Category: Genetics/Genomics Page 9 of 11

A Call For Action: Genetic Testing Before Prescriptions

On January 12, 2013

In Biology, Genetics/Genomics, Lecture, Medicine

By Prachiti Dalvi

Structure of Codeine

Codeine is an opioid pain medication; but if you are a poor metabolizer of a particular enzyme (CYP2D6), you will experience no pain relief from this drug. However, if your doctor could administer something called pharmacogenetic testing, she would know to simply give you morphine (an active metabolite of codeine) instead. For now, this kind of testing isn’t available.

Mary Relling, PharmD

Mary V. Relling, PharmD, the Chair of Pharmaceutical Sciences at St. Jude’s Children Hospital spoke about the need to implement pharmacogenetic testing on Thursday, January 10. A number of tests have recently emerged that are ready for prime time. When we know that some drugs may have adverse effects for people with particular genetic phenotypes, it is unethical to prescribe these drugs without knowing the patient’s genetic status.

However, Relling said there are a number of barriers to integrating pharmacogenetic tests into clinical care: fragmentation of our healthcare system, a focus on sick-care rather than disease prevention, a lack of evidence for clinical utility or cost-effectiveness, complex underlying lab results, and a lack of a centralized system for recording patient information.

The best way to break through these barriers is to conduct testing preemptively, Relling said. We can simply take drop of blood when the baby is born and run genetic tests. “Genetic tests are lifetime results. It makes sense to have it in the background, just as we know a patient’s age, weight, sex, etc.,” Relling said. The barriers discussed above can be avoided to a certain extent at St. Jude’s because they have adopted a team approach to patient care and a 100% electronic system for recording patient records.

The growing affordability of genotyping makes using preemptive pharmacogenetic testing more feasible, she said. The cost of sequencing one or two genes in the past will now produce results for 225 genes. Two years ago, the Clinical Pharmacogenetics Implementation Consortium (CPIC) studied how to migrate pharmacogenetic testing from the laboratory into routine patient care. They looked for gene-drug pairs associated with potential risks of life-threatening toxicity, serious adverse effects, or lack of effectiveness. Eleven of the genes CPIC determined met the threshold for high-risk were found to have profound effects on 33 drugs.

Relling said approximately 48% of patients receiving drugs at St. Jude’s received orders for at least one of those pharmacogenetically high-risk medications.

She said the question now is how to use genetic test results rather than whether a genetic test should be ordered. In the coming years, we will have to address how to maintain the fine balance of providing the clinician with enough information to treat the patient and overwhelming the patient with genetic testing results that are difficult to interpret.

This lecture was a part of the Genomics and Personalized Medicine Forum sponsored by the Duke Institute for Genome Sciences and Policy (IGSP).

A Passion for Research

By Prachiti Dalvi

On November 19, 2012

In Biology, Cancer, Genetics/Genomics, Students

By Prachiti Dalvi

Akash Shah, Trinity ’13

“Research enables me to think about a question that excites me and helps patients,” says Trinity senior Akash Shah. A biology major, philosophy minor, and a candidate for the Genome Sciences and Policy Certificate, Akash became interested in genomics as a freshman in the Genome Focus. Originally from Fullerton, CA, Akash was drawn to Duke because of its its immense biomedical research enterprise. He also loved the fact that at Duke, the medical school, law school, and business school were on the same campus as the undergraduate campus.

Intrigued by the research his professor Dr. Hunt Willard was conducting, he asked to get involved. His work in Dr. Willard’s lab dealt with artificial human chromosomes. More specifically, he was working with others in the lab to identify which regions of the chromosome would be deleted when transformed into human cells.

Now, Akash works in the Nevins Lab, where he looks at candidate genes in the epidermal growth factor receptor (EGFR) pathway: an important pathway in many cancers. When growth factors bind to the external portion of the receptor, the receptor becomes activated. Side effects of receptor activation include tumor growth and metastasis. When scientists target genes associated with this pathway, they can increase tumor cells’ sensitivity to pathway inhibitors and better prevent tumor cell reproduction.

http://www.youtube.com/watch?v=zE4BkAw_lL4

The advent of computational genomics has allowed for major advances in the field. Fifteen to twenty years ago, cloning genes was considered a PhD project, and now, it is something an undergraduate can do.

Akash’s favorite aspect of research at Duke is its collaborative nature. Faculty members work with another and across departments. His research is not limited to labs at Duke. In fact, he as also worked with professors at UCLA and Harvard. The culture of research varies from one university to the next; thus, Shah encourages undergraduates to do research at different institutions. “It gives you a chance to succeed in different cultures.”

When he is not in the lab, Akash enjoys playing cricket and exploring local restaurants with friends. During his time at Duke, he has been involved with numerous organizations, and has become an integral part of the Genome Research and Education Society (GRES). During his sophomore year, he founded a program in which undergraduates shadowed other undergraduates doing genomics research. In order to make research more accessible to undergraduates, Akash has helped organize career talks, including MD/PhD information sessions. After graduating from Duke in the spring, Akash hopes to begin medical school, and eventually pursue a career in academic medicine so he can continue conducting research. He has worked extensively in cancer genomics research and hopes to explore cancer stem cells in the future.

When the Genome Gets Personal

By sa160@duke.edu

On November 15, 2012

In Genetics/Genomics, Lecture, Medicine

By Nonie Arora

It has been almost ten years since the first draft sequence of the human genome was completed in 2003, and some patients are starting to see benefits in clinic.

Dean Nancy Andrews

Dr. Nancy Andrews, Dean of the School of Medicine, recently spoke to undergraduate students about “When the Genome Gets Personal” over a hearty dinner of chicken stuffed with goat cheese, rice pilaf, and caramelized brussel sprouts. She was the latest guest in the 2012 Chautauqua West Lecture Series.

Andrews explained how DNA sequencing analysis can lead to a new diagnosis for patients. Even if the disease is not treatable, a diagnosis can mean a lot to patients and families, said Andrews.

“We are pushing boundaries between taking care of patients and doing research. The lines are blurry,” she said. Researchers want to sequence patient DNA to find causes for genetic diseases and, at times, to help individual patients who don’t have a diagnosis, according to Andrews.

She said it is easy to find variations in DNA sequence, but much, much harder to know how to interpret the changes. One of the tricky situations researchers face is telling parents or patients what they have found when they are not certain of the finding’s significance. She chairs a committee at Duke that is working on standards to help guide researchers to know what to report and how to design informed consent forms.

Andrews said DNA sequencing is already being used in clinical care: about $5 billion a year is spent on clinical sequencing. However, this sequencing is highly focused on genes relevant to the clinical situation; insurance companies will not yet support exploratory whole-genome sequencing. Andrews pointed out that there is a potential for exploitation by private for-profit companies with DNA sequencing capability, which may overstate their claims or capabilities.

Complicated scenarios can arise when sequencing is done in families. Among other issues, “There is a very real possibility of learning dad is not the biological father,” Andrews said.

Example of a pedigree generated from discussion of family history with patients, modified from Wikimedia Commons

Andrews said that clinical geneticists are going to need algorithms for interpreting sequence data and standard principles for revealing information for patients. These are under development at Duke and across the country.

Ultimately, Andrews thinks that personalized medicine “shouldn’t just be about genetics and genomics but [it should] also incorporate many other types of clinical data, including imaging studies and patient preferences, as well as a deep understanding of environmental factors.”

Igniting U.S. health care's 'escape fire'

By Ashley Yeager

On September 21, 2012

In Behavior/Psychology, Cancer, Cardiology, Genetics/Genomics, Global Health, Medicine

The film Escape Fire explores what's fanning the flames of the health care debate. Credit: escapefiremove.com

By Ashley Yeager

Imagine lighting a match to protect yourself from the flames of a fire.

It’s probably not the first thing you would think to do to stop from being burnt. But when there’s no other escape, the technique works. In 1949, Robert Wagner Dodge became living proof when he lived through the Mann Gulch fire by setting his surroundings on fire.

Now, his actions have become a metaphor for drastic ways government and industry should change U.S. health care before it too burns everything in its path.

Escape Fire: The Fight to Rescue American Healthcare showcases the health care system’s metaphorical blaze. The award-winning documentary, described as the “Inconvenient Truth” of the health care debate, opens nationwide in October. But members of the Duke community saw it for free on Wed., Sept. 19. They were also able to participate in a post-film panel discussion, which fleshed out a few potential escape fires for the health care industry.

“I think working with one patient at a time can help everyone become healthier,” said Annie Nedrow, a primary care physician and the associate director of Duke Integrative Medicine, which sponsored the event. But as the film points out, the current system rewards doctors for the number of patients they see, not the amount of time they spend with each person or the plans they may develop to help that patient prevent and manage disease.

Ironically, almost 75 percent of health care costs are spent on preventable diseases. The film, directed by Matthew Heineman and Susan Froemke, illustrates this statistic through anecdotes, where a band-aide, pill or even invasive surgery, such as inserting a stent to relieve heart blockages, provides immediate relief but does nothing to address the underlying causes of illnesses – typically diet and lifestyle.

Preventable diseases are 75% of our health care costs. Credit: escapefiremovie.com

“There’s got to be a shift in our culture, one where we actually have access to safe parks to exercise, healthy food, and the time to eat it,” said Adam Perlman, Duke Integrative Medicine’s executive director. He also agreed with Nedrow that a new system should invest more in primary care and health promotion, rather than disease treatment.

To set an example and test the feasibility of such a system, Duke Integrative Medicine has opened a primary care practice that limits the number of patients each physician sees so the doctors can spend more time with each patient and create a more holistic approach to that person’s health.

Perlman said that health coaching could be another important aspect of correcting the healthcare system. He explained that doctor X might tell a patient to lower his blood sugar, doctor Y then tells him to lower his blood pressure, and all the patient really wants to do is dance at his daughter’s wedding. “A health coach helps the patient reach those bigger goals by connecting the dots and helps them execute the plan to get there,” he said.

The film and remarks prompted many audience members to question what it would take to change the current system. Nedrow, who said she has been inspired by books on creativity and innovation, suggested that it was dialogues like the one they were having that could ignite change to repair the broken model of health care or create a new system.

More innovation, however, may mean that more people need to step into the fire and strike a match, rather than run and try to dodge the flames.

Trinity Junior in Phoenix for Summer, Doing Real Research

By sa160@duke.edu

On July 23, 2012

In Biology, Genetics/Genomics, Medicine, Students

By: Nonie Arora

Sonya Jooma, Trinity '14, provided by Steve Yozwiak

Rising Trinity Junior Sonya Jooma is in Phoenix, Arizona this summer working at the Translational Genomics Research Institute (TGen) as an intern in the TGen-Duke Biomedical Futures Program. This is the first year TGen and Duke have partnered to offer a funded biomedical research internship exclusively for Duke students. Jooma and a second Duke undergrad, Geoff Houtz, are the first two students to participate in this pilot program.

The TGen-Duke Biomedical Futures Program joins the growing list of Duke programs for students excited about genomics, such as the Genome FOCUS program and the Institute for Genome Sciences & Policy Summer Fellowship. In fact, the Genome FOCUS spurred Jooma’s enthusiasm for genomics research. Last year, she worked in the John Willis lab researching plant genetics as part of the Howard Hughes Research Fellows Program.

Her project at TGen, in the lab of Dr. Lisa Baumbach-Reardon, centers on the genetic basis of Infantile Spinal Muscular Atrophy. This disease causes muscle weakness and abnormality at birth. Afflicted children often die before their second birthday. According to Jooma, there are cases of this disease for which the genetic basis is unknown. As part of her lab’s exome sequencing project, they hope to identify mutations involved in the disease.

Jooma says her TGen experience has been great so far. She finds it similar to working in a research lab at Duke because of the similar lab hierarchy. However, she appreciates that TGen has overarching specific goals that focus on translating discoveries to clinical diagnostics and therapies. Jooma also looks forward to attending professional development workshops and presenting her work at TGen’s annual intern research symposium in July.

Ultimately, Jooma’s experience at TGen will be one of many exciting research projects: she hopes to pursue a career in biology research.

CSI-House teams could make better medical diagnoses

By Ashley Yeager

On June 28, 2012

In Biology, Cardiology, Computers/Technology, Genetics/Genomics, Lecture, Medicine

By Ashley Yeager

Comparing a child's DNA to his parents' could help with identification of hard-to-diagnose genetic diseases. Credit: Henrik Jonsson/iStockphoto

Dr. Gregory House, star of House, M.D., and the lab techs on CSI never fail at their jobs. But that’s Hollywood. In real life, diagnosing illnesses and sequencing DNA isn’t so straightforward. It doesn’t always lead to a happy ending either, especially for children who are sick but can’t be diagnosed, even by gifted, real-life doctors.

That’s exactly why geneticist David Goldstein has teamed with pediatrician Vandana Shashi to combine a little House and CSI to identify apparent genetic diseases and quickly end some families’ diagnostic odysseys.

So far, the team has provided likely genetic diagnoses in six of 12 children it has worked with, said Goldstein at a Cardiovascular Research Center Seminar Series talk on June 27.

The children were referred to Shashi for a pilot study where she would record their symptoms, or phenotypic behavior, much like House. Then, Goldstein and his team at the Center for Human Genome Variation collected DNA samples from the children and both of their biological parents.

Using next-generation genetic sequencers, as well as traditional DNA scanners, Goldstein and his team looked for genetic variations between the children’s and parents’ complete genome. Like looking at DNA to identify a criminal, Goldstein and his genetics team are scouring the sequences for genetic fingerprints of the diseases disrupting the children’s lives.

Once variations were identified, the entire team looked for known diseases with similar gene mutations and symptoms. Goldstein explained that the study not only pinpointed the undiagnosed congenital diseases in some patients but also presented new genes that could also be linked to the illnesses. The study’s success has led to the creation of the Genome Sequencing Clinic.

The clinic will begin to help the families of the 50,000 children (out of the four million) born each year in the US with difficult-to-diagnose genetic diseases. These types of studies will likely be the “earliest drivers for large-scale genetic sequencing,” Goldstein said.

But, he cautioned, “there’s a whole lot of junk,” or variation, in DNA. Every genome has the narrative potential for devastating diseases, and that means that House-CSI teams, like Shashi and Goldstein’s, need to be extremely careful when making diagnoses, especially if the results will influence treatment, he said.

Citation: Clinical application of exome sequencing in undiagnosed genetic conditions. Need, A. et. al. 2012. J. Med Genet. 49:6 353-361. doi:10.1136/jmedgenet-2012-100819

Lab "cloud" goes global

By Ashley Yeager

On June 15, 2012

In Computers/Technology, Faculty, Genetics/Genomics, Mathematics, Physics

By Ashley Yeager

A network of individual computers are linked through a server. Credit: TAS Software

The National Science Foundation has awarded computer scientist Jeff Chase $300,000 to move a computer cloud he now has in his lab to the university’s campus network, and beyond.

Chase has been building the cloud to improve server networks. In his new model, servers, the computers that process requests and deliver data over a local network or the Internet, have become critical, public infrastructures with open, flexible, secure, robust and decentralized control.

The work, once reproduced outside of the lab, will let Duke scientists across campus and throughout the world to more easily connect to one another through existing networks and to share computational services and access data, according to Tracy Futhey, Duke’s vice president for information technology and chief information officer.

Based on software-defined networking and other technologies, the new, on-demand cloud services will be launched through a distinct network that connects science resources, such as the large datasets generated in physics and genomics experiments.

The project is part of the NSF-funded Global Environment for Networking Innovation, or GENI.

Chase’s work was also recognized on June 14 when the White House launched an initiative, US Ignite, to develop a publicly available system of advanced networks based on important contributions from GENI scientists. Duke is among more than 60 universities across the country that has participated in the project.

Rethinking science on pandemic-potential viruses

By Ashley Yeager

On May 18, 2012

In Animals, Biology, Genetics/Genomics, Global Health, Medicine, Students

By Ashley Yeager

Debates over experiments subjecting ferrets to modified bird-flu strains had scientists and politicians seriously questioning how to approach and publish studies on pandemic-potential viruses. Credit: J. Smalley/NaturePL.com

Making mutant forms of bird flu and publishing the results caused a major squawk in the public and in the political and scientific communities over the last year.

The issue was whether the new mutants could ward off a major pandemic of bird flu or start one, explained Stephanie Holmer, a graduate student in Duke’s Department of Cell Biology.

She raised the issue during the May 18 meeting of the Science and Society Journal Club.

The row began when researchers at the University of Wisconsin-Madison and the Erasmus Medical Center in the Netherlands independently tweaked strains of the H5N1 virus, commonly named the bird flu. The strains, the teams report, are more easily transmitted between ferrets, the lab-double for humans.

“The fear was that if the mutant forms of the virus got out of the lab, bioterrorists could use them to make a super-virus and start a pandemic. But there was not any guarantee that what the scientists had was a weapon. The mutant strains weren’t even that efficient at killing a ferret,” Holmer said.

During the forum, about a dozen students and faculty from departments across campus debated whether this kind of research should have been done, if journal editors should publish the full results and what can be done to prevent future squawks about similar types of research.

Electron micrograph of influenza A virus. (Centers for Disease Control, Erskine Palmer)

Scientists want to study H5N1 to find out how fast the virus mutates and how virulent those strains are in mammals, including humans. So far, outbreaks of the non-mutant form of the bird flu in humans have been limited. The cases, about 100 to 200 from 2003-2012, have occurred most often in Indonesia, Egypt and Vietnam, according to statistics from the World Health Organization.

In two separate papers, the teams from Madison and the Netherlands reported the strains of H5N1 that seemed to be more virulent in ferrets. The Madison team submitted its paper to Nature; the Netherlands’ team submitted to Science. Both papers came under government scrutiny before they were published because the methods in each could potentially be misused to make a bioweapon.

But the researchers had already presented their data at conferences, and they had institutional approval to initiate the experiments, facts that led Subhashini Chandrasekharan, co-coordinator of the journal club, to wonder aloud why it took until the point of publication to prompt a government and scientific scuffle over the experiments and the results.

“I’m not a virologist, but I don’t find any reason that the study should not be done or that the results should not be published. The jump of this virus from birds to humans is going to happen. It’s only a matter of time. If we already understand the mutations, then we’ll be faster at finding treatments and vaccines,” Chandrasekharan said.

She added that if a bioterrorist is going to make a weapon from a virus, it didn’t seem likely that they’d need the papers, which were finally approved for publication on April 20, to make the mutations. They’d do it anyway, she said, explaining that preventing publication was probably not going to be “the wall” to stop a terrorist from plotting an attack.

That issue, of course, raises another whole set of squawks.

Genome Institute 2.0 is the "Interactome"

By Karl Bates

On May 3, 2012

In Genetics/Genomics

Guest post from Kendall Morgan, IGSP Communications

When the Institute for Genome Sciences & Policy (IGSP) first opened its doors 10 years ago, the interdisciplinary unit was Duke’s response to the dawning of a revolution. Today, genomics is a very real and ever-growing force in biology, medicine, politics and popular society, and the IGSP is responding by throwing its doors open even wider.

Members of the Duke faculty anywhere on campus with an interest in the genome sciences or their societal implications are invited to join the IGSP “interactome.”

The Institute’s renewed emphasis on an open membership policy is a key outcome of the IGSP 2.0 evaluation and planning process launched by IGSP Director Huntington Willard last year in anticipation of the IGSP’s tenth-year review in 2012. The internal review process was designed to assess the extent to which the structure of the IGSP was optimal for the future of genome sciences and policy both on campus and beyond.

“Genomics looks quite different now than it did in 2000 or even just a few years ago,” Willard said. “The Institute must be designed to adapt to both the current and future landscape of opportunities and challenges in the genome sciences and society. This will take faculty and students from all across campus. For Duke to meet that challenge, IGSP 2.0 is all about being inclusive, flexible, open.”

Huntington Willard, Director of the Duke Institute for Genome Sciences & Policy

Other outcomes of the IGSP 2.0 strategic planning process include a funding initiative aimed to foster new interdisciplinary teams of faculty focused on significant questions in any aspect of genome sciences and its implications for individuals, society and the world. The IGSP is also launching a new ‘Omics Data Analysis Core Resource as a complement to the Institute’s stable of data-generating genome technology facilities.

“We are committed to faculty recruitment and development and to enhance and catalyze innovative and meaningful scholarship across the full spectrum of genome sciences and policy,” Willard said. “Importantly – and as a statement of purpose – these strategies require us to engage and enable faculty and students at all levels, not just in the IGSP, but across the institution.”

Following the people and events that make up the research community at Duke

Category: Genetics/Genomics Page 9 of 11

A Call For Action: Genetic Testing Before Prescriptions

A Passion for Research

When the Genome Gets Personal

Igniting U.S. health care's 'escape fire'

Trinity Junior in Phoenix for Summer, Doing Real Research

CSI-House teams could make better medical diagnoses

Lab "cloud" goes global

Rethinking science on pandemic-potential viruses

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Genome Institute 2.0 is the "Interactome"