How turning off a single gene could help block weight gain

first_img Turning off the function of a single protein-coding gene — called USF1 — could offer insight into how to treat a handful of cardiometabolic diseases like obesity, diabetes, and atherosclerosis. Lessening the gene’s expression activates calorie-burning brown fat, keeping mice lean even when they’re fed a high-fat diet. Here’s what lead researcher Dr. Pirkka-Pekka Laurila of the University of Helsinki said about the findings, published in the new Science Translational Medicine.What happens when you block USF1’s expression?When USF1 expression is blocked in mice, the mice are protected against weight gain, even when fed a high-fat diet. In humans, individuals who had a lesser amount of USF1 gene product improved their lipid levels, were more insulin sensitive, and developed fewer plaques in the arteries.How did that impact fat in the body?When USF1 was inactivated in the mice, the brown adipose [fat] tissue became more active in burning fats and lipids. It cleared sugar and triglycerides more rapidly from the circulation, improving blood lipid levels.advertisement About the Author Reprints By Megan Thielking Jan. 28, 2016 Reprints News Editor What’s the potential usefulness of that finding?These findings suggest that USF1 could be a therapeutic target for cardiovascular and metabolic disease. Genes have evolved to serve well-defined functions in our bodies. How can loss of USF1 be beneficial for metabolism? In the Paleolithic period, with a cycle of famine and feast, USF1 might have been an important player in storing energy. In the current world, with constant feast, the energy-storing function of USF1 might be redundant.For more Lab Chats, subscribe to the free Morning Rounds newsletter. [email protected] @meggophone Tags geneticsmedical researchweight gain A heavy set man rests on a bench. Rogelio V. Solis/AP Lab ChatHow turning off a single gene could help block weight gain Megan Thielkinglast_img read more

Scientists unveil the ‘most clever CRISPR gadget’ so far

first_img Sharon Begley Tags CRISPRgenome editingHarvard Harvard University biochemist David Liu and post-doctoral fellow Alexis Komor, who led the work, have filed a provisional patent application on their invention, which changes one-letter misspellings in DNA called point mutations. Liu is a consultant to and cofounder of Editas Medicine, a genome-editing company in Cambridge, Mass., that went public in February. Church is also a cofounder of Editas.“Most known human genetic variations associated with disease are point mutations,” said Liu. “Current gene-editing methods aren’t particularly good at correcting those.”The problem addressed by the new technique is not the usual one discussed with CRISPR, namely, off-target effects. That refers to changing a region of the genome other than the intended one. While early genome-editing experiments had that problem, there has been “tremendous progress” in fixing it, said Dr. Keith Joung of Massachusetts General Hospital. Senior Writer, Science and Discovery (1956-2021) Sharon covered science and discovery. About the Author Reprints But another problem remains.The workhorse of the CRISPR system is an enzyme that cuts DNA. In some cases, simply cutting out a disease-causing gene might be enough to achieve a cure, as with cancer-causing genes. If deleting a gene isn’t sufficient, and a replacement gene is also required to treat a particular disease, CRISPR can carry substitute DNA, such as a healthy cystic fibrosis gene.But genomes don’t take kindly to being cut. When the CRISPR enzyme whacks the double helix, the cell tries to “get the broken ends back together,” Liu said. Molecules in the cell grab the four basic components of DNA — represented by the letters A, T, C, and G — from the cellular soup and cram them into the cleaved DNA like someone pushing spackle into the crack of a Ming vase; other molecules cut out segments of DNA.“Having these random insertions or deletions is unhelpful,” Liu said. How does CRISPR work? Feng Zhang explains with a nursery rhymeVolume 90%Press shift question mark to access a list of keyboard shortcutsKeyboard ShortcutsEnabledDisabledPlay/PauseSPACEIncrease Volume↑Decrease Volume↓Seek Forward→Seek Backward←Captions On/OffcFullscreen/Exit FullscreenfMute/UnmutemSeek %0-9 facebook twitter Email Linkhttps://www.statnews.com/2016/04/20/clever-crispr-advance-unveiled/?jwsource=clCopied EmbedCopiedLive00:0001:5201:52  read more

Dalí’s being dug up for a paternity test. But is his DNA intact?

first_imgIn the LabDalí’s being dug up for a paternity test. But is his DNA intact? Even if you didn’t take art history classes in school, you probably know Salvador Dalí’s work. One of the surrealist’s most famous paintings, “The Persistence of Memory,” is the one with the melting clocks.But memory is not the only thing that persists — a woman who has claimed to be Dalí’s daughter for over a decade has not given up. To support her contention, Pilar Abel has had two previous paternity tests performed — one with inconclusive results, another that allegedly never sent her results. Now a Spanish court has granted her request to have Dalí’s body exhumed from a crypt in Catalonia so a third test can be conducted.But Dalí has been dead for nearly 30 years. Can a sample of his DNA still give Abel a definitive answer?advertisement Related: Kate Sheridan Please enter a valid email address. Leave this field empty if you’re human: However, Dalí’s DNA may be in shorter fragments — which may mean this DNA profiling technique will be less reliable. In Poinar’s experience, the average length of a DNA fragment from skeletal remains is about 70 to 80 base pairs — so the average fragment would likely have only part of a satellite region. If many of these microsatellites are compromised, then the analysis loses a lot of statistical power.Instead, he and other ancient DNA experts working in more specialized labs prefer sequencing full genomes and comparing a collection of single nucleotide polymorphisms, or SNPs (pronounced “snips”), which are variations in just one base pair.The burial environment — what kind of casket Dalí was buried in could have an effect, for example, or any kind of treatment his body received before burial — can have a impact on the condition of DNA. Only the people on the ground during the exhumation — and those who actually sequence the sample — will know what state the DNA is in, noted Reena Roy, an associate professor in the forensic science program at Pennsylvania State University. Without being there or using other techniques to determine how degraded the DNA actually is, she said, “one can only speculate.”Roy suspects Dalí’s DNA could be in decent shape — “it’s only 30 years old,” she said. She’d still use STR analysis first, but if that didn’t seem to work, she’d consider using miniSTR testing, which uses the same principles but focuses on smaller DNA segments.Bottom line: Though the circumstances around the particular paternity case may be a bit surreal, the techniques themselves are not; STR analysis is usually done in paternity cases, Roy said.“This is so routine these days.” General Assignment Reporter Kate covers biotech startups and the venture capital firms that back them. The researchers working with Dalí’s DNA will need to consider two main issues: contamination during the exhumation and working with degraded DNA afterward, Poinar said.Though Dalí died in 1989 — certainly not ancient history — “your DNA degrades the minute you die,” Poinar said. He and his students will often define ancient DNA as “anything that’s buried in the ground.”A sample will likely come from one of three places: hair, a molar tooth, or a small but very compact bone in the skull near the inner ear. Hair is pretty resistant to contamination, Poinar said, and the bone — called the petrous bone — has the most DNA per gram of any part of the skeleton.A standard forensics lab might take these samples, extract DNA, and look at a set of more than a dozen “microsatellites,” Poinar said. Each microsatellite can range from 100 to 400 DNA base pairs long and can vary in only so many ways —  in which DNA bases repeat and how many times they repeat. (These repeating sequences are called short tandem repeats, or STRs; looking for them is called STR analysis.)For comparison, the human genome is about 3 billion base pairs long. The possible patterns are numerous enough that determining if two samples come from the same person — or if the donor of one sample is likely related to the other — is very possible. Photo illustration: STAT; Photo: AFP/Getty Images Newsletters Sign up for Daily Recap A roundup of STAT’s top stories of the day. Genetic fossil-hunters dig through HIV’s long history for clues to new treatments [email protected] About the Author Reprints @sheridan_kate “Yes and no,” said Hendrik Poinar, principal investigator at the McMaster Ancient DNA Center in Ontario, Canada. The success of the test will depend on a lot of factors — including, possibly, which kind of analysis is done.Poinar isn’t involved in the case, but he is trying to solve a mystery about another famous 20th-century artist. He’s analyzing the remains of poet and Nobel laureate Pablo Neruda to determine if a bacteria was involved in his death in 1973.advertisement By Kate Sheridan June 29, 2017 Reprints Privacy Policylast_img read more

Their genes put them at high risk of Alzheimer’s. So they’re experimenting — on themselves

first_imgHealthTheir genes put them at high risk of Alzheimer’s. So they’re experimenting — on themselves “It gets overwhelming, in terms of, ‘What the heck do I do?’” said Theresa, an APOE4 carrier who did not want her full name used to protect her privacy. “That’s one of the benefits of this APOE4 group: We discuss all these things, and try and clarify them to make sense of it all.” About the Author Reprints One approach that’s circulated heavily in the community is the low-carb, high-fat “ketogenic diet.” Much like the popular Atkins diet, it’s meant to retrain the body to use fat, rather than glucose, as its primary source of fuel. Ketogenic diets first proved useful in the 1920s to prevent seizures in some patients with epilepsy — hinting that the diet may have a broader neuroprotective effect. The diet has not been shown to improve cognition in people with APOE4, but it remains popular among carriers of the genetic variant, who hope it could help stave off dementia.Others have adopted episodic fasting. They draw hope from what’s known as the Nigerian paradox: Although the APOE4 allele is frequently found among elderly Nigerians, they’re not at increased risk of Alzheimer’s. African-Americans, by contrast, are just as likely to have the APOE4 allele, but develop the disease at much higher rates. The biggest difference in the populations is that the Nigerians have a lower incidence of cardiovascular disease — as well as lower levels of fats and cholesterol in their blood. So it’s possible that the Nigerian diet, which can include periods of low calorie intake, might protect against dementia. (There is some more general evidence that fasting can help prolong life, though the majority of the work has been conducted in animals.) ‘Beyond amyloid’: A look at what’s next in Alzheimer’s research “I’m nowhere as zealous or strict about my diet as some of our members. The idea of living life without a cucumber or tomato is depressing to me.” The concept of episodic fasting has won over George, a 62-year-old from Colorado who asked that only his first name be used to protect his privacy.He watched his mother decline from Alzheimer’s and then learned in 2009 that he carried the APOE4 gene. As it turns out, so does his wife. They consult regularly with Dr. Steven Gundry, a cardiothoracic surgeon by training who has written two diet books and sells a line of dietary supplements. (He has also backed actress Gwyneth Paltrow’s often less-than-scientific wellness site, Goop.) Among his controversial tips: Avoid foods containing lectins, such as tomatoes, peppers, beans, lentils, and pasta.George said the diet resonates with him: “I want to go back to the way our ancestors lived.”Every two weeks, he fasts for four to five days. He religiously tracks his food intake, and is constantly on the move. (He was the one doing cartwheels across the conference room to keep up his cardio.) George also regularly pays out of pocket to test a number of blood biomarkers, including sdLDL, a type of cholesterol that Gundry believes is a primary “mischief maker” in people with the APOE4 genetic variant. If George doesn’t like the number he sees on the lab readout, he tweaks his diet to try to raise or lower his sdLDL. “I’m probably more crazy than most people,” George conceded. Kale crackers and hibiscus tea: My five days on a ‘fasting diet’ Shelley Alvarado helps her dad, Joseph Gleason, take his jacket off at his retirement home. Sandy Huffaker for STAT Related: By Meghana Keshavan Aug. 22, 2017 Reprints SAN DIEGO — Everyone at the meeting had one thing in common: a ticking time bomb buried in their DNA.The engineers, physicians, financiers, and farmers gathered here this month all had learned through genetic testing that they carry a copy or two of APOE4, an allele of the gene APOE that substantially increases their risk of developing Alzheimer’s. It’s a disease with no good treatment, and no good prevention strategy. So carriers scour the internet to devise their own tactics for keeping their brains healthy: a high-fat diet. Episodic fasting. Oils. Supplements. Regular blood tests to monitor a specific type of cholesterol. Exercise, exercise, exercise — even including barefoot cartwheels across the conference room floor.Some of these ideas have modest scientific backing; others are more speculative. All are fair game for APOE4 carriers who are desperate to ward off the frightening tumble into dementia that they’ve seen afflict far too many of their relatives.advertisement White nationalists are flocking to genetic ancestry tests. Some don’t like what they find Mainstream scientists point out that such theories, while intriguing, are still far from validated. Gundry, for instance, said he has some anecdotal evidence but has published no rigorous clinical trials to back his views on using diet to forestall Alzheimer’s. And while there’s a whole cottage industry of books and games that promise to help preserve brain health, there just isn’t a lot of evidence behind it.“The data, I must say, is soft,” Mahley said. “It’s very hard to prove these lifestyle things. Lifestyle is a soft science, and nutrition is a soft science — because people respond to diets very differently.”Lacy visits with her dad at his retirement home. Sandy Huffaker for STATFighting to save every brain cellOutside of sharing some DNA, sisters Lacy and Alvarado don’t have a lot in common. Lacy’s a left-leaning psychiatrist, and a bit of a Buddhist. Alvarado, a surgical nurse, is fairly conservative and a devout Christian. They were never all that close, until recently — when they found out that they both carry APOE4.  Having watched their parents decline, they know all too well what that could mean. Their father, a World War II vet, was a physician, and their mother helped found a school for autistic children in Long Beach, Calif. That school, Alvarado joked, was her mother’s fourth child — written in equally in her will. But their parents’ memories of their accomplishments have largely all gone now, and the sisters have been powerless to halt the progression of dementia. “These trials [of various diets] are expensive. If no money’s to be made with a little white pill, who’s going to fund them?” Researchers urge FDA to lower the bar — a little — on Alzheimer’s drug approvals The advent of low-cost genetic sequencing has opened up the secrets of our DNA — allowing us to learn about our Neanderthal origins, our tendency towards lactose intolerance, even (perhaps) our risk of developing tendon injuries when we work out. But that knowledge comes at a cost: Science often can tell us what diseases we’re predisposed to get, but not how to forestall them.A simple Google search about Alzheimer’s prevention turns up countless prospective remedies — and few answers. One site might suggest eating more blueberries, while another pushes coconut oil, and a third touts the virtues of oily fish. Amid the cacophony, the carriers gathered here for an APOE4 support group have, in effect, turned themselves into miniature science experiments, which they dub n=1 studies.advertisement [email protected] Related: @megkesh Tags agingdementiageneticsresearch Related: Related: Related: Biotech Correspondent Meghana covers biotech and contributes to The Readout newsletter. And while many APOE4 carriers believe that dietary changes offer hope for preventing the disease, it’s been difficult to test that theory, said Dr. Rudolph Tanzi, director of the genetics and aging research unit at Massachusetts General Hospital. He’s working with a company to develop a supplement for brain health, but said it’s much harder to find funding to test low-cost lifestyle interventions, such as cutting out carbohydrates.“These trials are expensive,” he said. “If no money’s to be made with a little white pill, who’s going to fund them?”Alvarado and her sister, Betty Gleason Lacy, with their father. The sisters both carry the APOE4 genetic variant, which has been linked to a higher risk of late-onset Alzheimer’s. Sandy Huffaker for STATTheories abound, but the science is scantA quick science lesson: The APOE gene gives the body instructions on how to produce a protein called apolipoprotein E. This protein ultimately helps regulate cholesterol levels in the blood. There are three major variants to the gene, called e2, e3, and e4. They only differ slightly. But the “very, very tiny” difference in APOE4 “has a profound effect on the way the protein is handled,” said Dr. Robert Mahley, an Alzheimer’s researcher at the University of California, San Francisco, who first discovered the APOE protein about 17 years back. It’s still largely not known how APOE4 increases the risk of Alzheimer’s. It is, however, associated with a buildup of protein clusters, called amyloid plaques, that accumulate in the brains of people with the disease. These toxic proteins can cause neurons to die, causing symptoms to progressively worsen.The disease has a number of co-risk factors — such as diabetes, smoking, and hypertension — so Mahley suggests that his patients control their cholesterol, maintain normal blood pressure, and aggressively treat their diabetes in hopes of reducing their chances of getting Alzheimer’s. But beyond such measures, science offers few answers to those with APOE4. Finding out you carry APOE4 can be terrifying. About 1 in 10 adults will develop Alzheimer’s by the age of 65; by age 85, that risk goes up to 50 percent. Carry one copy of the allele, and you have triple the likelihood to develop late-onset Alzheimer’s disease. Carry two copies, and your chances go up twelvefold. Sisters Betty Gleason Lacy and Shelley Alvarado are staring down that grim genetic math. They have a deep family history of Alzheimer’s: Their mother, grandmother, and great-grandmother all developed the condition. Their father, too, has dementia, though it likely has a different root.Each sister carries a single copy of APOE4. Their brother carries two. The sisters know how the disease can slowly take hold; they’ve seen their parents — once headstrong, accomplished, and independent — fade into shadows of their former selves. The pharmaceutical industry can offer no real hope: Drug after drug after drug has flopped in clinical trials. So Lacy is doing her own research, crisscrossing the country as a citizen scientist, attending conferences like this one to try to gain new insights from others with the APOE4 variant.“I feel very compelled to demystify this disease,” Lacy said. “We do not have to live with the old myth that there’s no hope, and there’s no cure.” The problem, of course, is that it’s not a myth: There is no cure for Alzheimer’s. Lacy tried to change her mother’s diet so that it more closely matches her own high-fat, low-carb approach — heavy on leafy greens, fish, nuts, and plant-based oils —  but that’s proven near-impossible in her mother’s group home. So the daughters have decided that the next time their mother falls ill, they’ll let the infection take its course rather than fighting to keep her alive. That’s what she would have wanted. In the meantime, they’re sharing tips with new friends at the APOE4 meetup, which was organized to coincide with Low Carb USA, a dietary conference in San Diego. “We’re the canaries in the coal mine,” Alvarado said.The meetup was conceived by Julia Gregory, a former marriage counselor who discovered five years back that she carried two copies of the APOE4 gene. She was just about to turn 50, and had sent in a saliva sample to the genetic testing service 23andMe. She found her results were alarming, to say the least. And the advice she was given was certainly lacking: Her doctors could offer few suggestions beyond crossword puzzles and square dancing to prevent the onset of Alzheimer’s.So Gregory began to commiserate — and brainstorm — with the fellow APOE4 carriers she found on 23andMe’s forums. The participants shared lifestyle tips and research insights. Eventually, Gregory formalized the group into a nonprofit called APOE4 Info. Gregory now runs the organization full time, moderating the site’s online forum and consulting individually with people who have recently learned of their APOE4 status. She, too, experiments with her diet, but in moderation. “I’m nowhere as zealous or strict about my diet as some of our members,” she said. “The idea of living life without a cucumber or tomato is depressing to me.” Meghana Keshavan Dr. Rudolph Tanzi, Alzheimer’s researcher This year’s meetup drew a few dozen APOE4 carriers from around the world, who attended lectures suggesting a link between diabetes and Alzheimer’s and talked up their own experiments, often with technical proficiency that might rival a decorated neuroscientist.“I think I’m a much healthier person after having gotten involved in this group,” said Diana Ross, 83, a carrier who attended the meetup. She’s cut down on carbs and boosted her intake of vegetables and protein, and said her doctor has been pleased with the results.Members also discussed the broader implications of carrying APOE4, including the possibility of genetic discrimination. Alvardo, the surgical nurse, worries about how her peers will respond if she slips up at work: Will her colleagues read a momentary lapse of memory at face value, or as a sign of something deeper? As for Lacy, these days, she is expanding her psychiatric practice to serve a more geriatric population — by counseling patients on the lifestyle and dietary tips she’s trying out herself. It’s still a long shot, but she’s confident that these lifestyle changes will help.“I feel motivated,” she said, “to save every brain cell I can.”  Lifestyle changes to stave off Alzheimer’s? Hints, no proof Julia Gregory, founder of APOE4 Infolast_img read more

Pharmalittle: Greek parliament to probe Novartis bribery scandal; N.J. county goes after Purdue shareholders

first_imgPharmalot Alex Hogan/STAT About the Author Reprints Hello, everyone, and how are you this fine morning? We are doing reasonably well, thank you, especially since the Pharmalot campus is especially quiet so far. The short person is sleeping in, since there is a winter break in our part of the universe, and the official mascots are following suit. This gives us space and time to quaff a few cups of stimulation and forage for tidbits. So here you go. We hope your day goes well and you conquer the world. And, as always, do keep in touch …Camden County in southern New Jersey has joined hundreds of counties nationwide in suing Purdue Pharma for its role in the opioid crisis, but in an unusual step, the county also named as co-defendants members of the Sackler family, who control the company, The Wall Street Journal reports. The lawsuit, filed Wednesday in Superior Court in the city of Camden, is a rare example of plaintiffs seeking to hold Purdue’s controlling shareholders personally responsible for allegedly marketing opioids in a deceptive manner that downplayed risks and helped spark widespread addiction. What’s included? Log In | Learn More Pharmalittle: Greek parliament to probe Novartis bribery scandal; N.J. county goes after Purdue shareholders By Ed Silverman Feb. 22, 2018 Reprints @Pharmalot GET STARTEDcenter_img Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr. What is it? [email protected] Ed Silverman STAT+ is STAT’s premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. Unlock this article — plus daily coverage and analysis of the pharma industry — by subscribing to STAT+. First 30 days free. GET STARTED Pharmalot Columnist, Senior Writer Ed covers the pharmaceutical industry. Tags legalopioidspharmaceuticalspharmalittleSTAT+Vaccineslast_img read more

Trump opioid plan writes in favoritism to single company’s addiction medication

first_img Tags addictionopioidspharmaceuticalspolicy Politics STAT+ is STAT’s premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. About the Author Reprints [email protected] Trump opioid plan writes in favoritism to single company’s addiction medication What is it? Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr. WASHINGTON — The White House’s national strategy to combat the opioid crisis, unveiled last week, would expand a particular kind of addiction treatment in federal criminal justice settings: a single drug, manufactured by a single company, with mixed views on the evidence regarding its use.Federal prisons should “facilitate naltrexone treatment and access to treatment” to inmates as they transition out of incarceration, according to a fact sheet circulated by the administration. A White House spokesman later confirmed to STAT that the document referred specifically to naltrexone in its injectable form. Log In | Learn More center_img Timothy D. Easley/AP GET STARTED What’s included? Lev Facher By Lev Facher March 26, 2018 Reprints Washington Correspondent Lev Facher covers the politics of health and life sciences. @levfacher Unlock this article — plus daily intelligence on Capitol Hill and the life sciences industry — by subscribing to STAT+. First 30 days free. GET STARTEDlast_img read more

They built a game-changing cancer-killing therapy. Now they’re taking on a new kind of CAR-T therapy

first_img Unlock this article by subscribing to STAT+ and enjoy your first 30 days free! GET STARTED Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr. What is it? NIH The two former Kite Pharma executives behind a game-changing cancer-killing technology are launching their next act: a new company to develop a suite of so-called off-the-shelf CAR-T therapy assets, designed so that they do not need to be personalized for each cancer patient.Allogene Therapeutics, which was unveiled Tuesday morning, has raised $300 million to acquire and advance a portfolio of experimental cell therapies previously controlled by Pfizer. As a consequence of the deal, Pfizer is getting out of the business of being a major CAR-T player, though it will take a 25 percent ownership stake in Allogene. Biotech Log In | Learn More They built a game-changing cancer-killing therapy. Now they’re taking on a new kind of CAR-T therapy By Rebecca Robbins April 3, 2018 Reprints GET STARTED What’s included? STAT+ is STAT’s premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. Tags biotechnologylast_img read more

He turns color into a precision tool to untangle the ‘dance of molecules’

first_imgLeave this field empty if you’re human: Why is color such an important part of what you do?So our dyes, our colored molecules, are not just colored, they also are fluorescent. That means they don’t just absorb light, they absorb one color of light and they emit another color of light. And that phenomenon is incredibly useful for studying biological systems. You can shine one color of light on a biological specimen that has a fluorescent molecule in it and you can see that molecule in a sea of billions of other molecules that are not fluorescent, down to this single molecule level. Nucleus of a cell stained with Janelia Fluor dyes JF549 and JF646.Brian English In the LabHe turns color into a precision tool to untangle the ‘dance of molecules’ Fruit fly larvae expressing protein tag in neurons stained with Janelia Fluor dye, JF635.Bill Lemon and Philipp Keller1/4PreviousNextWhat can we color inside the body?Modern genetics allows us to color different cells in the brain, so we can color neurons and not color other cells like astrocytes, glia, etc. We can color specific sub-cellular structures, like the nucleus where the DNA is housed, and not other portions of the cell. We can even go deeper and color specific molecules that control gene expression or molecules that are part of a particular organelle or particular sub-cellular structure, and then just look at how those molecules move.It seems like you’re trying to develop a more painterly palette for the sciences. Why?We’re trying to expand the palette because everything has to work together: the microscopes, the molecular biology to express the tags and other proteins inside the cell, and the data analysis. The ability to tune these dyes allows us to better match different limitations in the optics and the lasers, and the molecular biology.And so the goal of my lab is to figure out: Can we squeeze in a different color? Can we extend it farther to the red to give another channel? Fine-tuning these molecules gives us options, so we can work with microscopes and biologists to try and get as much information out of a single experiment as possible.What does it feel like when one of your dyes has hit its mark?The first time we ever made a Janelia Fluor dye, I remember looking over and thinking: “Wow, that looks like a really bright.”When we sent it up to some collaborators at Harvard, I got an email back saying “my postdoc just texted me and they said these dyes are so bright, [they’re] crying at the microscope.” And at that point, we realized that we might actually have something here. Jeffery DelViscio/STAT What’s the most enjoyable part of this kind of work?One of the great things about Janelia is that we actually get to give away a lot of our technology. That’s one of the mantras here. That allows us to send out thousands of vials of dye around the world every year. The ability to send these things out is enabling science and a lot of people are very grateful, very surprised. I’ll get an e-mail and sometimes the stuff will be in their lab the next day. (Author’s note: Luke’s email, incidentally, is [email protected])And the most rewarding part of this is when it’s a postdoc who’s desperate and I send them some stuff and I get an email back a week later saying, ‘thank you, you’ve you’ve rescued my project.’What are your future hopes for the dyes you’re creating?Right now our molecules that we’ve made are really focused on basic research and understanding how molecules behave inside a cell, but these improved imaging technologies could also be used for other things. For example, most drug discovery high-throughput screens are done with fairly low resolution, very slow imaging technologies. And so if we could adapt these very bright dyes and these improved microscopes to drug discovery, you might be able to find new drugs that are modulating really fast interactions inside a cell that can be the cause of certain cancers.Another thing is just understanding how the brain works. We’re actually moving toward using our dyes in conjunction with protein engineering to fashion new sensors that sense brain activity voltage changes. Basic research in the brain could ultimately lead to research on different dysfunctions in the brain, like neurodegenerative diseases.Luke Lavis Jeffery DelViscio/STATWhat’s the thing that you’d really like to do that you can’t do right now?We’re making all these wonderful colors and in many cases we don’t have enough ways to attach these molecules to proteins inside a cell. We have maybe three or four different methods to attach these dyes and we now have many more colors. So one thing that we can’t do is utilize this [full] palette of dyes that we’ve created.What did you see in color chemistry that gave you enough conviction to continue on with it?I think one thing that I’ve learned from biologists is that they’re always pushing the envelope, always right at the edges of what’s possible using the tools that are available. To a chemist, if you make a dye that’s five or ten-fold brighter, that’s kind of incremental, but to a biologist all they say is, ‘now I can do so many more experiments.’How would you categorize the things that you’ve been able to see with the system color tagging that you’ve helped create?Looking at images, using our dyes, it’s amazing the choreography that occurs inside a cell. You think it’s just this jumble of molecules and in many ways it is. But then you see these definite tracks. This thing is hanging out over here and then suddenly it moves. It stops at a particular place in a cell — there are there are barriers to diffusion. There are different things going on and we don’t understand how they work or what they’re really doing.As a chemist you realize that a cell, in all this wonderful complexity, is just a collection of molecules, and we need to understand how those molecules move and interact because that’s basically the the spark of life — it’s how living systems work. Jeffery DelViscio/STAT Stable binding sites of SOX2, a protein that is involved in the transcription of genetic information, determined with Janelia Fluor dye, JF549.James Liu If you look at color in marketing and it uses a bright palette, it’s meant to grab your attention. How is that same palette useful to science and how does it help us see in a different way?One of the great things about color is that it allows you to differentiate between different things, right? We color-code files. We sort our Legos by color. The question is: Can we do the same thing inside a cell?advertisement Newsletters Sign up for Daily Recap A roundup of STAT’s top stories of the day. Please enter a valid email address. Cells in the process of cell division, stained with Janelia Fluor dye JF646. Wes Legant and Eric Betzig ASHBURN, Va. — Luke Lavis paints the insides of cells, but he’s not an artist, he’s a color chemist.As head of molecular tools and imaging at Janelia Research Campus, Lavis is responsible for helping to bring varicolored detail to the hectic, colorless tangle of biological systems.During a recent interview in his lab, he talked about how the colored dyes his team creates could be useful for drug discovery, why he loves giving them away for free, and how color can reveal life’s spark. This interview has been edited for clarity.advertisement Fruit fly larvae expressing protein tag in neurons stained with Janelia Fluor dye, JF635.Bill Lemon and Philipp Keller Privacy Policy Chad Binns Tags research A typical human cell really doesn’t have inherent color. And so we have to engineer different ways to add color to structures inside a cell.The beauty of modern molecular genetics is that we can fuse a fluorescent protein, or a tag, that will grab a fluorescent dye, onto a particular structure within a cell or a specific protein inside the cell. And because of that we can then color in that particular structure or that protein and then watch these individual molecules as they move around.The cell is made up of a bunch of different molecules and so the ability to image and track the behavior of different molecules in the same cell and watch how they interact really allows us to untangle the complicated dance of molecules in a biological cell. It’s sort of like putting numbers on a ballroom dance contestant. We’re trying to basically tag each one of the partners and watch how they move around — we are giving them really colorful ballroom dresses. Stable binding sites of SOX2, a protein that is involved in the transcription of genetic information, determined with Janelia Fluor dye, JF549.James Liu By Jeffery DelViscio July 30, 2018 Reprintslast_img read more

The IPO boom has been particularly kind to biotech in Massachusetts

first_imgBiotech About the Author Reprints Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr. Tags biotechnologyfinanceSTAT+ Fifteen Massachusetts biotechs went public in the first seven months of this year, surpassing the state’s total for all of 2017 and putting the white-hot sector on a potential record-setting pace, according to a new industry report.Led by Rubius Therapeutics (RUBY), a Cambridge biotech created by Flagship Pioneering that raised about $277 million in an IPO this summer, the 15 companies attracted nearly $1.7 billion in investments through July, said the report, by the Massachusetts Biotechnology Council, a trade group. Unlock this article — plus daily coverage and analysis of the biotech sector — by subscribing to STAT+. First 30 days free. GET STARTED By Jonathan Saltzman — Boston Globe and Kate Sheridan — STAT Aug. 29, 2018 Reprints Jonathan Saltzman — Boston Globe and Kate Sheridan — STAT What’s included? Kendall Square in Cambridge, Mass. Pat Greenhouse/The Boston Globe STAT+ is STAT’s premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. What is it? GET STARTED The IPO boom has been particularly kind to biotech in Massachusetts Log In | Learn More last_img read more

We created a transparent pharmacy benefit management company. Here’s why

first_imgFirst Opinion Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr. STAT+ is STAT’s premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. By Michael A. Perry Nov. 14, 2018 Reprints What is it? Log In | Learn More Although pharmacy benefit managers (PBMs) have been part of American health care since the 1970s, how they make money is a mystery for many people outside of the industry. Calls for transparency have resounded in the media and at all levels of government with growing frequency in recent years. Often, pharmacy benefit managers respond by touting their transparent programs, but within the industry, “transparency” can mean many different things, making it a shell game.My colleagues and I realized that the opacity of pharmacy benefit managers was bad for patients — and for business. So, we started BeneCard PBF, a pharmacy benefit manager that focuses on people, not profits. Over the last 10 years we have grown the company by defining transparency in a meaningful way that serves patients’ needs, not through mergers and acquisitions, which run the risk of taking our focus off patients in favor of growing company profits. What’s included? Unlock this article by subscribing to STAT+ and enjoy your first 30 days free! GET STARTEDcenter_img We created a transparent pharmacy benefit management company. Here’s why Michael A. Perry About the Author Reprints Adobe GET STARTED [email protected] Tags insurancepharmaceuticalsSTAT+last_img read more