Food trucks and dogwoods in bloom along Ellis Avenue.

Welcome to LabBook, our weekly roundup of University of Chicago Medicine & Biological Sciences research news from around campus and the internet. Each Friday, LabBook will recap the week on the blog, with links to news stories about our faculty and their research.

THIS WEEK ON THE BLOG

• Pulmonary hypertension is a dangerous condition causing high blood pressure in the arteries near the lungs, but a study by Dr. Marni Gomberg-Maitland featured in the Chicago Tribune found that it’s commonly misdiagnosed.
• Patients with severe anorexia nervosa are notoriously difficult to treat, and it has the highest mortality rate of any mental disorder. But work by Dr. Daniel Le Grange shows that when the goals for treatment are set collaboratively between patients and their care givers, the number of patients who complete treatment triples.
• The big medical news of the week was Angelina Jolie’s announcement that she had a prophylactic double mastectomy because she carries the gene mutation that puts her at high risk for breast cancer. Science Life took a look at what some of our breast cancer experts, including Dr. David Song, Dr. Swati Kulkarni and Dr. Funmi Olopade, had to say about Jolie’s decision and the implications of genetic screening for cancer.
• Finally, companies use “cloud computing” to help run their businesses on big servers from Amazon and Google instead of building them on their own, so why can’t scientists too? This week UChicago launched the Bionimbus Protected Data Cloud, the first cloud-based computing system that lets researchers analyze genetic cancer information without the costly infrastructure normally needed to process massive amounts of data on their own.

Until now, researchers authorized by the National Institutes of Health (NIH) to analyze their Cancer Genome Atlas (TCGA) had to set up a secure, compliant computing environment capable of managing and analyzing terabytes of data, download the data — which could take weeks — and then install the appropriate tools needed to perform the desired analysis.

Now, the University of Chicago is launching the first secure cloud-based computing system that will enable researchers to access and analyze human genomic cancer information without the costly and cumbersome infrastructure normally needed to download and store massive amounts of data.

The Bionimbus Protected Data Cloud, which is the only NIH-approved cloud-based system for TCGA data, will be equipped with the most commonly used query pipelines and will allow researchers to focus solely on the analysis of large-scale cancer genome sequencing, which experts believe can unlock paths to appropriate treatment, early detection and prevention of cancer.

“Our hope is that the Bionimbus environment will help democratize access to cancer genomics data so that more researchers can fruitfully work with large datasets to understand genomic variations that seem to be one of the keys to the precise diagnosis and treatment of cancer,” said Dr. Robert Grossman, principal investigator of the Bionimbus project and professor of medicine at the University of Chicago Medicine.

The Bionimbus Protected Data Cloud continues to add to its current stable of the most widely used sets of cancer DNA from TCGA, including breast, ovarian and prostate.

TCGA is a comprehensive project to improve the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. TCGA contains data from more than 6,000 cancer patients, spanning 20 different types of cancer. The TCGA is a collaboration between the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the NIH.

“The Bionimbus Protected Data Cloud provides cancer researchers a simple way to analyze TCGA data without having to become experts at managing big data,” said Kenna Shaw, director of the TCGA Program Office.

Dr. Megan McNerney, instructor of pathology at University of Chicago, used Bionimbus to analyze data that led to her discovery that gene CUX1, which acts as a tumor suppressor, is frequently inactivated in acute myeloid leukemia.

“Bionimbus was critical for my work, as it was used it for all aspects of the project, including secure storage of protected data, quality control of next-generation sequencing results, alignments, expression analysis, and algorithm development,” she said. “The strength of Bionimbus, however, is the support that is provided for end users, which enabled both expert and non-expert team members to use the cloud.”

The cloud technology for the Bionimbus Protected Data Cloud was developed in part by the Open Science Data Cloud, a National Science Foundation-supported project that is developing cloud infrastructure to manage, analyze and share large scientific datasets.

Health care news has been dominated today by the New York Times op-ed by actress Angelina Jolie, in which she announced that she decided to have a prophylactic double mastectomy because she carried a genetic mutation that puts her at very high risk for developing breast cancer. Jolie has a mutation to the BRCA1 gene that gives her an 87 percent lifetime risk of breast cancer and a 50 percent lifetime risk of ovarian cancer. Her mother died of ovarian cancer at the age of 56, and given her family and genetic history she decided to act now.

David Song, MD

“This is increasingly common because now we have the ability to genetically detect familial breast cancer early and to preemptively remove the risk of breast cancer in someone’s life,” he said. “When a woman gets the diagnosis for this gene mutation, it’s very important for her to consult with her surgeon and her reconstructive surgeon so that an individualized plan is set forth for her and prescribed for her. There are women that opt for monitoring, regular MRIs and exams, and women that say, ‘Listen, this is a ticking time bomb and I want this taken care of,’ much like Angelina Jolie did. And we’re seeing an increasing number of women opting for the latter choice.”

Prophylactic mastectomies can greatly reduce the risk of breast cancer in women with a genetic predisposition. However, only 5-10 percent of breast cancers are the result of gene mutations in BRCA1 and BRCA2, another gene linked to breast cancer risk. If cases like hers are rare, why are more and more women turning to mastectomies to prevent breast cancer?

Swati Kulkarni, MD

Such a difficult decision rests on understanding someone’s genetic risk for developing cancer. Our Cancer Risk Clinic identifies and counsels people with an increased risk of all forms of cancer due to family history, medical and genetic conditions or lifestyle factors. Once the risks are determined, they design individualized cancer screening and risk reduction plans, including elective surgery such as a prophylactic mastectomy.

The Cancer Risk Clinic is part of the Center for Clinical Cancer Genetics and Global Health, which is conducting ongoing research on genetic and environmental risk factors for cancer, appropriate screening methods, and effective treatments. Oncologist and genetics expert Dr. Funmi Olopade, is an expert on hereditary breast cancer and cancer risk assessment. In the video below she talks about her research and the collaborative approach to developing new cancer treatments here at the University of Chicago.

Further Reading & Viewing:

More links to resources to help understanding genetic risks for cancer and context on prophylactic mastectomies:

• FAQ on genetic cancer risk assessments
• National Cancer Institute fact sheet on preventative mastectomies
• Breast cancer care at the University of Chicago Medicine
• Excellent explainer from National Geographic’s Carl Zimmer on the history of the BRCA gene
• Dr. Song also spoke to ABC Chicago about the implications of a major surgery like a double mastectomy
• Dr. Olopade spoke to ABC Chicago as well for a second story, urging caution for preventative surgical approaches to breast cancer, even when a women has a genetic risk
• Time Magazine referred to Dr. Lainie Ross’s research on the ethics of screening children for genes that could reveal a risk of adult onset diseases such as breast cancer
• Breast cancer surgeon Dr. Nora Jaskowiak spoke to both WGN and CBS Chicago about the Jolie’s decision

Jaimie Oh contributed to this post

Daniel Le Grange, PhD

More than 85 percent of those who enrolled in the trial completed treatment—almost three times the usual retention rate. Read more in our Newsroom:

“The results were far better than most people in the field would have expected,” said Daniel Le Grange, PhD, professor of psychiatry and director of the eating disorders program at the University of Chicago and the principal investigator for the data-coordinating center. “Many of these patients were profoundly ill. The prevailing wisdom is that current treatments have not been effective and patients are best served by refeeding in the hospital setting. This study showed that specific modification of these behavioral approaches could overcome the high dropout rates and lead to meaningful positive change.”

Science Life spoke to Le Grange last fall about his research on using chat rooms to facilitate family-based treatment for eating disorders. Find out more about the UChicago Eating Disorders Program.

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Touyz S, Le Grange D, Lacey H, Hay P, Smith R, Maguire S, Bamford B, Pike KM, & Crosby RD (2013). Treating severe and enduring anorexia nervosa: a randomized controlled trial. Psychological medicine, 1-11 PMID: 23642330

Mardi Gomberg-Maitland, MD, MSc

“I think we were not surprised by the general results,” said Dr. Mardi Gomberg-Maitland, a cardiologist and director of the pulmonary hypertension program at the U. of C. Medicine. “We’re seeing patients started on medications inappropriately … Patients are often misclassified, and given the wrong diagnosis.”

…

The study examined the medical histories of 140 patients who were ultimately referred in 2010 and 2011 to pulmonary hypertension centers at the U. of C., the University of Michigan and the Baylor College of Medicine in Houston. The researchers found that many of the patients had been misdiagnosed before they received the correct diagnosis of pulmonary hypertension.

“We’re hoping that the paper shows that we need to improve educational efforts, and that we’re a team. We want referrals early so that patients can live longer and feel better,” Gomberg-Maitland said.

The University of Chicago Medicine is one of the largest pulmonary hypertension centers in the world, treating more than 1,000 patients per year. Find out more about our comprehensive treatment options at:

uchospitals.edu/specialties/heart/services/pulmonary-hypertension/.

Welcome to LabBook, our weekly roundup of University of Chicago Medicine & Biological Sciences research news from around campus and the internet. Each Friday, LabBook will recap the week on the blog, with links to news stories about our faculty and their research.

THIS WEEK ON THE BLOG

• On Monday, Reader’s Digest told the story of Nick Metcalf, a college student who suddenly couldn’t swallow, and how Dr. Marco Patti was able help with a minimally invasive surgery.
• On Tuesday, we spoke to thoracic surgeon Dr. Christopher Wigfield, the newest member of our lung transplant team, about why lung transplants are the most difficult organ transplant procedure, and the technology in store to improve patient outcomes.
• On Wednesday, US News & World Report covered new research by Dr. Scott Eggener showing that cholesterol-lowering statins can improve survival rates for patients with a type of cancer called renal cell carcinoma.
• Also on Wednesday, we reported from the annual University of Chicago Medicine Discovery and Impact event. This year’s topic was the microbiome, or the world of bacteria and microbes living in and around us, and how they shape our health.
• And finally, yesterday we spoke to neurobiologist Sliman Bensmaia, whose work on the sense of touch continues to amaze. This time he and his colleagues showed how an organism can perceive a tactile stimulus through a prosthetic hand equipped with sensors that can transmit electrical signals to the brain.

Hope you didn’t put away all your jackets yet, it looks like a chilly weekend in Chicago. See you next week.

Without the sense of touch, using a robotic prosthetic arm is like using a skill crane in the arcade.

Scientists have made tremendous advances toward building lifelike prosthetic limbs that move and function like the real thing. Researchers at the University of Pittsburgh have developed algorithms that allowed a paraplegic woman to feed herself by controlling a robotic arm with her thoughts, and many labs across the country are working on ways to read intended movements from the brain to improve the performance of robotic limbs.

These are amazing accomplishments, but an important element to creating a realistic replacement for a hand is the sense of touch. Without somatosensory feedback from the fingertips about how hard you’re squeezing something or where it’s positioned relative to the hand, grasping an object is about as accurate as using one of those skill cranes to grab a stuffed animal at an arcade. Sure, you can do it, but you have to concentrate intently while watching every movement. You’re relying on your sense of vision to compensate for the lack of touch.

Sliman Bensmaia, PhD

Bensmaia spoke about how important the sense of touch is to creating a lifelike experience with a prosthetic limb.

“If you lose your somatosensory system it almost looks like your motor system is impaired,” he said. “If you really want to create an arm that can actually be used dexterously without the enormous amount of concentration it takes without sensory feedback, you need to restore the somatosensory feedback.”

The researchers performed a series of experiments with rhesus macaques that were trained to respond to stimulation of the hand. In one setting, they were gently poked on the hand with a physical probe at varying levels of pressure. In a second setting, some of the animals had electrodes implanted into the area of the brain that responds to touch. These animals were given electrical pulses to simulate the sensation of touch, and their hands were hidden so they wouldn’t see that they weren’t actually being touched.

Using data from the animals’ responses to each type of stimulus, the researchers were able to create a function, or equation, that described the requisite electrical pulse to go with each physical poke of the hand. Then, they repeated the experiments with a prosthetic hand that was wired to the brain implants. They touched the prosthetic hand with the physical probe, which in turn sent electrical signals to the brain.

Bensmaia said that the animals performed identically whether poked on their own hand or on the prosthetic one.

“This is the first time as far as I know where an animal or organism actually perceives a tactile stimulus through an artificial transducer,” Bensmaia said. “It’s an engineering milestone. But from a neuroengineering standpoint, this validates this function. You can use this function to have an animal perform this very precise task, precisely identically.”

The FDA is in the process of approving similar devices for human trials, and Bensmaia said he hopes such a system is implemented within the next year. Producing a lifelike sense of touch would go a long way toward improving the dexterity and performance of prosthetic hands, but he said it would also help bridge a mental divide for amputees or people who have lost the use of a limb. Until now, prosthetics and robotic arms feel more like tools than real replacements because they don’t produce the expected sensations.

“If every time you see your robotic arm touching something, you get a sensation that is projected to it, I think it’s very possible that in fact, you will consider this new thing as being part of your body,” he said.

Sliman Bensmaia’s work was also covered recently by Nature News & Comment in an article about the work being done around the country to bring the sense of touch to prosthetic arms.

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Berg, J., Dammann, J., Tenore, F., Tabot, G., Boback, J., Manfredi, L., Peterson, M., Katyal, K., Johannes, M., Makhlin, A., Wilcox, R., Franklin, R., Vogelstein, R., Hatsopoulos, N., & Bensmaia, S. (2013). Behavioral Demonstration of a Somatosensory Neuroprosthesis IEEE Transactions on Neural Systems and Rehabilitation Engineering, 1-1 DOI: 10.1109/TNSRE.2013.2244616

Jack Gilbert, PhD, at the Discovery & Impact event on the microbiome on May 1, 2013

“Every single one of you has 100 trillion bacterial cells on you, and those 100 trillion cells are found all over your body.”

That’s probably not the most comforting message to hear as you’re sitting down to dinner, but as Jack Gilbert reassured the crowd assembled at the University of Chicago Medicine Discovery & Impact event last Wednesday evening, these bacteria play a vital role in our health and well-being.

“We’re fundamentally built to live with these guys. We’ve been evolving with them for 5 million years, and we’ve built up these wonderful intricate relationships with them,” he said. The event, hosted by Karen and Jim Frank, president and CEO of Wheels Inc., at the JW Marriott in Chicago, brought attendees together with physicians, scientists and researchers from the University of Chicago Medicine and Biological Sciences Division who are studying the microbiome and how it affects human health and disease.

Gilbert, assistant professor of ecology & evolution at the University of Chicago and environmental microbiologist at Argonne National Laboratory, gave the opening remarks, then attendees participated in a series of breakout sessions with UChicago experts focused on every aspect of how the microbiome affects our health, from how our diets and lifestyles can change the bacterial ecosystems within our bodies, to the impact of widespread use of antibiotics and the explosion of food allergies and autoimmune diseases.

It was an extraordinary gathering of some of the nation’s leading experts working toward a better understanding of how those 100 trillion cells shape our lives, experts who all happen to be working at the University of Chicago. As Gilbert put it, “They’re all gathered here. We have the computational power. We have the expertise, and we have the ability to do this.”

All photos by Jason Smith

Jim Frank, president and CEO of Wheels Inc., speaks to the crowd in the JW Marriott ballroom

Kenneth Polonsky, MD, Executive Vice President for Medical Affairs at the University of Chicago Medicine and
Dean of the Division of the Biological Sciences

From the session on “Microbiomes and the World Around You,” (L-R): Folker Meyer, PhD, Computational Biologist at Argonne National Laboratory and Senior Fellow at the Computation Institute; Emily Landon, MD, Assistant Professor of Medicine and Medical Director of Antimicrobial Stewardship and Infection Control; Nicole Scott, PhD, Postdoctoral Fellow at Argonne National Laboratory

From the session on “Bacteria and Your Body,” Cathryn Nagler, PhD, Bunning Food Allergy Professor in the Department of Pathology, and Vaibhav Upadhyay, MD/PhD Student

Plenty of time for questions at the “Bacteria and Your Body” session

Scott Eggener, MD

Statins — drugs such as Crestor, Lipitor, Pravachol and Zocor — have anti-inflammatory and cell self-destruction properties, and previous research has shown that these drugs may lower the risk of developing some types of cancer. The new research, presented Tuesday at the annual meeting of the American Urological Association in San Diego, suggests that the drugs might fight kidney cancer.

“Given that one in four Americans over 45 years of age take a statin and renal cell carcinoma occurs most often in men ages 50 to 70, it may be prudent to prospectively evaluate if statins protect against [cancer] progression,” study author Dr. Scott Eggener, an associate professor of urologic oncology at the University of Chicago, said in a meeting press release.

Dr. Eggener was recently featured in Science Life for his work on a clinical trial of “focal therapy” for prostate cancer that uses a precisely targeted laser to burn away cancer cells instead of using more aggressive invasive surgery.

Lung transplants are perhaps the most difficult and complex organ transplant procedures.  Not only are they vital organs with no artificial replacement, but they are also highly susceptible to infections and failure even after a successful transplant surgery.

The newest member of the lung transplant team at the University of Chicago Medicine, thoracic surgeon Dr. Christopher Wigfield, aims to improve outcomes for transplant recipients through his combination of surgical experience and clinical research in lung transplantation. He also has studied the impact of donor and procurement related issues, and was recently named Director of Educational Affairs at the International Society of Heart and Lung Transplantation.

Science Life spoke to Dr. Wigfield recently about the complexities of lung transplants, and what new technologies are on the horizon that could revolutionize the field. The following is an edited version of that conversation.

Why are lung transplants such a complex procedure?

Christopher Wigfield, MD

Why are they so difficult to remove?

You have to physically almost chisel them out at times yet avoiding excessive tissue injury. With fibrotic lung diseases and suppurative diseases like cystic fibrosis, patients have been through so many cycles of inflammation and worsening that the lungs are stuck. Most mammalian species have a pleural lining that separates the lung from the inner chest wall. There’s a little fluid that allows it to be slippery, and there’s a “negative pressure” that facilitates this movement. If you have repeated cycles of lung infection or fibrosis, this space is almost completely obliterated. You have to recreate that space in its three dimensional shape and isolate major vascular structures that perfuse the whole cardiac output into the lungs safely, before you ever get near implanting the new lung. Then do it all again on the other side.

What other preparations go into the procedure before implantation?

You have a fair bit of preparation to make the bronchus available for the anastomosis. We allow enough of the vessels coming away from the heart available in a safe fashion to connect recipient with donor. So you’re doing major thoracic surgery, you’re doing major airway surgery, major vascular surgery, and heart-lung bypass at the same time. These operations demand some endurance and perseverance. Even watching can be exhausting. For us it’s always like running a marathon, but you had better be prepared for it.

Aren’t lungs much more prone to infections after the transplant because they’re exposed to air?

Correct, that is one of the long-term issues. Lungs are rejected more than other organs. They are chronically dysfunctional more often than other organ systems, so we expect only 50 percent of our lung transplants to function fully longer than five years. We’ve made a big difference over the last decade, significantly improving survival in the surgical aspects of lung transplantation, but this chronic lung dysfunction that occurs is still not really fully understood. It has to do at least partially with the fact that you breathe airborne toxins, bacteria and other contaminants in with every breath. The lung is a huge immunogenic organ because it’s exposed to the outer atmosphere, like skin. With other organs, they’re implanted and only see what comes through the bloodstream. For lungs it’s both.

How does the multidisciplinary approach to lung transplantation at the University of Chicago appeal to you as a surgeon?

This subspecialty will not be functional if you don’t do it in a truly interdisciplinary setting. You need the whole team on board: pulmonologists, thoracic surgeons, coordinators, and PAs. And you need to have a very low threshold for pulling expertise from all corners, so that you can decide on the adequate candidates for transplantation. Together we provide very adequate surveillance in the long term. Since these patients are more prone to have certain infections because of immunosuppression, we work with infectious disease specialists very closely. They are more prone to have risks of certain cancers, and therefore need close advice of other specialties. They are more prone to have renal dysfunction because of the medications. They also have a chance of developing diabetes because they get steroids, so you can see it goes in all directions. That’s why it has to be a truly multidisciplinary effort. That’s how we can get good results.

Is that something unique to the University of Chicago?

Yes, collaboration is an attraction to work here, but there’s always room for improvement. It starts with selection and ends with surveillance of the patient. Communication with the specialists is vital. An academic setting like this where there’s good collaboration to begin with is the only way to do lung transplantation.  Of course the patient has some responsibility as well.

What are some of the research developments you’re looking forward to in the near future?

There are some developments that now bring at least the prospect of an artificial lung to the horizon. It’s not a total artificial lung, and presently a system called ECMO, extra corporeal membrane oxygenation, that over the years has been refined and is now coming to more and more clinical use in these patients. We either bridge them to transplantation, or if the lungs were dysfunctional after transplantation, bridge them to recovery. That used to be a very difficult scenario with poor outcomes, where you had at least 40 to 50 percent mortality at that stage. Those odds are turning more and more in our favor with more experience and more refined technology support. We really have much better systems, and we have them here at UChicago to support patients with ECMO for transplantation when necessary.

Number two is a massive development. It’s really going to bring in a new era of transplantation: optimizing lungs when they come from the donor prior to implantation with a system called Ex-Vivo Lung Perfusion. This should be arriving in major American hospitals within a year. Canadian trials and European trials have proven the feasibility, the efficacy and the superiority of using this system over extended criteria donor lungs. These would normally pose added risk when we transplant. This system is now going through FDA approval, and it’s not a matter of whether we should be doing this, but which system we will adapt. We fully optimize the lungs and utilize the maximum number of lungs to serve our lung transplant candidate population better.

So does this system refurbish the donor lungs before they’re transplanted?

There is more to it than that. It helps you assess the lungs for their function before you even have to intervene. Quite often that tells you that a donor lung is good, although it didn’t look so great when I first assessed it. The whole area of intervention for those lugs is wide open.

This type of preliminary assessment wasn’t possible before?

It wasn’t possible because the systems to take lungs out and perfuse them were purely scientific. This is now a clinical application. The lungs stay sterile and safe. The outcomes the Canadian group published and presented have provided excellent outcomes, scientific data that is very convincing. I’m at a loss as to why the FDA hasn’t already approved this.

What are your plans for implementing it here at the University of Chicago?

It has to be one solution to be considered very seriously. My appointment here may allow us to put that into practice at the University of Chicago. We have an excellent group of surgeons and physicians who have expertise and are very adaptable to this type of procedure. We have a group of extremely experienced perfusionists, and we have a larger group of patients who would benefit from this. If we can distinguish ourselves as a center of excellence in this area, we would be a dominating center in lung transplant. This is an exciting time for lung transplantation.

Find out more about the lung transplant program at the University of Chicago Medicine at uchospitals.edu/specialties/transplant/lung.html.

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