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Immunology, Medical Education, Medicine and Literature

Stanford alumnus writes children’s book to inspire next generation of curious minds

Stanford alumnus writes children’s book to inspire  next generation of curious minds


Soon there will be a new superhero children’s book available, but these superheroes aren’t from Marvel comics. The book, Rose’s Superhero Birthday: An Immune Cell Treasure Hunt, is about the immune cell superheroes that keep us healthy.

Angela Landrigan, PhD, did her graduate and postdoctoral training in immunology at Stanford’s medical school, where she studied how immune cells respond to cancer. She now works at a private company that develops software used to analyze immunology “big data.” She’s also a busy mom to two energetic, curious girls, which led her to write and illustrate a children’s book to make learning about the immune system fun. I spoke with Angela last week about her new book, which she plans to distribute on her website.

What inspired you to write a children’s book?

My kids led me to write this book, particularly my 4-year-old Violet. Sometimes I work from home analyzing datasets, and she’ll look over my shoulder and ask me all these deep questions about cells and what they do. Plus we talk through the details of everyday things, like if she gets a cut or flu shot. I realized that kids can pick up a startling amount of detail, and they’re so thirsty and eager for knowledge.

So I wrote the book to answer Violet’s questions, then I quickly realized that I have the opportunity to teach more children and even parents and caregivers about how our immune cells work. Immunology is becoming an increasingly popular topic in the public health conversation — anything from vaccine awareness to disease epidemics. My book can help people to have less fear of the unknown and to be better equipped to make decisions that influence their own lives and public health.

How did you develop the characters and storyline for your book?

The main character emerged because my daughter Violet wanted me to tell her new stories every night before bed. So I created this character who goes on adventures.

The book follows a 7-year-old girl named Rose, who is really excited about science. She asks her immunologist-Mom for a science-themed birthday party with a B-cell birthday cake and a treasure hunt for stuffed animal immune cells. The next day, Rose invites all her friends over for a play date to create and act out a play on how immune cells work together in concert to get rid of a virus.

I’ve tried to capture the joy of creation, exploration and discovery of childhood, while engaging kids to think deeper.

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Chronic Disease, Dermatology, Immunology, Pain, Research, Science, Stanford News

Stanford researchers investigate source of scarring

Stanford researchers investigate source of scarring

2570500512_22e7fdcd48_zIf you’ve ever had a piercing that you’ve let grow closed, you’ll know that the healing process isn’t perfect. There’s almost always a little dimple to remind you of that perhaps questionable choice you may (or may not) have made during early adulthood.

Now former Stanford pediatric dermatologist Thomas Leung, MD, PhD, and developmental biologist Seung Kim, MD, PhD, have published some interesting research in Genes and Development regarding the healing and scarring process. Their findings may one day lead to advances in regenerative medicine.

As Leung, who is now an assistant professor at the University of Pennsylvania’s Perelman School of Medicine explained in an email to me:

One of the great mysteries in biology is how salamanders and worms regenerate lost body parts following trauma. In contrast to wound healing, tissue regeneration restores tissue to their original architecture and function, without a scar.  Although less dramatic, a few examples of mammalian tissue regeneration exist, including liver and digit tip regeneration.  These examples suggest that the underlying mechanisms driving tissue regeneration may still be intact in humans and perhaps we may use them for regenerative medicine.

The researchers studied how the ears of mice heal from a hole punched through the thin tissue (much like  ear piercing in humans). In many strains of mice, the holes partially fill but remain visible. In a few others, the holes heal with little perceptible scarring. Leung and Kim found that the strains of mice that heal well lack production of a protein that normally recruits white blood cells to the injury; blocking the ability of the protein, called Sdf1, to signal to the white blood cells resulted in enhanced tissue regeneration and less scarring in mice that would normally have been unable to close the hole.

Because the drug used to block Sdf1 signalling is already used clinically in humans for another purpose, Leung is hopeful that it can quickly be tested in humans struggling to heal  chronic or slow-healing wounds. He is currently designing a clinical trial to test the drug, called AMD3100.

The implications of improved wound healing with less scarring stand to benefit many more people than just those wishing away the physical evidence of a hasty cosmetic decision. Tens of millions of surgical incisions are made every year, and not all heal well. Scar tissue is less flexible than normal skin and can significantly interfere with function. In addition, people with certain medical conditions such as diabetes or poor circulation can face ongoing disability or amputation when wounds don’t heal. But the group that inspired Leung to conduct the research is especially poignant.

As Leung explained:

 The inspiration for this work was driven by our clinical experience.  At Stanford, I co-directed the Epidermolysis Bullosa (EB) clinic.  EB is a rare genetic skin disease (about eight babies are affected per million births in this country), where affected patients lack a protein that binds the skin together, resulting in fragile skin. Incidental trauma like rubbing of skin against clothing tears the skin and leaves a scar.  This endless cycle of trauma and scarring and fibrosis inevitably leads to decreased joint function and complete loss of hand function by teenage years.

My recent article for Stanford Medicine magazine and the accompanying video shed light on this devastating condition. Even a small improvement in the pain these children suffer would be a tremendous step forward. And, although Kim emphasizes that greater feats in regenerative medicine (limb regeneration, anyone?) are still years of research away, this finding shows that we’re making progress.

Previously: Limb regeneration mysteries revealed in Stanford studyTo boldly go into a scar-free future: Stanford researchers tackle wound healing and Life with epidermolysis bullosa: “Pain is my reality, pain is my normal”
Photo by The Guy with the Yellow Bike

Immunology, Infectious Disease, Precision health, Research, Stanford News, Transplants

A blood test that monitors for post-lung-transplant rejection and infection

A blood test that monitors for post-lung-transplant rejection and infection

lungsA team under the direction of Stanford bioengineer Steve Quake, PhD, has shown that a noninvasive blood test can accurately diagnose lung-transplant rejection. The test also simultaneously detects infections by patient-imperiling microbes.

About 3,500 lung transplant procedures are performed annually worldwide. But median survival after the graft barely exceeds five years, trailing the outcomes for kidney, heart, liver and other solid organ transplants. Chronic organ rejection is the biggest single factor. Infection (for which recipients are at high risk due, ironically, to their post-transplant regimen of immune-suppressing drugs given to reduce the likelihood of organ rejection) is another leading contributor.

In a study published in Proceedings of the National Academy of Sciences, Quake and his associates demonstrated that the test, which involves high-throughput sequencing of DNA, flags organ rejection by detecting increasing amounts of donor DNA in a recipient’s blood. The relatively low-cost test doesn’t require the highly invasive removal of lung tissue, and it can also screen for myriad bacterial, viral and fungal pathogens.

In another study in 2014, Quake and Stanford colleagues had come up with a similar blood test to determine whether a heart-transplant recipient was headed for organ rejection. The new study expands the test’s applicability to lung transplantation – and suggests that its utility may extend to solid organs in general, including more-frequently performed procedures such as kidney transplantation (more than 17,000 in the United States alone in 2014).

With better than half of all lung-transplant patients suffering organ rejection in just the first year after their operation, this advance holds great clinical potential. Quick, accurate diagnosis is the first step toward appropriate treatment.

Previously: A simple blood test may unearth the earliest signs of heart transplant rejection, Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health and Might kidney-transplant recipients be able to toss their pills?
Photo by Lorraine Santana

Autoimmune Disease, Chronic Disease, FDA, Immunology, Pediatrics, Research, Stanford News

Can a safe, cheap pill prevent type 1 diabetes?

Can a safe, cheap pill prevent type 1 diabetes?

happy pillType 1 diabetes, an autoimmune disorder once known as juvenile diabetes because it tends to strike during adolescence or earlier, affects one in every 300 people. With the diagnosis comes the certainty of a lifetime of insulin injections, made necessary due to the destruction of insulin-producing cells in the pancreas by a misguided immune system.

Insulin is a hormone that alerts the body to the presence of glucose in the blood, typically after a meal. In insulin’s absence, the body’s tissues fail to take up glucose, a key energy source. Without several-times-daily insulin shots, type 1 diabetes patients’ blood sugar levels can shoot up to dangerous heights – a condition called hyperglycemia.

There’s never been any way to prevent type 1 diabetes, although it can be predicted based on the detection of self-targeting antibodies in a blood test. But screening for type 1 diabetes this way hasn’t been particularly useful, because there’s been nothing to be done for patients diagnosed in the asymptomatic phase except wait for them to become hyperglycemic and put them on insulin.

Now, an elaborate mouse study by Stanford immunologist and structural biologist Paul Bollyky, MD, PhD, shows that it might be possible to intervene during the asymptomatic stage of type 1 diabetes – using a pharmaceutical compound that’s been on the global market for more than 40 years and has a terrific safety record – thereby stopping the immune system’s stupid but relentless destruction of the pancreas’s vital insulin-producing cells, and stave off hyperglycemia indefinitely.

Bollyky and his colleagues first showed that a particular substance, hyaluronan, builds up near insulin-producing cells in mice developing the murine equivalent of type 1 diabetes, confirming earlier findings in postmortem human pancreatic tissue that had been supplied to Bollyky’s team by the Juvenile Diabetes Research Foundation.

“We wondered what would happen if we prevented that buildup,” Bollyky told me when I interviewed him for my news release on the study. “And we knew a drug that does that.”

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Autoimmune Disease, Genetics, Immunology, Science, Stanford News, Technology

Women and men’s immune system genes operate differently, Stanford study shows

Women and men's immune system genes operate differently, Stanford study shows

A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes connected with the immune system switch on and off more frequently than other genes, and those same genes operate differently in women and men. What’s more, the differences in gene activity are mostly not genetic.

A couple of years ago, geneticists Howard Chang, MD, PhD; Will Greenleaf, PhD, and others at Stanford invented a way to map the epigenome – essentially the real time on/off status of each of the 22,000 genes in our cells, along with the switches that control whether each gene is on or off.

Imagine a fancy office vending machine that can dispense 22,000 different drinks and other food items. Some selections are forever pumping out product; other choices are semi permanently unavailable. Still others dispense espresso, a double espresso or hot tea depending on which buttons you push. The activity of the 22,000 genes that make up our genomes are regulated in much the same way.

That’s a lot to keep track of. But Chang and Greenleaf’s technology, called ATAC-seq, makes it almost easy to map all that gene activity in living people as they go about their lives. Their latest study, published in Cell Systems, showed that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases, and also that men and women use different switches for many immune system genes. That sex-based difference in activity might explain the much higher incidence of autoimmune diseases in women — diseases like multiple sclerosis, lupus and rheumatoid arthritis.

The team took ordinary blood samples from 12 healthy volunteers and extracted immune cells called T cells. T cells are easy to isolate from a standard blood test and an important component of the immune system. With T cells in hand, the team looked at how certain genes are switched on and off, and how that pattern varied from individual to individual. Chang’s team also looked at how much change occurred from one blood draw to the next in each volunteer.

Chang told me, “We were interested in exploring the landscape of gene regulation directly from live people and look at differences. We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.”

Even in identical twins, he said, one twin could have an autoimmune disease and the other could be perfectly well. And, indeed, the team reported that over a third of the variation in gene activity was not connected to a genetic difference, suggesting a strong role for the environment. “I would say the majority of the difference is likely from a nongenetic source,” he said.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using
Photo by Baraka Office Support Services

Global Health, HIV/AIDS, Immunology, Research, Stanford News, Women's Health

HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected

HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected

virally infected cellsWhen it comes to immune cells, “it takes all kinds” isn’t too bad a description of what makes for the best composition of our fighting force for warding off viruses, bacteria and incipient tumors. But in a study just published in Science Translational Medicine, Stanford infectious-disease immunologist Catherine Blish, MD, PhD, and her colleagues have found, unexpectedly, that high diversity in the overall population of one particular type of immune cells strongly correlates with an increased likelihood of subsequent infection by HIV.

The investigators had figured that diversity in so-called natural killer cells, or NK cells, would be a strength, not a detriment. “Our hypothesis was wrong,” Blish (much of whose research focuses on NK cells) told me. In this study,  it was higher, rather than lower, diversity in this immune-cell population that turned out to be associated with increased HIV susceptibility.

NK cells, fierce white blood cells that help fight viruses and tumors, harbor various combinations of receptors on their surface. Some receptors recognize signs of our other cells’ normalcy, while others recognize signs that a cell is stressed — due, say, to viral infection or cancerous mutation. On recognizing their targeted features on other cells’ surfaces, an NK cell’s “normalcy” receptors tend to inhibit it, while its stress-recognizing receptors activate it.

All told, NK cells can have many thousands of different combinations of these receptors on their surfaces, with each combination yielding a slightly different overall activation threshold. At birth, our NK cells are pretty similar to one another. But as they acquire life experience – largely from viral exposure, Blish thinks – they increasingly diverge in the specific combinations of receptors they carry on their surfaces.

From my news release on the study:

In order to assess the impact of NK-cell diversity on adult humans’ viral susceptibility, Blish and her associates turned to blood samples that had been drawn during the Mama Salama Study, a longitudinal study of just over 1,300 healthy … Kenyan women. [T]he researchers carried out a precise analysis of NK cells in the women’s blood and observed a strong positive correlation between the diversity of a woman’s NK cell population and her likelihood of becoming infected with HIV.

This correlation held up despite the women’s being statistically indistinguishable with respect to age, marital status, knowledge of sexual partners’ HIV status, history of trading sex for money or goods, sexually transmitted disease status or reported frequency of recent unprotected sex.

And the NK-diversity-dependent difference in these women’s likelihood of HIV infection was huge. From my release:

Those with the most NK-cell diversity were 10 times as likely as those with the least diversity to become infected. A 10-fold risk increase based solely on NK-cell diversity is far from negligible, said Blish. “By way of comparison, having syphilis increases the risk of contracting HIV two- to four-fold, while circumcised men’s HIV risk is reduced by a factor of 2.5 or 3,” she said.

These surprising findings  could spur the development of blood tests capable of predicting individuals’ susceptibility to viral infection.

Previously: Study: Pregnancy causes surprising changes in how the immune system responds to the flu, Revealed: Epic evolutionary struggle between reproduction and immunity to infectious disease and Our aging immune systems are still in business, but increasingly thrown out of balance
Photo by NIAID

Imaging, Immunology, Mental Health, Neuroscience, Research, Stanford News

Are iron, and the scavenger cells that eat it, critical links to Alzheimer’s?

Are iron, and the scavenger cells that eat it, critical links to Alzheimer's?

iron linkIf you’ve been riding the Alzheimer’s-research roller-coaster, brace yourself for a new twist on that wrenching disease of old age.

In a study published in Neurobiology of Aging, Stanford radiologists Mike Zeineh, MD, PhD,  and Brian Rutt, PhD, and their colleagues used a ultra-powerful magnetic-resonance-imaging (MRI) system to closely scrutinize postmortem tissue from the brains of people with and without Alzheimer’s disease. In four out of five of the Alzheimer’s brains they looked at, but in none of the five non-Alzheimer’s brains, they found what appear to be iron-containing microglia – specialized scavenger cells in the brain that can sometimes become inflammatory – in a particular part of the hippocampus, a key brain structure that’s absolutely crucial to memory formation as well as spatial orientation and navigation.

Zeineh and Rutt told me they don’t know how the iron gets into brain tissue, or why it accumulates where it does. But iron, which in certain chemical forms can be highly reactive and inflammation-inducing, is ubiquitous throughout the body. Every red blood cell that courses through our microvasculature is filled with it. So one possibility – not yet demonstrated – is that iron deposits in the hippocampus could result from micro-injury to small cerebral blood vessels there.

As surprising as the iron-laden, inflamed microglia Zeineh, Rutt and their associates saw in Alzheimer’s but not normal brains was what they didn’t see. Surprisingly, in the brain region of interest there was no consistent overlap of either iron or microglia with the notorious amyloid plaques that have been long held by many neuroscientists and pharmaceutical companies to be the main cause of the disorder. These plaques are extracellular aggregations of a small protein called beta-amyloid that are prominent in Alheimer’s patients’ brains, as well as in mouse models of the disease.

Because they weren’t able to visualize small, soluble beta-amyloid clusters (now believed to to be the truly toxic form of the protein), Rutt and Zeineh don’t rule out a major role for beta-amyloid in the early developmental stages of pathology in Alzheimer’s.

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

Linking cancer gene expression with survival rates, Stanford researchers bring “big data” into the clinic

Linking cancer gene expression with survival rates, Stanford researchers bring "big data" into the clinic

Magic 8 ball“What’s my prognosis?” is a question that’s likely on the mind, and lips, of nearly every person newly diagnosed with any form of cancer. But, with a few exceptions, there’s still not a good way for clinicians to answer. Every tumor is highly individual, and it’s difficult to identify anything more than general trends with regard to the type and stage of the tumor.

Now, hematologist and oncologist Ash Alizadeh, MD, PhD; radiologist Sylvia Plevritis, PhD; postdoctoral scholar Aaron Newman, PhD; and senior research scientist Andrew Gentles, PhD, have created a database that links the gene-expression patterns of individual cancers of 39 types with the survival data of the more than 18,000 patients from whom they were isolated. The researchers hope that the resource, which they’ve termed PRECOG, for “prediction of cancer outcomes from genomic profiles” will provide a better understanding of why some cancer patients do well, and some do poorly. Their research was published today in Nature Medicine.

As I describe in our release:

Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. By doing so, it may be possible to learn what has gone wrong in the cancer cells, and give ideas as to how best to block the cells’ destructive growth. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.

Instead, the researchers pulled back and sought patterns that might become clear only when many types of cancers, and thousands of patients were lumped together for study:

Gentles and Alizadeh first collected publicly available data on gene expression patterns of many types of cancers. They then painstakingly matched the gene expression profiles with clinical information about the patients, including their age, disease status and how long they survived after diagnosis. Together with Newman, they combined the studies into a final database.

“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” said Alizadeh. “Then we could ask what we could learn more broadly.”

The researchers found that they were able to identify key molecular pathways that could stratify survival across many cancer types:

In particular, [they] found that high expression of a gene called FOXM1, which is involved in cell growth, was associated with a poor prognosis across multiple cancers, while the expression of the KLRB1 gene, which modulates the body’s immune response to cancer, seemed to confer a protective effect.

Alizadeh and Plevritis are both members of the Stanford Cancer Institute.

Previously: What is big data?Identifying relapse in lymphoma patients with circulating tumor DNA,  Smoking gun or hit-and-run? How oncogenes make good cells go bad and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Photo by CRASH:candy

Immunology, Nutrition, Stanford News, Videos

A Stanford dietician talks food sensitivities

A Stanford dietician talks food sensitivities

Ever wondered what the difference between a food allergy and a food sensitivity is? Neha Shah, MPH, RD, CNSC, a registered dietician at the Stanford Digestive Health Center, sheds some light in a new video.

In people with food allergies, she explains, the immune system responds to the presence of the food, which isn’t the case for food sensitivities. People with food allergies have to avoid the culprit foods entirely, whereas people with food sensitivities can sometimes have small amounts of the food – though they must figure out what their threshold is. (Too much and the offending food might set off other symptoms like gas, bloating or diarrhea.) Shah uses lactose intolerance as an example of a very common food sensitivity and describes how people can understand their threshold.

Previously: Peanut products and babies: Now okay?, Stanford dietitian explains how – not just what – you eat matters, Taking a bite out of food allergies: Stanford doctors exploring new way to help sufferers, Eating nuts during pregnancy may protect baby from nut allergies and Ask Stanford Med: Pediatric immunologist answers your questions about food allergy research

Autoimmune Disease, Immunology, Public Health, Research, Sleep, Stanford News

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

Cause of 2009 swine-flu-vaccine association with narcolepsy revealed?

syringesBack in 2001, in the wacko cinematic tour de farce “Rat Race,” British actor Rowan Atkinson – a.k.a. the iconic “Mr. Bean” – put a humorous face on narcolepsy, a rare, chronic, incurable and lifelong sleep disorder that can strike at any time, even in the heat of a foot race.

In 2009, narcolepsy suddenly became, for a time, not quite so rare.

The swine flu pandemic sweeping the world that year was no joke. In the United States alone, the H1N1 strain of influenza virus responsible for that pandemic resulted in 274,304 hospitalizations and 12,469 deaths, as mentioned in our news release on a just-published study in Science Translational Medicine.

There probably would have been far more hospitalizations and deaths had not several vaccines tailored to that particular influenza strain been rushed to the market. Two vaccines in particular — Focetria, manufactured by Novartis, and Pandemrix, made by GlaxoSmithKline — are credited with saving a lot of lives in Europe. But there was a dark side. As our news release notes:

Populations that had been immunized with GlaxoSmithKline’s Pandemrix vaccine showed an increase in narcolepsy, but those immunized with Novartis’ Focetria did not.

That’s not news; it’s been known for some time. But the findings in the new study, whose senior author is Stanford neuroimmunologist Larry Steinman, MD, may explain why.

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