of comfort zone, use science to improve human health

Stanford Medicine grads urged to break out of comfort zone, use science to improve human health

On Saturday, 195 graduates of the School of Medicine sat under a large white tent on the Alumni Green pondering the next chapter in their medical training. Many of them hadn’t been sure if they would make it to this milestone and, for some, the future seemed uncertain. But the message from Lucy Shapiro, PhD, a recipient of the National Medal of Science, was clear, “Step out of your comfort zone and follow your intuition,” she said. “Don’t be afraid of taking chances. Ask, ‘How can I change what’s wrong?'”

Shapiro told the Class of 2015 how she spent years performing solitary work in the laboratory before she “launched a one-woman attack” to influence health policy and battle the growing threat of infectious disease on the global stage. My colleague Tracie White captures Shapiro’s powerful speech in a story today about the commencement ceremony:

Her attack began with taking any speaking engagement she could get to educate the public about antibiotic resistance; she walked the corridors of power in Washington, D.C., lobbying politicians about the dangers of emerging infectious diseases; and she used discoveries from her lab on the single-celled Caulobacter bacterium to develop new, effective disease-fighting drugs.

Her lab at Stanford made breakthroughs in understanding the genetic circuitry of simple cells, setting the stage for the development of new antibiotics. Shapiro told the audience that over the 25 years that she has worked at the School of Medicine, she has seen a major shift in the connection between those who conduct research in labs and those who care for patients in clinics.

“We have finally learned to talk to each other,” said Shapiro, a professor of developmental biology. “I’ve watched the convergence of basic research and clinical applications without the loss of curiosity-driven research in the lab or patient-focused care in the clinic.”

grads walkingShapiro went on to tell the audience that bridging the gap between the lab and the clinic “can make the world a better place.” Lloyd Minor, MD, dean of the School of Medicine, agreed with these sentiments and told graduates that there has never been a better time for connecting advances in basic research with breakthroughs in clinical care. “You are beginning your careers at an unprecedented time of opportunities for biomedical science and for human health,” he said.

The 2015 graduating class included 78 students who earned PhDs, 78 who earned medical degrees, and 39 who earned master’s degrees. Among them was Katharina Sophia Volz, the first-ever graduate of the Interdepartmental Program in Stem Cell Biology and Regenerative Medicine. “Everybody here is reaching for the stars. We can do the best work here of anywhere,” she said.

Previously: Stanford Medicine’s commencement, in pictures, Abraham Verghese urges Stanford grads to always remember the heritage and rituals of medicineStanford Medicine honors its newest graduatesNational Medal of Science winner Lucy Shapiro: “It’s the most exciting thing in the world to be a scientist” and Stanford’s Lucy Shapiro receives National Medal of Science
Photos by Norbert von der Groeben

Mental Health, Research, Science, Technology

Fear factor: Using virtual reality to overcome phobias

Fear factor: Using virtual reality to overcome phobias

3493601806_7f5512fe6d_zPast research has shown that virtual reality can be effective in treating phantom limb syndrome, helping smokers kick their nicotine habit, easing patients’ pain and reducing post-traumatic stress disorder symptoms, among other things. Now a pair of engineering students at Santa Clara University in California are exploring the potential of the technology to assist individuals in overcoming their fear of heights and other anxiety-related conditions.

The design duo behind the project are undergrads Paul Thurston and Bryce Mariano. The students partnered with Kieran Sullivan, PhD, a psychology professor at Santa Clara, to develop a simulation tool that guides patients through a controlled virtual environment populated with phobia-triggering features. More details about the system were provided in this recent university story:

They started with a fear of heights simulation. As the patient takes in a 360-degree view from atop a building, the therapist can alter the virtual height and the resultant view—backing off or increasing exposure as needed according to the patient’s emotional response. While the team stresses that their tool is for use by trained therapists, not for sufferers to use on their own, Thurston notes that just knowing you can take the goggles off while immersed in the experience may make this form of treatment more approachable for some.

“Another aspect of our project that has been very important to us is to keep it affordable as well as accessible for future development,” said Mariano. “By using economical hardware and developing the simulation using the Unity Game Engine, which is 100 percent free and readily available, we hoped to create a platform that would allow others to easily pick up the project where we left off and continue expanding on the library of simulations to treat the widest possible range of phobia patients.”

Previously: From “abstract” to “visceral”: Virtual reality systems could help address pain and Can behavioral changes in virtual spaces affect material world habits?
Via CBS San Francisco
Photo by Amber Case 

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

Stanford researchers suss out cancer mutations in genome’s dark spots

Stanford researchers suss out cancer mutations in genome's dark spots

lighted pathOnly a small proportion of our DNA contains nucleotide sequences used to make proteins. Much of the remainder is devoted to specifying how, when and where those proteins are made. These rules are encoded in our DNA as regulatory elements, and they’re what makes one cell type different from another, and keep them from running wild like children in an unattended classroom. When things go awry, the consequences (like rampant growth and cancers) can be severe.

Geneticist Michael Snyder, PhD, and postdoctoral scholar Collin Melton, PhD, recently combined information from The Cancer Genome Atlas, a national effort to sequence and identify mutations in the genomes of many different types of cancers, with data from the national ENCODE Project, which serves as an encyclopedia of DNA functional regions, or elements. Their aim was to better understand the roles that mutations in regulatory regions may play in cancer development.

Snyder and Melton found that fewer than one of every thousand mutations in each cancer type occurs in the coding region of a gene. In contrast, more than 30 percent of the mutations occur in regulatory regions. The study was published this morning in Nature Genetics.

As Snyder explained to me:

Until recently, many mutations outside the coding regions of genes have been mostly invisible to us. Cancer researchers largely focused on identifying changes within coding regions. Using ENCODE data, we’ve been able to define some important regions of the genome and found that certain regulatory regions are often enriched for mutations. This opens up a whole new window for this type of research.

Snyder, who leads Stanford’s genetics department and directs the Stanford Center for Genomics and Personalized Medicine, likens looking for cancer-causing mutations only in coding regions as “looking under the lamppost” for keys lost at night. Until recently, the coding regions of genes were the most well-studied, and unexpected mutations stood out like a sore thumb. We’ve known there’s a lot more of the genome outside the coding regions, but until the ENCODE project was largely completed in 2012, researchers were often in the dark as to where, or even how, they should look.

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Genetics, Microbiology, Research, Science

Make it or break it — or both: New research reveals RNA’s dual role

Make it or break it — or both: New research reveals RNA's dual role

7314255232_8ee9474b2e_zBehind every big biomedical breakthrough lies boatloads of basic biology. In that vein, a new finding published today in Cell shakes up a fundamental view of RNA, the bridging material necessary to convert genes into proteins.

Previously, it was well known that RNA is degraded, broken down into its constituent parts so it could be used again. Otherwise, used RNA would accumulate in the cell, clogging it up. But everyone assumed that RNA was degraded only after it had transmitted its message to build a protein.

Now, a team of researchers led by Lars Steinmetz, PhD, professor of genetics, have discovered that RNA is broken down while it’s communicating the blueprint for protein assembly, a process known as translation. One end of the RNA is still making proteins while the other is being dismantled.

“In the bigger picture, decaying RNA was thought to be of little interest biologically,” Steinmetz said. “Our findings show that it contains hallmarks of the translation process.”

That finding could change the way researchers examine gene expression in live cells. Current methods use drugs that “freeze” the translation process, but that artificial interference alters the measurements of protein creation. A new method — which involves looking at the products of the RNA degradation — simplifies that process and produces more accurate results, said Wu Wei, PhD, a senior research scientist in biochemistry who worked on the research.

“People think that RNA is translated or degraded, but actually they can happen at the same time,” Wei said.

The researchers made the discovery almost accidently, when they spotted an unusual pattern in the byproducts of RNA that remained in the cell.

So far, their work has been in living yeast cells, but Wei said the team plans to move next to examining RNA degradation in human cells.

“Our approach provides a simple and straightforward way to measure ribosome dynamics in living cells. Both this study and research performed by our collaberators have proven that it is a powerful tool to investigate the regulation of translation, said Vicent Pelechano, PhD, who is based in Steinmetz’s laboratory at the European Molecular Biology Laboratory and designed the experimental aspects of the study.

Previously: The politics of destruction: Short-lived RNA helps stem cells turn on a dime, Step away from DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health and RNA Rosetta stone? Molecules’ second, structural language predicted from their first, linear one
Image by AJ Cann

Bioengineering, Global Health, Imaging, In the News, Science, Videos

Microscopes for the masses: How a Stanford bioengineer is helping everyone “think like scientists”

Microscopes for the masses: How a Stanford bioengineer is helping everyone "think like scientists"

In a recent KQED QUEST Science postManu Prakash, PhD, a Stanford professor of bioengineering, describes his goal of making science accessible to everyone. His lab is mailing a Foldscope to anyone who submits a question he or she would like to use it to answer, and surprising and ingenious queries have been arriving from places like South Sudan, Iran, Ukraine, and India. This is creating a network of people who “think like scientists” (that is, ask their own questions about the world), because in Prakash’s words, “science is about ideas,” not access to fancy labs. Watch the video to learn more.

Previously: Miniature chemistry kit brings science out of the lab and into the classroom or field, Foldscope beta testers share the wonders of the microcosmosManu Prakash on how growing up in India influenced his interests as a Maker and entrepreneur, Dr. Prakash goes to Washington and Stanford bioengineer develops a 50-cent paper microscope

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