Category Archives: Gene Medicine

8 October 2007

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2007 jointly to

Mario R. Capecchi, Martin J. Evans and Oliver Smithies

for their discoveries of "principles for introducing specific gene modifications in mice by the use of embryonic stem cells"

This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine from basic research to the development of new therapies.

Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make "knockout mice" for all genes available within the near future.

With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.

Information about the development and function of our bodies throughout life is carried within the DNA. Our DNA is packaged in chromosomes, which occur in pairs one inherited from the father and one from the mother. Exchange of DNA sequences within such chromosome pairs increases genetic variation in the population and occurs by a process called homologous recombination. This process is conserved throughout evolution and was demonstrated in bacteria more than 50 years ago by the 1958 Nobel Laureate Joshua Lederberg.

Mario Capecchi and Oliver Smithies both had the vision that homologous recombination could be used to specifically modify genes in mammalian cells and they worked consistently towards this goal.

Capecchi demonstrated that homologous recombination could take place between introduced DNA and the chromosomes in mammalian cells. He showed that defective genes could be repaired by homologous recombination with the incoming DNA. Smithies initially tried to repair mutated genes in human cells. He thought that certain inherited blood diseases could be treated by correcting the disease-causing mutations in bone marrow stem cells. In these attempts Smithies discovered that endogenous genes could be targeted irrespective of their activity. This suggested that all genes may be accessible to modification by homologous recombination.

The cell types initially studied by Capecchi and Smithies could not be used to create gene-targeted animals. This required another type of cell, one which could give rise to germ cells. Only then could the DNA modifications be inherited.

Martin Evans had worked with mouse embryonal carcinoma (EC) cells, which although they came from tumors could give rise to almost any cell type. He had the vision to use EC cells as vehicles to introduce genetic material into the mouse germ line. His attempts were initially unsuccessful because EC cells carried abnormal chromosomes and could not therefore contribute to germ cell formation. Looking for alternatives Evans discovered that chromosomally normal cell cultures could be established directly from early mouse embryos. These cells are now referred to as embryonic stem (ES) cells.

The next step was to show that ES cells could contribute to the germ line (see Figure). Embryos from one mouse strain were injected with ES cells from another mouse strain. These mosaic embryos (i.e. composed of cells from both strains) were then carried to term by surrogate mothers. The mosaic offspring was subsequently mated, and the presence of ES cell-derived genes detected in the pups. These genes would now be inherited according to Mendels laws.

Evans now began to modify the ES cells genetically and for this purpose chose retroviruses, which integrate their genes into the chromosomes. He demonstrated transfer of such retroviral DNA from ES cells, through mosaic mice, into the mouse germ line. Evans had used the ES cells to generate mice that carried new genetic material.

By 1986 all the pieces were at hand to begin generating the first gene targeted ES cells. Capecchi and Smithies had demonstrated that genes could be targeted by homologous recombination in cultured cells, and Evans had contributed the necessary vehicle to the mouse germ line the ES-cells. The next step was to combine the two.

For their initial experiments both Smithies and Capecchi chose a gene (hprt) that was easily identified. This gene is involved in a rare inherited human disease (Lesch-Nyhan syndrome). Capecchi refined the strategies for targeting genes and developed a new method (positive-negative selection, see Figure) that could be generally applied.

The first reports in which homologous recombination in ES cells was used to generate gene-targeted mice were published in 1989. Since then, the number of reported knockout mouse strains has risen exponentially. Gene targeting has developed into a highly versatile technology. It is now possible to introduce mutations that can be activated at specific time points, or in specific cells or organs, both during development and in the adult animal.

Almost every aspect of mammalian physiology can be studied by gene targeting. We have consequently witnessed an explosion of research activities applying the technology. Gene targeting has now been used by so many research groups and in so many contexts that it is impossible to make a brief summary of the results. Some of the later contributions of this year's Nobel Laureates are presented below.

Gene targeting has helped us understand the roles of many hundreds of genes in mammalian fetal development. Capecchis research has uncovered the roles of genes involved in mammalian organ development and in the establishment of the body plan. His work has shed light on the causes of several human inborn malformations.

Evans applied gene targeting to develop mouse models for human diseases. He developed several models for the inherited human disease cystic fibrosis and has used these models to study disease mechanisms and to test the effects of gene therapy.

Smithies also used gene targeting to develop mouse models for inherited diseases such as cystic fibrosis and the blood disease thalassemia. He has also developed numerous mouse models for common human diseases such as hypertension and atherosclerosis.

In summary, gene targeting in mice has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come.

Mario R. Capecchi, born 1937 in Italy, US citizen, PhD in Biophysics 1967, Harvard University, Cambridge, MA, USA. Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT, USA.

Sir Martin J. Evans, born 1941 in Great Britain, British citizen, PhD in Anatomy and Embryology 1969, University College, London, UK. Director of the School of Biosciences and Professor of Mammalian Genetics, Cardiff University, UK.

Oliver Smithies, born 1925 in Great Britain, US citizen, PhD in Biochemistry 1951, Oxford University, UK. Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.

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To cite this page MLA style: "The 2007 Nobel Prize in Physiology or Medicine - Press Release". Nobelprize.org. Nobel Media AB 2014. Web. 1 May 2017. <http://www.nobelprize.org/nobel_prizes/medicine/laureates/2007/press.html>

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The 2007 Nobel Prize in Physiology or Medicine - Press Release

Researchers from RCSI (Royal College of Surgeons in Ireland) and the University of Nice, France, may have discovered a gene, KCNQ1, that is associated with the survival of patients who have colon cancer.

The gene creates pore-forming proteins in cell membranes, known as ion channels. This could be an important breakthrough in the development of increasingly effective colon cancer therapies and new diagnostics that will provide an improved accuracy in the prognosis for colon cancer patients.

The research team, led by Professor Brian Harvey, Department of Molecular Medicine, RCSI, published their findings in the journal Proceedings of the National Academy of Sciences of the USA (PNAS). They identified the molecular mechanisms by which the KCNQ1 gene suppresses both the growth and spread of colon cancer cells.The gene functions by producing an ion channel protein, trapping a tumour promoting protein (beta-catenin) in the cell membranes before it can enter the nucleus of the cell to cause the growth of more cancer cells.

In over 300 colon cancer patients, those who had higher expressions of the KCNQ1 gene were found not only to have a longer survival but also less chance of relapse. Commenting on the significance of the discovery, Professor Harvey said:

It could open up the possibility of developing new drug treatments that will be able harness the suppressive properties of the gene to target the colon specifically, without exposing other tissues in the body to unnecessary chemotherapy. The development of more targeted treatments for colon cancer is vital to improve the prognosis and quality of life for colon cancer patients.In Ireland, bowel cancer is the second most common cause of cancer death as almost 2,500 Irish people are diagnosed with the cancer annually.

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RCSI scientists discover gene that blocks spread of colon cancer - Irish Medical News

THURSDAY, April 27, 2017 (HealthDay News) -- Even if obesity is "in your genes," regular exercise can help keep extra pounds at bay, a new study suggests.

Researchers found that when people carried a particular gene variant that raises obesity risk, regular exercise seemed to reduce the effects of their DNA -- by about one-third.

The gene in question is known as FTO. Studies show that people with a particular variant of the gene have a heightened risk of obesity.

But the gene's effects are not huge, or written in stone. Research has found that people who carry two copies of the FTO variant (one inherited from each parent) weigh about 6.5 pounds more than non-carriers, on average.

The new findings underscore one way to counter the gene's impact: Exercise.

"There are genes that appear to directly impact weight, but the effects are small," said lead researcher Mariaelisa Graff, of the University of North Carolina at Chapel Hill. "You still have a lot of choice over your behavior."

The study results are not exactly surprising, according to Dr. Timothy Church, an obesity researcher who was not involved in the work.

"This shows, once again, that genes are not your destiny," said Church. He is a professor of preventative medicine at Louisiana State University's Pennington Biomedical Research Center.

Church said regular exercise is particularly key in preventing excess weight gain in the first place -- and in keeping the pounds off after someone loses weight.

Exercise is less effective in helping obese people shed weight, Church said. Diet changes are the critical step there.

But the bottom line is that exercise matters, regardless of your genes, according to Dr. Chip Lavie, of the John Ochsner Heart and Vascular Institute, in New Orleans.

Lavie, who was not involved in the study, pointed to findings from his own research.

"[We] have published data that suggests the main cause of increasing obesity over the past five decades is the dramatic decline in physical activity," he said.

Gym memberships aside, Americans these days are less active at work, at home (through housework) and during leisure time, according to Lavie.

And the benefits of exercise go beyond weight control, he stressed. Physical activity boosts people's fitness levels -- which, Lavie said, is critical in preventing heart disease and living a longer, healthier life.

The new findings are based on over 200,000 adults, mostly of European descent, who'd taken part in previous health studies.

Graff and her colleagues analyzed information on their weight and exercise habits, and looked at how those factors "interacted" with 2.5 million gene variants.

FTO is the gene that is most strongly linked to obesity, Graff said.

And overall, her team found, active people who carried the obesity-linked FTO variant appeared more resistant to its effects than sedentary people.

On average, exercise weakened the variant's effects by about 30 percent, the researchers reported in the April 27 issue of PLOS Genetics.

There were some hints that exercise also affected some other weight-related genes. But the only clear relationship was with the FTO variant, according to Graff.

That, she noted, could be related to the broad way the study looked at exercise. The 23 percent of people who were least active were considered "inactive," while everyone else was deemed "active."

Church said he thinks research into the genetics of body weight will increasingly become useful.

If certain gene variants affect people's response to a low-carb diet or aerobic exercise, for example, that could help in "tailoring" weight-loss plans, he suggested.

"The science is rapidly evolving," Church said, "and there's still a lot to learn. But I think that's the direction this is going."

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No Excuses: Exercise Can Overcome the 'Obesity Gene' - Glens Falls Post-Star

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Goal is vaccine that targets inflammation in joints

Using CRISPR technology, a team of researchers led by Farshid Guilak, PhD, at Washington University School of Medicine in St. Louis, rewired stem cells' genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter inflammation. The technique eventually could act as a vaccine for arthritis and other chronic conditions.

Using new gene-editing technology, researchers have rewired mouse stem cells to fight inflammation caused by arthritis and other chronic conditions. Such stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy),develop into cartilage cells that produce a biologic anti-inflammatory drug that, ideally, will replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation.

The cells were developed at Washington University School of Medicine in St. Louis and Shriners Hospitals for Children-St. Louis, in collaboration with investigators at Duke University and Cytex Therapeutics Inc., both in Durham, N.C. The researchers initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation.

The research is availableonline April 27 in the journal Stem Cell Reports.

Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed, said Farshid Guilak, PhD, the papers senior author and a professor of orthopedic surgery at Washington University School of Medicine. To do this, we needed to create a smart cell.

Many current drugs used to treat arthritis including Enbrel, Humira and Remicade attack an inflammation-promoting molecule called tumor necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, said Guilak, also a professor of developmental biology and of biomedical engineering and co-director of Washington Universitys Center of Regenerative Medicine. If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint.

As part of the study, Guilak and his colleagues grew mouse stem cells in a test tube and then used CRISPR technology to replace a critical mediator of inflammation with a TNF-alpha inhibitor.

Exploiting tools from synthetic biology, we found we could re-code the program that stem cells use to orchestrate their response to inflammation, said Jonathan Brunger, PhD, the papers first author and a postdoctoral fellow in cellular and molecular pharmacology at the University of California, San Francisco.

Over the course of a few days, the team directed the modified stem cells to grow into cartilage cells and produce cartilage tissue. Further experiments by the team showed that the engineered cartilage was protected from inflammation.

We hijacked an inflammatory pathway to create cells that produced a protective drug, Brunger said.

The researchers also encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, Guilaks team has begun testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drug the TNF-alpha inhibitor that would protect the synthetic cartilage cells that Guilaks team created and the natural cartilage cells in specific joints.

When these cells see TNF-alpha, they rapidly activate a therapy that reduces inflammation, Guilak explained. We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, its possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders.

With an eye toward further applications of this approach, Brunger added, The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine.

Brunger JM, Zutshi A, Willard VP, Gersbach CA, Guilak F. Genome engineering of stem cells for autonomously regulated, closed-loop delivery of biologic drugs. Stem Cell Reports. April 27, 2017.

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health (NIH), grant numbers AR061042, AR50245, AR46652, AR48182, AR067467, AR065956, AG15768, OD008586. Additional funding provided by the Nancy Taylor Foundation for Chronic Diseases; the Arthritis Foundation; the National Science Foundation (NSF), CAREER award number CBET-1151035; and the Collaborative Research Center of the AO Foundation, Davos, Switzerland.

Authors Farshid Guilak, and Vincent Willard have a financial interest in Cytex Therapeutics of Durham, N.C., which may choose to license this technology. Cytex is a startup founded by some of the investigators. They could realize financial gain if the technology eventually is approved for clinical use.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Stem cells edited to fight arthritis - Washington University School of Medicine in St. Louis

Doctors have long known that genetics can predispose some people to gain weight despite a healthy lifestyle while others seemingly never gain an ounce no matter how much they eat. A new study sheds light on how people can counteract their genetic makeup, even if it's in their DNA to put on more weight than others.

Researchers from University of North Carolina Chapel Hill, the University of Copenhagen and other institutions conducted a meta-analysis examining 60 past genetic studies to see if physical activity could mitigate the effects a genetic predisposition to weight gain.

"Decline in daily physical activity is thought to be a key contributor to the global obesity epidemic," the authors wrote. However, they explained that genetic make-up may also play a role in weight gain for people who are not physically active.

They screened for 2.5 million genetic variants in 200,452 adults and also separated the subjects between those who were physically active -- about 77 percent -- and those who were physically inactive, about 23 percent. The researchers then looked at different markers that would indicate if a person was overweight including their body-mass index, waist circumference and hip-to-waist ratio.

They found those with a genetic variation that predisposed them to gain weight -- called an FTO gene -- had the ability counteract the effects that gene through exercise. By looking at the data they found that those with the FTO gene who were physically active were able to reduce the weight-gain effects associated with the gene by about 30 percent.

Dr. Goutham Rao, chairman of Family Medicine and Community Health at University Hospitals Cleveland Medical Center, said this type of research is key in helping patients better understand their weight and health.

"Despite that sort of bad luck of having a genetic predisposition to obesity if you are physically active ... you're not going to reduce risk of obesity entirely but you reduce it significantly," Rao said.

The mechanism that leads to people with FTO to be predisposed to gain weight is still not fully understood, but Rao said it's key to give people encouragement that taking healthy steps has an effect even if they haven't reached their goal weight.

"The message is to be sympathetic," Rao said. Explaining he tells frustrated patients, "if you weren't doing your best you would weigh a lot more and be much less healthy."

Dr. Kevin Niswender, associate professor of medicine, molecular physiology and biophysics at Vanderbilt University Medical Center, said the study took on the "really interesting question" of if people can counteract their genetics through their lifestyle.

"This study definitively confirms that lifestyle has an impact," he said.

During their research the team also discovered 11 new genetic variants that likely predispose a person to weight gain and they said more may be found through similar studies.

"In future studies, accounting for physical activity and other important lifestyle factors could boost the search for new obesity genes," said Mariaelisa Graff of the University of North Carolina at Chapel Hill, the lead author of the study. "To identify more genes whose effects are either dampened or amplified by physical activity, we need to carry out larger studies with more accurate measurement of physical levels."

Niswender said finding new variants that indicate predisposition for weight gain can help give a better understanding of the complex mechanisms behind obesity.

"For a long time we've been searching for this gene, the gene that causes obesity and it's just not like that," Niswender."there are a bunch of genes that cause obesity and the effect of each gene variant is really quite small."

Graff said more study should need to be done to get more accurate measurements of the participants' physical activity. The researchers classified those as having a sedentary job, commute and leisure time as "inactive" while everyone else was declared physically active. Additionally, the study was done primarily in people of European descent, so the findings may not be be easily extrapolated to other groups.

Continued here:
Exercise can help offset effects of 'fat gene,' study finds - ABC News

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April 25, 2017 -A team from the University of Virginia School of Medicine has developed a quicker way to examine the impact of gene mutation on patient health, potentially changing the way cancer labs conduct research into precision medicine and personalized therapies.

The methodology, which uses a virus similar to HIV to replace normal genes with specific mutations, may even be speedier and more cost effective than the CRISPR gene editing technology that currently forms the basis for much of the industrys cutting-edge genomics work.

"Every patient shouldn't receive the same treatment. No way. Not even if they have the same syndrome, the same disease," said UVA researcher J. Julius Zhu, PhD, who led the team that created the new technique. "It's very individual in the patient, and they have to be treated in different ways."

The process of understanding and testing a specific mutations impact on disease development and the usefulness of particular therapies has thus far been slow and painful, said Zhu, who holds positions in UVA's Department of Pharmacology and the UVA Cancer Center.

"You can do one gene and one mutation at a time, he said. Even with the CRISPR [gene editing] technology we have now, it still costs a huge amount of money and time and most labs cannot do it, so we wanted to develop something simple every lab can do. No other approach is so efficient and fast right now.

In addition to ramping up the velocity of studying gene mutations, the new approach may be able to reduce failures in the research process by giving researchers a more sensitive, targeted way to stimulate gene activity.

"The problem in the cancer field is that they have many high-profile papers of clinical trials [that] all failed in some way," Zhu said. "We wondered why in these patients sometimes it doesn't work, that with the same drug some patients are getting better and some are getting worse. The reason is that you don't know which drugs are going to help with their particular mutation. So that would be true precision medicine: You have the same condition, the same syndrome, but a different mutation, so you have to use different drugs."

Zhu has already used the method to analyze approximately 50 mutation of the BRaf gene, which has been tied to tumor development and certain neurodevelopmental disorders. He envisions that the technique will also help unlock the secrets of other diseases, such as Alzheimers, cystic fibrosis, and a variety of cancers all of which are top priorities for precision medicine researchers.

As the marketplace for targeted therapies and associated precision medicine technologies approaches the $100 billion mark, techniques that can help cancer researchers accelerate the development of new treatments will continue to be in high demand.

Drastically reducing the time from hypothesis to bedside will likely produce financial benefits for research labs as well as clinical benefits for patients.

You'd need to spend 10 years to do what we are doing in three months, so it's an entirely different scale, said Zhu. Now, hopefully, we can do 40 or 100 of them simultaneously."

Continue reading here:
UVA Gene Mutation Research Method Speeds Precision Medicine - Health IT Analytics

Elizabeth McNally, MD, PhD, director of the Center for Genetic Medicine, delivered the keynote address at Computational Research Day, on human genome sequencing.

Northwesterns 4th Annual Computational Research Day brought together more than 350 faculty members and students to showcase innovative research projects, share recent insights and tools, and strengthen the computational research community throughout the university.

The event, co-sponsored by Feinberg and hosted by Northwestern Information Technology on the Evanston campus, featured presentations, a poster competition, workshops, software demos and group discussions, all centered on leveraging computational methods to answer complex research questions.

Rex Chisholm, PhD, vice dean of Scientific Affairs and Graduate Education, kicked off the conference with an opening address discussing the Northwestern Medicine Enterprise Data Warehouse, which currently holds more than 40 terabytes of clinical and research data.

We are in a completely different world today, where instead of paper records, everybodys health is now captured in an electronic record, said Chisholm, also the Adam and Richard T. Lind Professor of Medical Genetics. The ability to put that data together in a single place and start to think about big data approaches to identifying patterns in that collection of data is a major game-changer.

Chisholm also spoke about the opportunity for merging such health information with data from the NUgene Project, a genomic biobank sponsored by the Center for Genetic Medicine, which has so far sequenced the genomes of more than 1,000 participants. What we really want to do is combine that 100 terabytes of human sequence data with that 40 terabytes of phenotypic data and do an all-by-all comparison, Chisholm said. Its a classic example of a big data opportunity. And its certain that this approach once we figure out how to do it is going to completely revolutionize how we think about disease: how we think about treatment of disease, how we diagnose disease, and how we actually help people prevent disease.

Elizabeth McNally, MD, PhD, director of the Center for Genetic Medicine, delivered a keynote address on human genome sequencing and echoed the opportunities offered by computational research. This really is an area where there has been a lot of need for big data analysis and its definitely not shrinking anytime soon, said McNally, also the Elizabeth J. Ward Professor of Genetic Medicine.

Gary Wilk, a PhD student in the laboratory of Rosemary Braun, PhD, MPH, assistant professor of Preventive Medicine in the Division of Biostatistics, presented at the poster session.

In addition to biomedical research, the conference also highlighted the use of computing in a wide range of other disciplines, from economics and engineering to applied physics and the social sciences. A guest keynote address was delivered by Desmond Patton, PhD, MSW, assistant professor at the Columbia University School of Social Work, who presented on his research into innovating gang violence prevention through qualitative analysis and natural language processing of social media data.

During the speaker sessions, Paul Reyfman, MD, a fellow in pulmonary and critical care, shared his research using transcriptomics to investigate lung diseases.

Gary Wilk, a PhD student in the laboratory of Rosemary Braun, PhD, MPH, assistant professor of Preventive Medicine in the Division of Biostatistics, presented his research, Genetic Variants Modulate Gene Regulation by microRNAs in Cancer, at the events poster session.

We came up with a novel approach using computational methods to integrate many different molecular cancer datasets from large cancer cohorts, and we applied them to find these results, Wilk said.

At the poster session award ceremony, Yoonjung Yoonie Joo, a Health and Biomedical Informatics PhD student in the Driskill Graduate Program (DGP), received second-place for Phenome-wide Association Studies of Polycystic Ovary Syndrome (PCOS), her research with principal investigator M. Geoffrey Hayes, PhD, associate professor of Medicine in the Division of Endocrinology.

Our project identified several significant phenotypic associations with PCOS risk alleles, including diabetes and its comorbidities, Joo said. We suggested novel etiologic pathways underlying PCOS susceptibility loci, enabling biomedical researchers to potentially discover new therapeutic targets for PCOS treatment in the future.

The first-place prize was awarded to Shannon Brady, in the Weinberg College of Arts and Sciences, with third-place going to Jamilah Silver, in the School of Education and Social Policy.

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Scientists and Students Share Insights at Computational Research Day - Northwestern University NewsCenter

April 27, 2017

Two papers published today by the Journal of the Royal Society of Medicine, debate gene editing and the health of future generations. Stage and screen actress Kiruna Stamell, who has a rare form of dwarfism, proposes that gene editing does not represent an improvement in healthcare; while Dr Christopher Gyngell, a research fellow at the Oxford Uehiro Centre for Practical Ethics, argues that provided it is well regulated, gene editing could greatly improve the health of our descendants.

Stamell writes that if gene editing is used simply to 'disappear' certain conditions and thus certain types of people, we must look at the ethics and impact of this more broadly and redefine what it means to be 'healthy' on a micro and macro level.

She believes that gene editing has far-reaching complications that affect more than individual health. She says: "Gene editing, if only available to certain groups, will drive social inequality further as those who can't afford it are left behind or discriminated against for having been born, when the opportunity was there for them to never have existed at all."

Stamell asks: "Will those people be left unsupported by a society that prefers to weed them out rather than allow them access and a share of its wealth and benefits?" She voices concern for future generations as variation is edited out. "Small differences begin to be perceived as greater ones and society's ability to adapt and accommodate differences will shrink" she says. She concludes that a community of people who have forgotten how to adapt and embrace diversity can't be healthy for anyone.

Gyngell discusses the difficult and complex questions raised about disability, diversity and risks to human health. How to distinguish healthy forms of human diversity from disease and disability is, he writes, a subject of intense debate in philosophy but we should not let conceptual uncertainty be a barrier to the development of gene editing.

The use of gene editing in research, he writes, will greatly increase our knowledge of development and could lead to novel treatments for disease. He says: "Using gene editing to study early development could lead to a greater understanding of the causes of infertility and to better treatment options."

Gyngell goes onto describe how gene editing will be able to correct the mutations associated with fatal genetic disorders such as Tay Sachs disease and Duchenne muscular dystrophy. The incidence of these conditions can be reduced by using genetic selection techniques but, according to Gyngell, we may have reasons to prefer gene editing. He says: "Selection prevents disease by changing who comes into existence, whereas gene editing ensures those who come into existence have the best shot of living a full life."

Gyngell concludes that a case-by-case system of regulation for gene editing could work to both reduce rates of fatal genetic disease and avoid risking traits that may represent valuable types of diversity.

Explore further: Will AAV vectors have a role in future novel gene therapy approaches?

More information: Christopher Gyngell. Gene editing and the health of future generations, Journal of the Royal Society of Medicine (2017). DOI: 10.1177/0141076817705616

Kiruna Stamell. Why gene editing isn't the answer, Journal of the Royal Society of Medicine (2017). DOI: 10.1177/0141076817706278

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These changes, known as epigenetic modifications, control the activity of our genes without changing the actual DNA sequence. One of the main epigenetic modifications is DNA methylation, which plays a key role in embryonic ...

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The search for the genetic determinants of extreme longevity has been challenging, with the prevalence of centenarians (people older than 100) just one per 5,000 population in developed nations.

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Actress Kiruna Stamell debates gene editing with ethicist Dr. Christopher Gyngell - Medical Xpress

Researchers have taken an important step toward better lung cancer treatment by using blood tests to track genetic changes in tumors as they progress from their very earliest stages.

With experimental tests that detect bits of DNA that tumors shed into the blood, they were able to detect some recurrences of cancer up to a year before imaging scans could, giving a chance to try new therapy sooner.

It's the latest development for tests called liquid biopsies, which analyze cancer using blood rather than tissue samples. Some doctors use these tests now to guide care for patients with advanced cancers, mostly in research settings. The new work is the first time tests like this have been used to monitor the evolution of lung tumors at an early stage, when there's a much better chance of cure.

Only about one third of lung cancer cases in the United States are found at an early stage, and even fewer in other parts of the world. But more may be in the future as a result of screening of longtime smokers at high risk of the disease that started a few years ago in the U.S.

Early-stage cases are usually treated with surgery. Many patients get chemotherapy after that, but it helps relatively few of them.

"We have to treat 20 patients to cure one. That's a lot of side effects to cure one patient," said Dr. Charles Swanton of the Francis Crick Institute in London.

The new studies he led suggest that liquid biopsies might help show who would or would not benefit from chemotherapy, and give an early warning if it's not working so something else can be tried.

Cancer Research UK, a charity based in England, paid for the work, and results were published online Wednesday by Nature and the New England Journal of Medicine .

To be clear: This kind of care is not available yet the tests used in these studies are experimental and were customized in a lab to analyze the genes in each patient's cancer. But the technology is advancing rapidly.

The company that generated the tests for the study in Nature California-based Natera Inc. plans to offer the tests for research by universities and drug companies later this year and hopes to have a version for routine use in cancer care next year.

"This is coming, and it's coming fast," said Dr. David Gandara, a lung specialist at the University of California, Davis, who had no role in the studies but consults for two companies developing liquid biopsies. A test that could spare many people unnecessary treatment "would be huge," he said.

In the studies, researchers analyzed tumors from about 100 people with non-small cell lung cancer, the most common form of the disease. Even in these early-stage cases, they found big variations in the number of gene flaws, and were able to trace how the tumors' genes changed over time.

People with many gene or chromosome problems were four to five times more likely to have their cancer return, or to die from their disease within roughly two years.

They also looked at 14 patients whose cancers recurred after surgery, and compared them to 10 others whose did not. Blood tests after surgery accurately identified more than 90 percent of them that were destined to relapse, up to a year before imaging tests showed that had occurred.

The results suggest that using liquid biopsy tests to help select and adjust treatments is "now feasible," at least from a scientific standpoint, the authors write.

A big issue is cost, though. Liquid biopsies sold now in the U.S. cost nearly $6,000. Tests that more narrowly track a patient's particular tumor gene changes, like the one in these studies, may cost less. They may save money in the long run, by preventing futile treatment, but this has yet to be shown.

Liquid biopsy video: https://www.youtube.com/watch?v=fPKqtPcPvd4

Lung cancer treatment info: https://www.cancer.org/cancer/non-small-cell-lung-cancer/treating/by-stage.html

Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

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Blood test offers hope for better lung cancer treatment - ABC News

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