Houston Methodist Research Institute
From Translation to Transformation
Foreword
A warm welcome from the physicians, scientists, and staff of the Houston Methodist Research Institute. As I write this, we are marking an important milestone, the opening of our new building — one designed for collaboration, equipped with exceptionally advanced technology, and home to some of the world’s finest research scientists, physicians, and engineers. It’s an extraordinary place, and I believe it is where many of the hardest challenges faced by patients and their doctors may be solved. In fact, when I’m asked what we’re hoping to do here, I say that our goal is to change the future of medicine. This is a bold stance. There is a chance of sounding overconfident, or naïve. At worst, it could be considered hubris. But I prefer to think of it as a calculated risk — the kind that’s inherent to the very best science, and that is needed when the pace of meaningful innovation has grown increasingly slow, and increasingly expensive. We plan to reverse that trend, effecting true change in the status quo. This is, I believe, the place and time to do it. Our approach is genuinely multidisciplinary; fueled by unrestrained creativity; driven by new technology; aggressively focused on human disease and its treatment; and both literally and figuratively just steps from the patient’s bedside. In this, it follows directly from the research tradition established at Houston Methodist by Dr. Michael E. DeBakey, whose spirit influences everything we do here. I hope the following pages will give you a sense of our approach and show a sampling of some of the work that we are doing here. I’m honored to be a part of it.
Mauro Ferrari, Ph.D. Ernest Cockrell Jr. Distinguished Endowed Chair President and CEO, Houston Methodist Research Institute Director, Institute for Academic Medicine Executive Vice President, Houston Methodist
A transformational vision for medical research
From its initial conception, the Houston Methodist Research Institute was always intended to be different from other medical research institutes. Directly affiliated with one of the nation’s finest hospitals, the Research Institute has the central objective of developing treatments with ready applicability to human disease — using its physical connection to the hospital to streamline the process of translating laboratory research to treatments and cures for patients. Today, this emphasis is being taken even further. With a new 440,000-square-foot research building that is connected to and integrated with Houston Methodist Hospital, the Research Institute is adopting a new, transformational approach to medical research.
The toughest challenges Despite extraordinary advances in the understanding and treatment of human disease, there remain significant, central challenges that have defied the development of categorically effective treatment. The Houston Methodist Research Institute is deliberately focusing on these challenges, working towards improved understanding, and new treatments for the most dangerous diseases our patients face: • Metastatic cancers • Heart disease • Neurological injury and neurodegenerative disease • Diabetes • Infectious disease • Orthopedic injury Our approach combines highly advanced technological resources with collaborative approaches that are designed to help research scientists draw from any field that has applicability to the work at hand. A truly Multidisciplinary approach The nature of scientific education, grant funding, and institutional structure has long had the unintended effect of creating narrow
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silos, grouping together researchers within a single discipline (e.g., medicine, biology, chemistry, and engineering) and suppressing collaboration across these disciplines. At the Houston Methodist Research Institute, in contrast, we are actively encouraging multidisciplinary research teams and methodologies. Further, we are aggressively integrating scientists from fields that are historically separated from traditional medical research: physics, mechanical engineering, materials science, computer science, mathematics, and emerging hybrid fields such as bioinformatics — combining scientific investigation with advanced algorithms that can extract meaningful, actionable conclusions from vast amounts of undifferentiated data. NATIONAL LEADERSHIP Our faculty’s combination of complementary and contrasting ability, training, and background is reflected in the fact that we are the only institution in the country to have three funded National Cancer Institute (NCI) Centers, one in each of the most innovative NCI focus areas: Systems Biology, Nanotechnology, and Physics-Based Oncology.
Technological emphasis Active multidisciplinary collaboration is aided by an institute-wide commitment to advanced technology — not only as a tool to aid in research, but also as an end in itself. So on the one hand, we can use advanced micrography to visualize nanoscale structures. On the other, we can combine a microbiologist’s understanding of a biological process with an engineer’s ability to design and construct a nanoscale device that mimics or disrupts that process — creating a new technology with a potential therapeutic application. Focus on clinical application A final defining characteristic of the Houston Methodist Research Institute is an approach to research program selection that favors work which pushes beyond basic science and theoretical research to focus on translational and clinical applications. Essentially, we prioritize research that drives directly towards the bedside, and whose intended result is directly applicable to the clinical treatment of human disease.
The facility
The Houston Methodist Research Institute makes its home in a new 12-story building that is integrated directly into the Texas Medical Center campus of Houston Methodist Hospital. This connection is significant and deliberate: it is a physical commitment to our vision of research that links directly to patients’ needs, and it helps to ensure that our faculty and staff never lose sight of the reasons why they are performing their work. Vertical integration The Houston Methodist Research Institute and its laboratory and technological resources also offer a vertically integrated approach to translational and clinical research — allowing researchers and scientists to progress from idea to molecule to clinical (patient) application in a single facility. Workspace The 440,000-square-foot Research Institute building includes some 150,000 square feet of laboratory space, a 70,000-square-foot vivarium, and office space for 90 principal investigators, and 800 research fellows and support staff. It also includes fully networked and videoconference-enabled auditorium space, boardrooms, and lecture halls. 6
Houston Methodist Research Institute
Strategically planned common areas, including nine coffee bars and lounges, are designed to encourage the sharing of ideas and facilitate collaborations that might be missed if scientists simply stayed in their labs. This deliberate flexibility extends to many open-form lab spaces as well, with movable, modular benches, and tables linked to flexible overhead power and utility drops. Advanced technology Another distinguishing element of the Houston Methodist Research Institute is the extraordinary array of technological resources that are available to support the scientists who work here.
Cyclotron. Used to create radioactively tagged isotopes for imaging and research, the cyclotron at the Houston Methodist Research Institute is connected through an underground system of shielded conduits to select labs in the building — allowing rapid, efficient transmission of these short-lived particles to the labs where they are needed. Imaging. In addition to industry-standard imaging modalities, the main imaging suite in the Houston Methodist Research Institute includes: • Single photon emission computed tomography (SPECT) equipment, which uses gamma rays to provide a truly three-dimensional view of the internal structures of the body
MITIE The Houston Methodist Institute for Technology, Innovation & Education sm
MITIESM is a highly advanced, American College of Surgeons–certified education and research institute, created and directed by Dr. Barbara Bass, holder of the John F. Jr. and Carolyn Bookout Distinguished Endowed Chair of Surgery and chair of the Department of Surgery at Houston Methodist Hospital. Occupying the entire fifth floor of the Houston Methodist Research Institute, MITIE offers over 35,000 square feet of training and research space, including a virtual hospital, procedural skills lab, and research operating rooms. MITIE is designed to provide training to practicing physicians and their teams in new, advanced surgical techniques, and the use of new medical technologies. It also helps them maintain skills in safe, simulated environments. MITIE’s research mission is focused on developing validated measures of competence in procedural skills, computer-aided surgery, robotics, and the development of new surgical techniques and technology. • Wide-bore magnetic resonance imaging (MRI), providing a wide field of view and ultra-high-power scanning ability • Positron emission tomography (PET), which can detect the presence and behavior of radioactive isotope markers within the body — providing valuable information about biological activity, disease progression, or other physical functions Microscopy. In keeping with the institution’s active involvement in nanotechnology research, the Houston Methodist Research Institute has invested in high-resolution microscopy that can resolve images at the nanometer level — down to scales as small as one-billionth of a meter. These technologies include: • A confocal laser scanning microscope • An in-vivo multi-photon laser scanning microscope
Spectroscopy. The Houston Methodist Research Institute also has a Coherent anti-Stokes Raman Scattering (CARS) spectroscope — a device that applies laser light to materials such as human tissue, then analyzes the ways in which the material scatters the light. Differences in the way that the light is scattered provides insight into the molecular behavior of the material or the tissue; differences in the ways that healthy tissue and diseased tissue scatter light may ultimately make a CARS spectrograph into a valuable non-invasive diagnostic tool. Good Manufacturing Practice (GMP) facility. The GMP facility at the Houston Methodist Research Institute is approved by the FDA for the on-site production of molecules, medications, and vaccines for translational and clinical research purposes.
Translational Research The Houston Methodist Research Institute focuses primarily on translational research — aiming to bridge the gap between laboratory science and clinical research through multidisciplinary approaches designed to speed up the development of new therapies and new cures. This “bench to bedside” approach is reflected in the research currently underway here, with physicians, scientists, and engineers using cutting-edge technologies, creativity, and ingenuity to develop new treatments for disease.
Bioinformatic approaches to medical research
Dr. Stephen Wong is holder of the John S. Dunn Distinguished Endowed Chair in Biomedical Engineering, director of the bioengineering and bioinformatics programmatic core, and Chief Research Information Officer at the Houston Methodist Research Institute. In an example of the distinctly different approach the Research Institute takes toward scientific disciplines, Dr. Wong is a computer scientist, bioengineer, medical physicist, and systems biologist, rather than a medical doctor.
Drug repositioning One challenge that Dr. Wong and his collaborators are addressing is the slowing pace of new drug development. This is partly the result of the extended process required to bring a new drug from development through clinical testing to final regulatory approval, and partly the result of scientists’ running out of known biological targets to hit. Dr. Wong’s team is instead using computer algorithms to search for existing or approved drugs whose side effects and mechanisms may make them applicable to other illnesses. In one example, he and his team have identified a new use for a drug, dasatinib, already approved to treat certain types of leukemia. Based on his computer analysis, he has identified it as a candidate for use against breast cancer stem cells. A second drug, sunitinib (used to treat certain kidney cancers) may also be effective against breast cancer metastasis to the brain. Since these drugs are already FDA approved, they have gone directly to Phase II clinical trials under the direction of Dr. Jenny Chang, Director of the Houston Methodist Cancer 8
Houston Methodist Research Institute
Center. In effect, Dr. Wong’s approach has reduced from 10 years to 18 months, the time it takes to move an investigational drug into the clinical trials stage.
Cancer stem cell modeling Cancer stem cells are known to be the precursor cells from which cancer cells are created; some consider them the “root” of cancer. These cells are, however, extremely difficult to isolate. Using advanced microscopic imaging and molecular biology techniques, Dr. Wong and his team are working to develop a better understanding of breast cancer stem cells, and to create mathematical and computational models for simulating their behavior. Dr. Wong received a National Cancer Institute Center Grant, supporting research in this field at the new Center for Modeling Cancer Development. By learning how these cells react to different types of stimuli, Dr. Wong hopes to develop a comprehensive computer model that can accurately predict the response of these elusive stem cells to different medications. If he and his team are successful, they will have created an accurate, virtual stem cell that can help predict the response of these stem cells to different medications — potentially helping predict what drugs will be effective in preventing cancer from spreading, or even killing it off altogether.
Image-guided intervention for lung, prostate, and breast cancer With many types of lung cancer, diagnosis alone can require as many as four different imaging studies and image-guided biopsy procedures. Dr. Wong and his team
2 are working to develop a new system using 3D molecular imaging to guide a fine needle into potentially cancerous nodules in a patient’s lungs, view the nodules through an integrated microscope, and draw cells from the nodule for testing. If these nodules prove cancerous, the same system will be used to destroy them using radiofrequency ablation — pinpoint pulses of high-frequency energy. Partnering with the surgeons at Houston Methodist, Dr. Wong and his team are extending their image-guided device platform for use in prostate and breast cancer cases as well. This work was supported by a grant from the Cancer Prevention Research Institute of Texas (CPRIT).
New approaches to combat neurodegenerative disease In another project, Dr. Wong and his team are using advanced computational analysis and high-throughput imaging to gain new understanding of, and develop new treatments for, neurodegenerative diseases such as Alzheimer’s disease. This computerized approach, based on rapid imaging and analysis of the billions of neurons and trillions of synapses that make up the human brain, was jumpstarted by a multi-million dollar donation from the Ting Tsung and Wei Fong Chao Foundation.
Gene signatures for cancer stem cells
Cancer is, in its simplest sense, uncontrolled cell growth. Within any cancer patient’s cancerous growth, however, there are different types of cells. Cancer stem cells are the original source of the cancerous activity, seemingly directing the progression of the cancer. Yet these cells are exceptionally difficult to locate and isolate, and in many cases they are powerfully resistant to known chemotherapy agents — meaning that while chemotherapy can sharply reduce or even eliminate much cancerous growth, it often leaves the stem cells untouched. This can leave the patient vulnerable to cancer recurrence or metastasis.
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1: A molecular model of sunitinib bonded to the RET proto-oncogene — a gene that drives development of certain cancers 2: Dr. Stephen Wong. 3: CARS spectroscope image of the glandular structure of the prostate. 4: CARS spectroscope image of human breast cancer cells. 5: A cluster of cancerous breast cells; stem cell marked in red. 6: Arrows indicate breast cancer stem cells with mesenchymal connective tissue characteristics. 7: Lung blood vessels with a representation of an image-guided needle for lung cancer diagnosis and therapy.
Dr. Jenny Chang, director of the Houston Methodist Cancer Center, focuses on the nature and behavior of cancer stem cells in her research. In one study,* she and her team demonstrated that after patients with certain types of breast cancer receive chemotherapy or hormone treatments, the percentage of these tumor-initiating stem cells in the remaining malignancy actually increases — potentially increasing the aggressiveness of the cancer that remains. In a second study,** Dr. Chang and her colleagues focused on a portion of these resistant cancer stem cells, studying patterns in the way their genes are expressed. They found significant similarities between the genetic behavior of these resistant cells and that of mesenchymal stem cells — a noncancerous stem-cell variety that gives rise to certain connective tissues. This overlap may provide new insight into the mechanisms by which this type of cancer stem cell generates new malignancies, and may ultimately suggest vulnerabilities that can be attacked by the next generation of cancer-fighting drugs. * Journal of the National Cancer Institute. 2008 May 7;100(9):672-9. ** Proceedings of the National Academy of Sciences of the U.S.A. 2009 Aug 18;106(33):13820-5.
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New understanding of group A streptococcus
Dr. James M. Musser, holder of the Fondren Endowed Distinguished Chair; chair of the Department of Pathology and Laboratory Medicine; Director, Center for Molecular and Translational Human Infectious Diseases Research; and Senior Member of the Houston Methodist Research Institute; is internationally known for his work in infectious disease research, including the study of group A streptococcus (GAS). This bacterium causes diseases ranging from strep throat to necrotizing fasciitis — the so-called “flesh-eating” disease. In three major papers published in the Proceedings of the National Academy of Sciences, Dr. Musser and colleagues reported major advances in our understanding of the genetic makeup of these bacteria, and in understanding how they interact genetically with the host over the course of an infection.
GAS molecular pathogenomics* In two of these studies, the team sequenced complete genomes of bacteria involved in three different epidemics of “flesh-eating”
A false-color scanning electron micrograph of group A streptococcus bacteria (shown in blue). Image courtesy Dr. James M. Musser.
bacteria, learning that differences in the ways that patients responded to the infection may in fact be related to subtle but significant differences in the genetic makeup of different bacteria within the same strain — suggesting new ways to attack the most virulent forms.
GAS-host interaction** In the third study, Musser’s team mapped the precise ways in which GAS changes gene expression in host cells during an infection cycle — providing an extraordinary, day-by-day, gene-level portrait of the ways that the human immune response is defeated by the GAS infection, and potentially providing new insights into ways to disrupt or prevent these infections. * Proceedings of the National Academy of Sciences of the U.S.A. 2010 Jan 12;107:888-893. Proceedings of the National Academy of Sciences of the U.S.A. 2010 Mar 2;107:4371-6. ** Proceedings of the National Academy of Sciences of the U.S.A. 2010 Mar 9;107:4693-8
siRNA delivery through multi-stage nanoscale vectors
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Engineered nanoscale materials are man-made molecular structures whose size is measured in nanometers (one nanometer = one billionth of a meter). Their minute size, and their ability to serve as protective carriers for therapeutic drugs or other molecules, makes them one of the most promising avenues for translational medical research. Dr. Mauro Ferrari, President and CEO of the Houston Methodist Research Institute, is at the forefront of the field. He led the development of the National Cancer Institute’s program in nanotechnology, which remains the largest nanomedicine program in the world. Dr. Ferrari also leads two of the Research Institute’s National Cancer Institute Innovation Centers: the Physical Sciences-Oncology Center and the Center of Cancer Nanotechnology Excellence. One of his specialties is using nanoparticles to carry strands of small interfering RNA (siRNA) into diseased cells. siRNA molecules are short segments of genetic code that play an important role in controlling gene expression — essentially turning genes on and off. Customized strands of this siRNA have great therapeutic potential, as they may be able to disrupt the growth and replication of cancer cells in the body. The challenge is in their delivery: siRNA molecules are fragile, and are quickly degraded when injected into a patient to treat a malignancy. As outlined in Nature Reviews Clinical Oncology, Dr. Ferrari and his colleague Rita Serda have proposed a novel way of delivering these delicate molecules directly to disease sites in the body, using a two-stage system of nanoparticle carriers to protect siRNA and deliver it where it is needed.
4 1,2: False-color scanning electron micrographs of “mother ship” nanoparticles attaching to cell membranes. 3: False-color scanning electron micrographs of “mother ship” nanoparticles in solution. 4: An artist’s rendering of a “mother ship” nanoparticle discharging its secondary payload of therapeutic siRNA particles.
protecting it from enzymatic damage or immune system attack. These first-stage particles are designed to attach to the cell surface and be drawn into the cell interior, where they then release the second stage — nanoparticles containing therapeutic siRNA molecules — directly into the spaces inside the cell where they are needed. Nature Reviews Clinical Oncology 7. 485-486 (September 2010)
The first stage is a larger particle — the “mother ship” — designed to safely carry its payload through the body while Houston, Texas
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Biosynthetic “fracture putty”
The most severe bone injuries are often repaired with a combination of bone grafts, pins, plates, screws, and even external fixators that hold pieces of bone in position during the healing process. These repairs often necessitate multiple surgeries and extended periods of recuperation. Even so, patients are often left with uneven results in terms of function. Sometimes, doctors treating these “non-union” fractures have no choice but to amputate the affected limb. Through a grant from the U.S. Department of Defense, orthopedic surgeon Dr. Bradley Weiner, Dr. Ennio Tasciotti, and a team from the Research Institute and other institutions are working to develop a different method for the repair of these severe orthopedic injuries — a point of particular interest for the Department of Defense, which is seeking more effective ways to avoid amputation and return soldiers to health after traumatic injury. In the project, Dr. Weiner and his colleagues have developed a form of “fracture putty” — called a BioNanoScaffold — designed to be injected into the site of the shattered bone. This putty includes nanoporous silicon embedded with bone growth factors; as it hardens, it will bear weight. In the meantime, the body’s own cells will gradually infiltrate the putty and begin creating new bone. As the putty slowly degrades, the regenerating bone will bear an
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1: BioNanoScaffold material (gray spheres) and growth factors (magenta) are injected into the fracture site. 2: As the material hardens, the body’s bone-creating cells infiltrate the area. 3: The BioNanoScaffold material naturally deteriorates, leaving behind healthy cells. 4: New bone forms, completing the healing process.
increasing share of the patient’s weight — aiding in functional recovery and strengthening the bone. Successful results may one day change the way severe injuries to bones are treated and may help to prevent countless amputations, for soldiers and civilians alike.
“ BioNanoScaffolds combine the mechanical advantages
of biodegradable synthetic polymers with the biological functions of natural biomaterial scaffolds. This approach achieves the correct strength requirements while enhancing the regeneration of healthy bone tissue at the fracture site.
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– Bradley K. Weiner, MD Vice Chair,
Department of Orthopedic Surgery
Medical Director, Surgical Advanced Technology Lab
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Nanoscale MRI contrast agents
Nanoparticles may have applications in imaging as well. Magnetic resonance imaging, or MRI, uses magnetic fields to agitate the water molecules that exist in every part of the human body. The resulting changes in the behavior of these molecules are recorded — and the difference in the way these molecules react in various tissues helps to create a picture of the tissues themselves. In many cases, special contrast agents are used to increase the visibility of certain physiological structures or specific types of tissue — such as diseased or cancerous
tissues. The most common such contrast agents are based on ions of the element gadolinium, which must be specially modified to reduce their toxicity to the patient. This modification, however, reduces the effectiveness of the contrast agent. Dr. Paolo Decuzzi has developed a new way to safely deliver gadolinium-based contrast agents while also making them up to 50 times more effective in MRI scans — potentially helping doctors make clearer, more accurate diagnoses.
A rendering of the discoidal nanostructures used to carry contrast agent–embedded nanoparticles for intravenous delivery. Each discoidal structure is approximately 1,000 nm in diameter.
His new method, published in Nature Nanotechnology, involves inserting gadolinium contrast agents into tiny pores — a few billionths of a meter in diameter — generated in silicon-based nanoparticles. These nanoparticles are then delivered intravenously to the patient. This method simultaneously protects the patient from chemical toxicity while making the contrast agent more effective. Nat Nanotechnol. 2010 Nov;5(11):815-21.
nDS2 Membrane
Control Circuit
Sensor Unit
Battery
Drug Resevoir
Nanochannel delivery systems: toward an “artificial gland” A conceptual rendering of an artificial gland Traditional delivery methods for potent medications such as chemotherapy drugs include IV infusion or bolus injection. These methods tend to create concentrated, high-toxicity surges of medication that exceed therapeutic levels for the patient; the effective dose is only achieved for a short period as the drug’s concentration declines.
Rendering of an nDS nanochannel membrane, showing the route traveled by a therapeutic molecule as it is released into a patient’s body
A possible solution is an implantable device — a nanochannel delivery system, or nDS — that releases medication at a controlled rate over a long period of time. In pursuit of this vision, Dr. Alessandro Grattoni, Dr. Mauro Ferrari, and their fellow researchers have demonstrated that nanochannel “membranes,” designed to suit the molecular size of the drug agent, can be used as part of an implantable system that releases medication at a steady rate, maintaining an effective drug
concentration in the patient over extended periods of time. Further, the application of low-voltage electrical field to the nanochannel membrane can adjust the rate of drug delivery, suggesting a remotely regulating — or even self-regulating — drug delivery system: an “artificial gland.” Additional testing of the nDS concept took place in space aboard the SpaceX Dragon spacecraft. The microgravity of space allows experiments on nanochannel distribution to be carried out on a merely microscopic scale — orders of magnitude larger than earthbound nanoscale experimentation. Pharm Res. 2011 Feb; 28(2):292-300.
Self-powered proteomic diagnostics
Human blood is filled with protein biomarkers. Rapid assay systems can detect the presence or absence of these biomarkers in a blood sample, or even assess the levels of particular markers — in many cases providing almost immediate diagnostic information. Most rapid assay systems, however, require pumps, power supplies, and fluid handling systems, limiting their portability and utility. Dr. Lidong Qin and his colleagues have developed a tiny, self-powered chip that uses the energy output from a chemical reaction to separate blood into plasma
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and cells, then rapidly determines the presence and levels of numerous diagnostic proteins in the plasma. The physician or lab technician need only place a tiny blood sample on the chip, then press a button on the surface. A chemical reaction taking place between two microscopic layers of the chip then draws the blood plasma downward through nanochannels into the chip, separating the plasma from the blood and putting the plasma in contact with a preset array of antibodies — with their visible reaction recording the results of the assay.
A rendering of a droplet of blood on the surface of an assay chip. Spheres represent proteins in plasma.
To support his development of new, integrated proteomic micro-devices like these for cancer diagnosis, Dr. Qin received the CPRIT Scholar in Cancer Research Award from the Cancer Prevention Research Institute of Texas. Lab Chip. 2009 Jul 21; 9(14):2016-20.
Clinical Research Clinical research describes the carefully regulated process of testing new medications and new therapies in a clinical setting. A successful clinical trial is the final step before a new treatment can be rolled out to the larger patient population and they are a critical part of the work we do at the Houston Methodist Research Institute. In fact, the active programs of clinical research at the Research Institute help provide Houston Methodist patients with ready access to novel treatments — helping to advance the standard of the care we provide.
Neurostimulation treatment for heart failure
Heart failure describes the condition in which the heart muscle is unable to pump effectively to deliver sufficient blood and oxygen to the body. A progressive disease, it is extremely dangerous, with as many as 75 percent of patients diagnosed with heart failure dying within 12 months. Dr. Guillermo Torre-Amione, a specialist in heart failure at the Houston Methodist DeBakey Heart & Vascular Center, was the principal investigator of a study that aimed to treat heart failure not by adding additional medications to the patient’s regimen, but rather through electrical stimulation of spinal nerves. The study used technology similar to that of a pacemaker to deliver tiny electrical impulses to areas on the spinal cord that affect the function of the heart. These impulses are designed to moderate the body’s natural inflammatory response to heart injury from heart attack or infection — a response that actually plays a major role in worsening the heart’s condition. The study tested the effectiveness of neurostimulation in 10 patients with heart failure. Dr. Torre and his team hope that neurostimulation will help improve the heart’s pumping ability, help control blood pressure, and reduce the number of fatal cardiac arrhythmias in patients — ultimately serving as the first step toward a new and effective treatment for heart failure. Fluoroscope images of neurostimulation leads implanted along a patient’s spinal nerves
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Neuroprotective medication for spinal cord injury
The potentially destructive nature of the secondary response to trauma was the focus of another clinical research trial, this one seeking to assess the effectiveness of a drug treatment for patients who have suffered spinal cord injury. Led by Dr. Robert G. Grossman, who holds the Robert G. Grossman Chair in Neurosurgery at the Houston Methodist Neurological Institute, the trial was conducted by the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury. The trial was supported by the U.S. Department of Defense through the Christopher & Dana Reeve Foundation, and Houston Methodist Hospital was the coordinating center for NACTN and for the trial.
In this Phase I trial, investigators tested the effectiveness of a neuroprotective drug called Riluzole in limiting the neurological effects of traumatic spinal cord injury. Riluzole blocks the entry of sodium and calcium ions into injured nerve cells. The hope of the study is that Riluzole will control the cascading damage caused by entry of these ions into nerve cells in the spinal cord. If the study is a success, it will be an important step towards reducing the devastating effects of spinal cord injury.
Activating BAT for weight reduction and metabolic control
The human body has been found to contain two different types of fatty (adipose) tissue — white adipose tissue, or WAT, and brown adipose tissue (BAT). Brown adipose tissue is present in newborn infants, in whom it burns stored fat molecules to generate heat and maintain body temperature. Until recently, it was assumed that BAT is not present in adults. Advanced imaging studies have, however, shown that adults do have BAT deposits in certain areas of the body. Further research has shown that BAT in adults plays an important role in balancing body weight and controlling metabolic parameters such as insulin sensitivity. Dr. Willa Hsueh, co-director of the Center of Excellence in Diabetes, Obesity and Lipids at Houston Methodist Hospital, is actively pursuing research aimed at understanding in detail the ways in which BAT works. In addition, she and her team are working to develop new ways to stimulate the beneficial effects of BAT, and even to drive the body to increase production of BAT by promoting differentiation of fat precursor cells into BAT rather than WAT. Ultimately, it may prove possible to engage the body’s own processes to help control weight and correct the errors in insulin sensitivity that can contribute to metabolic syndrome and diabetes.
Dr. Willa Hsueh
Pioneering robot-assisted surgery
Advanced computer-aided surgical robots are showing excellent results in surgical repairs — and Houston Methodist Hospital is a leader in their operating-room use. Dr. Gerald Lawrie, who holds the Michael E. DeBakey, M.D. Chair in Cardiac Surgery at the Houston Methodist DeBakey Heart & Vascular Center, has pioneered the use of the da Vinci surgical robot in performing a highly effective mitral valve repair procedure he designed called the “American Correction.”
The da Vinci ® Surgical System in use
This procedure was originally performed as an open procedure — with a cut through the sternum, called a sternotomy. Dr. Lawrie worked with the da Vinci robot for several months, crafting the surgery as a robot-aided, less-invasive procedure performed through
four small incisions in the patient’s side. These incisions allow the introduction of three tiny surgical arms and a 3D stereofocal microscopic camera. The surgeon controls the surgical instruments through an interface that provides pinpoint control and even greater precision than the surgeon’s own hands. Dr. Lawrie’s approach is remarkable in that rather than compromising the original technique to fit the robot, he uses the robot as a tool to perform the entire original repair technique without opening patients’ chests. This innovation results in outcomes that match those from the open repair while also reducing pain and speeding recovery time for the patient.
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Plato’s Cave: Advanced 3D anatomical modeling
In planning for invasive surgical procedures or focused radiation therapy, physicians have long had to extrapolate from many different sources of information to get an accurate, complete picture of the patient’s anatomy and the course of the disease. X-rays, CT scans, MRI, functional MRI, diffusion tensor imaging (DTI), high-resolution ultrasound (HRUS), four-dimensional fluid dynamics, and PET scans all give physicians some of the information they need, but they are at best still separate pieces of a complex puzzle. Dr. E. Brian Butler, chair of Radiation Oncology at Houston Methodist Hospital, worked with Houston Methodist’s 3D advanced visualization expert Paul Sovelius to develop a remarkable 3D system that combines the data from multiple types of scans to create a single, comprehensive digital image of the patient’s internal anatomy. They call it Plato’s Cave, in a reference to the allegory of prisoners in a cave whose perception of reality was limited to shadows on a cave wall. Only through escaping this cave would these prisoners come to understand the true nature of the world. Analogously, physicians can use this new 3D “dual-reality” technology to gain a truly accurate internal view of a treatment area. They can then navigate through this 3D view to help them precisely plan a surgery; develop a radiation plan that maximizes radiation delivery to cancerous tissues while minimizing its absorption by healthy tissues; or even perform a detailed surgical simulation in advance of the actual procedure. Plato’s Cave may ultimately change the ways that surgeons and radiologists approach cases — helping to increase accuracy and improve patient outcomes.
Plato’s Cave: high-resolution 3D image of a patient’s internal anatomy, including bones, organs, and blood vessels
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Houston Methodist Research Institute
The Houston Methodist Research Institute (at center) in the Texas Medical Center, Houston, Texas
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Houston Methodist Research Institute 6670 Bertner Street Houston, TX 77030 houstonmethodist.org/research
Cover photo: Aker/Zvonkovic Photography