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METHODOLOGY The Research and Education Newsletter of Houston Methodist

SPRING 2016

Landmark preclinical nanoparticle study shows efficacy for triple negative breast cancer treatment by Gale Smith & Maitreyi Muralidhar

A team of investigators from the Houston Methodist Research Institute may have transformed the treatment of metastatic triple negative breast cancer by creating the first drug delivery system to successfully eliminate lung metastases in mice models. Results from this landmark study appeared in Nature Biotechnology. Mauro Ferrari, Ph.D., president and CEO of the Houston Methodist Research Institute and Haifa Shen, M.D., Ph.D., are co-senior authors on the paper.

In this study, 50 percent of the mice treated with the new drug delivery system had no trace of metastatic disease after eight months. That’s equivalent to about 24 years of long-term survival following metastatic disease for humans. >> CONT. PAGE THREE

We invented a method that actually makes the nanoparticles inside the cancer and releases the drug at the site of the cellular nucleus. We were able to do what standard chemotherapy drugs, vaccines, radiation, and other nanoparticles have all failed to do.

– Mauro  Ferrari, Ph.D. President and CEO Houston Methodist Research Institute


Contents Contents

FROM THE PRESIDENT Our physicians and scientists wake up every day with the goal of transforming the lives of patients by developing more effective treatments and cures. We invite you to learn about a few of the projects moving closer to the clinic and examples of the collaborative approach we take to solving medical challenges.

by xxxxxxxxxxxxxxxx

Featured News

In a Nature Biotechnology paper that could mark a watershed moment

Landmark preclinical nanoparticle study shows efficacy for triple negative breast cancer treatment...... 1

in the treatment of metastatic breast cancer, my coauthors and I describe a novel multi-stage drug delivery system - injectable

Research Highlights: Neurosciences

nanoparticle generator (iNPG) - that generates nanoparticles inside

Restoring movement to paralyzed muscles................................................4

time ever, we showed that 50 percent of mice treated with the iNPG

Tracing Alzheimer’s disease with a cyclotron....................................6

to almost 24 years of long-term survival in humans.

Study shows stroke and TIA patient outcomes best at experienced centers............................7 Research Highlights: Heart & Vascular Leading the way in the surgical treatment of complex cardiac tumors..................................................8

the tumor cells and releases the drug within the nucleus. For the first were free of metastatic disease after eight months which is equivalent

James M. Musser, M.D., Ph.D. and an international team of researchers have identified genetic changes that increase virulence of group A streptococcus which could be targeted for vaccine development. Under the direction of Philip Horner, Ph.D., our researchers are working on restoring movement to paralyzed muscles using neuroregeneration. In a PLOS One report that has captured the attention of both the medical community and the news media, John Cooke, M.D., Ph.D., and a team of scientists from Houston Methodist and Stanford University report that adults who use proton pump inhibitors are between 16-21 percent more likely to experience a heart attack than people who don’t – a finding that could change the way these common antacids are used.

The international Pumps & Pipes symposium........................................ 10

In this issue you will also read about how Michael Reardon, M.D., the world’s foremost expert in cardiac

Nanoneedles for generating new blood vessels in mice....................... 12

visualize these tumors. Our researchers are using nanotechnology to generate new blood vessels and a 4-D

Heart attack risk increases 16-21% with use of common antacid........... 14 Research Highlights: Cancer Hundreds of cancer possibilities arise from common skin mole mutation............................................... 16 New “4-D” lung cancer model could quicken discoveries.............. 18 Research Highlights: Translational Research Scientists identify molecular triggers for intercontinental epidemics of group A streptococcus..................... 20 Tracking aging and delivering genes with high-throughput microfluidics.....22 Education News Resident profile: Albert Huang, M.D........................... 24 First graduate from Swansea-Houston Methodist collaboration...................25 Summer research student program.................................................25 Of Interest New faculty members.....................26 In memory of David Bricker............27

autotransplantation for the treatment of complex cardiac tumors, is making use of 3-D printing to better lung cancer model to mimic tumor progression. We have also developed novel microfluidics-based platforms and are using them to study mechanisms of aging. The year 2015 also saw several key faculty recruitments in the priority areas identified in our strategic plan - Biotherapeutics & Regenerative Medicine; Outcomes, Quality & Health Care Performance; and Precision Medicine. An internationally recognized expert in the field of circulating tumor cells (CTCs) to combat cancer metastasis, Dario Marchetti, Ph.D., joined us as the new director of the Biomarker Research Program. Marc Garbey, Ph.D., joined Houston Methodist in August as the scientific director of the newly formed Center for Computational Surgery. A computational science guru, Garbey will be working on creating an intelligent operating room to improve patient safety, enhance real-time tracking of OR activities, and improve patient outcomes. We are also pleased to announce the arrival of Adaani Frost, M.D., an expert in pulmonary hypertension with extensive clinical research experience. Frost will be the director of the new Lung Center. Please join me in welcoming these new faculty members. On the education front, we graduated the first student from the collaborative doctoral program between Swansea University and the Houston Methodist Research Institute. As we celebrate these milestones, we are also acutely aware of the challenges ahead of us and the work that still needs to be done. In August 2015, we were deeply saddened by the loss of David M. Bricker. A science writer par excellence, David’s personal fight against cancer and that of many others across the world, reinforces our commitment to take on some of the toughest challenges in medicine.

Mauro Ferrari, Ph.D. Ernest Cockrell Jr. Distinguished Endowed Chair President and CEO, Houston Methodist Research Institute Professor of Biomedical Engineering in Medicine Director, Institute for Academic Medicine Executive Vice President, Houston Methodist Senior Associate Dean and Professor of Medicine Weill Cornell Medical College, New York, NY Read more online: HoustonMethodist.org/hmrinews


>> CONT. FROM PAGE ONE

First injectable nanoparticle generator could radically transform metastatic breast cancer treatment The majority of cancer deaths are due to metastases to

delivery process. The first component is the nanoporous

the lung and liver, for which there is no cure. Existing

silicon material that naturally degrades in the body. The second

cancer drugs provide limited benefit due to their inability

component is a polymer made up of multiple strands that

to overcome biological barriers in the body and reach the

contain doxorubicin. Once inside the tumor, the silicon

cancer cells in sufficient concentrations. Houston Methodist

material degrades, releasing the strands. Due to natural

nanotechnology and cancer researchers have solved this

thermodynamic forces, these strands curl-up to form

problem by developing a drug that generates nanoparticles

nanoparticles that are taken up by the cancer cells. Once

inside the lung metastases in mice.

inside the cancer cells, the acidic pH close to the nucleus

This new treatment strategy enables sequential passage through the biological barriers to transport the drug into

causes the drug to be released from the nanoparticles. Inside the nucleus, the active drug acts to kill the cell.

the heart of the cancer. The active drug is only released

Ferrari, who is considered one of the founders of

inside the nucleus of the metastatic disease cell, avoiding

nanomedicine and oncophysics (physics of mass transport

the multidrug resistance mechanisms of the cancer cells.

within a cancer lesion), and the Houston Methodist team

This strategy effectively kills the tumor and provides significant

are hopeful that this new drug could help cancer physicians

therapeutic benefit in all mice, including, never before seen

cure lung metastases from other origins, and possibly

long-term survival in half of the animals.

primary lung cancers as well.

Houston Methodist has developed good manufacturing practices (GMP) for this drug and plans to fast-track the research to obtain FDA-approval and begin safety and efficacy studies in humans in 2017. “I would never want to overpromise to the thousands of cancer patients looking for a cure, but the data is astounding,” said Ferrari, the Ernest Cockrell Jr. Presidential Distinguished Chair at the Houston Methodist Research Institute and senior associate dean and professor of medicine, Weill Cornell Medicine. “We’re talking about changing the landscape of curing metastatic disease, so it’s no longer a death sentence.” The Houston Methodist team used doxorubicin, a cancer therapeutic that has been used for decades but has adverse side effects to the heart and is not an effective treatment

may sound like science fiction, “ This like we’ve penetrated and destroyed the Death Star, but what we discovered is transformational. If this research bears out in humans and we see even a fraction of this survival time, we are still talking about dramatically extending life for many years. That’s essentially providing a cure in a patient population that is now being told there is none, said Ferrari.

against metastatic disease. In this study, doxorubicin was packaged within the injectable nanoparticle generator that is made up of many components. Shen, a senior member of the department of nanomedicine at Houston Methodist Research Institute, explains that each

Xu R, Zhang G, Mai J, et al. An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nat Biotechnol. 2016 Mar 14. Epub ahead of print.

component has a specific and essential role in the drug The work was supported by grants from Department of Defense (W81XWH-09-1-0212 and W81XWH-12-1-0414), National Institute of Health (U54CA143837 and U54CA151668), and The Cockrell Foundation.

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Research Highlights: Neurosciences

Restoring Movement to Paralyzed Muscles by Gale Smith

Philip Horner, Ph.D., an expert on the use of stem cells to replace damaged brain and spinal cord tissue, is the scientific director of the Houston Methodist Neurological Institute’s new Center for Neuroregeneration. “Phil brings incredible experience in adult central nervous system regeneration, stem cells and gene therapy,” said Gavin Britz, MBBCh, chair of the Department of Neurosurgery. “His knowledge in cell repair and regenerative medicine will be a boon for our patients, and also extend the reach of neurosurgery science at Houston Methodist.” Horner comes to Houston Methodist from the University of Washington School of Medicine, where he was a professor of stem cell biology and neural repair in the Department of Neurological Surgery. He was also affiliated with UW’s Institute for Stem Cell & Regenerative Medicine. His research focuses on the manipulation of a patient’s own stem cells to regenerate cells damaged or lost following traumatic injuries. Horner and his team use two methods to create healthy pathways for an impulse to follow. The most common therapy is one in which a ball electrode is placed on the surface of the brain or spinal cord to create a broad area of activity. The second, more challenging technique requires implantation of wires in the brain or spinal cord. Ideally, the wires are placed in both

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RESEARCH HIGHLIGHTS The Hebbian theory is correct: neurons that fire together, wire together. What this means is that if you place these reprogrammed cells into an injured environment, they will behave as injured cells. Therefore, it is

crucial that rehabilitative technologies are put into place to create a pattern of movement, or deliberate action potentials that you want to restore.

– Philip Horner, Ph.D. Scientific Director, Center for Neuroregeneration Houston Methodist

the brain and spinal cord since the brain controls the spinal

“Instead of putting wires in the central nervous system,

cord. “The problem with wires is their ultimate rejection by the

activity-driving neurons would be equipped with channels

nervous system. In addition, we need to increase the power

that are light-sensitive. We could then install a series of

fairly continuously to assure adequate operation,” says Horner.

LEDs subcutaneously in the patient. For quadriplegia, for

The ultimate technology to create healthy neuronal pathways is optigenetics, according to Horner. Close to FDA approval for the restoration of sight in patients with macular degeneration,

example, we could begin with simply finding the pathways that can be stimulated with light to get some hand function. I think that’s very feasible,” says Horner.

optigenetics uses light to control the movement of neurons.

Currently, Horner and colleagues are working on a clinical

Optigenetics is a medical science gleaned through the study

trial in collaboration with the government of Andalusia, Spain.

of how ocean algae detected sunlight. Researchers learned

The study will reprogram skin fibroblasts into new cells with

that algae move by way of their flagella, which are equipped

the capacity to make new connections in the spinal cord for

with channels that are sensitive to certain wavelengths of sunlight.

chronically paralyzed patients.

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Research Highlights: Neurosciences

Tracing Alzheimer’s Disease with a Cyclotron The discovery of beta-amyloid, or β-amyloid, plaques in the brain inspired the design of a pioneering class of radiotracers for Alzheimer’s diagnosis with positron emission tomography (PET) imaging. Recent studies have shown that tau may be an even more effective marker for Alzheimer’s disease than β-amyloid. At Houston Methodist, physicians and scientists are developing a new class of radioactive biomarkers, or tracers, which can track abnormal levels and tangles of abnormal tau protein in the brain with PET. Brain inflammation, another key player in the development and progression of the disease, is also being measured with PET in a handful of centers around the world, including Houston Methodist. Together with β-amyloid, these two disease indicators provide a powerful approach to assessing disease progression.

In PET scans for Alzheimer’s disease we primarily use two radioactive particles–Carbon-11 and Fluorine-18–and with them we label tracers to image amyloid, abnormal tau and inflammation. In the Alzheimer’s brain, we see high levels of all three tracers. With PET imaging we can scan people at the various stages of the disease, even before symptoms develop.

– Joseph C. Masdeu, M.D., Ph.D. G  raham Family Distinguished Chair for Neurological Sciences Houston Methodist

Houston Methodist is one of the few medical institutions in Texas to have a cyclotron and cGMP radiopharmaceutical lab for the production of clinical grade radiotracers on-site. This aids in the production of clinically useful radiotracers that have a suitable half-life to decay quickly and reach inert stability in the body to minimize patient exposure to radiation. This is important for Carbon-11 labelled tracers for amyloid and inflammation with a half-life of 20.3 minutes, as well as the Flourine-18 labelled tracers for tau with a half-life of 109.8 minutes. The Nantz National Alzheimer Center at Houston Methodist is currently conducting several studies that incorporate radionuclide neuroimaging to detect abnormalities or injury to the brain. Dr. Masdeu is the principal investigator in majority of these studies that seek to clarify the neurobiology of Alzheimer’s and other neurodegenerative disorders. “But I could not pursue any of these studies without the asset of the Houston Methodist Cyclotron and Radiopharmaceutical Core, led by director Max Yu, Ph.D. says Masdeu.

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Study shows stroke and TIA patient outcomes best at experienced centers Researchers from Houston Methodist Hospital and five partner institutions used data from a major stroke clinical study to show that medical centers with more experience and expertise in aggressive medical management had a significantly positive impact on patient outcomes. This, according to research published in Neurology. Conducted from 2008-2013, Stenting and Aggressive

The study, Chiu said, also found that

Medical Management for the Prevention of Recurrent

the rates of excellent blood pressure

Ischemic Stroke (SAMMPRIS) was a National Institutes

and cholesterol control were superior

of Health-funded randomized clinical trial. The study

for patients who had undergone AMM

enrolled 451 patients in 50 institutions, who had suffered

at the more experienced centers. As

strokes or TIAs (also known as “mini-strokes”) attributed

for whether or not other factors

to severe stenosis (blockage) of a major intracranial artery.

besides a center’s experience might

The effectiveness of aggressive medical management

account for the better outcomes, he

or AMM versus stenting as a treatment was compared,

believes his team’s findings make a strong case.

with the former resulting in lower rates of recurrence and mortality. Using the SAMMPRIS patient data, a team led by

When we compared the frequencies of all known

David Chiu, M.D., Elizabeth Blanton Wareing Chair of

baseline characteristics and stroke risk factors,

the Houston Methodist Eddy Scurlock Stroke Center

there were a few differences between high-enrolling

and professor of clinical neurology at Hosuton Methodist,

centers and low-enrolling centers but the only factor

evaluated whether the experience of the stroke center and the expertise of the staff in using AMM for strokes

that explained the disparity in outcomes between

and TIAs led to the better outcomes.

the two groups was the center’s experience.

“We compared the rates of recurrent stroke or death for patients receiving aggressive medical management at the 12 centers with the highest study enrollment to

– David Chiu, M.D Elizabeth Blanton Wareing Chair of the Houston Methodist Eddy Scurlock Stroke Center Hosuton Methodist

those who received the treatment at the 38 with the lowest enrollment,” said Chiu. “We found a significant difference in the rates after both 30 days—1.8 percent for the high-volume centers and 9.8 percent for the low-volume centers—and after 2 years—7.3 percent versus 20.9 percent.”

Chiu D, Klucznik RP, Turan TN, et al. Enrollment volume effect on risk factor control and outcomes in the SAMMPRIS trial. Neurology. 2015 Dec 15;85(24):2090-7.

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Research Highlights: Heart & Vascular

Leading the way in the surgical treatment of complex cardiac tumors by Maitreyi Muralidhar

Cardiac tumors are rare and when malignant, are often associated with limited treatment options and dismal prognosis. They can either be primary tumors that arise from the heart or secondary tumors that have metastasized to the heart. For malignant and complex benign tumors, complete surgical resection is often the only optimal treatment option.

Photo: Robert Seale

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Michael Reardon, M.D. Allison Family Distinguished Chair of Cardiovascular Research Houston Methodist DeBakey Heart & Vascular Center


Reardon, M.D., the Allison Family Distinguished Chair in Cardiovascular Research and chief of the

Very few physicians or institutions have the experience or expertise in

division of cardiac surgery, is forging new pathways

performing cardiac autotransplantation.

in the surgical treatment of cardiac tumors. In a recent publication in the Annals of Thoracic Surgery,

Reardon has performed more cardiac

Reardon et. al. report on their experience with

autotransplants than any other surgeon

surgical treatment for 95 cases of primary cardiac sarcomas between 1990−2015. To date, this is the largest published surgical resection series of primary cardiac sarcomas in the world. In comparison, the Mayo Clinic comes in second with a published

in the world. In a previous study published in Annals of Thoracic Surgery, Reardon et. al. have shown

record of 34 cases over a 32-year period.

that autotransplantation is a feasible

Primary cardiac tumors that involve the left atrium

and safe technique to treat malignant

and the left ventricle are generally the most challenging to treat using standard surgical

and complex benign left-sided cardiac

techniques. This is due to anatomical constraints

tumors that are inaccessible via

and inaccessibility associated with the location. These limitations also make complete resection

RESEARCH HIGHLIGHTS

Houston Methodist cardiac surgeon, Michael

ordinary surgical resection.

technically difficult to achieve. Standard surgical approaches are also associated with a high incidence of recurrence in these tumors. Cardiac autotransplantation is a surgical procedure that can overcome limitations such as anatomic

Reardon is also making use of 3-D models to map out

inaccessibility to allow complete resection in complex

anatomical and structural specifications of tumors before

tumors. During autotransplantation, the patient is

embarking on such complex surgical procedures. MRI data

first put on cardiopulmonary bypass. The heart is

from a patient is fed into a specific computer program and

removed and the surgeon then resects the tumor,

sent to a 3-D printer to create the patient-specific 3-D

makes any necessary repairs to the heart structure,

models. Reardon recently used a 3-D model to better

inspects the heart, great vessels and left atrium

visualize a secondary heart tumor whose location was

for tumor infiltration, and then implants the heart

going to make the operation very challenging.

back into the patient. This technique allows optimal accessibility to the tumor for complete removal and

Using a 3-D model can take all the guess work out of

accurate reconstruction. In addition, unlike donor

planning for a complex surgical procedure. Reardon believes

heart transplantation that requires the timely availability

that in the future, surgeons will be able to look at a holographic

of a suitable donor heart, autotransplantation uses

display of a person’s anatomy and virtually perform the

the patient’s own heart, avoids lengthy wait time

procedure even before opening up the patient.

for donor organs and the need for prolonged immunosuppression.

Ramlawi B, Leja MJ, Abu Saleh WK, et al. Surgical Treatment of Primary Cardiac Sarcomas: Review of a Single-Institution Experience. Ann Thorac Surg. 2016 Feb;101(2):698-702.

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Research Highlights: Heart & Vascular

QUICK FACTS HOUSTON METHODIST

7 2,043 814,309 101,508 20,000 4,500 1,607 603 567 44 11,734 1,001 440,000 100,000 TOP 20 $47.8 M $131 M 10

Hospitals Operating beds

The International Pumps & Pipes Global Industries

Outpatient visits Admissions

Employees

Physicians Credentialed researchers Faculty Trainees

(residents, postdoctoral fellows & students)

GME programs

The 9th annual Pumps & Pipes symposium united professionals from the health care, aerospace and energy sectors to examine current cross-industry challenges and technologies.

CME, GME & MITIE learners Clinical protocols Sq.ft. dedicated research building with 12 stories and 150 lab benches Additional sq.ft. research space embedded throughout the hospital U.S. domestic hospital based research institutes Annual extramural funding Annual research expenditures

“ Pumps & Pipes is about the transfer of

knowledge between the energy world, the cardiovascular world and, more recently, the aerospace world. The other guy’s toolkit is something that we emphasize over and over because that’s where the solution often resides — we just need the opportunity to network and bring people together to explore ideas.

– Alan B. Lumsden, M.D. Walter W. Fondren III Distinguished Endowed Chair Houston Methodist DeBakey Heart & Vascular Center


RESEARCH HIGHLIGHTS

Symposium: Compare Notes

The most recent gathering in December of 2015, themed Discovery Pathways, featured several captivating presentations including, a NASA presentation, Getting to Mars; a live transcatheter aortic valve replacement broadcast from the clinical hybrid operating room; a live webcast from Keele University Observatory in England on the newly discovered Photo: Robert Seale

Jupiter-sized exoplanet, WASP-142B; and Making Sense of Drilling Data, by ExxonMobil. A total of 280 people attended the event at Houston Methodist. The 9-hour webcast was streamed to 2900 connections in 27 states and 44 countries. Pumps & Pipes is not only for industry professionals. The symposium now offers a community outreach program for

Alan B. Lumsden, M.D. Walter W. Fondren III Distinguished Endowed Chair Houston Methodist DeBakey Heart & Vascular Center

science, technology, engineering and math (STEM) students.

“Technology and competence transfer is a high priority for

In 2015, 40 students from eight Houston schools attended

us, and there is a strong drive to explore an international

the Pumps & Pipes symposium and hundreds of students

interactive platform between sectors to foster the sharing

watched the symposium webcast in classrooms around the

of knowledge and innovation,� said Stephen R. Igo, executive

city. At a new Mentors for Mentors symposium convened in

director of the Pumps & Pipes program.

the first half of 2015, fifteen educators from seven Houston Independent School District campuses attended a Pumps

Pumps & Pipes is growing internationally with plans for

& Pipes externship to learn how to apply concepts from

an affiliate in Europe to be headquartered in Stavanger,

engineering and medicine to challenges in both disciplines.

Norway. Visit pumpsandpipes.com for more information.

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Research Highlights: Heart & Vascular

NANONEEDLES FOR GENERATING NEW BLOOD VESSELS IN MICE by Maitreyi Muralidhar

Associate Professor of Nanomedicine, Ennio Tasciotti, Ph.D., and his collaborators from Imperial College London have developed a prototype of biodegradable nanoneedles that are 1,000 times smaller than a strand of human hair and are designed to deliver nucleic acids to specific body parts. This could be a new frontier in the treatment of degenerative diseases, damaged organs, transplant rejection, and musculoskeletal injuries.

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techniques, enabling precise control over the diameter of the tip, pore size, and length of the needle. The pores on the needle impart the nanoneedles with sponge-like features that allow them to load, retain and release a substantial amount of nucleic acids, nanoparticles, and proteins, when compared to traditional, solid structures. In addition, the size and shape of these nanoneedles allow them to bypass and effectively penetrate the outer membrane of a cell without causing any trauma. In their study, featured on the cover of Nature Materials, Tasciotti’s team describe how these nanoneedles could co-deliver DNA and siRNA with greater than 90% efficiency, while avoiding sub-cellular compartments designed to degrade the payload of nucleic acids. Furthermore, they demonstrated the unprecedented ability to efficiently deliver genes to a localized area of tissue yielding a

experiments revealed “ Our the efficiency of nanoneedles to improve the vascularization of specific areas via the generation of new blood vessels. This could be expanded to provide personalized treatment for each patient by locally reprograming cells of interest to achieve any desired effect.

Houston Methodist Research Institute using photolithography

RESEARCH HIGHLIGHTS

The biodegradable nanoneedles were fabricated at the

significant increase in the generation of new blood vessels.

– Ennio Tasciotti, Ph.D. Associate Professor of Nanomedicine Houston Methodist

New blood vessel formation continued over a 14-day period without any adverse effects or inflammation. Given the inherent biodegradability and biocompatibility of porous silicon, the use of nanoneedles is safe as they dissolve leaving behind a harmless compound, orthosalicilic acid, that is readily absorbed by the human body. Tasciotti who is also the director of the Center for Biomimetic Medicine and his team are now aiming to expand on these results. They envision developing nano-based bandages that contain nanoneedles to deliver specific genes for inducing local cell programming, and to aid in rapid wound healing and

This type of treatment will one day be able to provide therapy for conditions like ischemic heart disease or to prepare the local tissue microenvironment prior to the implant of tissue engineering scaffolds. Additional findings on the interface between cells and nanoneedles were published in the April 2015 edition of ACS Nano by Tasciotti and his collaborators from Imperial College London.

tissue response. In addition, they are exploring the role of nanoneedles in providing mechanical cues to cells to stimulate the regeneration of stem cell populations without relying on the use of any bioactive factor but relying only on the mechanical forces imparted on the target cell population.

Chiappini C, De Rosa E, Martinez JO, et al. Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. Nat Mater. 2015 May;14(5):532-9.

The ability to gain direct access to the cytoplasm and

Chiappini, C. Martinez JO, De Rosa E et al. Biodegradable nanoneedles for

induce high efficiency site-specific genetic reprograming

localized delivery of nanoparticles in vivo: exploring the biointerface. ACS Nano.

is an unmet need that could pave the way for new

2015 May 26;9(5):5500-9.

treatment approaches.

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Research Highlights: Heart & Vascular

HEART ATTACK RISK INCREASES 16-21% WITH USE OF COMMON ANTACID by David Bricker

Adults who use proton pump inhibitors are between 16 and 21 percent more likely to experience a heart attack than people who don’t use the commonly prescribed antacid drugs, according to a massive new study by Houston Methodist and Stanford University scientists. An examination of 16 million clinical documents representing 2.9 million patients also showed that patients who use a different type of antacid drug called an H2 blocker have no increased heart attack risk. The findings, reported in PLOS ONE, follow a Circulation report from 2013 in which scientists showed how -- at a molecular level -- PPIs might cause long-term cardiovascular disease and increase a patient’s heart attack risk.

“ Our earlier work identified that the PPIs c

Teflon-like lining of the blood vessels. Tha

taking PPIs may be at greater risk for hea of patients, we asked what happened to medications for the stomach.

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vascular medicine specialist Nicholas J. Leeper, M.D. In the present study, the researchers found a clear and significant association between exposure to PPIs and the occurrences

PPIs come in a variety of slightly different chemical forms, always ending with the suffix “-prazole,” for example, omeprazole

of heart attack.

or lansoprazole. Brand examples of PPIs

“By looking at data from people who were given PPI drugs

are Nexium, Prilosec, and PrevAcid.

primarily for acid reflux and had no prior history of heart

RESEARCH HIGHLIGHTS

The PLOS ONE study’s principal investigator was Stanford

disease, our data-mining pipeline signals an association with a higher rate of heart attacks,” said the PLOS ONE report’s lead author, Nigam H. Shah, M.B.B.S., Ph.D., an assistant professor of biomedical informatics at Stanford, where the

H2 blockers are another type of antacid drug. They are

work was done. “Our results demonstrate that PPIs appear

not believed to be associated with increased risk of heart

to be associated with elevated risk of heart attack in the

attack or cardiovascular disease. Examples of the drug are

general population, and H2 blockers show

cimetidine and ranitidine. Brand examples of H2 blockers

no such association.”

are Zantac and Tagamet.

The estimated increase of heart attack risk ranges from

The researchers collected data from two repositories

16 to 21 percent, because of uncertainty in the estimation

– STRIDE (Stanford Translational Research Integrated

process, Shah said.

Database Environment), which contains information about

The FDA estimates about 1 in 14 Americans has used

subset of information for 1.1 million patients from the

proton pump inhibitors. In 2009, PPIs were the third-most

Web-based electronic medical records company Practice

taken type of drug in the U.S., and are believed to account

Fusion, Inc. Both sources of patient information were

for $13 billion in annual global sales. Doctors prescribe

anonymized before the researchers accessed the data.

1.8 million Stanford hospital and clinic patients, and a

PPIs to treat a wide range of disorders, including gastro-esophageal reflux disease, or GERD, infection

The group scanned the databases for patients who were

by the ulcer-causing bacterium Helicobacter pylori,

prescribed proton pump inhibitors or other drugs, such as

Zollinger-Ellison syndrome, and Barrett’s esophagus.

H2 blockers, and also looked to see if a given patient had

The drugs can also be purchased over the counter.

a mention of having experienced a major cardiovascular event, such as myocardial infarction (heart attack), in their medical record. Patients who had used PPIs were found to be at 1.16-1.21-fold-increased risk of heart attack.

can adversely affect the endothelium, the

A 2013 report to Circulation by several of the present

at observation led us to hypothesize that anyone

report’s coauthors, including Cooke, raised the possibility

art attack. Accordingly, in two large populations

general population.

people that were on PPIs versus other

that PPIs could lead to cardiovascular disease in the

In the future, the researchers say they hope to conduct a large, prospective, randomized trial to determine whether

– John Cooke, M.D., Ph.D. Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research Houston Methodist

PPIs are harmful to a broader population of patients.

Shah, NH, Lependu, P, Bauer-Mehren. A. et al. PLoS One. 2015 Jun 10; 10 (6): e 0124653.

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Highlights Cancer Research Highlights:

Hundreds of cancer possibilities arise from common skin mole mutation by David Bricker

A Houston Methodist-led team of international scientists has identified hundreds of possible new genes in mice that could transform benign skin growths into deadly melanomas. An initial mutation, called BrafV600E, is found in 70 percent or more of benign birthmarks and moles in humans, and has long been believed to precede the development of melanomas, even though the Braf mutation alone does not seem to be enough to cause cancer. What skin cancer researchers have not had – until the present report in Nature Genetics – is a list of genes or genetic pathways that, once altered, work with the Braf mutation to cause cancer. The mutation BrafV600E is found in 70 percent or more of benign birthmarks and moles in humans. Scientists believe the Braf mutation alone isn’t enough to cause cancer. A variety of subsequent mutations identified in the present study, however, make melanomas possible. “We want to know what exactly must happen after someone acquires this mutation in Braf that causes something even worse to happen,” said Houston Methodist Research Institute cancer geneticist Michael Mann, Ph.D., the Nature Genetics report’s lead author. “We want to understand how this Braf mutation makes people vulnerable, susceptible to melanoma, so that we can help identify new targets for slowing or stopping growth.”

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RESEARCH HIGHLIGHTS

The scientists used a genetic tool, a transposon called “Sleeping Beauty” that was developed by Houston Methodist cancer geneticists Nancy Jenkins, Ph.D., and Neal Copeland, Ph.D., and an animal model developed by UC San Francisco cancer geneticist Martin McMahon, Ph.D., to identify the candidate cancer genes, or CCGs, that unleash BrafV600E’s terrible potential.

By using Sleeping Beauty transposon mutagenesis strategically, our group was able to identify an incredible

By letting Sleeping Beauty loose in the model’s genome and looking for meaningful outcomes, the scientists were able to identify 1,232 altered CCGs that, with BrafV600E, led to

number of genes that may cause nevi — moles and other

melanomas.

skin marks — to become cancerous. As we expected,

A comparison of human genes equivalent to those the

we haven’t just identified single genes that respond to the Braf mutation, but whole pathways that appear to contribute to cancer development. This is important, because if you look at it tumor by tumor, the same pathways may appear to be engaged, but not because

scientists identified in mice showed that more than 500 human genes, sampled from melanoma patients, were “enriched” for mutations and that these mutations appeared to be related to patient survival. A genetic survey of human melanoma patients whose skin biopsies already contain BrafV600E and other relevant mutations could be helpful to oncologists in predicting patient outcomes.

of changes to the same genes. If you looked only at

Last, the researchers found that one human gene, CEP350,

singular genes, you could miss what is really going

not previously been named a melanoma tumor suppressor

on, biologically.

gene. CEP350 encodes a protein believed to be crucial

appears to be required for tumor suppression. CEP350 had

for cell division. - M  ichael Mann, Ph.D. Cancer Geneticist Houston Methodist Research Institute

Mann MB, Black MA, Jones DJ, et al. Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma. Nat Genet. 2015 May;47:486-95.

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Highlights Cancer Research Highlights:

NEW “4-D” LUNG CANCER MODEL COULD QUICKEN DISCOVERIES by David Bricker

Without good models to study cancer metastasis -- the spread of cancer cells from one organ to another — cancer researchers have struggled to understand tumor progression fully, and

Researchers at Houston Methodist have invented a new, ex vivo lung

new therapies targeting the

the model are published in The Annals of Thoracic Surgery. The model

main causes of death are slow to come.

cancer model that mimics the process of tumor progression. Tests of developed by Min P. Kim, M.D. and colleagues produces results quickly and solves the problems of existing models used to study cancer progression. “Our model truly captures the phenomenon of cancer metastasis,” said Houston Methodist thoracic surgeon and Assistant Professor of Surgery Kim, the report’s principal investigator. The model can be used to study the progression of other cancers besides lung. The “4-D” model is created by removing all the cells from a vertebrate lung, leaving the enveloping matrix, which provides support for cell growth and development. The native lung matrix, once cells are removed, is further modified and placed in a bioreactor to allow for human tumor cells to grow.

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cells to form 3-D nodules that grow over time. Kim called an earlier version of the model “3-D ex vivo.” The new model’s fourth dimension is flow, Kim explained, as the latest version incorporates the movement of fluids between lungs through blood vessels. This fourth dimension allows the model to show the growth of primary tumors, the formation of circulating tumor cells (CTCs) and formation of metastatic lesions. These three steps of cancer progression aren’t a part of any single in vitro or ex vivo model. And unlike in vivo models of metastasis, which often require researchers to wait months for information about metastasis progression, the 4-D model can provide data in a matter of days. Kim and his colleagues also investigated gene expression in cancer cells during different phases of tumor progression. They found the gene signatures of experimental CTCs were associated with poor survival in lung cancer patients. “The model allowed for the isolation of unique gene signature of circulating tumor cell phase of metastasis, which may provide a clue to the mechanism of tumor progression,” Kim said. In future experiments, Kim said his group will focus on the unique gene signatures of circulating tumor cells to better understand the mechanism of tumor progression. Kim said this may provide

RESEARCH HIGHLIGHTS

Unlike other tumor models, the 4-D model allows the tumor

Phase II NECTAR Trial for Triple Negative Breast Cancer Houston Methodist will be the lead site on a Phase II multi-center clinical trial called NECTAR, designed to test Everolimus and Cisplatin combination therapy as a treatment for triple negative breast cancer (TNBC). Jenny C. Chang, Emily Herrmann Chair in Cancer Research and director of the Houston Methodist Cancer Center, initiated the original pilot study that identified Everolimus, a drug commonly used to treat kidney cancer, as a potential treatment for TNBC. The drug is thought to work by blocking enzymes needed for cell growth and blood flow to the tumor. The Triple Negative Breast Cancer Program at Houston Methodist is designed to integrate care for all women diagnosed with TNBC, and the NECTAR trial delivers on their commitment to fighting the most aggressive form of breast cancer.

ideas for new therapies that stop metastatic spread in patients with lung cancer. Also contributing to the Annals paper were Dhruva Mishra, Ph.D. (lead author), and Michael J. Thrall, M.D. (Houston Methodist), and Chad J. Creighton, Ph.D., Yiqun Zhang, and Fengju Chen (Baylor College of Medicine). The coauthors received funding support from the American Association for Thoracic Surgery Graham Research Foundation, the Houston Methodist Foundation, the National Institutes of Health, and the Cancer Research & Prevention Institute of Texas.

Mishra DK, Compean SD, Thrall MJ, et al. Human Lung Fibroblasts Inhibit Non-Small Cell Lung Cancer Metastasis in Ex Vivo 4D Model. Ann Thorac Surg. 2015 Oct;100(4):1167-74.

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Research Highlights: Translational Research

Scientists identify molecular triggers for intercontinental epidemics of group A streptococcus by Gale Smith

For the first time, scientists from the United

According to James M. Musser, M.D., Ph.D., principal investigator

States, Finland, and Iceland have pinpointed

Methodist Research Institute, the research showed, at the

molecular genetic events that contribute to epidemics of group A Streptococcus, which can cause everything from strep throat to “flesh-eating” disease. Researchers from Houston Methodist, the National Institute

and the Fondren Presidential Distinguished Chair Houston individual nucleotide level, factors that contributed to epidemics of group A streptococcus (GAS). “People may say, ‘So what?’ The answer to the ‘so what?’ is that this now gives us the opportunity to begin thinking about what we call translational medicine tools,” said Musser. “We can use this information in developing therapeutics, advanced diagnostic techniques and new ways to prevent, or at least to

of Allergy and Infectious Diseases, and

dampen, epidemics.”

international collaborators report their findings

According to the World Health Organization, GAS causes more

in the Journal of Clinical Investigation.

than 600 million cases of human disease every year. The majority of cases are group A streptococcus pharyngitis, more commonly known as strep throat. But group A strep is also the major cause of preventable pediatric heart disease caused by rheumatic fever and rheumatic heart disease. On the far end of the spectrum, group A strep also causes necrotizing fasciitis. Musser and team found that group A strep is a model organism to study the molecular basis of epidemic disease. Researchers have known for more than a century that this organism can cause epidemics, but no one has been able to fully address the cause. Now with next generation sequencing, scientists are able to sequence the entire genome of the bacteria, just as we do in humans. Group A streptococcus was selected as the model organism for study due to the high quality of its strain sample and its very small genome, which allows it to be sequenced in its entirety in thousands of isolates. The researchers’ original hypothesis, which turned out to be correct, was predicated on changes in the GAS pathogen. To address this hypothesis, Musser and the international team sequenced the genome of thousands of strains, precisely defining every base pair in the strain.

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RESEARCH HIGHLIGHTS

Houston Methodist Receives $2.8 Million to Identify Lung Cancer Therapy Targets by Erika Hayes and Rebecca Hall, Ph.D. Stephen Wong, Ph.D., John S. Dunn, Presidential Distinguished Chair in Biomedical Engineering was awarded a $2.8 million 5-year UO1 grant from the National Cancer Institute (NCI) to identify non-small cell lung cancer (NSCLC) therapy targets critical for tumor-stroma crosstalk. “The surprise was that the changes involved alterations in the genes encoding two potent toxins

The supporting stromal tissue of the lung contains tumor suppressing properties,

that contribute to human infections,” said Musser.

but as a tumor develops, the stroma adapts to promote tumor growth and invasion. This collusive relationship relies on communication between the tumor and stroma

The researchers found that in the epidemic form

known as crosstalk pathways. The proposed research exploits these tumor-stroma

of group A streptococcus, which manifests as

crosstalk pathways as a largely untapped source of drug targets.

necrotizing fasciitis or the “flesh-eating” disease, there were three significant changes within the

Strong candidate targets would be critical for crosstalk, and when they are checked,

genetic regulatory region of the pathogenic bacteria.

would stop the stroma from nurturing tumor growth. This is the focus of the NCI

The regulatory region is involved in how genes are

funded project that will be done in collaboration with Vivek Mittal, director of the

transcribed and proteins are made. These specific

Neuberger Berman Foundation Lung Cancer Laboratory at Weill Cornell Medical

genetic changes resulted in the creation of single

College. Wong’s lab will use a novel multi-cellular network model (P2GWAS) to

nucleotide polymorphisms, or SNPs.

predict tumor-stroma crosstalk signaling pathways based on RNA-Seq data

Musser’s team found that two of those SNPs result in the increased production of two important toxins called streptolysin O and Streptococcus pyogenes NAD-glycohydrolase. The third SNP creates a form of one of those toxins that becomes more active than the original form. All three SNPS contribute to building an organism that is a more virulent machine.

Think about the thermostat in your house controlling temperature. If you want to make your house hotter, or if group A strep wants to make itself hotter or more virulent, it just turns up the heat a little bit via these two toxin genes.

– James M. Musser, M.D., Ph.D. Fondren Presidential Distinguished Chair Houston Methodist

generated from clinical NSCLC specimens in Mittal’s lab. Wong , who is also the Chief Research Information Officer of the Houston Methodist Hospital, says that the work has tremendous potential for the development of novel therapeutic strategies that may complement existing cancer treatments. The goal is to accelerate clinical trials either as monotherapies or as complements to existing conventional treatments for lung cancer.

the goal is to provide more efficient “ Ultimately, and cost-effective treatments for the patients. This focus always benefits from collaboration. Stephen Wong, Ph.D. John S. Dunn, Presidential Distinguished Chair in Biomedical Engineering Houston Methodist

More collaborations are in the works including a partnership with Baylor College of Medicine to apply this approach to breast cancer and with M. D. Anderson Cancer Center for application to ovarian cancer.

Zhu L, Olsen RJ, Nasser W, et al. A molecular trigger for intercontinental epidemics of group A Streptococcus. J Clin Invest. 2015 Sep;125(9):3545-59.

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Research Highlights: Translational Research

and

Tracking Aging Delivering Genes with

High-Throughput

Microfluidics by Maitreyi Muralidhar

A team of researchers at the Houston

Microfluidic devices contain microsize channels generated

Methodist Research Institute, led by

manipulation of small volumes of fluids (microliters to

Associate Professor of Nanomedicine,

through photolithography techniques that allow control or picoliters). In a recent publication in the Proceedings of the National Academy of Sciences, Qin and his team report

Lidong Qin, Ph.D., has been developing

on a microfluidic system that could have a significant

microfluidics-based platforms that

on longevity and aging.

enable rapid and high-throughput

The microfluidic, single-cell analysis chip, enables the

molecular and cellular assays for applications ranging from aging research to gene therapy.

impact on understanding the effect of calorie restriction

visualization and analysis of the lifespan of a single yeast cell. Budding yeast or Saccharomyces cerevisiae, has long been used as a model system for studying aging due to its short lifespan and the ease with which it can be genetically manipulated. In the traditional lifespan assay, mother yeast cells were grown on agar plates and daughter cells were separated and removed manually by microdissection.

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Qin and his team have also designed another

accurately tracking the lifespan of mother cells. However,

microfluidic device that could facilitate novel

the traditional manual microdissection method is inefficient

approaches for gene therapy delivery. In a recent

(repeated every hour for 3 days) and incompatible with high

issue of Science Advances, Qin and team address

resolution microscopy tracking. Qin’s microfluidic single-cell

gene knockdown in hard-to-transfect cells. By squeezing

analysis chip overcomes these limitations by retaining only

cells through microposts or barriers in the device, they

the mother cells inside the microfluidic chambers while

forced open transient pores in the cell membrane. Through

washing off daughter cells automatically.

these open pores, molecules added to the cell media can

RESEARCH HIGHLIGHTS

The process of removing daughter cells is critical for

passively diffuse into the cell. This process of deforming the This chip has allowed them to view and track single cells

membrane and opening up transient pores can be used to

throughout their lifespan by fluorescence microscopy.

deliver a range of materials such as proteins, transcription

With this technique, Qin and his team were able to confirm

factors, single-stranded DNA, siRNAs, and large-sized

that yeast on a low-calorie diet live much longer than yeast

plasmids into almost any cell type, including hard-to-

on a standard diet.

transfect cells. Qin and his team used this membrane deformation method to deliver sgRNA and Cas9 to achieve successful genome editing.

Our device can track around 100 mother cells. In 2-3 days, we can

With their wide-ranging applications, microfluidics devices developed by Qin and his group have provided a fast, high-throughput, and accurate approach that opens up new avenues for research in several areas.

assay the lifespan of 10 different strains-that corresponds to analyzing around 1,000 mother cells and performing 30,000 micro-dissections. If we were using the traditional method, this would take 4-5 skilled individuals almost 3-4 weeks to complete.

– Lidong Qin, Ph.D. Associate Professor of Nanomedicine Houston Methodist

The microfluidics device, termed High-throughput-Yeast-Aging-Analysis chip (HYAA-chip) provides automated whole-lifespan tracking with fine spatiotemporal resolution and large-scale data quantification of single yeast cell aging.

Jo MC, Liu W, Gu L et al. High-throughput analysis of yeast replicative aging using a microfluidic system. Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9364-9. Han X, Liu Z, Jo M et al. CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation. Science Advances. 2015 Aug 14;1(7):e1500454.

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Education News

RESIDENT PROFILE

Albert Huang, M.D.

a general surgery resident at Houston Methodist by Thomas Ellington Albert Huang, M.D., a general surgery resident at Houston Methodist, is in his third year of research with the Houston Methodist Institute for Technology, Innovation & Education (MITIESM) and the Department of Surgery where his work has focused on medical device design and computational surgery. During his research fellowship, he worked under the guidance of Brian Dunkin, M.D., the John F., Jr. and Carolyn Bookout Chair in Surgical Innovation and Technology, Marc Garbey, Ph.D., the scientific director of the Center for Computational Surgery, and Barbara Bass, M.D., the John F., Jr. and Carolyn Bookout Presidential Distinguished Chair of the Department of Surgery. Together, they are designing an intelligence system for the operating room. The system will create an enhanced awareness of the many simultaneous activities taking place, help improve surgeon performance and increase patient safety and comfort. Huang and Dunkin also filed a provisional patent for a novel medical device that allows a surgeon to maintain a Albert Huang, M.D. General Surgery Resident

greater sense of direction within the body while performing flexible endoscopic procedures. The device works similarly to a compass, but uses gravity rather than magnetism to assess orientation. This allows surgeons to see where they are circumferentially within a body cavity. Huang notes, “Performing a dissection in a straight line during an endoscopic procedure like POEM, when all you have is pink tissue to look at, can be really difficult. If you very gradually start to deviate from a straight line, you may not even know it.� POEM, which stands for Per-Oral Endoscopic Myotomy, is a minimally invasive, natural orifice procedure where a small incision is made in the mucosa of the esophagus and the stomach to relax the lower esophageal sphincter and allow food to pass properly.

Opportunities to innovate in the clinical setting inspired Huang to make Houston Methodist his first choice for surgical residency. He noted Bass’s speech during his interview as having a particularly strong influence. Bass described Houston Methodist as a place that supports resident individuality and helps them become the best at what they are interested in, rather than fitting them into a set mold.

This appealed to Huang, who has always had a passion for innovation and thinking outside the box. His interest in surgery was originally prompted, when he began working on tissue engineering and organ fabrication in the lab of Joseph Vacanti, M.D. at Harvard Medical School. This experience provided his first exposure to surgery and his subsequent medical schooling served as an inspiration for the design of his clothing line, Collateral Concepts. His designs consider the concepts of human anatomy and take into account lines of movement, vascular structures, and neurological structures for coming up with innovative approaches to garment construction. As he heads back to the clinic for his residency, Huang plans to continue his passion for medtech innovation in and out of the OR, and he hopes to continue to innovate with his colleagues at Houston Methodist throughout his career.

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In summer of 2015, the Houston Methodist Research Institute welcomed 60 students to take part in the annual Summer Student Program. This year’s cohort hailed from renowned universities, both domestic and international, including Harvard, Massachusetts Institute of Technology and Imperial College London . During the ten-week program, students were assigned a Houston Methodist faculty mentor who guided them through a research project. Students also attended a weekly lecture series, attended a variety of social events, and presented their research at a public exhibition.

On July 23, 2015, Matthew Ware earned his

New this year was the inclusion of surgery as one of the research areas. The inaugural

Ph.D. in Nanotechnology and became the first

Fields Rosenberg Summer Surgical Internship Program is a revival of the DeBakey

student to graduate from the collaborative

Program, which was disbanded in 2005. The Fields Rosenberg program sponsors five

doctoral program between Swansea University

undergraduate students to spend ten weeks working under the guidance of Houston

and the Houston Methodist Research Institute.

Methodist surgical faculty, where they observe surgical cases and explore surgically

Under the guidance of faculty mentors Paul Rees,

oriented research questions. Topics this year ranged from bloodless lung transplantation

Ph.D., of Swansea University, and Biana Godin

to gastric bypass revision surgery.

Vilentchouk, Ph.D., MScPharm of the Houston Methodist Research Institute, Ware’s work in the four-year program culminated in a dissertation entitled Development of Engineering Approaches to Studying Dose Response In Vitro for Nanomedicine Applications. The program, which began in 2012, has two students currently at Houston Methodist and two more are expected to join in early 2016.

The program is named for the families of Wade Rosenberg, M.D., Assistant Professor of Clinical Surgery at Houston Methodist, and his wife, Amy Fields Rosenberg, who cultivated the revival effort. Rosenberg, who participated in the original DeBakey program, understands the value of early exposure to the field of surgery as a catalyst to pursuing a surgical career. “I wouldn’t be who I am today if I had not had the opportunity,” Rosenberg stated in reference to his participation in the DeBakey Program. The Rosenbergs worked to establish the structure of the program, recruit surgical faculty at Houston Methodist to participate as mentors and reached out to the M.B. & Edna Zale Foundation to garner support for the program. In response to a match challenge by the Zale Foundation, additional support was provided by the Houston Texans and individual donor Keith Rutherford. Their contributions will ensure the program continues to run for future generations.

Matthew Ware, pictured second from right, after his graduation ceremony, surrounded by his family, faculty mentors, and Houston Methodist staff.

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EDUCATION NEWS

FIRST GRADUATE FROM SWANSEAHOUSTON METHODIST COLLABORATION

Summer Research Student Program


OF INTEREST

NEW FACULTY MEMBER

Houston Methodist recruits New Director of the Biomarker Research Program Dario Marchetti, Ph.D., joined Houston Methodist in September 2015 as the new Director of the Biomarker Research Program. Previously, Marchetti was at Baylor College of Medicine where he held the “Jack L. Titus” Endowed Professorship in the Department of Pathology & Immunology. At Houston Methodist, Marchetti will be managing an interdisciplinary translational research laboratory and will develop a collaborative biomarker program with faculty across numerous disciplines. Marchetti’s main priorities will be to better understand why cancer recurs and how to decipher the molecular heterogeneity of circulating tumor cell subsets shed from tumors and responsible for metastases. He has held academic appointments of increasing responsibilities since 1979, and served on the editorial boards of journals, as a grant reviewer for national and international funding agencies, and as a consultant for biotechnology Dario Marchetti, Ph.D. Director, Biomarker Research Program

companies. His research has received continued peer-reviewed funding for more than 25 years from federal, state, institutional and private organizations.

Adaani Frost, M.D., joins Houston Methodist as Director of the Lung Center Adaani Frost, M.D., has been appointed as the Director of the new Lung Center at Houston Methodist. An expert in pulmonary hypertension, Frost joins us from Baylor College of Medicine where she was the Director of their Pulmonary Hypertension Center since 2002. Frost brings with her extensive clinical research experience in pulmonary diseases including pulmonary arterial hypertension and idiopathic pulmonary fibrosis. She has an M.D. from the Memorial University of Newfoundland, Canada and was qualified as a fellow of the Royal College of Physicians and Surgeons of Canada in 1990. Adaani Frost, M.D. Director, Lung Center

Garbey, establishes Center for Computational Surgery at Houston Methodist Marc Garbey, Ph.D., has joined Houston Methodist as scientific director of the Center for Computational Surgery. He was previously professor in the Department of Computer Science and the Department of Biology and Biochemistry at the University of Houston. Garbey, who specializes in applied mathematics, is working with Houston Methodist Hospital surgeons and the Houston Methodist Institute of Technology, Education and Innovation (MITIE) to create an intelligent operating room (OR). The primary goal is to rethink operating room functions and integrated technologies to improve patient safety during surgery, enhance real-time tracking of OR activities, and improve patient outcomes. This project uses devices to collect and process operating room and surgical technology data to optimize the OR setting. Devices include sensors placed on anesthesia machines to detect when a patient is under Marc Garbey, Ph.D. Director, Center for Computational Surgery

26

anesthesia. Other sensors track a patient’s location in real time, from the pre-operation area to the operating and recovery rooms.


OF INTEREST

BOARD OF DIRECTORS Houston Methodist Research Institute Steven D. Arnold

Laurie H. Glimcher, M.D.

John F. Bookout

Antonio M. Gotto, M.D., D.Phil

John F. Bookout, III

Mark A. Houser

Marc L. Boom, M.D.

Catherine S. Jodeit

Timothy Boone, M.D., Ph.D.

Evan H. Katz

Giorgio Borlenghi

Rev. Kenneth R. Levingston

Joseph R. "Rod" Canion

Vidal G. Martinez

Albert Chao

Gregory V. Nelson

Ernest D. Cockrell, II

Stuart W. Stedman

John P. Cooke, M.D., Ph.D.

Andrew C. Von Eschenbach, M.D.

Dan O. Dinges

Martha Walton

Mauro Ferrari, Ph.D.

Elizabeth B. Wareing

Joe B. Foster

Ewing Werlein, Jr.

In memory of David OF BrickerDAVID BRICKER IN MEMORY David M. Bricker, research and science

In his memory, the Houston Methodist Research

publications manager for Houston Methodist

Institute has established the Bricker Award for

passed away after a battle with cancer on

Science Writing in Medicine. The award recognizes

August 16, 2015. An exceptional science

talented and respected writers who have the skill

writer, David used his background in science

to craft technical medical research advances into

and journalism to convey abstract scientific

must-read stories, and the tenacity to place them

discoveries in simple language, making him

in the public spotlight.

invaluable for communicating Houston Methodist research discoveries to the masses. Anyone who had the opportunity of working

We are accepting donations through "The David M. Bricker Memorial Fund" to carry on David’s legacy of mentorship by supporting his fellow science

with David came away impressed by his

writers in their education and careers. To make donations,

zeal and enthusiasm for making science

go to www.houstonmethodist.org/brickeraward

accessible and interesting for the non-scientific person. His writing inspired us to

and click on "Donate Now". Choose “Other” as the

seek knowledge through science, and break through the boundaries of medicine.

option in the “Please use my gift for” section and

David’s articles were a mainstay of Methodology and some of the last articles

specify “In memory of David M. Bricker.”

written by him are featured in this issue.

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Houston Methodist Research Institute 6670 Bertner Ave. Houston | TX 77030

UPCOMING EVENTS

UPCOMING EVENTS

April 1, 2016

April 11, 2016

Second Annual David M. Underwood Center for

International Leadership Experience and Development (ILEAD)

Digestive Disorders: Exploring Frontiers in the

CME credit available

Management of Digestive and Liver Disorders 2016 CME credit available

April 2, 2016 Below the Beltline: 2016 - Insider's Guide to Male and Female Pelvic Health Across the Lifespan

CME credit available

April 29, 2016 Southwest Valve Summit IV

CME credit available

May 9, 2016 Deciphering Human Immune Responses to

April 9, 2016 5th Annual Symposium on Enhancing Geriatric

Cancer Immunotherapy

Understanding and Education (SEGUE):

June 17, 2016

Geriatric Ophthalmology for Non-Geriatricians

Orthopedics for the Primary Care Physician

CME credit available

CME credit available

Go to houstonmethodist.org/hmrievents for more information.

METHODOLOGY

The Research and Education Newsletter of Houston Methodist

Editor-in-Chief Rebecca Hall, Ph.D. Managing Editor and Writer Maitreyi Muralidhar, MS Design & Creative Lead Doris T. Huang

Contributing Writers David Bricker Thomas Ellington Erika Hayes Gale Smith Public Relations Contact Gale Smith 832.667.5843 gsmith@houstonmethodist.org

Read more online: houstonmethodist.org/hmrinews Office of Communications and External Relations Institute for Academic Medicine Houston Methodist Email: news@houstonmethodist.org IAMNEWS-005 | 03.2016 | 1730

Methodology Newsletter Spring 2016  
Methodology Newsletter Spring 2016