Category Archives: Gene Medicine

By Laurie McginleyThe Washington Post

The oncologist was blunt: Stefanie Joho's colon cancer was raging out of control and there was nothing more she could do. Flanked by her parents and sister, the 23-year-old felt something wet on her shoulder. She looked up to see her father weeping.

"I felt dead inside, utterly demoralized, ready to be done," Joho remembers.

But her younger sister couldn't accept that. When the family got back to Joho's apartment in New York's Flatiron district, Jess opened her laptop and began searching frantically for clinical trials, using medical words she'd heard but not fully understood. An hour later, she came into her sister's room and showed her what she'd found.

"I'm not letting you give up," she told Stefanie. "This is not the end."

That search led to a contact at Johns Hopkins University, and a few days later, Joho got a call from a cancer geneticist co-leading a study there.

"Get down here as fast as you can!" Luis Diaz said. "We are having tremendous success with patients like you."

What followed is an illuminating tale of how one woman's intersection with experimental research helped open a new frontier in cancer treatment with approval of a drug that, for the first time, targets a genetic feature in a tumor rather than the disease's location in the body.

The breakthrough, now made official by the Food and Drug Administration, immediately could benefit some patients with certain kinds of advanced cancer that aren't responding to chemotherapy. Each should be tested for that genetic signature, scientists stress.

"These are people facing death sentences," said Hopkins geneticist Bert Vogelstein. "This treatment might keep some of them in remission for a long time."

A pivotal small trial

In August 2014, Joho stumbled into Hopkins for her first infusion of the immunotherapy drug Keytruda. She was in agony from a malignant mass in her midsection, and even with the copious amounts of OxyContin she was swallowing, she needed a new fentanyl patch on her arm every 48 hours. Yet within just days, the excruciating back pain had eased. Then an unfamiliar sensation hunger returned. She burst into tears when she realized what it was.

As months went by, her tumor shrank and ultimately disappeared. She stopped treatment this past August, free from all signs of disease.

The small trial in Baltimore was pivotal, and not only for the young marketing professional. It showed that immunotherapy could attack colon and other cancers thought to be unstoppable. The key was their tumors' genetic defect, known as mismatch repair (MMR) deficiency akin to a missing spell-check on their DNA. As the DNA copies itself, the abnormality prevents any errors from being fixed. In the cancer cells, that means huge numbers of mutations that are good targets for immunotherapy.

The treatment approach isn't a panacea, however. The glitch under scrutiny which can arise spontaneously or be inherited is found in just 4 percent of cancers overall. But bore in on a few specific types, and the scenario changes dramatically. The problem occurs in up to 20 percent of colon cancers and about 40 percent of endometrial malignancies cancer in the lining of the uterus.

In the United States, researchers estimate that initially about 15,000 people with this defect may be helped by this immunotherapy. That number is likely to rise sharply as doctors begin using it earlier on eligible patients.

Joho was among the first.

Even before Joho got sick, cancer had cast a long shadow on her family. Her mother has Lynch syndrome, a hereditary disorder that sharply raises the risk of certain cancers, and since 2003, Priscilla Joho has suffered colon cancer, uterine cancer and squamous cell carcinoma of the skin.

Stefanie's older sister, Vanessa, had already tested positive for Lynch syndrome, and Stefanie planned to get tested when she turned 25. But at 22, several months after she graduated from New York University, she began feeling unusually tired. She blamed the fatigue on her demanding job. Her primary-care physician, aware of her mother's medical history, ordered a colonoscopy.

When Joho woke up from the procedure, the gastroenterologist looked "like a ghost," she said. A subsequent CT scan revealed a very large tumor in her colon. She'd definitely inherited Lynch syndrome.

She underwent surgery in January 2013 at Philadelphia's Fox Chase Cancer Center, where her mother had been treated. The news was good: The cancer didn't appear to have spread, so she could skip chemotherapy and follow up with scans every three months.

By August of that year, though, Joho started having relentless back pain. Tests detected the invasive tumor in her abdomen. Another operation, and now she started chemo. Once again, in spring 2014, the cancer roared back. Her doctors in New York, where she now was living, switched to a more aggressive chemo regimen.

"This thing is going to kill me," Joho remembered thinking. "It was eating me alive."

Genetics meets immunology

Joho began planning to move to her parents' home in suburban Philadelphia: "I thought, 'I'm dying, and I'd like to breathe fresh air and be around the green and the trees.' "

Her younger sister wasn't ready for her to give up. Jess searched for clinical trials, typing in "immunotherapy" and other terms she'd heard the doctors use. Up popped a trial at Hopkins, where doctors were testing a drug called pembrolizumab.

"Pembro" is part of a class of new medications called checkpoint inhibitors that disable the brakes that keep the immune system from attacking tumors. In September 2014, the treatment was approved by the FDA for advanced melanoma and marketed as Keytruda. The medication made headlines in 2015 when it helped treat former President Jimmy Carter for melanoma that had spread to his brain and liver. It later was cleared for several other malignancies.

Yet researchers still don't know why immunotherapy, once hailed as a game changer, works in only a minority of patients. Figuring that out is important for clinical as well as financial reasons. Keytruda, for example, costs about $150,000 a year.

By the time Joho arrived at Hopkins, the trial had been underway for a year. While an earlier study had shown a similar immunotherapy drug to be effective for a significant proportion of patients with advanced melanoma or lung or kidney cancer, checkpoint inhibitors weren't making headway with colon cancer. A single patient out of 20 had responded in a couple of trials.

Why did some tumors shrink while others didn't? What was different about the single colon cancer patient who benefited? Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Hopkins, and top researcher Suzanne Topalian took the unusual step of consulting with the cancer geneticists who worked one floor up.

"This was the first date in what became the marriage of cancer genetics and cancer immunology," Pardoll said.

In a brainstorming session, the geneticists were quick to offer their theories. They suggested that the melanoma and lung cancer patients had done best because those cancers have lots of mutations, a consequence of exposure to sunlight and cigarette smoke. The mutations produce proteins recognized by the immune system as foreign and ripe for attack, and the drug boosts the system's response.

And that one colon-cancer patient? As Vogelstein recalls, "We all said in unison, 'He must have MMR deficiency!' " because such a genetic glitch would spawn even more mutations.

When the patient's tumor tissue was tested, it was indeed positive for the defect.

The researchers decided to run a small trial, led by Hopkins immunologist Dung Le and geneticist Diaz, to determine whether the defect could predict a patient's response to immunotherapy. The pharmaceutical company Merck provided its still-experimental drug pembrolizumab. Three groups of volunteers were recruited: 10 colon cancer patients whose tumors had the genetic problem; 18 colon cancer patients without it; and 7 patients with other malignancies with the defect.

The first results, published in 2015 in the New England Journal of Medicine, were striking. Four out of the 10 colon cancer patients with the defect and 5 out of the other 7 cancer patients with the abnormality responded to the drug. In the remaining group, nothing. Since then, updated numbers have reinforced that a high proportion of patients with the genetic feature benefit from the drug, often for a lengthy period. Other trials by pharmaceutical companies have shown similar results.

The Hopkins investigators found that tumors with the defect had, on average, 1,700 mutations, compared with only 70 for tumors without the problem. That confirmed the theory that high numbers of mutations make it more likely the immune system will recognize and attack cancer if it gets assistance from immunotherapy.

For Joho, now 27 and living in suburban Philadelphia, the hard lesson from the past few years is clear: The cancer field is changing so rapidly that patients can't rely on their doctors to find them the best treatments.

"Oncologists can barely keep up," she said. "My sister found a trial I was a perfect candidate for, and my doctors didn't even know it existed."

Her first several weeks on the trial were rough, and she still has some lasting side effects today joint pain in her knees, minor nausea and fatigue.

"I have had to adapt to some new limits," she acknowledged. "But I still feel better than I have in five years."

See the original post here:
IT'S A START: Newly approved gene therapy may help 4 percent of cancer patients - Sarasota Herald-Tribune

Scientist in Baltimore has discovered a catfish gene that, when activated in a rodent brain, can sense electromagnetic fields. There are numerous animals, throughout all types and species, expect humans (supposedly), that can sense the feeble network of Earths electromagnetic global field. The glass catfish is one of those animals and Galit Pelled, the lead researcher and associate professor at John Hopkins University School of Medicine and Kennedy Kreiger Institute, plus his team are hoping its electromagnetic perceptive gene (EPG) will one day be used to manipulate heart and brain cells. This non-evasive wireless technique of controlling human cells could replace pacemakers, treat epilepsy, or even help create an interface between the human brain and a machine.

Previously, researchers discovered similar genes in bacteria and birds but those created a chemical compound responsible for sensing the magnetic fields. This recent discovery, which was presented by Pelled at the 2017 International IEEE EMBS Conference on Neural Engineering, is different since the gene works alone for function and is, therefore, simpler to manipulate.

By injecting different strands of the catfish gene into frog eggs, Pelled and his lab mates were eventually able to discover which eggs responded to magnets and which bits of DNA were responsible for the electromagnetic perception.

While Assaf Gilad, co-author of the study and an associate professor of radiology at Johns Hopkins Medicine, says We dont know exactly what the protein is doing, they do know the end result. The responsible protein adheres to a cell surface and then the cell is filled with calcium. In heart cells and neurons, a sudden flush of calcium turns the cell on, so it begins to beat or fire. By expressing the genes in a group of brain cells, and later, a living rat brain, the team of researchers could activate the neural cells with only an electromagnetic field and no other devices.

Currently, doctors are able to treat conditions such as epilepsy and depression, ailments related to misfiring neurons, using invasive deep brain stimulation. Gilad hopes that with EPGs, delivered by gene therapy or transplants, these illnesses could be eased through wireless manipulation instead. Similarly, electromagnetic genes have the likelihood to be useful for heart conditions too, replacing traditional pacemakers with a biological one made EPGs. The ability to remotely control neuronal activity is big, says Gilad. But its still in the early, experimental stages.

At the moment, researchers have only identified one part of the glass catfishs electromagnetic sensing abilities and their current focus is understanding the system in general with immediate medical applications as their goal.

More News to Read

comments

Read the original post:
Home Science Research Scientist Discovered a Catfish Gene, When activated in a Rodent Brain, Can... - TrendinTech

SUNDAY, June 4, 2017 (HealthDay News) -- A twice-daily pill could help some advanced breast cancer patients avoid or delay follow-up sessions of chemotherapy, a new clinical trial reports.

The drug olaparib (Lynparza) reduced the chances of cancer progression by about 42 percent in women with breast cancer linked to BRCA1 and BRCA2 gene mutations, according to the study.

Olaparib delayed cancer progression by about three months. The drug also caused tumors to shrink in three out of five patients who received the medication, the researchers reported.

"Clearly the drug was more effective than traditional chemotherapy," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"This is a group where a response is more difficult to obtain -- a young group with a more aggressive form of cancer -- and nonetheless we saw a close to 60 percent objective response rate," he said.

The study was funded by AstraZeneca, the maker of Lynparza.

Olaparib works by cutting off the avenues that malignant cancer cells use to stay alive, said lead researcher Dr. Mark Robson. He's a medical oncologist and clinic director of Clinical Genetics Service at Memorial Sloan Kettering Cancer Center in New York City.

The drug inhibits PARP, an enzyme that helps cells repair damaged DNA, Robson said.

Normal cells denied access to PARP will turn to the BRCA genes for help, since they also support the repair of damaged DNA, Robson said.

But that "backup capability" is not available to breast cancer cells in women with BRCA gene mutations, Robson said.

"When you inhibit PARP, the cell can't rescue itself," Robson said. "In theory, you should have a very targeted approach, one specifically directed at the cancers in people who have this particular inherited predisposition."

Olaparib already has been approved by the U.S. Food and Drug Administration for use in women with BRCA-related ovarian cancer. Robson and his colleagues figured that it also should be helpful in treating women with breast cancer linked to this genetic mutation.

The study included 302 patients who had breast cancer that had spread to other areas of their body (metastatic breast cancer). All of the women had an inherited BRCA mutation.

They were randomly assigned to either take olaparib twice a day or receive standard chemotherapy. All of the patients had received as many as two prior rounds of chemotherapy for their breast cancer. Women who had hormone receptor-positive cancer also had been given hormone therapy.

After 14 months of treatment, on average, people taking olaparib had a 42 percent lower risk of having their cancer progress compared with those who received another round of chemotherapy, Robson said.

The average time of cancer progression was about seven months with olaparib compared with 4.2 months with chemotherapy.

Tumors also shrank in about 60 percent of patients given olaparib. That compared with a 29 percent reduction for those on chemotherapy, the researchers said.

Severe side effects also were less common with olaparib. The drug's side effects bothered 37 percent of patients compared with half of those on chemo. The drug's most common side effects were nausea and anemia.

"There were fewer patients who discontinued treatment because of toxicity compared to those who received chemotherapy," Robson said. "Generally it was pretty well tolerated."

Only about 3 percent of breast cancers occur in people with BRCA1 and BRCA2 mutations, the researchers said in background notes.

Despite this, the results are "quite exciting," said Dr. Julie Fasano, an assistant professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York City.

Olaparib could wind up being used early in the treatment of metastatic breast cancer as an alternative to chemotherapy, and future studies might find that the drug is effective against other forms of breast cancer, Fasano said.

"It may be a practice-changing study, in terms of being able to postpone IV chemotherapy and its associated side effects" like hair loss and low white blood cell counts, Fasano said.

Lichtenfeld noted that olaparib also places less burden on patients.

"It may be easier for women to take two pills a day rather than go in for regular chemotherapy," Lichtenfeld said. "Clearly, this is a treatment that will garner considerable interest.

The findings were scheduled to be presented Sunday at the American Society of Clinical Oncology's annual meeting, in Chicago. The study was also published June 4 in the New England Journal of Medicine.

Read the original:
Drug Helps Fight Breast Tumors Tied to 'Cancer Genes' - The Tand D.com

An experimental cancer medicine called larotrectinib has shown promise in treating a diverse range of cancers in people young and old, researchers said at a major cancer conference in the United States.

The treatment targets a genetic abnormality which is often found in rare cancers including salivary gland cancer, juvenile breast cancer, and a soft tissue cancer known as infantile fibrosarcoma which are particularly difficult to treat. This abnormality also occurs in about 0.5% to 1% of many common cancers.

In the study released at the American Society of Clinical Oncology conference, 76% of cancer patients both children and adults with 17 different kinds of cancer responded well to the medicine.

A total of 79% were alive after one year. The study is ongoing. And 12% went into complete remission from their cancer.

The clinical trial included 55 patients 43 adults and 12 children. All had advanced cancers in various organs, including the colon, pancreas and lung, as well as melanoma.

These findings embody the original promise of precision oncology: treating a patient based on the type of mutation, regardless of where the cancer originated, said lead study author David Hyman, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York.

We believe that the dramatic response of tumours with TRK fusions to larotrectinib supports widespread genetic testing in patients with advanced cancer to see if they have this abnormality.

Researchers said 76% of cancer patients both children and adults with 17 different kinds of cancer responded well to the medicine. (Shutterstock)

Made by Loxo Oncology Inc., larotrectinib is a selective inhibitor of tropomyosin receptor kinase (TRK) fusion proteins. TRK proteins are a product of a genetic abnormality when a TRK gene in a cancer cell fuses with one of many other genes, researchers said.

The US Food and Drug Administration has not yet approved the treatment for widespread use.

The treatment was well tolerated by patients, and the most common side effects were fatigue and mild dizziness.

If approved, larotrectinib could become the first therapy of any kind to be developed and approved simultaneously in adults and children, and the first targeted therapy to be indicated for a molecular definition of cancer that spans all traditionally-defined types of tumors. said Hyman.

Follow @htlifeandstyle for more

Visit link:
New cancer medicine targets rare genetic flaw, finds study - Hindustan Times

The founding mission of MIT may seem like an unusual meal-time story for a child. But when Mark Bathe was growing up, it was a regular topic of conversation around the dinner table.

That is because Bathes father, mechanical engineer Klaus-Jrgen Bathe, was a long-standing, proud MIT faculty member, and regularly talked about MIT founder William Barton Rogers mission for the Institute.

Bathes father was a huge presence in his childhood, and his enthusiastic descriptions of MITs focus on fundamental yet hands-on science to benefit society made quite an impression on him. My father was the lens through which I saw the world, Bathe says.

So when Bathe was admitted to both MIT and another university as a senior in high school, there was little doubt in his mind as to where he would be enrolling.

Bathe joined MITs Department of Mechanical Engineering as an undergraduate, where he considers himself fortunate to have been trained in a broad and fundamental, yet problem-oriented, manner.

But with a longstanding desire to impact human health through medicine, Bathe moved on to graduate research in biomechanical engineering, in part under the stewardship of Alan Grodzinsky, a professor of biological, mechanical, and electrical engineering, and director of the MIT Center for Biomedical Engineering.

After receiving his PhD in 2004, Bathe decided to deepen his understanding of biomolecules by moving to the University of Munich in 2006, to carry out postdoctoral research in biological physics.

He then returned to MIT in 2009, joining the Department of Biological Engineering, where he established an interdisciplinary research group focused on using approaches from engineering, chemistry, physics, and computer science to understand and solve problems in applied biology.

I find the new emerging world of personalized medicine fascinating, Bathe says. In particular, the prospect of using gene-editing tools to correct disease-causing mutations that are either inherited or acquired, as well as the use of messenger RNAs to express specific proteins that are needed to alleviate disease.

Bathe, now an associate professor of biological engineering at MIT, creates a huge variety of programmed three-dimensional shapes out of single strands of synthetic DNA, a process known as DNA origami. These nanoparticles may ultimately be deployed as structural scaffolds to deliver vaccines, drugs, or even gene-editing tools such as CRISPR-Cas9 to specific parts of the body, he says.

Once delivered, the therapeutic payload could be released to edit the faulty genes that cause certain diseases.

It amazes me that with two therapeutic tools, namely CRISPR for gene editing and therapeutic messenger RNAs for protein production, we could, in principle, cure nearly any disease, potentially with minimal side-effects, but only if we can figure out how to successfully deliver these tools to act highly specifically in the target cells of interest, such as the gut, lungs, brain, or other organs, he says.

Tackling this problem can only be achieved through an interdisciplinary, long-term research effort, he believes.

Targeted therapeutic delivery is a highly interdisciplinary problem, involving everything from very applied, clinical medicine to basic macromolecular chemistry of nucleic acids and proteins, as well as the physics and engineering of macromolecular transport, Bathe says.

As a starting point, his laboratory, which includes engineers, chemists, computer scientists, and physicists, developed DAEDALUS (DNA Origami Sequence Design Algorithm for User-defined Structures), an algorithm designed to automate the process of assembling DNA nanoparticles. DAEDALUS, which takes a simple 3-D representation of the object and determines how this should be assembled from the DNA strands, can build any type of enclosed 3-D shape.

As a result, the algorithm, combined with new nucleic acid synthesis procedures, which were published in a paper in the journal Science last year, are allowing Bathe and his team to build the nanoparticles far more quickly and easily than was previously possible.

Despite decades of research into the delivery of nucleic acids and proteins, and the considerable potential for these therapeutics in clinical medicine, little progress has been made as measured by FDA-approved therapies, says Bathe. This is likely due in part to our poor understanding of macromolecular transport in the complex human anatomy, but also due to the lack of techniques available to engineer delivery tools, he says.

Were hopeful that fully synthetic, viral-like nucleic acid nanoparticles developed in our lab offer a new opportunity for the rational engineering of delivery tools for gene-centric therapies, he explains.

Working with with the Stanley Center for Psychiatric Research, Bathe and his team are also investigating novel methods of imaging patient-derived neuronal cells, in a bid to better understand how genes affect the signals sent between individual neurons in the brain.

He is also investigating the use of DNA and other molecules to store and process information, with density that is orders of magnitude higher than conventional silicon-based computing hardware.

When not in the classroom or his laboratory, Bathe takes part in a range of outdoor activities, including cycling, running, skiing, and hiking, as well as indoor swimming with MITs Masters Swim Team. He also greatly enjoys an occasional sprint triathlon on summer weekends.

My favorite weekend in the Boston area, however, is a ferry ride down to Marthas Vineyard for a bike ride around the island, ending with a swim and lobster roll by the seaside in Edgartown, he says. I cant recommend it highly enough!

Read the rest here:
Deploying therapeutic payloads to cells - MIT News

CHICAGOWhen Merck & Co.s Keytruda won approval last week to treat tumors based on a common biomarkerrather than the location in the body where the tumor originated, talk was thatthe true start of precision medicine had arrived.

The $1.3 billion market cap biotech Loxo Oncology is hoping to be a part of that journey. At the American Society of Clinical Oncology meeting Saturday, Loxo posted the latest data for its experimental larotrectinib (LOXO-101), amedicationit hopes will treat an array of cancers innearly a dozen sites across the body.

The data showed that 50 larotrectinib patients withtumors harboring tropomyosin receptor kinase (TRK) fusions had a 76% objective response rate (ORR) across tumor types. The drug met its primary endpoint; key secondary endpoints, including progression-free survival and duration of response, had not yet been reached.

The data drewfrom three trials, a phase 1 study in adults, a phase 2 study called Navigate, and a phase 1/2 pediatric trial called Scout.The results were based on the intention-to-treat principle, using the first 55 TRK fusion patients enrolled to the three trials, regardless of their prior therapy or tumor-tissue diagnostic method.

In all, 44 adults and 12 younger patients were enrolled, with tumors identified by 14 different lab tests. The TRK fusion patients carried a host of primary diagnoses, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor, infantile fibrosarcoma, lung cancer and more.

The confirmed overall response rate was 76% in 50 patients, with these rates generally consistent across tumor types, TRK gene fusions, and various diagnostic tests, Loxo said in a statement.

In the pediatric setting, larotrectinib also showed promising activity in the presurgical management of patients with infantile fibrosarcoma, with three patients treated to best response.

The drug, developed in partnership with Array Biopharma,has a breakthrough designation from the FDA to treat children and adults with metastatic or inoperable solid tumors that test positive for the TRK biomarker, and who've either failed on previous treatments or have no acceptable alternatives.

In the safety department, Loxo says that seven(13%) of the study patients had their doses reduced because of side effects, but no patients stopped taking larotrectinib after suffering side effects.

All patients whose doses were lowered experienced tumor regression, which then continued on the reduced dose. Nearly all of the dose reductions were due to infrequent neurocognitive adverse events, likely a result of on-target TRK inhibition in the [central nervous system], Loxo explained.

Loxo added that sixpatients responded to larotrectinib but later progressed, a pattern referred to as acquired resistance.

The company is gathering other evidence forlarotrectinib'sapplication for FDA approval, slated for late this year or early next. Acentral, independent radiology review will be performed in the second half of 2017, and Loxo plans to announce that data before the end of the year. A separate assessment by independent radiologists, not yet conducted, will also be required to support its regulatory filing, the companynotes.

TRK is a neuron-stimulating factor that is active in fetal development but has its expression switched off later in life. In some cases, the TRK gene can fuse with other genes and reactivate, causing various forms of cancer.

Loxo's development program for the drug is agnostic to any particular tumor type, focusing instead on recruiting patients whose cancer cells express the TRK gene. If approved, the drug could be prescribed across multiple solid tumor types on the strength of genetic testing for neurotrophic TRK (NTRK) fusion proteins, which it will do with the help of Roche.

RELATED: Merck's Keytruda wins first FDA nod to treat genetically ID'd tumors anywhere in the body

NTRK mutations crop up in a small percentage of patients with any particular cancer, but they add up. The company estimated last year that between 1,500 and 5,000 late-stage cancer patients could be eligible for treatmentin the U.S. each year, with a similar number in Europe.

[T]he larotrectinib TRK fusion story fulfills the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach," said David Hyman, lead investigator in the Navigate trial and chief of the early drug development service at Memorial Sloan Kettering Cancer Center."It is now incumbent upon the clinical oncology and pathology communities to examine our testing paradigms, so that TRK fusions and other actionable biomarkers become part of the standard patient workup."

The company also has two follow-up candidatesLOXO-292 and LOXO-195which target other cancer-causing genes resulting from fusions with kinase genes.

Original post:
Prepping for FDA filing, Loxo rolls up data on its site-agnostic cancer med larotrectinib - FierceBiotech

Carleton College will award the Bachelor of Arts degree to the 505 graduating members of the Class of 2017 onSaturday,June 10, in a ceremony beginning at 9:30 a.m. on the lawn west of Hulings Hall on the Carleton campus. A celebratory picnic on the Bald Spot will follow. In the event of severe weather, commencement will be held indoors at the Recreation Center. Seating is available to accommodate all guests, whether outdoors or indoors, and no tickets are required. The ceremony will also be broadcasted live online (https://apps.carleton.edu/events/commencement/livestream/).

Following President Steve Poskanzers opening remarks,Reina Desrouleaux '17, chemistry major from Silver Spring,Maryland (whose speech is titled [insert meaningful life experience here]) and Eli Ruffer '17, chemistry major from Highland Park, Illinois (whose speech is titled Tyler, the Prospective Student)will address the Class of 2017, families and friends, and faculty. In additionally, Carleton College will confer an honorary doctorate upon Kathy L. Hudson 82, former Deputy Director for Science, Outreach, and Policy at the National Institutes of Health, who will briefly address the class.

The highest honor given by the College, conferred honoris causafor the sake of honorthis years honorary degree recipient is Dr. Kathy L. Hudson, former Deputy Director for Science, Outreach, and Policy at the National Institutes of Health (NIH).

Throughout her distinguished career, Hudson has served the public by ensuring that advances in genomics and other rapidly moving areas of medical research are paired with wise and effective public policies.

After earning a B.A. in biology from Carleton College and a M.S. in microbiology from the University of Chicago, Hudson obtained her Ph.D. in molecular biology from the University of California, Berkeley. Although she trained for a career in research, Hudson discovered that her real passion was science policy. As an American Association for the Advancement of Science (AAAS) Fellow in Washington DC, she worked for the U.S. House of Representatives and then the Congressional Office of Technology Assessment.

After a stint in the office of the Assistant Secretary for Health at the Department of Health and Human Services, Hudson joined the National Human Genome Research Institute (NHGRI) as assistant director. While there she made a compelling case to scientists, public policy experts, and lawmakers about the need for federal legislation to guard against genetic discrimination. She also helped to broker an historic agreement between the public and private human genome projects, which was announced by President Bill Clinton in the White House in 2000.

In 2002, Hudson left NHGRI to found and direct the Genetics and Public Policy Center at Johns Hopkins University. She became a leader in educating and advising about science and policy issues in genetics. Also at Hopkins, Hudson was an Associate Professor in the Institute of Bioethics and the Institute of Genetic Medicine. It was Hudson who did much of the work to assemble the talented and dedicated team that, in 2008 after years of effort, achieved passage of the landmark Genetic Information Nondiscrimination Act.

In 2009, Hudson returned to the National Institutes of Health, becoming the Deputy Director for Science, Outreach, and Policy. In that capacity helped found and launch the National Center for Advancing Translational Sciences. She also had a major hand in the design and launch of three national scientific projects the BRAIN Initiative, the Precision Medicine Initiative, and the Cancer Moonshot. In addition, she led efforts to revise the rules that govern participation of human subjects in research, modernize clinical trial reporting, expand scientific data sharing, and develop appropriate oversight for rapidly moving areas of medical research, including stem cells and gene editing.

On top of her many duties and responsibilities, Hudson made time to serve as a strong and tireless advocate for the role of women in science. She personally mentored a group of young women who are now moving into key leadership roles with a wide range of innovative biomedical research and policy initiatives.

Earlier this year Hudson left government service, and is working as an advisor to companies and research institutes as they forge new directions at the forefront of biomedical research.

For further information, including disability accommodations, contact the Carleton College Office of College Communications at(507) 222-4309or emailkraadt@carleton.edu. The commencement site is located on the Carleton campus between College and Winona Streets in Northfield.

Read the original here:
Carleton College to hold its 143rd Commencement Ceremony June 10 - Carleton College News

Hillsboro native Dr. Nancy J. Cox was honored this spring as the first recipient of the Richard M. Caprioli Research Award. Dr. Cox is currently the director of the Vanderbilt Genetics Institute in Nashville, TN.

The daughter of the late Gene and Helen Cox, she is a 1974 graduate of Hillsboro High School and was selected as the second Hillsboro Education Foundation Distinguished Alumni Award recipient in 2002.

Dr. Cox earned her bachelor of science degree in biology from the University of Notre Dame in 1978 and her doctorate in human genetics from Yale University in 1982.

She completed a postdoctoral fellowship in genetic epidemiology at Washington University and was a research associate in human genetics at the University of Pennsylvania.

In 1987, she was hired at the University of Chicago. She was appointed full professor in the departments of medicine and human genetics in 2004 and chief of the section of genetic medicine the following year.

In 2012, she was named a University of Chicago Pritzker Scholar. In 2015, Dr. Cox was hired at Vanderbilt University School of Medicine as the Mary Phillips Edmonds Gray Professor of Genetics, founding director of the Vanderbilt Genetics Institute and director of the Division of Genetic Medicine in the Department of Medicine. She is a fellow of the American Association for the Advancement of Science

Throughout her career as a quantitative geneticist, Dr. Cox has sought to identify and characterize the genetic component to common human diseases and clinical phenotypes like pharmacogenomics traits (how genes affect drug response).

Her work has advanced methods for analyzing genetic and genomic data from a wide range of complex traits and diseases, including breast cancer, diabetes, autism, schizophrenia, bipolar disorder, Tourette syndrome, obsessive-compulsive disorder, stuttering and speech and language impairment.

Through the national Genotype Tissue Expression (GTEx) project, Dr. Cox also contributed to the development of genome predictors of the expression of genes, and she also has investigated the genetics of cardiometabolic phenotypes such as lipids, diabetes and cardiovascular disease.

With colleagues at the University of Michigan, Dr. Cox is generating content for the Accelerating Medicine Partnership between the National Institutes of Health (NIH), U.S. Food and Drug Administration, biopharmaceutical companies and non-profit organizations. The goal of the partnership is to identify and validate promising biological targets, increase the number of new diagnostics and therapies for patients, and reduce the cost and time it takes to develop them.

Dr. Cox is co-principal investigator of an analytic center within the Centers for Common Disease Genomics, another NIH initiative that is using genome sequencing to explore the genomic contributions to common diseases such as heart disease, diabetes, stroke and autism. A major resource for the Cox lab is Vanderbilts massive biobank, BioVU, which contains DNA samples from more than 230,000 individuals that are linked to de-identified electronic health records.

Dr. Cox is the author or co-author of more than 300 peer-reviewed scientific articles. She is former editor-in-chief of the journal Genetic Epidemiology, and is the current president of the American Society of Human Genetics.

For developing new methods that have aided researchers worldwide in identifying and characterizing of the genetic and genomic underpinnings of diseases and complex traits, Dr. Cox is the first recipient of the inaugural Richard M. Caprioli Research Award.

Dr. Cox and her husband, Dr. Paul Epstein live in Nashville, TN, and have two grown daughters, Bonnie Epstein and Carrie Epstein.

Read the original post:
Hillsboro Native Earns Honors At Vanderbilt - thejournal-news.net

June 1, 2017 This microscopic image of fibroblast cells shows the induction of cell fusion by a newly described gene and its protein, called myomerger. Multi-nucleus cells expressing genes needed to form skeletal muscle can be seen in flower-like clumps forming as cells fuse together. Reporting results in Nature Communications, the researchers seek ways to develop regenerative therapies for muscle disorders by getting stem cells to fuse and form functioning skeletal muscle tissues. Credit: Cincinnati Children's

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature Communications reports scientists identify a new gene essential to this process, shedding new light on possible new therapeutic strategies.

Led by researchers at the Cincinnati Children's Hospital Medical Center Heart Institute, the study demonstrates the gene Gm7325 and its protein - which the scientists named "myomerger" - prompt muscle stem cells to fuse and develop skeletal muscles the body needs to move and survive. They also show that myomerger works with another gene, Tmem8c, and its associated protein "myomaker" to fuse cells that normally would not.

In laboratory tests on embryonic mice engineered to not express myomerger in skeletal muscle, the animals did not develop enough muscle fiber to live.

"These findings stimulate new avenues for cell therapy approaches for regenerative medicine," said Douglas Millay, PhD, study senior investigator and a scientist in the Division of Molecular Cardiovascular Biology at Cincinnati Children's. "This includes the potential for cells expressing myomaker and myomerger to be loaded with therapeutic material and then fused to diseased tissue. An example would be muscular dystrophy, which is a devastating genetic muscle disease. The fusion technology possibly could be harnessed to provide muscle cells with a normal copy of the missing gene."

Bio-Pioneering in Reverse

One of the molecular mysteries hindering development of regenerative therapy for muscles is uncovering the precise genetic and molecular processes that cause skeletal muscle stem cells (called myoblasts) to fuse and form the striated muscle fibers that allow movement. Millay and his colleagues are identifying, deconstructing and analyzing these processes to search for new therapeutic clues.

Genetic degenerative disorders of the muscle number in the dozens, but are rare in the overall population, according to the National Institutes of Health. The major categories of these devastating wasting diseases include: muscular dystrophy, congenital myopathy and metabolic myopathy. Muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. The most common form is Duchenne MD.

Molecular Sleuthing

A previous study authored by Millay in 2014 identified myomaker and its gene through bioinformatic analysis. Myomaker is also required for myoblast stem cells to fuse. However, it was clear from that work that myomaker did not work alone and needed a partner to drive the fusion process. The current study indicates that myomerger is the missing link for fusion, and that both genes are absolutely required for fusion to occur, according to the researchers.

To find additional genes that regulate fusion, Millay's team screened for those activated by expression of a protein called MyoD, which is the primary initiator of the all the genes that make muscle. The team focused on the top 100 genes induced by MyoD (including GM7325/myomerger) and designed a screen to test the factors that could function within and across cell membranes. They also looked for genes not previously studied for having a role in fusing muscle stem cells. These analyses eventually pointed to a previously uncharacterized gene listed in the database - Gm7325.

Researchers then tested cell cultures and mouse models by using a gene editing process called CRISPR-Cas9 to demonstrate how the presence or absence of myomaker and myomerger - both individually and in unison - affect cell fusion and muscle formation. These tests indicate that myomerger-deficient muscle cells called myocytes differentiate and form the contractile unit of muscle (sarcomeres), but they do not join together to form fully functioning muscle tissue.

Looking Ahead

The researchers are building on their current findings, which they say establishes a system for reconstituting cell fusion in mammalian cells, a feat not yet achieved by biomedical science.

For example, beyond the cell fusion effects of myomaker and myomerger, it isn't known how myomaker or myomerger induce cell membrane fusion. Knowing these details would be crucial to developing potential therapeutic strategies in the future, according to Millay. This study identifies myomerger as a fundmentally required protein for muscle development using cell culture and laboratory mouse models.

The authors emphasize that extensive additional research will be required to determine if these results can be translated to a clinical setting.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Nature Communications (2017). DOI: 10.1038/NCOMMS15665

Adding just the right mixture of signaling moleculesproteins involved in developmentto human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

A team led by Jean-Franois Ct, researcher at the IRCM, identified a ''conductor'' in the development of muscle tissue. The discovery, published online yesterday by the scientific journal Proceedings of the National ...

Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant ...

Johns Hopkins researchers report they have inadvertently found a way to make human muscle cells bearing genetic mutations from people with Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy is a chronic disease causing severe muscle degeneration that is ultimately fatal. As the disease progresses, muscle precursor cells lose the ability to create new musclar tissue, leading to faster ...

Researchers at Sanford Burnham Prebys Medical Research Institute (SBP) have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting ...

A University of California, Berkeley, study of mice reveals, for the first time, how puberty hormones might impede some aspects of flexible youthful learning.

The bacteria in a child's gut appears to be influenced as early as its first year by ethnicity and breastfeeding, according to a new study from McMaster University.

The human body runs according to a roughly 24-hour cycle, controlled by a "master" clock in the brain and peripheral clocks in other parts of the body that are synchronized according to external cues, including light. Now, ...

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature ...

Cholesterol, a naturally occurring compound at the lung surface, has been shown to have a clear effect on the properties of this nanoscale film that covers the inside of our lungs. Cholesterol levels in this system may affect ...

Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Link:
One gene closer to regenerative therapy for muscular disorders - Medical Xpress

Paul Cerrato says he first started researching precision medicine almost 30 years ago.

"Back then it wasn't called precision medicine, but when I was in graduate school I did my final master's thesis on 'biochemical individuality' that was the buzzword," said Cerrato, a healthcare journalist. "That was the beginnings of the thinking about personalizing care: trying to understand how each human body is different before they can figure out how to treat individuals."

Fast forward three decades and the excitement around precision medicine seems to finallybe at a tipping point thanks to maturing technology, more cost-effective gene sequencing and momentum-building federal projects such as the Precision Medicine Initiative and the Cancer Moonshot.

[Also:How Penn Medicine primed its IT infrastructure for precision medicine]

But the obstacles are also substantial from the high cost of drugs for precision oncology, lack of widespread interoperability, skepticism on the part of some clinicians and challenges related to patient engagement.

At the Healthcare IT News Precision Medicine Summit in Boston on June 12, Cerrato, along with Beth Israel Deaconess Medical Center CIO John Halamka, MD, will discuss the obstacles and opportunities facing personalized medicine.

Halamka knows well about the opportunities. And not just because he's a renowned expert on health information technology. His wife, Kathy, was successfully treated for breast cancer with help from some sophisticated precision medicine tools and techniques.

Cerrato and Halamka just finished a book together, Realizing the Promise of Precision Medicine, due to be published by Elsevier in October. In it, they offer some insights into Kathy's treatment, but focus more generally on the transformative potential of personalized care, exploring the role of electronic health records, patient-facing mobile apps, health information exchange and more.

They're hopeful about the future. But cognizant that some substantial hurdles will need to be overcome along the way.

"When we were researching the book there was a lot of positive data, but also quite a bit of skepticism, and criticism of the whole concept that precision medicine should have such an important role in patient care," said Cerrato.

One of the central goals of their book, and their talk in Boston this month, is to counter the misapprehension of many clinicians that precision medicine has limited applications in the real-world care settings.

For instance, he said, many physicians argue: "'Personalized medicine? We already do that. We don't need to spend another $200 or $300 million on a precision medicine initiative because we already provide personalized care on a daily basis.'

"Of course, the answer to that is, that's personalized care with a lower-case P," said Cerrato. "We're talking about something much more sophisticated and much more involved: genomics and microbiome and lots of other risk factors. The average doc might be personalizing medicine by switching from one antibiotic to another, or asking patients if they have liver disease before they decide to use a statin, or those kinds of things. That's personalization, but those are the baby steps."

Another objection has less to do with changing culture and mindset and more to do with financial realities, he said. And this one in the near term, at least has some merit.

"The second obstacle we're dealing with is the objection of some thought leaders in clinical medicine that precision medicine will simply cost too much," said Cerrato. "There's some substance to that objection. You look at the cost of precision medicine drugs that have been coming out the past couple years they're really astronomical. And the return on investment, very often, is limited, especially in cancer care," where hugely expensive drugs are sometimes only able to prolong life for a few months or a year.

"It's a work in progress," he said. "We don't have a simple answer to that. But we've got to put it out there. One of the reasons we want to give a presentation like this and write a book like this is we want to convince docs in the trenches, and thought leaders in clinical care, that precision medicine really is a model they should be following. In order to do that, we really should be up front about their criticisms. We have to address them directly."

Another common concern is that "physicians' workloads would be greatly increased if they had to start practicing precision medicine on a daily basis," said Cerrato. "You're talking about mountains and mountains of information. How do you translate that so a physician who only has 15 minutes with a patient can use that in daily care?"

Again, not an unreasonable point to make. Gene sequencing is still pretty expensive, too. But even if it cost a dollar, the average primary care physician does not know how to interpret genomic data."

Technology also poses big challenges, especially while interoperability remains elusive. "Without interoperability, precision medicine is really not going to get too far."

EHRs too are lagging badly in their ability to handle data-intensive genomics. "Right now we're not at the stage where a physician can just open up his electronic health record and say 'OK, what does this patient's gene sequencing look like?' We're not there yet."

But there are big reasons for optimism, too. As Halamka said, Kathy's treatment benefited greatly from technologies such as Clinical Query 2, software at Beth Israel Deaconess that allows physicians to see anonymized health records of cohorts of patients, tailored by different demographic and clinical parameters.

"It looks at all the patients who have had similar signs and symptoms and lab values and shows what were the treatment recommendations for those patients," said Cerrato. "It allowed the oncology team to individualize the care for Kathy so it would meet her needs, while eliminating the possibility of her getting treated with a protocol that would do more harm than good."

Most precision medicine and genomics work is still being done at advanced academic medical centers such as BIDMC, of course.

But on a smaller scale, there's still big promise for other types of personalized treatments.

"There are certain aspects of the field that are already happening right now. Especially in the field of diabetes, there's enough out there in terms of mobile apps and other digital tools, that is allowing physicians who are interested to practice precision medicine today," said Cerrato.

"Scripps has come out with an app for asthmatics, and it does a lot of the heavy lifting for clinicians by allowing patents to put in some basic parameters about their peak flow readings and their medication use and a few other things," he added. "When a doc uses that for the asthmatic patient, they don't have to do all the work. The technology of the app will do it for them. It has built-in decision trees to help them make better decisions on a personalized basis."

The bottom line, said Cerrato, is that there are some aspects of precision medicine that are working for some docs now and there are some aspects that remain in the future either because they're not educated enough to know how to do it, or the clinical data is not there yet."

How long it takes for genomics and personalized treatments to become commonplace still depends on the answers to a host of clinical, financial, technological and cultural questions, he said, but "I do think it will be the standard of care in the future."

Twitter:@MikeMiliardHITN Email the writer: mike.miliard@himssmedia.com

Like Healthcare IT News on Facebook and LinkedIn

See the article here:
Promise of precision medicine depends on overcoming big obstacles - Healthcare IT News