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

My baby, my… virus? Stanford researchers find viral proteins in human embryonic cells

My baby, my... virus? Stanford researchers find viral proteins in human embryonic cells

Wysocka - 560

One thing I really enjoy about my job is the opportunity to constantly be learning something new. For example, I hadn’t realized that about eight percent of human DNA is actually left-behind detritus from ancient viral infections. I knew they were there, but eight percent? That’s a lot of genetic baggage.

These sequences are often inactive in mature cells, but recent research has shown they can become activated in some tumor cells or in human embryonic stem cells. Now developmental biologist Joanna Wysocka, PhD, and graduate student Edward Grow, have shown that some of these viral bits and pieces spring back to life in early human embryos and may even affect their development.

Their research was published today in Nature. As I describe in our press release:

Retroviruses are a class of virus that insert their DNA into the genome of the host cell for later reactivation. In this stealth mode, the virus bides its time, taking advantage of cellular DNA replication to spread to each of an infected cell’s progeny every time the cell divides. HIV is one well-known example of a retrovirus that infects humans.

When a retrovirus infects a germ cell, which makes sperm and eggs, or infects a very early-stage embryo before the germ cells have arisen, the viral DNA is passed along to future generations. Over evolutionary time, however, these viral genomes often become mutated and inactivated. About 8 percent of the human genome is made up of viral sequences left behind during past infections. One retrovirus, HERVK, however, infected humans repeatedly relatively recently — within about 200,000 years. Much of HERVK’s genome is still snuggled, intact, in each of our cells.

Wysocka and Grow found that human embryonic cells begin making viral proteins from these HERVK sequences within just a few days after conception. What’s more, the non-human proteins have a noticeable effect on the cells, increasing the expression of a cell surface protein that makes them less susceptible to subsequent viral infection and also modulating human gene expression.

More from our release:

But it’s not clear whether this sequence of events is the result of thousands of years of co-existence, a kind of evolutionary symbiosis, or if it represents an ongoing battle between humans and viruses.

“Does the virus selfishly benefit by switching itself on in these early embryonic cells?” said Grow. “Or is the embryo instead commandeering the viral proteins to protect itself? Can they both benefit? That’s possible, but we don’t really know.”

Wysocka describes the findings as “fascinating, but a little creepy.” I agree. But I can’t wait to hear what they discover next.

Previously: Viruses can cause warts on your DNA, Stanford researcher wins Vilcek Prize for Creative Promise in Biomedical Science and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Photo of Joanna Wysocka by Steve Fisch

otolaryngology, Research, Science, Stanford News, Stem Cells

Molecular sleuthing uncovers new clue toward deafness cure

Molecular sleuthing uncovers new clue toward deafness cure

In another step along the path toward finding cures for deafness, Stanford scientists report they have discovered a subset of cells in the mammalian utricle, the inner ear structure that controls balance, that can regenerate into hair cells when damaged.

The study was published today in Nature Communications, and senior author Alan Cheng, MD, explained the significance of the findings to me this way:

We rely on our inner ear sensory organs to hear and sense motion. Such functions require specialized hair cells to detect the vibrations of sound or motion. Once lost, hair cells needed for hearing do not regenerate and thus hearing loss is permanent, while those to sense motion can regenerate to a limited degree. Until now, the origin of these regenerated hair cells and the mechanisms that limit this process of regeneration in the utricle have not been clear. Here, we found two distinct populations of such hair cell progenitors in the neonatal mouse utricle, where they can regenerate lost hair cells. Unlike the utricle from older mice, the degree of regeneration and also cell division at this age are a lot more robust.

The study also provides an improved understanding of the molecular pathway that leads to this transformation, knowledge that could maybe one day be used to help researchers figure out how to artificially encourage hair cell renewal in humans.

Previously: Understanding hearing loss at the molecular level, New version of popular antibiotic eliminates side effect of deafness and Stanford chair of otolarnygology discusses future regenerative therapies for hearing loss

Events, Genetics, Patient Care, Pediatrics, Research, Stanford News, Stem Cells

“It’s not just science fiction anymore”: Childx speakers talk stem cell and gene therapy

“It’s not just science fiction anymore": Childx speakers talk stem cell and gene therapy

childx PorteusAt the Childx conference last week there was a great deal of optimism that stem cell and genetic therapies are about to have a huge impact on many childhood disease. “It’s not just science fiction anymore,” Matthew Porteus, MD, PhD, told the audience. “We can correct mutations that cause childhood diseases.”

The session was hosted by Stanford professor Maria Grazia Roncarolo, MD, who until recently was head of the Italy’s Telethon Institute for Cell and Gene Therapy at the San Raffaele Scientific Institute in Milan. Roncarolo pointed out that there are more than 10,000 human diseases that are caused by a single gene defect. “Stem cell and gene therapies can be used to treat cancer and other diseases,” Roncarolo said.

Two such diseases are sickle cell disease and severe combined immune deficiency. In both cases, a single nucleotide change in DNA becomes a deadly defect for children with the bad luck to have them. Porteus is working on very new genome editing technologies that allow clinicians to go in and fix those DNA typos and cure diseases.

Stanford dermatology researcher Anthony Oro, MD, PhD is working to do something similar with skin cells for a painful blistering disease called epidermolysis bullosa. Children with EB lack a functional gene for one of the proteins that anchors the layers of skin together. Oro and Stanford Institute for Stem Cell Biology and Regenerative Medicine scientist Marius Wernig, MD, PhD, are taking defective skin cells from patients, transforming them into embryonic-like stem cells, fixing the gene defect, and then growing them back into skin stem cells and then layers of skin ready for transplantation. Oro says that they have shown that they can do this in a scalable way in mice, and they hope to start a clinical trial in humans soon.

One of the challenges to genetic therapy is that it often requires putting the gene into blood stem cells to deliver it to the body, but the high dose chemotherapy or radiation that is necessary to remove the bodies own blood stem cells and make way for the transplanted cells is very dangerous in itself. Researchers like Stanford researcher Hiromitsu Nakuchi, MD, PhD, are exploring gentler ways to make space in the body for the transplanted cells. He has discovered that simply by feeding mice a diet deficient in a particular amino acid, blood stem cells begin to die. Other cells in the body don’t seem to be as strongly affected. A dietary solution may eventually allow clinicians to avoid using the highly toxic treatments that have traditionally been used for blood stem cell transplant.

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Research, Science, Stanford News, Stem Cells

Bridging the stem-cell gap: Stanford researchers identify unique transition state

Bridging the stem-cell gap: Stanford researchers identify unique transition state

474026463_87cca6b272_zIn 2006, Shinya Yamanaka, MD, PhD, turned the stem-cell world upside down when he showed it was possible to take mature, specialized cells such as those found in skin and convert them to a pluripotent state simply by exposing them to a few key proteins. The discovery earned Yamanaka the Nobel Prize in Physiology or Medicine in 2012 and sparked an explosion of stem-cell science.

Although the exact steps of the reprogramming process are unknown, scientists have thought it proceeded mostly as a two-step pathway that essentially rewinds the march to specialization that normally occurs during development. Now Marius Wernig, MD, and his colleagues at the Stanford Institute for Stem Cell Biology and Regenerative Medicine have uncovered an intermediary state through which the cells must pass to successfully acquire pluripotency (a term that describes a cell’s ability to become nearly any cell type in the body). The researchers published their findings in today’s  Nature.

As Wernig described in my article on the research:

This [finding] was completely unexpected. It’s always been assumed that reprogramming is simply a matter of pushing mature cells backward along the developmental pathway. These cells would undergo two major changes: they’d turn off genes corresponding to their original identity, and begin to express pluripotency genes. Now we know there’s an intermediary state we’d never imagined before.

Cells in this “bridge” state express cell surface markers that are distinct from those found on fibroblasts (the starting cell type) and on successfully reprogrammed iPS cells. They also express specific transcription factors that likely contribute to the cells’ progression through the reprogramming process.

The researchers believe it may be possible to increase the efficiency of reprogramming in cells that typically resist the process (these cell types include highly specialized cells or cancer cells). But they’re more excited about peeking into the inner workings of a transformation that’s been both revolutionary and mysterious.

“We’re learning more and more about how cells accomplish this really unbelievable task of reverting to pluripotency,” Wernig told me. “Now we know that the cell biology of this process is novel, and this intermediary state is unique.”

Previously: Congratulations to Marius Wernig, named Outstanding Young Investigator by stem cell society, The end of iPS? Stanford scientists directly convert mouse skin cells to neural precursors and Human neurons from skin cells without pluripotency?
Photo by Alexis R

Genetics, Pediatrics, Podcasts, Research, Stem Cells

Countdown to Childx: Stanford expert highlights future of stem cell and gene therapies

Countdown to Childx: Stanford expert highlights future of stem cell and gene therapies

RoncaroloNext month’s inaugural Childx conference will bring a diverse group of experts to Stanford to discuss big challenges in infant, child and maternal health. Today, in a new 1:2:1 podcast interview, stem cell and gene therapy expert Maria Grazia Roncarolo, MD, provides an interesting preview of a once-controversial area of research that will be featured at the conference.

Roncarolo talks about the history and future of stem cell and gene therapy treatments, which have recovered from tragic setbacks such as the 1999 death of 18-year-old Jesse Gelsinger in an early gene therapy trial. The early problems forced researchers to reevaluate what they were doing, with the result that the entire field has reemerged stronger, she explains:

I would say that there were major problems, that we underestimated the complexity that it takes to manipulate the genome, and to introduce a healthy gene to fix a genetic disease. However, from these mistakes and from these tragedies, we learned a lot. We were really forced as doctors, and more importantly, as scientists, to go back to the bench and develop better technologies and to understand more of what was required. … [Today] we use better vectors — which are the carriers to introduce the healthy gene — we know much more about what we have to do to prepare the patient to receive the gene therapy, and we also learned that we need to do a very careful monitoring of the patients to really understand where the gene lands in the genome.

At the Childx conference, Roncarolo will moderate a panel on “Definitive Stem Cell and Gene Therapy for Child Health,” hosting such guests as GlaxoSmithKline’s senior vice president of rare diseases, Martin Andrews, and Nadia Rosenthal, PhD, founding director of the Australian Regenerative Medicine Institute.

Information about registration for Childx, being held here April 2–3, is available on the conference website.

Previously: Stanford hosts inaugural Childx conference this spring and Stanford researchers receive $40 million from state stem cell agency
Photo by Norbert von der Groeben

Cancer, Stanford News, Stem Cells, Videos

A look at stem cells and “chemobrain”

A look at stem cells and "chemobrain"

As many as 75 percent of cancer patients experience memory and attention problems during or after their treatment, and up to 3.9 million are afflicted by long-term cognitive dysfunction. This foggy mental state, often referred to as “chemobrain,” can also affect cancer survivors’ fine motor skills, information processing speed, concentration and ability to calculate.

In this recently posted California Institute for Regenerative Medicine video, Stanford physician-scientist Michelle Monje, MD, PhD, explains the role that damage to stem cells in the brain plays in the condition, outlines some of the interventions that can mitigate patients’ symptoms, and highlights efforts to develop effective regenerative therapies.

Previously: Stanford brain tumor research featured on “Bay Area Proud”, Emmy nod for film about Stanford brain tumor research – and the little boy who made it possible and Stanford study shows effects of chemotherapy and breast cancer on brain function

Events, Research, Science, Stanford News, Stem Cells

Live tweeting Stanford speakers at AAAS meeting

Live tweeting Stanford speakers at AAAS meeting

Whether you plan to spend the weekend wallowing in work, or canoodling on the couch (Happy Valentine’s Day!), you can follow Stanford Medicine researchers at the AAAS Annual Meeting, a gathering of thousands of scientists that will be held this weekend in San Jose.

Kicking off Friday (the conference officially began today), we’ll be live tweeting from the panel discussion “Informatics and Bioimaging: New Ways to Better Medicines,” featuring Stanford bioengineer Russ Altman, MD, PhD, from 10 to 11:30 `a.m.

Take a break for lunch, then check in to hear Steve Goodman, MD, PhD, Stanford’s associate dean of clinical and translational research, discussing “Responsible Data-Sharing for Clinical Trials” from 3 to 4:30 p.m.

Early Saturday, join Christopher Scott, PhD, director of the Stanford University Program on Stem Cells in in Society, as he addresses “Challenges in Communicating about Stem Cells” from 8 to 9:30 a.m.

Finally on Sunday, we’ll be tweeting as John Ioannidis, MD, DSc, director of the Stanford Prevention Research Center, discusses the “Reproducibility of Science: A Roadmap Forward” from 1 to 2:30 p.m.

We’ll sprinkle in other tweets throughout the weekend, and we’ll follow-up with a series of blog posts about the various talks. You can follow the tweets on the @StanfordMed feed or by using the hashtag #AAASmtg.

Previously: Live tweeting sessions at Stanford’s Med School 101, Live tweeting Jack Andraka’s Medicine X keynote and Live tweeting Big Data in Biomedicine

Biomed Bites, In the News, Research, Stem Cells, Technology, Videos

“It gives me the chills just thinking about it”: Stanford researcher on the potential of stem cells

"It gives me the chills just thinking about it": Stanford researcher on the potential of stem cells

Welcome to the last Biomed Bites of 2014. We’ll be continuing this series next year — check each Thursday to meet more of Stanford’s most innovative biomedical researchers. 

If you watch this video and aren’t moved by the passion and conviction of Stanford biologist Margaret Fuller, PhD, then email me. Seriously, I’ll try to talk some sense into you. Because Fuller’s enthusiasm for biomedicine is downright contagious. This is a professor who you want to teach biology.

Fuller, a professor of developmental biology and of genetics, works with adult stem cells, and she’s palpably gleeful about their potential to improve the health of millions.

“I was really struck and inspired by a recent article in the New York Times,” Fuller says in the video above. She’s talking about “Human Muscle Regenerated with Animal Help,” a 2012 piece that told the story of Sgt. Ron Strang, a Marine who lost part of his quadriceps in Afghanistan. Yet here is Strang, walking, thanks to the donation of a extracellular matrix from a pig. This paper-like sheet secreted signals instructing his stem cells to come to the rescue and build new muscle. “It was amazing,” Strang told the Times reporter. “Right off the bat I could do a full stride, I could bend my knee, kick it out a little bit…”

“This is really amazing,” Fuller agrees. “It gives me the chills just thinking about it. This is the kind of knowledge and advances of the basic work that I do… The hope is that understanding those underlying mechanisms will allow people to design small molecules and other strategies that can be used to induce our own adult stem cells to be called into action for repair.”

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

Previously: Center for Reproductive and Stem Cell Biology receives NIH boost, Why the competition isn’t adult vs. embryonic stem cells and Induced pluripotent stem cell mysteries explored by Stanford researchers

Biomed Bites, Genetics, Research, Stem Cells, Videos

Working on a gene therapy for muscular dystrophy

Working on a gene therapy for muscular dystrophy

Here’s this week’s Biomed Bites, a weekly feature that highlights some of Stanford’s most innovative research and introduces Scope readers to innovators in a variety of biomedical disciplines. 

The most common form of muscular dystrophy, Duchenne muscular dystrophy, is genetic, resulting from a defective gene on the X chromosome, so it affects primarily boys. That makes it a prime target for genetic therapy – currently the goal of Stanford geneticist Michele Calos, PhD.

Calos started out as a basic scientist, examining the nature of DNA and the controls of genes; they developed techniques used to insert new genes into existing cells and ensure they are turned on.

Now, Calos has found applications for her earlier research. Capitalizing on the work that won the 2012 Nobel Prize in Medicine, Calos and her team have set their sights on developing healthy muscle cells that can restore function for muscular dystrophy patients. Here’s Carlos in the video above:

We’re repairing the mutation in the patients’ cells… then putting back the correct copy of the gene, differentiating them into muscle precursors and injecting them into muscles where they can form healthy muscle fibers.

Calos said she and her team are currently perfecting the technique in mice, before it can be used in human patients. “Our dream really is to develop a therapy in the lab that would be translatable to clinical use in the future,” she said.

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

Previously: Elderly muscle stem cells from mice rejuvenated by Stanford scientists, New mouse model for muscular dystrophy provides clues to cardiac failure and Visible symptoms: Muscular-dystrophy mouse model’s muscles glow like fireflies as they break down

Aging, Men's Health, Research, Science, Stanford News, Stem Cells

Viva la hedgehog! Signaling protein also shown to be important in prostate growth

Viva la hedgehog! Signaling protein also shown to be important in prostate growth

6111053153_5b14f4570d_zOk, so it may *appear* that this post is just an excuse to post a cute hedgehog picture. After all, who could resist that little face? But this is really meant to be a quick shout-out to Stanford developmental biologist Philip Beachy, PhD, who has shown yet again that the signalling protein called hedgehog is critically important during many aspects of development.

In Beachy’s latest work, published earlier this week in Nature Cell Biology, he and his colleagues show that the precise control of when and where the hedgehog protein is made dictates the branching of tubules in the adult prostate (you may remember other recent work from Beachy’s lab about the role that hedgehog plays in bladder cancer, and what that could mean for patients). The findings of the current research suggest that aberrant hedgehog signalling could play a role in the prostatic hyperplasia, or non-cancerous enlargement of the prostate, which often happens as men age.

Previously: Drug may prevent bladder cancer progression, say Stanford researchers, Cellular culprit identified for invasive bladder cancer, according to Stanford study and Bladder infections – How does your body repair the damage?
Photo by Tiffany Bailey

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