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Applied Biotechnology, Bioengineering, Genetics, Research, Stanford News

A computer kit could lead to better way to design synthetic molecules

A computer kit could lead to better way to design synthetic molecules

SmolkeSlipping something small into cells to regulate gene expression has long been a goal of biomedical researchers. And there have been many efforts to do just that. Usually researchers concoct a teeny strip of microRNA, or miRNA, and hope it does the trick.

But now, researchers at Stanford’s Department of Bioengineering have developed a computer model to take the guesswork out of designing miRNA. The model determines how to assemble a molecule so it will measure the level of a certain compound in a cell and then use that information to regulate the expression of a gene.

The research is featured in the current edition of Nature Methods, and senior author Christina Smolke, PhD, describes the process in a release issued this week:

“You start with an idea of what you want to do in the cell, and then you build and iterate on a design over and over until you reach something close to what you want,” Smolke said. “As we design and build more sophisticated systems, we will want the ability to efficiently achieve precise quantitative behaviors, and being able to accurately predict relationships between the system inputs and outputs are important to achieving this goal.”

She and Smolke’s team — which includes former graduate student Ryan Bloom and former undergraduate Sally Winkler —tested the model on the well-known Wnt signaling pathway, which plays a key role in embryonic development, stem cell production and cancer. The synthesized miRNA correctly monitored the protein produced by the pathway, validating their model.

Becky Bach is a former park ranger who now spends her time writing about science or practicing yoga. She’s a science writing intern in the Office of Communications and Public Affairs. 

Previously: A non-surgical test for brain cancer?, From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies, Researchers engineer biological “devices” to program cells
Photo of Smolke by L.A. Cicero

Autoimmune Disease, Genetics, NIH, Research, Science

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

I don’t know about you, but I’m fascinated with the idea of the “microbiome.” If you’re unfamiliar with the term, it describes the millions upon millions of tiny, non-human hitchhikers that live on and in you (think bacteria, viruses, fungi and other microscopic life). Although the exact composition of these molecular roommates can vary from person to person, they aren’t freeloaders. Many are vitally important to your metabolism and health.

We’ve reported here on the Human Microbiome Project, launched in 2007 and supported by the National Institutes of Health’s Common Fund. Phase 2 of the project started last fall, with grants to three groups around the country to study how the composition of a person’s microbiome might affect the onset of diseases such as type 2 diabetes and inflammatory bowel disease, as well as its role in pregnancy and preterm birth. Now the researchers, which include Stanford geneticist Michael Snyder, PhD, have published an article in Cell Host & Microbe detailing what data will be gathered and how it will be shared.

As explained in a release by the National Human Genome Research Institute:

“We’re producing an incredibly rich array of data for the community from the microbiomes and hosts in these cohorts, so that scientists can evaluate for themselves with these freely available data which properties are the most relevant for understanding the role of the microbiome in the human host,” said Lita M. Proctor, Ph.D., program director of the Human Microbiome Project at NIH’s National Human Genome Research Institute (NHGRI).

“The members of the Consortium can take advantage of each other’s expertise in dealing with some very complex science in these projects,” she said. “We’re generating these data as a community resource and we want to describe this resource in enough detail so people can anticipate the data that will be produced, where they can find it and the analyses that will come out of the Consortium’s efforts.”

As I’ve recently blogged, data-sharing among researchers and groups is particularly important for research efficiency and reproducibility. And I’m excited to hear what the project will discover. More from the release:

For years the number of microbial cells on or in each human was thought to outnumber human cells by 10 to 1. This now seems a huge understatement. Dr. Proctor noted that the 10-to-1 estimate was based only on bacterial cells, but the microbiome also includes viruses, protozoa, fungi and other forms of microscopic life. “So if you really look at the entire microbial community, you’re probably looking at more like a 100-to-1 ratio,” she said.

Although thousands of bacterial species may make their homes with human beings, each individual person is host to only about 1,000 species at a time, according to the findings of the Human Microbiome Project’s first phase in 2012.

In addition, judging from the array of common functions of bacterial genes, if the bacteria are healthy, each individual’s particular suite of species appear to come together to perform roughly the same biological functions as another healthy individual. In fact, researchers found that certain bacterial metabolic pathways were always present in healthy people, and that many of those pathways were often lost or altered in people who were ill.

Stanford’s Snyder will join forces with researchers in the laboratory of George Weinstock, PhD, of the Jackson Laboratory for Genomic Medicine in Connecticut to investigate the effect of the microbiome on  the onset of Type 2 diabetes. Snyder may be uniquely positioned to investigate the causes of the condition. In 2012, he made headlines when he performed the first ever ‘omics’ profile of himself (an analysis that involves whole genome DNA sequencing with repeated measurements of the levels of RNA, proteins and metabolites in a person’s blood over time). During the process, he learned that he was on the cusp of developing type 2 diabetes. He was able to halt the progression of the disease with changes in exercise and diet.

Previously: Stanford team awarded NIH Human Microbiome Project grantElite rugby players may have more diverse gut microbiota, study shows and Could gut bacteria play a role in mental health?

Applied Biotechnology, Cancer, Genetics, Pediatrics, Research

Gene-sequencing rare tumors – and what it means for cancer research and treatment

Gene-sequencing rare tumors - and what it means for cancer research and treatment

Sequencing the genes of cancer patients’ tumors has the potential to surmount frustrating problems for those who work with rare cancers. Doctors who see patients with rare tumors are often unsure of which treatments will work. And, with few patients available, researchers are unable to assemble enough subjects to compare different therapies in gold-standard randomized clinical trials. But thanks to gene sequencing, that is about to change.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time

That’s the take-away from a fascinating conversation about the implications of personalized tumor-gene sequencing that I had recently with two Stanford cancer experts. Cancer researcher Julien Sage, PhD, is the senior author of a recent scientific paper describing sequencing of a pediatric tumor that affects only one in every 5 million people. Alejandro Sweet-Cordero, MD, an oncologist who treats children with cancer at Lucile Packard Children’s Hospital Stanford, is leading one of Stanford’s several efforts to develop an efficient system for sequencing individual patients’ tumors.

In their paper, Sage’s team (led by medical student Lei Xu) analyzed the DNA and RNA of one child’s unusual liver tumor, a fibrolamellar hepatocellular carcinoma. The cause of this form of cancer has never been found. Curious about what genes drove the tumor’s proliferation, the scientists identified two genes that were likely culprits, both of which promoted cancer in petri dishes of cultured cells. One of the genes, encoding the enzyme protein kinase A, is a possible target for future cancer therapies.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time. Sweet-Cordero is working to develop an efficient system for getting both the mechanics of sequencing and the labor-intensive analysis of the resulting genetic data completed in a few weeks, instead of the two to three months now required. “We’re trying to use this kind of technology  to really help patients,” Sage said. “If you’re dealing with a disease that may kill the patient very fast, you want to act on it as soon as possible.”

In addition to giving doctors clues about which chemotherapy drugs to try, gene sequencing gives them a new way to study tumors.

“What’s really important is that, instead of categorizing tumors based on how they look under a microscope, we’ll be able to categorize them based on their gene-mutation profile,” Sweet-Cordero said. Rather than setting up clinical trials based on a tumor’s histology, as doctors have done in the past, scientists will group patients for treatment trials on the basis of similar mutations in their tumors. “In my mind, as a clinical oncologist, this is the most transformative aspect of this technology,” he said. This is especially true for patients with rare tumors who might not otherwise benefit from clinical trials at all.

And for childhood cancers, knowing a tumor’s gene mutations could also help doctors avoid giving higher doses of toxic chemotherapy drugs than are truly needed.

“The way we’ve been successful in pediatric oncology is by being extremely aggressive,” Sweet-Cordero said. Oncologists take advantage of children’s natural resilience by giving extremely strong chemotherapy regimens, which beat back cancer but can also have damaging long-term side effects. “We end up over-treating significant groups of patients who could survive with less aggressive therapy,” Sweet-Cordero said. “If we can use genetic information to back off on really toxic therapies, we’ll have fewer pediatric cancer survivors with significant impairments.”

Meanwhile, Stanford cancer researchers are also tackling a related problem: the fact that not all malignant cells within a tumor may have the same genetic mutations, and they may not all be vulnerable to the same cancer drugs. Next month, the Stanford Cancer Institute is sponsoring a scientific symposium on the concept, known as tumor heterogeneity, and how it will affect the future of personalized cancer treatments.

Sage’s research was supported by the Lucile Packard Foundation for Children’s Health, Stanford NIH-NCATS-CTSA UL1 TR001085 and Child Health Research Institute of Stanford University. Sage and Sweet-Cordero are both members of the Stanford Cancer Institute, and the National Cancer Institute-designated Cancer Center.

Previously: Smoking gun or hit-and-run? How oncogenes make good cells go bad, Stanford researchers identify genes that cause disfiguring jaw tumor and Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers

Big data, Evolution, Genetics, In the News, Research, Science, Stanford News

Flies, worms and humans – and the modENCODE Project

Flies, worms and humans - and the modENCODE Project

It’s a big day in comparative biology. Researchers around the country, including Stanford geneticist Michael Snyder, PhD, are publishing the results of a massive collaboration meant to suss out the genomic similarities (and differences) among model organisms like the fruit fly and the laboratory roundworm. A package of four papers, which describe how these organisms control how, when and where they express certain genes to generate the cell types necessary for complex life, appears today in Nature.

From our release:

The research is an extension of the ENCODE, or Encyclopedia of DNA Elements, project that was initiated in 2003. As part of the large collaborative project, which was sponsored by the National Human Genome Research Institute, researchers published more than 4 million regulatory elements found within the human genome in 2012. Known as binding sites, these regions of DNA serve as landing pads for proteins and other molecules known as regulatory factors that control when and how genes are used to make proteins.

The new effort, known as modENCODE, brings a similar analysis to key model organisms like the fly and the worm. Snyder is the senior author of two of the papers published today describing some aspects of the modENCODE project, which has led to the publication, or upcoming publication, of more than 20 papers in a variety of journals. The Nature papers, and the modENCODE project, are summarized in a News and Views article in the journal (subscription required to access all papers).

As Snyder said in our release, “We’re trying to understand the basic principles that govern how genes are turned on and off. The worm and the fly have been the premier model organisms in biology for decades, and have provided the foundation for much of what we’ve learned about human biology. If we can learn how the rules of gene expression evolved over time, we can apply that knowledge to better understand human biology and disease.”

The researchers found that, although the broad strokes of gene regulation are shared among species, there are also significant differences. These differences may help explain why humans walk, flies fly and worms slither, for example:

The wealth of data from the modENCODE project will fuel research projects for decades to come, according to Snyder.

“We now have one of the most complete pictures ever generated of the regulatory regions and factors in several genomes,” said Snyder. “This knowledge will be invaluable to researchers in the field.”

Previously: Scientists announce the completion of the ENCODE project, a massive genome encyclopedia

Genetics, Medicine and Society, Pain, Research, Science, Stanford News

From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies

From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies

Basic RGBStanford bioengineer Christina Smolke, PhD, and her team have been on a decade-long mission to replicate how nature produces opium in poppies by genetically engineering the DNA of yeast and then further refining the process to manufacture modern day opioid drugs such as morphine, codeine and the well-known painkiller Vicodin.

Smolke outlined the methods in a report  (subscription required) published in this week’s edition of Nature Chemical Biology, which details the latest stages in the process of manufacturing opium-based medicines, from start to finish, in fermentation vats, similar to the process for brewing beer.

An article published today in the Stanford Report offers more details:

It takes about 17 separate chemical steps to make the opioid compounds used in pills. Some of these steps occur naturally in poppies and the remaining via synthetic chemical processes in factories. Smolke’s team wanted all the steps to happen inside yeast cells within a single vat, including using yeast to carry out chemical processes that poppies never evolved to perform – such as refining opiates like thebaine into more valuable semi-synthetic opioids like oxycodone.

So Smolke programmed her bioengineered yeast to perform these final industrial steps as well. To do this she endowed the yeast with genes from a bacterium that feeds on dead poppy stalks. Since she wanted to produce several different opioids, her team hacked the yeast genome in slightly different ways to produce each of the slightly different opioid formulations, such as oxycodone or hydrocodone.

“We are now very close to replicating the entire opioid production process in a way that eliminates the need to grow poppies, allowing us to reliably manufacture essential medicines while mitigating the potential for diversion to illegal use,” Smolke added.

While it could take several more years to refine these last steps in the lab, bioengineering opioids would eventually lead to less dependence on legal poppy farming, which has numerous restrictions and international dependencies from other countries. It would also provide a reliable supply and secure process for manufacturing important pain killing drugs.

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

Previously: Blocking addiction risks of morphine without reducing its pain-killing effects, Do opium and opioids increase mortality risk? and Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers 
Photo by Kate Thodey and Stephanie Galanie

Genetics, Humor, Medicine and Society, Science, Stanford News

Using epigenetics to explain how Captain America and the Incredible Hulk gained their superpowers

Using epigenetics to explain how Captain America and the Incredible Hulk gained their superpowers

When I was kid I used to watch the Incredible Hulk on TV and wait for Bruce Banner to fly into a rage, his muscles inflating like balloons, pants torn to shreds while his entire body turns green as he transforms into the Hulk. As I grew up, and learned more about the advances in genetics, it never occurred to me that cutting-edge genome-editing techniques could explain the scientific principles behind the Hulk’s metamorphosis or his fellow Marvel Comics star-spangled hero Captain America. In a recent Stanford Report story,  Sebastian Alvarado, a postdoctoral research fellow in biology, creatively applies the concepts of epigenetics to illuminate the process by which average Joes become superheroes.

As Alvarado notes in the piece and above video,  over the past  70 years scientists have developed tools for selectively activating and deactivating individual genes through chemical reactions, a process termed epigenetics. Similar to flipping on a light, switch gene expression can be “turned on” or “turned off. “We have a lot of genome-editing tools – like zinc finger nucleases, or CRISPR/Cas9 systems – that could theoretically allow you to epigenetically seek out and turn on genes that make your muscles physically large, make you strategically minded, incredibly fast, or increase your stamina,” he said.

In the case of Captain America, the process of deliberately switching on and off genes could offer a real-world explanation as to how scrawny Steve Rodgers gained extraordinary, strength, stamina and intelligence after being injected with “Super Solider Serum” and then blasted with  “Vita-Rays.” When it comes to Bruce Banner, a little more creative license is required. Alvarado’s theory is:

First, when gamma radiation hits DNA, it breaks the molecule’s double-stranded, ladder-like helix, a process known as chromothripsis. Your body can repair a few breaks without significant loss of function.

If many breaks occur – say, if you were caught in a giant gamma explosion – the repairs can become sloppy, and new instructions can be keyed into the genetic code. Alvarado suggested that it’s possible that when Banner’s DNA reassembled after the initial blast, it now included a handful of epigenetic switches. Instead of the switches being activated by light, however, the hormones produced when Banner is angry might flip the genetic switches to reconfigure his DNA to transform him into the big, green Hulk.

As for the Hulk’s skin turning green, anyone who has suffered a nasty bruise has firsthand knowledge of the process that might be behind this transformation. When you bruise, red blood cells at the point of injury die and the oxygen-carrying molecule on their surface, hemoglobin, begins to break up. One of hemoglobin’s metabolites, Alvarado said, is a molecule called biliverdin, which can make the blood appear green and is responsible for the avocado hue at the edge of a bruise.

Giant gamma explosion and epigenetics aside, there’s one question that has scientifically stumped Alvarado: How do the Hulk’s pants stay on after every transformation?

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

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From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Ethics, Genetics, Medicine and Society

Film documents rise and fall of a genome matching service – and poses tough ethical questions

Film documents rise and fall of a genome matching service - and poses tough ethical questions

Jesse_01When I think of “science fiction,” I picture three-eyed aliens with purple-and-gold tentacles — not the disturbing demise of a man, and a company, depicted in the film “The Perfect 46.”

Nor do I expect to ponder the ethics of a company that strives to produce genetically “pure” children.

Yet this is precisely the type of science fiction filmmaker Brett Ryan Bonowicz dished up to a sold-out Stanford crowd last week. Following the film, an all-star panel of genetics experts fielded questions.

The film’s premise is simple, and alluring. People can send their sequenced genome, along with their partner’s,  in to a company called The Perfect 46 and allow its proprietary algorithm to figure out if their children will be born genetic-defect free — or not.

“Jesse [Darden, the company’s CEO] wasn’t going to cure the diseases, he would just breed them out. It made a lot of people uncomfortable,” said one of the characters in the film.

So uncomfortable, in fact, that the company, and its leader Jesse Darden, played with a standout performance by actor Whit Hertford, unravels quite thoroughly – with Darden’s painful personal and professional demise forming the meat of “The Perfect 46’s” somewhat-tortured plot.

For me, the ethical quandary is a no-brainer: perfect – what fun is that? My husband and I are both far from perfect, and if we had a perfect child, it certainly wouldn’t be anything like us.

More seriously, however, the film poses thorny questions about the future of consumer genetics, a boom-and-bust field that’s both promising and terrifying. “The Perfect 46” doesn’t answer these questions, but the post-screening panelists delved into some of them.

During the talk, the experts made  it clear the technology featured in the film isn’t there – yet. Right now, if scientists sequence a genome , they don’t know the meaning of the many versions, or allele , of the gene that pop up. “Often, we don’t know if it’s disease-causing or not,” said panel member Michael Snyder, PhD, Stanford professor and chair of genetics.

Although the film takes place in the “near future,” corporations that provide basic genetic screening are already available, the experts said. And corporations may not be providing adequate counseling for potential parents, panel member Sandra Lee, PhD, a senior researcher at the Stanford Center for Biomedical Ethics, pointed out.

The Stanford-heavy audience seemed to dig the movie, but I thought the film would be more effective if its lessons were a little subtler and its pace a bit quicker.

Still, the questions it asks are real, even pressing, and not science-fictiony at all.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously:Stanford patient on having her genome sequenced: “This is the right thing to do for our family”, Stanford geneticist discusses genomics and medicine in TEDMED talk, New recommendations for genetic disclosure released and A conversation about the benefits and limitations of direct-to-consumer genetic tests
Screenshot of movie courtesy of Clindar

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Cancer, Genetics, Research, Science, Stanford News

Unraveling the secrets of a common cancer-causing gene

Unraveling the secrets of a common cancer-causing gene

The Myc protein can cause a lot of trouble when it’s mutated or expressed incorrectly. Under those condition it’s called an oncogene, and it’s associated with the development of more than half of all human cancers. But because its cellular influence is vast (it controls the expression of thousands of genes and regulatory molecules), it’s been tough for scientists to learn which of its many effects are cancer-causing.

Now oncologist Dean Felsher, MD, PhD, and his colleagues have found that just a handful of genes are responsible for the Myc oncogene’s devastating outcomes. Their work was published today in Cancer Cell. As I wrote in our release:

The genes identified by the researchers produce proteins that govern whether a cell self-renews by dividing, enters a resting state called senescence or takes itself permanently out of commission through programmed cell suicide. Exquisite control of these processes is necessary to control or eliminate potentially dangerous tumor cells.

In particular, the researchers found that Myc works through a family of regulatory RNA molecules that govern how (and when) tightly packaged genes in the DNA/protein complex called chromatin are made available for transcription into proteins that do much of the work of the cell. Understanding this process might help researchers find ways to throw a molecular wrench into the Myc mechanism.

“One of the biggest unanswered questions in oncology is how oncogenes cause cancer, and whether you can replace an oncogene with another gene product,” Felsher told me. “These experiments begin to reveal how Myc affects the self-renewal decisions of cells. They may also help us target those aspects of Myc overexpression that contribute to the cancer phenotype.”

The reliance of many cancer cells on oncogenes like Myc is called oncogene addiction. In many cases, blocking the expression of an oncogene, or tinkering with its activity, causes cancer cells to stop growing and tumors in animals to regress. Recently Felsher and his colleagues published an article in the Proceedings of the National Academy of Sciences describing how inactivating two oncogenes at once can work better to fight cancer in animal models by making it more difficult for the cancer cells to develop resistance to therapy.

Previously: Tool to identify the origin of certain types of cancer could be a “boon to doctors prescribing therapies” and  Smoking gun or hit-and-run? How oncogenes make good cells go bad

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Evolution, Genetics, Obesity, Research, Science, Stanford News

Tiny fruit flies as powerful diabetes model

Tiny fruit flies as powerful diabetes model

Seung Kim

Fruit flies in your kitchen are unquestionably annoying. But the next time you’re trying to bat one out of the air around your too-ripe apples and bananas (or maybe that’s just me?), spare a few seconds to realize how important the tiny insects have been to science. They’ve been a darling of developmental biology for decades, as researchers identified genes (subsequently shown to be shared in mammals and humans) critically important in the metamorphosis from egg to animal. Frankly, it’s hard to over-estimate their contribution to science.

Now they’re set to take up a starring role in diabetes research. Stanford developmental biologist and Howard Hughes Medical Institute investigator Seung Kim, MD, PhD, and research associate Sangbin Park, PhD, have devised a way to measure insulin levels in fruit flies at the picomolar level – the level at which insulin concentrations are measured in humans. They’ve done so by successfully tagging the fruit fly insulin-like-peptide 2, or Ilp2, with a chemical tag. Their research was published today in PLOS Genetics.

From our release:

The experimental model is likely to transform the field of diabetes research by bringing the staggering power of fruit fly genetics, honed over 100 years of research, to bear on the devastating condition that affects millions of Americans. Until now, scientists wishing to study the effect of specific mutations on insulin had to rely on the laborious, lengthy and expensive genetic engineering of laboratory mice or other mammals.

In contrast, tiny, short-lived fruit flies can be bred in dizzying combinations by the tens of thousands in just days or weeks in small flasks on a laboratory bench.

In 2002, Kim and developmental biologist Roel Nusse, PhD, surprised many researchers when they showed that fruit flies develop a diabetes-like condition when their insulin-producing cells are destroyed. Further research has been stymied, however, by the difficulty of accurately measuring circulating insulin levels in the tiny animals. When speaking to me about the research, Kim called the new technique a “breakthrough” in the field.

Unlike many previous attempts by many groups, Park found two places in Ilp2 where the tag can be placed without affecting its biological activity. This allowed Kim and Park to track Ilp2 through its life cycle, as it’s produced by neurons in the brain (this is different from humans, who make insulin in beta cells in the pancreas), secreted into the blood stream and binds to insulin receptors in cells throughout the body. Parsing the effect of each mutation on the way the body produces, secretes and responds (or not) to insulin is critical to further understand the disease and to devise new therapeutic approaches. More from our release:

Park and his colleagues then turned their attention to mutations associated with type-2 diabetes in genome-wide studies in humans. These studies don’t reveal how a specific mutation might work to affect development of a disease; they show only that people with the condition are more likely than those without it to have certain mutations in their genome. Hundreds of candidate-susceptibility genes have been identified in this way.

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Aging, Genetics, Imaging, Immunology, Mental Health, Neuroscience, Research, Women's Health

Stanford’s brightest lights reveal new insights into early underpinnings of Alzheimer’s

Stanford's brightest lights reveal new insights into early underpinnings of Alzheimer's

manAlzheimer’s disease, whose course ends inexorably in the destruction of memory and reason, is in many respects America’s most debilitating disease.  As I wrote in my article, “Rethinking Alzheimer’s,” just published in our flagship magazine Stanford Medicine:

Barring substantial progress in curing or preventing it, Alzheimer’s will affect 16 million U.S. residents by 2050, according to the Alzheimer’s Association. The group also reports that the disease is now the nation’s most expensive, costing over $200 billion a year. Recent analyses suggest it may be as great a killer as cancer or heart disease.

Alarming as this may be, it isn’t the only news about Alzheimer’s. Some of the news is good.

Serendipity and solid science are prying open the door to a new outlook on what is arguably the primary scourge of old age in the developed world. Researchers have been taking a new tack – actually, more like six or seven new tacks – resulting in surprising discoveries and potentially leading to novel diagnostic and therapeutic approaches.

As my article noted, several Stanford investigators have taken significant steps toward unraveling the tangle of molecular and biochemical threads that underpin Alzheimer’s disease. The challenge: weaving those diverse strands into the coherent fabric we call understanding.

In a sidebar, “Sex and the Single Gene,” I described some new work showing differential effects of a well-known Alzheimer’s-predisposing gene on men versus women – and findings about the possibly divergent impacts of different estrogen-replacement  formulations on the likelihood of contracting dementia.

Coming at it from so many angles, and at such high power, is bound to score a direct hit on this menace eventually. Until then, the word is to stay active, sleep enough and see a lot of your friends.

Previously: The reefer connection: Brain’s “internal marijuana” signaling implicated in very earliest stages of Alzheimer’s pathology, The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Protein known for initiating immune response may set up our brains for neurodegenerative disease, Estradiol – but not Premain – prevents neurodegeneration in woman at heightened dementia risk and Having a copy of ApoE4 gene variant doubles Alzheimer’s risk for women, but not for men
Illustration by Gérard DuBois

Stanford Medicine Resources: