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Global Health, Immunology, Research, Stanford News

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

Mark DavisThe vaccine field got a major boost today with the announcement that the Bill & Melinda Gates Foundation will invest $50 million in a new collaboration with Stanford’s School of Medicine to speed the development of vaccines for some of the world’s major scourges. The funds will support the new Stanford Human Systems Immunology Center, a multidisciplinary effort led by immunologist Mark Davis, PhD.

In recent decades, efforts to develop vaccines for major killers such as HIV and malaria have been stymied in part by the expense and time involved in conducting large-scale trials, which have often proved disappointing. Through the new initiative, scientists will use advanced immunological tools to better understand how vaccines provide protection and identify the most promising candidates to pursue in clinical trials.

What we need is a new generation of vaccines and new approaches to vaccination

“What we need is a new generation of vaccines and new approaches to vaccination,” said Davis, director of the Stanford Institute for Immunity, Transplantation and Infection. “This will require a better understanding of the human immune response and clearer predictions about vaccine efficacy for particular diseases.”

The 10-year initiative will involve multiple faculty from diverse fields, including medicine, engineering and computer science. It will capitalize on a range of technologies, some of which have been pioneered at Stanford, which can rapidly analyze individual cells and provide a detailed profile of the human immune response, with all of its various components.

“This grant will provide crucial support to Stanford’s world-class scientists as they collaborate with investigators around the globe to assess vaccines against some of the most formidable diseases of our time,” said Lloyd B. Minor, dean of Stanford’s medical school. “The Stanford Human Systems Immunology Center will help the most promising vaccine candidates to move quickly and efficiently from the lab to the front lines of treatment, impacting countless lives.”

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail
Photo of Mark Davis by Steve Fisch

Immunology, Infectious Disease, Public Health, Research

Is honey the new antibiotic?

Is honey the new antibiotic?

3535805377_807788e3e1_z…Well, not quite. But recent research shows that honey does have infection-fighting properties surprisingly similar to the common antibiotic ampicillin. And even more importantly, honey worked just as well against bacteria that had developed a resistance to ampicillin, which is good news as the medical community raises awareness about antibiotic resistance.

The study, which was recently published in PLOS ONE, compared the effects of Canadian honey and ampicillin on E. coli bacteria. The most common kind of antibiotics – beta-lactams, which includes ampicillin – work by destroying the cell wall of a bacterium. This prohibits the bacterium from surviving, growing, and reproducing. In the experiment, the researchers used scanning electron microscopy to visualize the changes in the bacterial cultures’ cell structures. They saw that honey and ampicillin had similar effects on the shapes of the E. coli, that they affected it to a similar degree, and that honey had equal effects on normal and antibiotic-resistant E. coli.

As reported on the PLOS blog:

While scientists have yet to confirm the exact compounds responsible, the results of the above study support the idea that honey and ampicillin may have similar antibacterial efficacies, with possibly different mechanisms of attack.

But before you start smothering your toast with gooey goodness each morning or adding heaping spoonfuls to your tea, keep in mind that more research is needed to better understand the potential for honey’s medicinal use.

Previously: A look at our disappearing microbes
Photo by bionicgrrl

Events, Immunology, Infectious Disease, Microbiology, Public Health

A look at our disappearing microbes

A look at our disappearing microbes

8146322408_5312e9deb2_zCould obesity, asthma, allergies, diabetes, and certain forms of cancer all share a common epidemiological origin? NYU microbiologist Martin Blaser, MD, thinks so – he calls these “modern plagues” and traces them to a diminished microbial presence in our bodies, caused by the overuse of antibiotics and the increased incidence of caesarian sections.

I attended a recent public lecture sponsored by UC Santa Cruz’s Microbiology and Environmental Toxicology department, during which the charismatic Blaser cited statistics about antibiotic use in childhood. Alarmingly, American children receive on average seventeen courses of antibiotics before they are twenty years old, taking a progressively bigger toll on their internal microbial ecosystems. We also have an unprecedented rate of c-sections – at nearly 33 percent. Babies delivered this way are deprived of contact with their mothers’ vaginal microbes, which in vaginal deliveries initiates the infant’s intestinal, respiratory, and skin flora. Breastfeeding has implications for beneficial bacterial transfer, too.

It’s not news that antibiotics are being overused – Stanford Medicine hosts an Antimicrobial Stewardship Program dedicated to this cause, and the CDC has been hosting a campaign for awareness about appropriate antibiotic use for several years, including their use in farm animals. (Seventy to eighty percent of antibiotic use takes place on farms to promote growth – that is, not for veterinary reasons.)

Overuse leads to antibiotic resistance, a serious problem. Meanwhile, research by Blaser and others – notably Stanford microbiologist David Relman, MD – has shown that abundant bacterial and viral life is essential to healthy bodies, and that imbalances in the microbial ecosystems that inhabit our gut play an important role in the chronic diseases of the modern age. Blaser said he is concerned that we’re going down a path where each generation has fewer and fewer species of microbes; part of his research is to compare human gut biodiversity in different parts of the globe, and people in remote areas of New Guinea have far more variety than those in Western nations.

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Aging, Genetics, Immunology, Infectious Disease, Research, Stanford News

In human defenses against disease, environment beats heredity, study of twins shows

In human defenses against disease, environment beats heredity, study of twins shows

Pfc. Lane Higson and Pfc. Casey Higson, identical twins serving in Iraq with the Enhanced Combat Aviation Brigade, 1st Infantry Division. The twins, natives of Myrtle Beach, S.C., joined the Army together and have not separated since.I’m one of those people who’ve paid to have their genomes analyzed for the purpose of getting a handle on susceptibility to this or that disease as time goes by. So it was with great interest that I came across a new study of twins conducted by immunologist Mark Davis, PhD, and fellow Stanford investigators. The study, published in CELL, shows that our environment, more than our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age.

Improving gene-sequencing technologies have focused attention on the role of genes in diseases. But the finding that the environment is an even greater factor in shaping our immune response should give pause to anyone who thinks a whole-genome test is going to predict the course of their health status over a lifetime.

“The idea in some circles has been that if you sequence someone’s genome, you can tell what diseases they’re going to have 50 years later,” Davis told me when I interviewed him for a news release I wrote on the study. But, he noted, the immune system has to be tremendously adaptable in order to cope with unpredictable episodes of infection, injury and tumor formation.

Davis, who heads Stanford’s Institute for Immunity, Transplantation and Infection, is worth taking seriously. He’s made a number of major contributions to the field of immunology over the last 30 years or so.  (Not long ago, I wrote an article about one of those exploits for Stanford Medicine.)

To find out whether the tremendous differences observed between different people’s immune systems reflec tunderlying genetic differences or something else, Davis and his colleagues compared members of twin pairs to one another. Identical twins inherit the same genome, while fraternal twin pairs are no more alike genetically than regular siblings, on average sharing 50 percent of their genes. (Little-known fun factoid: The percentage can vary from 0 to 100, in principle, depending on the roll of the chromosomal dice. But it typically hovers pretty close to 50 percent, just as rolling real dice gives you a preponderance of 6s, 7s, and 8s. Think of a Bell curve.)

Because both types of twins share the same in utero environment and, usually, pretty close to the same childhood environment as well, they make great subjects for contrasting hereditary versus environmental influence. (If members of identical-twin pairs are found to be no more alike than members of fraternal-twin pairs with respect to the presence of some trait, that trait is considered to lack any genetic influence.)

In all, the researchers recruited 78 identical-twin pairs and 27 pairs of fraternal twins and drew blood from both members of each twin pair. That blood was hustled over to Stanford’s Human Monitoring Center, which houses the latest immune-sleuthing technology under a single roof. There, the Stanford team applied sophisticated laboratory methods to the blood samples to measure more than 200 distinct immune-system cell types, substances and activities.

Said Davis: “We found that in most cases – including your reaction to a standard influenza vaccine and other types of immune responsiveness – there is little or no genetic influence at work, and most likely the environment and your exposure to innumerable microbes is the major driver.”

It makes sense. A healthy human immune system has to continually adapt to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more.

“The immune system has to think on its feet,” Davis said.

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail, Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before and Immunology escapes from the mouse trap
Photo by DVIDSHUB

Cardiovascular Medicine, Immunology, Medicine and Literature, Stanford News, Surgery

Stanford Medicine magazine’s big reads of 2014

Stanford Medicine magazine's big reads of 2014

brain attackThis year’s most-read Stanford Medicine magazine stories were all about the heart, surgery and the immune system – the themes of this year’s three issues. The top 10 (as determined by pageviews on our website):

Previously: Stanford Medicine magazine’s big reads of 2013 and Stanford Medicine magazine’s big reads of 2012
Illustration, from the article “Brain attack” in the Fall 2014 magazine issue, by Jeffrey Decoster

Immunology, Neuroscience, Research, Stanford News

Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice

Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice

brain in motionAttention, nerve cells: It’s not all about you.

As a new study in the Journal of Clinical Investigation led by Stanford neuroscientist Kati Andreasson, MD, shows, blocking the action of a single molecule situated on the surfaces of entirely different brain cells reversed memory loss and a bunch of other Alzheimer’s-like features in experimental mice.

The very term “neuroscience” strongly suggests that nerve cells, a.k.a. neurons, are the Big Enchilada in brain research – and, let’s face it, you wouldn’t want to leave home without them. But they’re far from the entire picture. In fact, neurons account for a mere 10 percent of all the cells in the brain. It may be that the mass die-off of nerve cells in the brains of people with Alzheimer’s disease may largely occur because, during the course of aging, another set of key players ensconced in that mysterious organ inside our skull and  known collectively as microglia begin to fall down on the job.

In  a release I wrote to explain the study’s findings in lay terms, I described microglia as the brain’s very own, dedicated immune cells:

A microglial cell serves as a front-line sentry, monitoring its surroundings for suspicious activities and materials by probing its local environment. If it spots trouble, it releases substances that recruit other microglia to the scene … Microglia are tough cops, protecting the brain against invading bacteria and viruses by gobbling them up. They are adept at calming things down, too, clamping down on inflammation if it gets out of hand. They also work as garbage collectors, chewing up dead cells and molecular debris strewn among living cells – including clusters of a protein called A-beta, notorious for aggregating into gummy deposits called Alzheimer’s plaques, the disease’s hallmark anatomical feature. … A-beta, produced throughout the body, is as natural as it is ubiquitous. But when it clumps into soluble clusters consisting of a few molecules, it’s highly toxic to nerve cells. These clusters are believed to play a substantial role in causing Alzheimer’s.

“The microglia are supposed to be, from the get-go, constantly clearing A-beta, as well as keeping a lid on inflammation,” Andreasson told me. If their job performance heads downhill – as seems to occur during the aging process – things get out of control. A-beta builds up in the brain, inducing toxic inflammation.

But by blocking the activity of a single molecule – a receptor protein on microglial cells’ surfaces  – Andreasson’s team got those microglia back on the job. They resumed chewing up A-beta, quashing runaway neuro-inflammation, squirting out neuron-nurturing chemicals. Bottom line: the Alzheimer’s-prone experimental animals’ IQs (as measured by mousey memory tests) rose dramatically.

Aspirin and similar drugs also tend to shut down the activity of this microglial receptor, which may or may not explain why their use seems to stave off the onset of Alzheimer’s in people who start using them regularly (typically for unrelated reasons) before this memory-stealing syndrome’s symptoms show up. But aspirin et al. do lots of other things, too – some good, some bad. The new findings suggest a compound carefully tailored to block this receptor and do nothing else might be a weapon in the anti-Alzheimer’s arsenal.

Previously: Another big step toward building a better aspirin tablet, Untangling the inflammation/Alzheimer’s connection and Study could lead to new class of stroke drugs
Photo by Henry Markham

Clinical Trials, Immunology, Research, Transplants

Transplant without lifelong drugs gives patient another chance

Transplant without lifelong drugs gives patient another chance

"DCIM100GOPRO"Imagine learning you have an illness. It’s the same illness that killed your mother. You watched her fade, the last years of her life dreadful to watch, unimaginably tough to endure. The same fate awaits you. Until… it doesn’t. Now there’s a therapy that just might save you.

That’s the story of San Francisco Bay Area resident Cynthia Alcaraz-Jew, featured in the fall issue of Stanford Medicine Magazine. Now in her late 40s, Alcaraz-Jew, like her mother, suffers from a rare genetic condition called Alport Syndrome. The ailment leads to kidney, ear and eye problems.

Alcaraz-Jew didn’t immediately luck out. Her kidneys failed first and her younger brother, Xavier, a perfect immunologic match, offered to donate his kidney. Great news, of course, but a transplant usually means years of immunosuppressive drugs, which leave bones brittle and can lead to infections, heart disease, or even, ironically kidney failure.

Thanks to her perfectly matched kidney, Alcaraz-Jew was able to enroll in a trial led by Stanford immunologist Samuel Strober, MD, that aims to wean transplant patients off immunosuppressive drugs. From the article:

Of the 24 kidney transplant patients with perfectly matched donors who enrolled in the trial beginning in 2000, 16, including Alcaraz-Jew, are living drug free, and three others are working to get off the medications, Strober says. The team is planning to publish a paper summarizing the research results in the near future.

And the photo? That’s Alcaraz-Jew and her husband swimming with whale sharks in Mexico earlier this year.

Previously: Stanford Medicine magazine traverses the immune system, Kidney-transplant recipients party without drugs — immune-suppressing anti-rejection drugs, that is, Might kidney-transplant recipients be able to toss their pills?  and Marked improvement in transplant success on the way, says Stanford immunologist
Photo courtesy of Cynthia Alcaraz-Jew

Chronic Disease, Imaging, Immunology, Neuroscience, Research, Stanford News

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

Patients' reaction to ME/CFS coverage in Stanford Medicine magazine

me-cfs-brain-zeineh

In the last few weeks, Stanford published two articles on chronic fatigue syndrome, a.k.a. myalgic encephalomyelitis, and the outpouring of positive feedback from ME/CFS patients has been tremendous. In my long-form Stanford Medicine story and video, I describe a young woman’s seven-year battle with the disease and the groundbreaking research being done by her physician, José Montoya, MD, and immunologist Mark Davis, PhD, to identify the biomarkers and root causes of ME/CFS. My colleague Bruce Goldman followed up with an elegantly written article describing the distinct differences between the brains of ME/CFS patients with those of healthy people, in a newly released study from this same research team.

While our primary job as medical science writers is to explain new research accurately, it’s a bonus to know that we captured the patient experience in a compassionate way, and that we have in some way eased their suffering with hope.

Here is a sampling of a few of these letters from around the world:

From British Columbia, Canada:
Thank you for an article that is very well done. I will be printing it for my MD and forwarding it to family and a few close friends because it captures this devastating illness so well. I will keep a copy for myself to remind me (on those dark days) that Dr. Montoya is in my corner.

From Sweden:
I would like to thank you for your very informative and interesting article! This kind of information of what research is going on at Stanford, etc., is very important for us patients with ME all over the world! There is a lot of disinformation coming out about this disease and I therefore very much appreciate your article and especially Dr. Montoya’s passionate engagement with this disease.

From Cali, Colombia:
Here in Cali, Colombia, the city of birth of Dr. Montoya, I feel very happy reading your excellent article, and learning the marvelous and difficult investigation performed by these brilliant scientists. I was moved to tears. Thank you.

From the San Francisco Bay Area:
I want to thank you very much for the powerful piece you wrote about ME/CFS. You tell the story in a very engaging way, which is so compelling. It’s not the usual doom/gloom/dark room story which my daughter and I have encountered frequently in what people write about ME/CFS. Family and friends with whom I have shared the article are appreciative of your writing so descriptively and articulately about all aspects of ME/CFS: the science, the inequity of research funding, the personal experience of a patient, the work of Drs. Montoya/Mark Davis/Holden Maecker.

From India:
Today I have gone through your article about Erin’s story. How she recovered from CFS had given me a ray of hope as I am also suffering from such an ailment for the last 6-8 years.

From Atlanta, Georgia:
I just read your beautifully written article on Immune System Disruption. First soccer caught my eye, then “swimming in the primordial soup of creative disruption” locked me in. I read every word … and I am going to spend the rest of the night in Atlanta copying [my internal medicine doctor] on the article.

From Australia:
Just wanted to thank you for your excellent article. It could really make a difference in raising awareness and I appreciate the quality of your writing. I have suffered from CFS/ME for many years in Australia and find the research project and your understanding very encouraging.

From the blogosphere:
I just wanted to thank you for taking the time to write such an in-depth, accurate article on our oft-ignored illness. Dr. Montoya is a hero within the ME/CFS community, but I didn’t know about the others at Stanford also working on ME/CFS — that gives me some hope for a better future! I plan to share your article on my ME/CFS blog and in several Facebook groups for ME/CFS that I belong to.

Previously: Some headway on chronic fatigue syndrome: Brain abnormalities pinpointedUnbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Stanford Medicine magazine traverses the immune system
Image, showing white matter differences between a ME/CFS patient sample an a healthy control, by Michael Zeineh/Stanford

Biomed Bites, Immunology, Infectious Disease, Research, Stanford News

Figuring out a parasite's secrets – insights from studying Toxoplasma gondii

Figuring out a parasite's secrets - insights from studying Toxoplasma gondii

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

You’ve probably heard that pregnant women shouldn’t get near the litter box. The reason is that many kitties carry a parasite called Toxoplasma gondii, which is transmitted through their feces. The parasite infects about 2 billion people worldwide, according to Stanford microbiologist John Boothroyd, PhD.

Boothroyd, who also serves as the associate vice provost for graduate education, directs a lab that has uncovered some of the basic biology of this single-celled protozoan parasite. Here’s Boothroyd in the video above:

Most of the time, this causes no significant disease, very few symptoms and probably something that most of these people will never know they were infected with. Occasionally, however, this parasite can cause devastating disease. It can affect the brain of the unborn child, it can cause severe neurological problems, it can even kill the developing fetus.

Toxoplasmosis, or infection with the parasite, can also cause serious complications in immunocompromised individuals. Boothroyd said he was drawn to the study of the T. gondii because it is clinically significant — he has the opportunity to help millions of people: “I wanted something where I felt the work we were doing was worth the many, many hours that I and the people I worked with put in to the daily effort.” T. gondii is also related to the Plasmodium parasites that cause malaria and some of the work from Boothroyd’s lab has been translated into insights into malaria.

Boothroyd’s team also identified the T. gondii protein that triggers the immune response in humans. With that knowledge, the investigators were able to insert the gene coding for that protein into yeast, letting the yeast produce the protein, “instead of having to grow the parasite in literally hundreds of thousands of mice a year and then killing those mice to get the parasite,” Boothroyd said. He went on to explain:

The situation in which Toxoplasma presents the most significant problem for the doctor and for the patient is in the pregnant woman. The challenge becomes first, is she infected, and if so, has the parasite crossed the placenta and reached the fetus. And third, what is the consequence of the infection in the fetus? All three of those we have addressed through our work.

Although much about the parasitic diseases remains unknown, Boothroyd is glad he picked T. gondii to focus on: “I think we’ve been able to do some real good with this work.”

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

Previously: Stanford microbiologist’s secret sauce for disease detection, Cat guts, car crashes and warp-speed Toxoplasma infections and Patrick House discusses Toxoplasma gondii, parasitic mind control and zombies

Global Health, Immunology, Pregnancy, Public Health, Stanford News, Technology

Stanford-developed smart phone blood-testing device wins international award

Stanford-developed smart phone blood-testing device wins international award

When I worked as an epidemiologist, one of my jobs was with a program that prevented perinatal hepatitis B infections. That’s when a woman with a chronic hepatitis B infection passes it on to her baby. Babies are more likely than almost any other group to develop chronic infections that can cause them years of health problems and will most likely cut their lives short.

In the U.S., most states have comprehensive testing programs to detect pregnant women with infections and strict protocols that require delivery hospitals to treat babies born to them with vaccination and antibodies to prevent infection with the virus. But a program like this requires a huge administrative and laboratory investment – and in many poverty-stricken parts of the world, this simply isn’t possible. In fact, in California, the vast majority of cases identified by the prenatal testing program are women who were born outside the United States, including many from Asia.

So when I heard the recent news that a team of four Stanford graduate students had won the Nokia Sensing XCHALLENGE, an international competition to for diagnostic devices, for a mobile test that could detect hepatitis B infections, I was pretty impressed and curious about how it could be implemented in those places. The competition is run by XPrize, the same group that has run several competitions for space exploration, and others for super-fuel efficient vehicles and ocean clean-up efforts.

The mobile version of the winning test was one of five awarded top prizes among 90 entrants. It was developed by engineering PhD candidates Daniel Bechstein, Jung-Rok Lee, Joohong Choi and Adi W. Gani, building on work previously done by Stanford professor of materials science and engineering Shan Wang, PhD, and Stanford immunologist  Paul Utz, MD. The device works because magnetic nanoparticles are grafted onto two biological markers: the hepatitis B virus and the antibody that our bodies make in response to the virus. Current tests for hepatitis B requires a full laboratory facility. A Stanford press release describes the device:

The students used a diagnostic strip that takes a finger prick of blood. The patient’s blood flows into a tiny chamber where it mixes with magnetic nanoparticles to form magnetically tagged biomarkers.

The test strip is inserted into a small magnetic detector… The smartphone is plugged into the detector, and its microprocessor helps to perform the test. It takes only a few minutes.

If the test finds the hepatitis B antigen in the blood, the patient is infected and needs treatment. For a newborn with an infected mother, the child needs both vaccination and antibody therapy.

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