METHODOLOGY The Research and Education Newsletter of Houston Methodist
Houston Methodist RNACore Awarded $4.8 Million for RNA Therapeutics and Research by the Cancer Prevention and Research Institute of Texas by Maitreyi Muralidhar
Scientists from the Houston Methodist Research Institute RNACore will receive $ 4.8 million from the Cancer Prevention and Research Institute of Texas (CPRIT) for pursuing RNA-based therapeutics and research. According to CPRIT, the award, called the Core Facilities Support Award (CFSA), “supports the establishment or enhancement of core research facilities that will provide valuable services to enhance the outcomes of scientifically meritorious cancer research projects”.
John Cooke, M.D., Ph.D., the principal investigator of the CPRIT grant, believes that this award will be a great boost to the research being conducted at the RNACore which serves as the RNAcore for the Progenitor Cell Biology Consortium of the National Heart, Lung and Blood Institute. >> CONT. PAGE THREE
The RNA Core will be the first entity in Texas to generate the new class of drugs known as RNA Therapeutics. These drugs can modify the function of cells in a beneficial manner. The grant funding will support the development and generation of RNA therapeutics, particularly for cancer immunotherapy. – John Cooke, M.D., Ph.D. Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research
FROM THE PRESIDENT The summer is the heart of innovation. It brings longer days, and for many of us, time for leisure and business travel, and fewer grant application deadlines. This treasured opportunity fosters creative thinking and problem solving – a critical ingredient to our success as researchers, educators and leaders in clinical care. It is this thread of creativity and innovation that seams the
Houston Methodist RNACore Awarded $4.8 Million................... 1 Breast Cancer Vaccines May Work Better with Silicon Microparticles..................................4 Houston Methodist Receives $6.5 Million Gift to Name Liver Center......................................5
stories in this issue of Methodology together. The clinical trials of Drs. Michael Reardon and Joseph Masdeu
are founded on the creative development of transcatheter aortic
In Orbit or on Earth, Implantable Device to Release Therapeutic Drugs Remotely........................................6
valve replacement (TAVR) technology and a neuroprotective drug called T-817MA to manage
Reprogrammed Cells Grow Into New Blood Vessels..........................8
Chang and Jaime Mejia to simplify the process of collaborative clinical trials with Weill Cornell
Creating Unsafe Neighborhoods for Cancer Cells............................ 10
Alzheimer’s symptoms. Another creative response to the challenges in translational research is the development of the multi-institutional CARE Consortium for Cancer trials lead by Drs. Jenny Medical College, Emory University, the University of Utah and Thomas Jefferson University. Our researchers are pushing the boundaries of medicine – Dr. Alessandro Grattoni is
Houston Methodist Researcher at the Forefront of Immunology Research....................................... 11
harnessing the power of nanotechnology for designing controlled drug release devices and
Gene Appears to “Skew” Production of Helper T Cells........ 11
this year for testing in preclinical models aboard the International Space Station.
Brain Tumor Cells Decimated by Mitochondrial “Smart Bomb”...... 13
Therapeutics for cancer, in addition to the constructs it currently produces for heart disease in
Clinical Research Highlights
Drs. Haifa Shen and Rongfu Wang are using silicon nanoparticles to boost the efficacy of cancer vaccines. Dr. Grattoni’s tiny 18 mm nDS drug delivery system will launch into space Dr. John Cooke has received a CPRIT grant to expand our RNACore to produce RNA partnership with the National Heart, Lung & Blood Institute – read more about both initiatives in this issue.
Transcatheter Alternative for Aortic Valve Replacement........... 14
I would like to announce several key Houston Methodist recruitments this year that are central
Slowing Brain Deterioration: The NOBLE Study......................... 16
Dr. Tanya Burkholder has joined us from the Division of Veterinary Resources at the National
CARE Consortium for Cancer......17
us from the University of Washington to lead our Neuroregeneration research program. Please
to continuing our legacy of innovation and expanding our academic mission and strategic initiatives. Institutes of Health to lead our Comparative Medicine Program. Dr. Phil Horner has joined welcome them to our team when you meet them in the halls and on shared committees.
Education News Houston Methodist, Imperial College London Discuss Future Scientific Collaboration, Joint Training Programs........................ 18
This issue of Methodology also celebrates the founding of the Sherrie and Alan Conover
Revolutionary Platform of Robotic Technology for Cardiac Arrhythmias.................................20
together we are leaders in medicine.
Center for Liver Disease & Transplantation. The generosity of Mr. and Mrs. Conover will support our deeply dedicated after hours caregivers, and save lives by supporting the advances in liver transplantation. We welcome the Conover family to the Houston Methodist family –
Mauro Ferrari, Ph.D. Of Interest Mauro Ferrari Honored With The Stodola Award......................23 John Cooke Receives Stanford University’s Outstanding Inventor Award...........................................23
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
RNACore receives award from the Cancer Prevention and Research Institute of Texas The RNACore produces research and clinical grade RNA, including modified mRNA (mmRNA) of any gene of interest, microRNA cassettes and noncoding RNA. For example, the core makes RNA constructs for investigators enabling them to generate induced pluripotent stem cells from adult humans. Induced pluripotent stem cells are similar to embryonic stem cells, but do not have the same ethical concerns. The core also makes RNA constructs that can transform stem cells into blood-forming cells, useful in patients with anemia. Currently a small unit, the RNACore is partially funded by the federal government. The new CPRIT grant will further help expand the services for cancer biologists. With the CPRIT funding, the RNACore aims to generate customized RNA constructs for cancer biologists and to accelerate their development for genome editing and cellular reprogramming purposes. The core researchers are also optimizing new methods for RNA delivery. These constructs and delivery vehicles will then be used for preclinical studies. Equipped with current Good Manufacturing Practice (cGMP) facilities designed to produce clinical grade radiopharmaceuticals, nanoparticles or biologicals for preclinical and clinical studies, the Houston Methodist Research Institute is uniquely positioned to generate pharmaceutical grade RNA for Phase I/II studies.
RECRUITMENT UPDATE Houston Methodist Research Institute Gets New Director for Comparative Medicine Program Tanya Burkholder, DVM, DACLAM, joined Houston Methodist Research Institute in May 2015, as the New Director of the Comparative Medicine Program. Previously, Dr. Burkholder served as Chief, Veterinary Medicine Branch, Division of Veterinary Resources at the National Institutes of Health (NIH). In that role, she directly supervised laboratory veterinarians and oversaw the work of veterinary technicians to ensure exceptional care of over 75,000 animals on the NIH main campus and at the NIH Animal Center, Poolesville, MD. Dr. Burkholder holds a Doctor of Veterinary Medicine degree from the Texas A&M University, College of Veterinary Medicine and has a diplomate from the American College of Laboratory Animal Medicine.
Breast cancer vaccines may work better with silicon microparticles by David Bricker The effectiveness of cancer vaccines could be dramatically boosted by first loading the cancer antigens into silicon microparticles, report scientists from Houston Methodist and two other institutions in Cell Reports. Model studies showed that microparticles loaded with an antigen, HER2, not only protected the antigen from premature destruction, but also stimulated the immune system to recognize and relentlessly attack cancer cells overexpressing the HER2 antigen.
“We could completely inhibit tumor growth after just one dose of the cancer vaccine in the animal model,” said principal investigator Haifa Shen, M.D., Ph.D. “This is the most amazing result we have ever seen in a tumor treatment study.” The success of the treatment, Shen and his team learned, appears to be the porous silicon microparticles (PSMs) themselves. In vivo and in vitro studies confirmed the microparticles stimulated a strong, sustained innate immune response at local sites of tumor activity and growth — with or without any antigen loaded. “We have shown for the first time that a microparticle can serve as a carrier for sustained release and processing of tumor antigens. But just as importantly, we learned the microparticles themselves appear to be enough to stimulate a type I interferon response, and were even transferred from one antigen-presenting cell to another to maintain a long-lasting antigen-releasing effect.” There are currently dozens of active clinical trials evaluating vaccines for cancer therapy. As yet, there are no FDA-approved vaccines for breast cancer. Such a vaccine might target HER2, a cell surface hormone receptor that is overexpressed in the tumor cells of 15 to 30 percent of breast cancer patients. Such cells are called HER2+ or HER2 positive. In this case, HER2 is both a naturally occurring hormone receptor and an antigen target for therapy. A vaccine against HER2 would train the immune system’s more destructive agents to recognize the cancer cells overproducing HER2 and destroy them, leaving healthy cells more or less alone. But so far, vaccines against HER2 have seen only moderate success.
Vaccines targeting the HER2 oncoprotein have been tried,” Shen said. “But these vaccines have mostly not been very potent because of inefficient vaccine delivery, a poor immune response at the site of the tumor, and other factors. We have shown that the PSM-mediated vaccine is not only potent enough to trigger tumor cell killing, but also modifies the tumor microenvironment in a way that favors tumor treatment.
– Haifa Shen, M.D., Ph.D. Assistant Professor of Nanomedicine Institute for Academic Medicine
An important aspect of PSM function is stimulating the body’s own immune system to fight cancer, Shen said. “PSMs persistently challenge the antigen-presenting cells to activate the T cells and the PSMs modify the tumor microenvironment so that the cytotoxic T cells maintain their activity.” Shen said the use of PSMs could work for any variety of cancer antigens and cancers, and that the PSMs could be loaded with multiple antigens for a single vaccine target, or multiple antigens for several targets. “Besides developing a highly potent breast cancer vaccine, we have also demonstrated that PSMs are versatile,” Shen said. “This technology platform can be applied by other scientists to develop vaccines for other types of cancers”. Xia X, Mai J, Xu R, et al. Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response. Cell Rep. 2015 May 12;11(6):957-66.
HOUSTON METHODIST RECEIVES $6.5 MILLION GIFT TO NAME LIVER CENTER The Center for Liver Disease and Transplantation at Houston Methodist Hospital is now named the Sherrie and Alan Conover Center for Liver Disease & Transplantation. The Conovers, who live in Estero, Florida, donated a $6.5 million gift to the center that will be used for research, outreach and education. Left to right: Marc L. Boom, M.D., R. Mark Ghobrial, M.D., Ph.D., Alan Conover, Edward Jones, Sherrie Conover, and Howard Monsour, M.D.
Generous gifts from caring people like Mr. and Mrs. Conover allow us to make investments in Leading Medicine. We are deeply appreciative for this gift which will have a very positive impact on people battling liver disease.
– Marc L. Boom, M.D. President and CEO Houston Methodist
Part of the gift will also be used to develop after hours resources and support for caregivers and family members who spend many days and nights away from home caring for loved ones at the hospital. “This substantial and thoughtful gift from the Conover family will allow us to expand our clinical and research programs even further,” said Center Director and Professor of Surgery, R. Mark Ghobrial, M.D., Ph.D. “We are currently involved in researching new forms of immunosuppression, strategies for reducing complications, and new ways to fight post-operative infection and this will give us a better chance to reach those goals.” In 2014, Ghobrial and his team performed 85 liver transplants, allowing them to become the leading center in the treatment of liver disease in the Texas Medical Center and the region.
In orbit or on Earth, implantable device will be commanded to
release therapeutic drugs remotely by David Bricker
Houston Methodist scientists received about $1.25 million from the Center for the Advancement of Science in Space (CASIS) at Florida’s Kennedy Space Center to develop an implantable device that delivers therapeutic drugs at a rate guided by remote control. The device’s effectiveness will be tested
Grattoni, Ph.D. “If we are able to show the
for drugs and a silicon membrane housing
aboard the International Space Station
technology works in vivo and is safe, it could
615,342 channels as small as 2.5 nm.
and on Earth’s surface. Austin-based
have an enormous impact on drug delivery
The channels are sized and shaped to
NanoMedical Systems Inc. and the
and patient care.” Houston Methodist
control drug release, and the exactness of
Houston Methodist Research Institute
Research Institute President and CEO and
the design is achieved using nanotechnology
are also supporting the five-year project,
Ernest Cockrell Jr. Presidential Distinguished
techniques developed by Grattoni and Ferrari.
bringing total funding to $1.92 million.
Chair, Mauro Ferrari, Ph.D., is the project’s
Drug movement through the channels is
co-principal investigator and will help
controlled by surface electrodes that “tune”
supervise the project.
the rate of drug delivery. Below the drug
“The prospect of developing and demonstrating a remotely controlled drug delivery implant excites us,” said
Grattoni’s device, called a nanochannel
principal investigator and Assistant
delivery system or “nDS,” is an 18 mm-wide
Professor of Nanomedicine Alessandro
squat cylinder. It contains a reservoir
reservoir is a battery and electronics that can be activated to influence the rate at which drugs exit through the porous membrane. The electrodes are controlled
The nanochannel delivery system, or nDS, delivers drugs at any rate. The 18 mm-wide implant shell (yellow) encases the drug reservoir (blue) and nanochannel membrane (grey area above reservoir), the electronic unit and radiofrequency antenna (green), and a battery (grey, bottom). On top of the nDS is the implant outlet (center top) and a drug injection port (top right). (Image by Grattoni laboratory)
The nDS would enable telemedicine that utilizes modern telecommunication and information technologies to provide clinical care from a remote or distant location, reducing costs associated with hospitalization and travel for treatment. We also imagine other valuable applications of the
technology, such as military emergency care, pre-clinical studies of newly discovered drugs, and care for astronauts on long space missions.
– Alessandro Grattoni, Ph.D. Assistant Professor of Nanomedicine Institute for Academic Medicine
via radio-frequency remote control. The
microchip-based devices may not be
Grattoni has also received close to $600,000
device will be tested in preclinical
suitable for long term treatments –
from the National Institute of General Medical
models aboard the International Space
despite their large volume, they have
Sciences to further develop this nanochannel-
limited drug storage capacity.
based technology to enable the in vivo analysis
There are three technologies available
Doctors may want to have control over
today that allow a patient to receive
the rate of drug delivery for several
drug infusions without having to visit a
reasons. Some drug regimens work
hospital or clinic. Among these are
better or are better tolerated when
wearable external pumps, implantable
delivered at regularly timed bursts,
multi-layered polymers that release drugs
while some drugs have been shown
as they erode, and implantable, metal-
to be more effective when delivered
gated devices. In Grattoni’s view, all
at specific times of day. In addition,
three types of devices have limitations.
doctors may also want to be able to
External pumps may carry risk of infection
stop or start drug delivery quickly in
around transdermal catheters and can be
response to changes in patients’
inconvenient. Drug-lined polymers may
health. With Grattoni’s nDS, this could
cause an initial burst in drug release and
be done remotely – potentially saving
are not tunable once implanted. Current
time and improving medical outcomes
of investigational drugs and dosing regimens.
for patients. Logo design by: Matthew Landry
Reprogrammed cells grow into new blood vessels by David Bricker
By transforming human scar cells into blood vessel cells, scientists at Houston Methodist may have discovered a new way to repair damaged tissue. The method, described in the journal Circulation, appeared to improve blood flow, oxygenation, and nutrition to areas in need. Scar cells are coaxed into becoming blood vessel cells with a new, small-molecule and protein therapy. In the paper, Houston Methodist scientists report these transformed cells self-assembled into vessels that improved blood flow. Cardiovascular scientists at Houston Methodist, with colleagues at Stanford University and Cincinnati Children’s Hospital, learned that fibroblasts — cells that cause scarring and are plentiful throughout the human body — can be coaxed into becoming endothelium, an entirely different type of adult cell that forms the lining of blood vessels. According to John Cooke, M.D., Ph.D., the principal investigator of this study, the regenerative medicine approach provides proof-of-concept for a small molecule therapy that could one day be used to improve the healing of cardiovascular damage or other injuries.
“ To our knowledge, this is the
first time that trans-differentiation to a therapeutic cell type has been accomplished with small molecules and proteins. In this particular case, we’ve found a way to turn fibroblasts into ‘shapeshifters’ nearly on command.
– John Cooke, M.D., Ph.D. Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research Department of Cardiovascular Sciences
such as VEGF, that are known to compel less differentiated
cells using infectious virus particles specially engineered to
cells into becoming endothelial cells.
Other research groups have managed to generate endothelial deliver gene-manipulating DNA to cells. The DNA encodes proteins called transcription factors to alter gene expression
Cooke and his colleagues reported to Circulation that
patterns in such a way that cells behave more like endothelial
about 2 percent of the fibroblasts were transformed from
cells. “There are problems with using viruses to transfer
fibroblasts into endothelial cells, a rate comparable to what
genes into cells,” Cooke said. “This gene therapy approach
other research groups have accomplished using viruses
is more complicated, and using viral vectors means a
and gene therapy. But Cooke said preliminary, as-yet-
possibility of causing damage to the patient’s chromosomes.
unpublished work by his group suggests they may be able
We believe a small-molecule approach to transforming the
to achieve transformation rates as high as 15 percent.
cells will be far more feasible and safer for clinical therapies.” That’s about where we think the yield of transformed cells The new method described by Cooke and his coauthors
needs to be,” Cooke said. “You don’t want all of the
starts with exposing fibroblasts to poly I:C (polyinosinic:
fibroblasts to be transformed as fibroblasts perform a
polycytidylic acid), a small segment of double-stranded
number of important functions, including making proteins
RNA that binds to the host cell receptor TLR3 (toll-like
that hold tissue together. Our approach will transform some
receptor 3), tricking the cells into reacting as if attacked
of the scar cells into blood vessel cells that will provide
by a virus. Cooke and coauthors reported to Cell in 2012
blood flow to heal the injury.”
that fibroblasts’ response to a viral attack — or, in this case, a fake viral attack — appears to be a vital step in diverting
In a second part of the study, the scientists introduced the
fibroblasts toward a new cell fate. After treatment with poly I:C,
transformed human cells into immune-deficient mice that
the researchers observed a reorganization of nuclear
had poor blood flow to their hind limbs. The human blood
chromatin, allowing previously blocked-off genes to be
vessel cells increased the number of vessels in the mouse
expressed. The fibroblasts were then treated with factors,
limb, improving circulation.
“The cells spontaneously form new blood vessels -- they self assemble,” Cooke said. “Our transformed cells appear to form capillaries in vivo that join with the existing vessels in the animal, as we saw mouse red blood cells inside the vessels composed of human cells.” Cooke said more preclinical studies are needed before his group begins clinical trials. “One of the next steps will be to see if we can rescue an animal from an injury. We want to know if the therapy enhances healing by increasing blood flow to tissues that may have been damaged by a loss of blood because of ischemia,” Cooke said.
Sayed N, Wong WT, Ospino F, et al. Transdifferentiation of human fibroblasts to endothelial cells: role of innate immunity. Circulation. 2015 Jan 20;131(3):300-9.
QUICK FACTS HOUSTON METHODIST
7 1,931 789,748 95,651 18,000 4,000+ 569 1,460 360 37 7 44 48
Hospitals Operating beds Outpatient visits Admissions Employees Physicians Faculty
Creating unsafe neighborhoods for cancer cells by James J. Mancuso
Cancerâ€™s ability to survive in and manipulate the tumor microenvironment (TME) depends on communication with the non-cancer cells which comprise the TME. Therapeutics that disrupt that communication would provide a new, highly specific therapy to stop the growth of cancer by depriving them of a hospitable environment for growth. The interactions occurring in the tumor microenvironment are numerous and diverse, due to the large number and variety of cells present. Finding the crucial interactions that allow cancer cells to thrive in the TME presents a problem as difficult as finding a needle in a hay stack. This challenge was taken up by a collaborative team headed by Stephen Wong, Ph.D. the John S. Dunn Presidential Distinguished Chair in Biomedical Engineering
at Houston Methodist and Dr. Vivek Mittal, Director of the Neuberger Berman Foundation Lung Cancer Laboratory from Weill Cornell Medical College.
(residents, postdoctoral fellows & students)
ACGME-accredited training programs
In a groundbreaking paper published last month in Cell Reports, this team of investigators determined the role of interactions with specific subpopulations of cells in tumor growth, metastasis, and drug development using a murine model of non-small cell lung cancer (NSCLC) and computational modeling.
GMEC-sponsored fellowship programs
Cell populations were sorted from normal and tumor lungs based on specific
Regularly scheduled CME activities
could see comprehensively how tumors change their neighbors and vice versa.
Live programs educating 10,071 physicians
cell surface markers and subjected to single cell RNA sequencing; this way they
The data from sequencing were incorporated into a sophisticated mathematical modeling tool called CCCExplorer that incorporated comprehensive data about known cell communication mechanisms. Simulations uncovered previously unknown pathways by which tumor cells communicate with their neighbors.
Sq.ft. dedicated research building with 12 stories and 150 lab benches
Additional sq.ft. research space embedded throughout the hospital
TOP 20 $130 M
U.S. domestic hospital based research institutes
The findings, expand a new front in the fight against cancer based on precision
Annual research expenditures
cancer specific simulation.
medicine that creates a hostile environment for cancer, based on patient and
Choi H, Sheng J, Gao D, et al. Li F, Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model. Cell Rep. 2015 Feb 24;10(7):1187-201.
Houston Methodist researcher at the forefront of immunology research by David Bricker & Maitreyi Muralidhar Roger Sciammas, Ph.D., Assistant Professor of Transplant Immunology in Surgery, will be receiving about $1.6 million over four years from the National Institute of Allergy and Infectious Diseases to study pathological antibodies produced from activated memory B cells during the chronic rejection of organ transplants. This builds on recent work that shows the antibody production by memory B cells in the body’s response to perceived foreign material — such as an organ or tissue donated from another person — depends on molecular switches. Sciammas and co-principal investigator and University of Chicago transplant biologist Anita Chong, Ph.D., will use single-cell tracking and advanced genetic techniques to learn more about these regulators. Of particular interest is whether these switches can in turn be therapeutically targeted in a way that improves organ transplant tolerance. When rejection occurs, memory B cell activation and antibodies are a common denominator. The scientists will also examine whether and how memory B cell function is affected by T cell costimulation blockade, a major immunosuppression treatment widely used in experimental transplantation.
studies will provide new insight into the associations of alloantibody and increased “ These incidence of transplant rejection as well as into new immunosuppressive strategies to control B cells and their antibody products. ”
– Roger Sciammas, Ph.D. Assistant Professor of Transplant Immunology in Surgery Institute for Academic Medicine
Close on the heels of the first award, Sciammas and his group also received $1.9 million from the National Institute of Allergy and Infectious Diseases to investigate molecular switches within T helper cells. T helper cells modify antibody production by B cells to enable protection from pathogens. Different forms of T helper cells are involved in providing immunity against different classes of microorganisms. Understanding the mechanisms and conditions behind how T helper cells respond to immune challenges could redefine strategies that could improve vaccine efficacy in the future. “This information could also be potentially harnessed in developing new approaches to prevent antibody production from transplant-specific B cells to prolong organ survival,” Sciammas stressed.
Gene appears to “skew” production of helper T cells by David Bricker
An important aspect of adaptive immunity is controlled by the gene Jmjd3, scientists from Houston Methodist and three other institutions have learned. Encoded by Jmjd3, the enzyme Jmjd3 is one of dozens of histone demethylases that shapes chromosome architecture and indirectly affects whether genes can be expressed. Led by Professor of Inflammation and Epigenetics, Rongfu Wang, Ph.D., the research team reported in Nature Communications that the absence of Jmjd3 appears to “skew” the production of helper T cells that assist the body’s response to infection. Their studies were conducted in preclinical models and human cell cultures. Our experiments specifically demonstrated that Jmjd3 deletion affected master regulators and epigenetic modifiers of T cell fate,” said Wang. “Regulation of T cell differentiation is essential to maintain the appropriate balance among T cell subsets to support immune balance and to prevent autoimmunity.” Understanding the mechanisms of how molecules, such as Jmjd3, regulate T cell differentiation will help define
epigenetic influences. This will inevitably lead to the development of innovative and effective strategies to intervene in T cell-associated diseases.
Li Q, Zou J, Wang M, et al. Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation. Nat Commun. 2014 Dec 22;5:5780.
- Rongfu Wang, Ph.D. Professor of Inflammation and Epigenetics Institute for Academic Medicine
INNOVATIONS IN MEDICAL RESEARCH: CONTRIBUTING TO FEDERAL INITIATIVES by Veronica Custer Karam
In 2014, the U.S. House Energy and Commerce Committee began the 21st Century Cures Initiative to address challenges that stifle the discovery, development and
HOUSTON METHODIST HOSTS THE MULTISCALE SYSTEMS BIOLOGY SYMPOSIUM
delivery of medical innovation in the United States. The initiative has solicited input and perspectives from across the medical research continuum including patients, research institutes, industry and federal agencies. As a national leader in translational research, Houston Methodist has served as a key resource for these policy discussions since their launch. Mauro Ferrari, Ph.D., on behalf of Houston Methodist, served as a panelist in a Congressional hearing held in the Texas Medical Center. Houston Methodist has met
For the second consecutive year, Houston Methodist hosted the Multiscale Systems Biology Symposium on April 16 and 17. The symposium is a joint venture of the Center for Modeling Cancer Development directed by Houston Methodist Research Institute’s Stephen Wong, Ph.D., PE, John S. Dunn Presidential Distinguished Chair in Biomedical Engineering, and the Center for Cancer Systems Biology directed by Tim Huang, Ph.D. of the University of Texas Health Science Center - San Antonio (UTHSCA). The symposium featured speakers from Houston Methodist, UTHSCA, Baylor College of Medicine, Weill Cornell Medical College, University of New Mexico School of Medicine, and University of California - Irvine. As the National Cancer Institute’s (NCI) Integrated Cancer Biology Program moves to its second, inter-center collaborative phase, the 90 attendees at the symposium sought to identify potential areas of common interest with funding potential. In attendance was Deputy Director of the NCI, Daniel Gallahan, Ph.D., of the Division of Cancer Biology. The 17 speakers over the two days, covered a range of topics relevant to cancer development, metastasis, and treatment, computational modeling, imaging, and molecular biology with a focus on finding ways to integrate these findings to gain a comprehensive understanding of individual cancers and effective treatments for them.
with leaders and provided written testimonies for both the U.S. House and parallel efforts in the U.S. Senate. Houston Methodist participated in the Senate Appropriations Committee hearing on “Driving Innovation through Federal Investments” with written testimony and has contributed as the U.S. Senate Health, Education, Labor and Pensions Committee began formulating their own medical innovation agenda this year. Visit appropriations.senate.gov to read the full written testimony.
Brain tumor cells decimated by mitochondrial “smart bomb” by David Bricker & Gale Smith
An experimental drug that attacks brain tumor tissue by crippling the cells’ energy source called the mitochondria, has passed early tests in animal models and human tissue cultures, say Houston Methodist scientists.
As reported on the cover of the April 2015
Medical options for brain tumor patients
a number of other crucial functions, and even
ChemMedChem, Kenneth R. Peak
are woeful, Baskin said. Gliomas a type of
cancer cells cannot grow and divide without
Presidential Distinguished Chair David
brain tumor, develop from brain cells called
S. Baskin, M.D., and Associate Research
astrocytes. Gliomas account for 20 to 30
Professor of Neurosurgery Martyn Sharpe,
percent of all tumors of the brain and
Ph.D., designed a drug called MP-MUS that
central nervous system.
destroyed malignant glioma cells. In other
An enzyme called MAO-B is over-expressed in brain tumor cells, which is the target of MP-MUS. This means that healthy cells and
experiments however, it did not seem to
Mitochondria are often referred to as the
their mitochondria are only exposed to low
adversely affect healthy human brain cells
“powerhouses” of cells — including misbehaving
levels of MP-MUS, Baskin says. On the other
in vitro. This compliments a soon to be
cancer cells — because they help cells create
hand, in tumor cells the vast majority of the
published extensive study showing that
energy. In cancer cells, this feature is partially
pro-drug is converted into P+-MUS, which
the same drug can treat human brain cancer
switched off, causing cells to rely on other
essentially traps the drug inside their
grown in the brains of murine models.
systems that generate energy. The numerous
mitochondria where it attacks the mitochondrial
Researchers hope to begin testing the drug
pill-shaped mitochondria in each cell perform
“We are very optimistic that we’ll get there,” said Baskin. “Our past work has shown that MP-MUS has very low toxicity until it gets into tumor cells. Once it arrives, it is changed to its active form P+-MUS, doing a lot of damage
We found that we could achieve profound effects with MP-MUS at very low concentrations.” Tumor cells have much more MAO-B, and when challenged, make even more MAO-B as a sort of defensive response. We hope that we are one step ahead of the cancer cells, as we are using that very fact to kill them.
where we want it to, leaving healthy brain
in human clinical trials in 2016 or 2017.
- D avid Baskin, M.D. Kenneth R. Peak Presidential Distinguished Chair Department of Neurosurgery
cells alone — a bit like a ‘smart bomb.’ To our knowledge, this is the first known example of selective mitochondrial chemotherapy, which we believe represents a powerful
Sharpe M, Han J, Baskin A, Baskin DS. Design and synthesis of a MAO-B-selectively activated prodrug based on MPTP:
new approach to brain cancer.”
a mitochondria-targeting chemotherapeutic agent for treatment of human malignant gliomas. ChemMedChem. 2015 Apr;10(4):621-8.
Clinical Research Highlights
Transcatheter Alternative for Aortic Valve Replacement by Maitreyi Muralidhar
Of the 1.5 million Americans diagnosed with aortic stenosis, more than 500,000 have severe aortic stenosis and 250,000 are symptomatic. Traditionally, surgical valve replacement, which involves an open heart procedure, was considered the gold standard for the treatment of severe aortic stenosis. Surgical valve replacement however poses substantial risks for patients whose age or co-morbidities make them unsuitable for open heart surgery.
The Houston Methodist Valve Clinic is a globally recognized leader in the use of technologies for transcatheter aortic valve replacement (TAVR), a less invasive treatment option for aortic stenosis. It has been shown in clinical trials at Houston Methodist and elsewhere that percutaneous valve replacement can achieve optimal results without the high risk of mortality and morbidity typically associated with major surgery for valve replacement. Michael J. Reardon, M.D., Allison Family Distinguished Chair in Cardiovascular Research and Professor of Cardiovascular Surgery with the Houston Methodist DeBakey Heart & Vascular Center, is the surgical principal investigator for multiple clinical trials being conducted at Houston Methodist.
Reprise III - Repositionable Percutaneous Replacement of Stenotic
Replacement and Transcatheter Aortic Valve
Aortic Valve Through Implantation of Lotus™ Valve System - Randomized
Implantation trial is designed to evaluate the safety
Clinical Evaluation trial, is a new TAVR study sponsored by Boston Scientific.
and efficacy of the Medtronic CoreValve System
In addition to Houston Methodist, this trial is being conducted at 60 centers
in the treatment of symptomatic, severe aortic
across the US, Canada, Western Europe and Australia. The study will
stenosis. Patients in this study are at intermediate
evaluate the safety and effectiveness of the Lotus™ Valve System in
risk for the traditional surgical aortic valve
symptomatic patients with severe aortic stenosis who are deemed
replacement procedure. SURTAVI is a follow-up
extreme or high risk for surgical valve replacement.
CLINICAL RESEARCH HIGHLIGHTS
The SURTAVI trial, also known as the Surgical
trial to the CoreValve High Risk study, the first and only trial that showed significant survival rates for a transcatheter aortic valve over a surgical aortic valve in a randomized study. The 2-year outcomes from this study, were published by Reardon et al. in the June issue of the Journal of the American College of Cardiology. Within the SURTAVI trial, the minimally invasive CoreValve implantation can be performed by way
“The Lotus™ valve is the first transcatheter aortic valve that is recapturable, repositionable and redeployable. Hence, if the valve is positioned improperly, it can be repositioned and redeployed. The ability to be completely deployed and locked into place and yet still retrieved is unique to this valve,” says Reardon, the international surgical principal investigator for Reprise III.
of transfemoral, subclavian, or direct aortic access. Approximately 2,500 patients will be enrolled from national and international sites. SURTAVI is a controlled study that will randomize patients to either receive a transcatheter aortic valve or undergo standard open heart surgery. All patients will be followed for a period of five years.
The study design will enable comparison of the new generation Lotus™ valve with one that is being used commercially everyday in the US, the CoreValve. Patients implanted with either of the devices will be followed for 5 years after the procedure. Currently, the Lotus™ valve is not sanctioned for use in the United States but has already been approved for use in Canada, Europe and Australia.
The SURTAVI trial gives us a chance to look at a group of aortic stenosis patients who are searching for a less invasive way to treat their disease. Less invasive means a shorter hospital stay and a shorter recovery time for these patients who had few, if any, options before.
Houston Methodist is also participating in Direct Flow Medical’s SALUS Trial which will evaluate the safety and effectiveness of the Direct Flow Medical (DFM) Transcatheter Aortic Valve System in patients at extreme surgical risk with severe aortic stenosis. The DFM System is a second generation TAVR device with a unique and novel design. The device uses an inflatable cuff, with a “conforming, formed in place, polymer support structure” that potentially enables better seal and helps prevent leakage around the new valve.
Contact LaShawna Green, BS, RN, CVRN-BC, at firstname.lastname@example.org for more information on these studies.
– Michael J Reardon, M.D. Allison Family Distinguished Chair in Cardiovascular Research Houston Methodist DeBakey Heart & Vascular Center
Clinical Research Highlights
Slowing Brain Deterioration:
The NOBLE Study by Gale Smith
Photo: Robert Seale
The NOBLE study was initiated in March 2014 by the Alzheimer’s Disease Cooperative Study (ADCS). It is a phase II clinical trial of T-817MA, a neurotropic agent with an undisclosed mechanism of action. NOBLE will compare the neuroprotective profile of T-817MA at once a day dosing to placebo in 450 patients with mild to moderate Alzheimer’s disease. Patients must have been taking donepezil (“Aricept”) or rivastigmine (“Exelon”), single or combined with memantine (“NamendaTM”), for at least four months before enrollment
Previous studies in preclinical models have shown this investigational drug may work by protecting brain cells, which would result in improved memory and cognition,” said Joseph C. Masdeu, M.D., Ph.D., the
in the trial, for symptom management. Study
Graham Family Distinguished Chair for Neurological Sciences and the
participants will be randomized to T-817MA
principal investigator of this study at Houston Methodist. “Our goal
is to find out if this drug is a viable option for our patients.
T-817MA is a neuroprotective drug that acts on amyloid-induced neurotoxicity and memory deficits. Positron emission tomography (PET) has shown through the use of biomarkers that abnormal amounts of beta amyloid are evident in the brain as many as 20 years before
Of more than five million Americans living with Alzheimer’s disease, almost two-thirds are women. American women are twice as likely to die of Alzheimer’s disease as they are from breast cancer. According to the Alzheimer’s Association, someone develops Alzheimer’s disease every 67 seconds. In 2013, 15.5 million caregivers provided an estimated 17.7 billion hours of unpaid care valued at more than $220 billion.
initial symptoms develop. In previous studies,
The NOBLE study is sponsored by Toyama Chemical Co., Ltd., FUJIFILM Group.
T-817MA has been shown to mitigate
Approximately 50 sites nationwide are offering this study to patients with mild to
amyloid-induced learning deficits in
moderate Alzheimer’s disease. Houston Methodist is the only study location in Texas.
experimental Alzheimer’s disease models.
CLINICAL RESEARCH HIGHLIGHTS
CARE CONSORTIUM FOR CANCER by Maitreyi Muralidhar
Houston Methodist has joined hands with four major academic and research institutions to form the Consortium for the Advancement of Research Excellence (CARE), a group committed to advancing cancer research through collaborative translational and clinical initiatives. This effort was led by Jaime Mejia, M.D. and Jenny Chang, M.D. from the Houston Methodist Cancer Center. The ultimate goal of the consortium is to expedite the translation of laboratory research to the clinic by supporting the development and execution of translational research studies that incorporate innovative molecular diagnostics, targeted therapeutic interventions, advanced statistical design and models for the implementation of effective personalized therapy. The consortium also aims to facilitate and simplify collaboration with industry, National Cancer Institute and other federal and private funding agencies, and advocacy organizations. By offering Institutional Review Board (IRB) reciprocity, the consortium ensures that once a protocol is reviewed and approved by one IRB, it is accepted by all other consortium institutions, making the review process simpler and less time consuming. This also enables the study to be conducted at all institutions in the consortium.
1) Thomas Jefferson University - Philadelphia (PA)
2) Houston Methodist Cancer Center - Houston (TX)
3) Huntsman Cancer Institute, University of Utah - Salt Lake City (UT)
4) Weill Cornell Medical College - New York (NY)
5) Georgia Cancer Center, Emory University - Atlanta (GA)
CARE Consortium Open & Enrolling Clinical Trials TEAL Study for Breast Cancer This study involves evaluating the Pathological Complete Response of the breast when three different drugs are combined together [trastuzumab emtansine (TDM-1) + Lapatinib + Abraxane] for the treatment of newly diagnosed HER2 positive breast cancer.
NECTAR Study for Triple (-) Breast Cancer The purpose of this study is to test the effectiveness of combining Cisplatin chemotherapy with Everolimus in subjects with residual triple negative breast cancer, who have already received chemotherapy prior to surgery. Go to clinicaltrials.gov to learn more.
Houston Methodist, Imperial College London discuss Future Scientific Collaboration, Joint Training Programs by David Bricker
Houston Methodist and Imperial College London leaders announced that they will jointly explore programs to develop new medical technologies and create Houston educational opportunities for Imperial College London medical students, graduate students, and postdoctoral fellows.
We are excited about developing unique educational and research opportunities with an institution as widely respected as Imperial College London. We see vast potential for collaboration and the rapid development of spectacular new therapeutics and medical technologies. Our partnership can reduce the time it takes for promising new medical technologies to get to patients, and provide a
wealth of educational and training opportunities to Imperial College London students and fellows who seek experience in Houston Methodist laboratories and clinics.
– Mauro Ferrari, Ph.D. President and CEO Ernest Cockrell, Jr. Presidential Distinguished Chair Houston Methodist Research Institute
Top row, left to right: Jonathan Weber (ICL), David Gann (ICL), Gavin Screaton (ICL), Mary A. Daffin (HM), and John F. Bookout III (HM). Bottom row, left to right: Marc Boom (HM), Dermot Kelleher (ICL), Mauro Ferrari (HM), and Joseph C. “Rusty” Walter III (HM).
Imperial College London students’ educational experiences by providing them with opportunities to hone their skills in Houston Methodist’s areas of clinical and research strength. “The Houston Methodist Research Institute and Imperial College London both share in their missions a commitment to work across disciplines and to translate their discoveries and innovations
Mapping the Road to Success in Academia The Houston Methodist Postdoctoral and Trainee Association (MAPTA) organized the inaugural MAPTA Winter Science Symposium on December 9, 2014, to help trainees and postdoctoral fellows foster new collaborations within Houston Methodist. The symposium also provided a platform for them to showcase their work, and exchange
into health and wealth improvements,” said
ideas about their research projects with fellow colleagues at the
Gann, Imperial College London Vice President of
Texas Medical Center.
Development and Innovation and a chartered civil engineer. “Collaboration is the name of the game and we look forward to discussing how we can create new models for enterprise and achievement between both institutions, in Houston and in London.” Imperial College London is a comprehensive research university in the British capital. It enrolls about 15,000 students, one-third of whom are graduate students, and receives over $484 million (£300 million) in grants and contracts each year. Imperial College London is consistently ranked among the world’s top 5 or 10 universities, depending on the ranking organization. The most recent QS World University Rankings placed Imperial College London second (tied with England rival University of Cambridge). Houston Methodist Research Institute Director of Operations Tong Sun says a partnership with Imperial College London might become a model for the international commercialization of new medical technologies. “The development of medical
Ferrari said the joint programs could also broaden
The inaugural edition of the symposium was a big success with almost 200 participants from 9 different institutions including MD Anderson Cancer Center, Baylor College of Medicine, University of Houston, Texas A&M, Texas Children’s Hospital, University of Texas Health Science Center at Houston, Prairie View A&M University, and Texas Heart Institute. From over 50 abstract submissions received from residents, postdocs and graduate students, awards were given away for the best oral and poster presentations based on performance. 2014 Awardees: Oral Presentations: • Postdoctoral Fellows, Clinical Fellows/Residents - 1st place: $ 1,000 – CARLY FILGUEIRA - 2nd place: $ 750 – BRANDON LIEBELT •
Graduate/Undergraduate students - 1st place: $ 1,000 – FRANK OSPINO
Poster Presentations: • Postdoctoral Fellows, Clinical Fellows/Residents - 1st place: $ 750 – JIA FAN - 2nd place: $ 500 – JACLYN JERZ •
Graduate/Undergraduate students - 1st place: $ 1,000 – THOMAS GENINATTI - 2nd place: $ 500 – STEFANO PERSANO - 3rd place: $ 500 – LAURA PANDOLFI - 3rd place: $ 500 – FRANK OSPINO
technologies has changed in many fundamental ways,” Sun said. “Increasingly, the commercialization of new technologies in medicine requires a global perspective. Imperial College London could one day be our strategic partner in overseeing clinical trials of a Houston Methodist technology in Europe, as we could be their partner in the U.S. or North America for technology they develop. We hope to learn a lot from this mutually beneficial partnership.”
REVOLUTIONARY PLATFORM OF
FOR CARDIAC ARRHYTHMIAS
Houston Methodist offers two laboratories that feature Hansen Medical’s robotic system for application and development of advanced, cutting-edge, catheter-based cardiovascular procedures. “We have one of the largest — if not the largest — experiences in the use of robotic ablation both for atrial fibrillation as well as ventricular tachycardia,” says Miguel Valderrábano, M.D., Professor of Cardiology and Chief of the Division of Cardiac Electrophysiology at Houston Methodist DeBakey Heart & Vascular Center. “We basically showed the world how to treat ventricular tachycardia with the robot.” One of the laboratories for advanced imaging and navigation focuses on the electrophysiological approach to cardiac ablation with robotics. The second advanced imaging and navigation laboratory is located in the Houston Methodist Institute for Technology, Innovation and Education (MITIESM) and is pioneering work with robotics in the non-electrophysiology realm. Future uses for robotics include clinical procedures — not necessarily cardiac in origin — that may benefit from robotic precision and control in smaller blood vessels of the peripheral vasculature.
Miguel Valderrábano, M.D., positioning the robotic arm in place.
The lab in MITIE is probably the most advanced laboratory in the world in advanced imaging and navigation. Now we can navigate catheters remotely,
without turning on the X-ray machine. It is highly accurate and has unprecedented stability and navigation capability.
– Alan B. Lumsden, M.D. Walter W. Fondren III Distinguished Chair Houston Methodist DeBakey Heart & Vascular Center
NANODAYS 2015 - Making Science Education Fun at Houston Methodist Future medical scientists ages 4 to 12 joined Houston Methodist Research Institute staff on Saturday, April 25, to celebrate NanoDays 2015. It is the fifth time the Houston Methodist Research Institute
interest in the science of nanotechnology. Children
has hosted the event, part of the NanoDays festival launched
participated in activities like the “MedMyst,” a game
by the Nanoscale Informal Science Education initiative (NISE)
designed and sponsored by the Rice Center for Technology
in 2008 and funded by the National Science Foundation.
in Teaching and Learning; “Nano Fabric,” a hands-on activity
The event is designed to engage the public and spark interest
showing how nano-sized whiskers can protect clothing
in the science of nanotechnology and its use in everyday life.
from stains by changing surface properties; “Diet Coke &
The number of institutions participating nationwide has
Mentos,” in which kids create a fountain by tossing candies
grown to more than 250.
into a soda-containing vessel; and “Thin Films,” a hands-on
With a record attendence of over 425 children and members of their families, this years event was designed to spark
activity in which kids create a dynamic, colorful bookmark using a super thin layer of nail polish on water.
Marialuisa Lectureship for Life Save the Date: September 14-15, 2015 The Marialuisa Lectureship award was established at The Ohio State University
This yearâ€™s awardee, Sir Thomas Hughes-Hallett, is the Imperial College London David and Susan
Comprehensive Cancer Center - Arthur
Heckerman Professor of Pediatrics
G. James Cancer Hospital and Richard
and Executive Chair of the Institute of
and of Microbiology and Immunology,
J. Solove Research Institute in 2000 by
Global Health Innovation. Sir Hughes-
the Ferrari family in memory of Marialuisa
and Commissioner of Royal Hospital Chelsea. The upcoming 2015
Ferrari. This annual event educates researchers, physicians, nurses, caregivers, and the community about the importance
Hallett is Chair of the End-of-Life Care Implementation Advisory Board lectureship at the Houston Methodist Research Institute will focus on end-of-life/palliative care. The topics covered will include spirituality and ethics, end-of-life care for children, inputs from families going through these decisions and feedback from recent medical school graduates on what they have been taught.
of symptom and pain management for
Visit houstonmethodist.org/hmrievents for more information on
the upcoming event.
2015 George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Annual International Meeting The George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Annual International Meeting, supported through a generous philanthropic donation by the George J. and Angelina P. Kostas Charitable Foundation, serves as an important catalyst in advancing the field of cardiovascular nanomedicine and fostering collaborations among nationally and internationally recognized clinicians, industry experts, researchers, and surgeons. It also serves as a valuable platform for collaboration between Houston Methodist and other academic institutions such as Northeastern University. This year, the meeting will explore the interface between regenerative cardiology and nanodelivery systems with the event projected for October 12, 2015 at Houston Methodist Research Institute in Houston, Texas. The conference will immediately precede the National Heart, Lung, and Blood Institute Progenitor Cell Biology Consortium. Visit houstonmethodist.org/hmrievents for more information.
Mauro Ferrari Honored with the Stodola Medal Mauro Ferrari, president and CEO of the Houston Methodist Research Institute and one of the founders of the field of nanomedicine, was awarded the 2015 ETH Zürich Stodola Medal, an honor bestowed by the Department of Mechanical and Process Engineering, ETH Zürich. Ferrari was honored at a special event in the Swiss banking capital, and also gave the honorary ETH Zürich Aurel Stodola Lecture, titled “MultiStage Vectors and Transport OncoPhysics,” on the ways in which advances in mechanical engineering can aid the rapid development of new medical technologies. Ferrari was selected from an international slate of distinguished
drugs where they are most needed — and only there. Ferrari is
scientists because he is a “globally recognized expert” in his
also an expert in “transport oncophysics,” an abstract approach
area. According to the department, the annual Stodola Medal
to modeling the movement of small molecules into and out of
and Lecture “commemorate the personality and the seminal
cancer cells, as well as the flow of energy. In 2011, Ferrari
contributions to the field of mechanical engineering of its former
co-wrote the much cited “What does physics have to do with
faculty member Aurel Stodola.” Stodola is best known for helping
cancer?” for the journal Nature, that explained the different
perfect the steam turbine. He may have been the first engineer
ways in which physics can contribute breakthroughs to cancer
to collaborate with a doctor — to invent a dynamic prosthetic
hand and arm. Stodola died in 1942. Past Stodola awardees include atmospheric chemist John Ferrari is an expert in the use of nanotechnology in medicine,
Seinfeld of CalTech (2008), metabolic engineer Greg
such as the use of nanometer-sized discs that seek out and
Stephanopoulos of MIT (2009), and fluid mechanics expert
bind to cancer cells before delivering bursts of toxic chemotherapy
Nobuhide Kasagi of the University of Tokyo (2013).
John Cooke receives Stanford University’s Outstanding Inventor Award Joseph C. “Rusty” Walter and Carole
30 patent filings by Stanford and most of
at the very heart of what we do. Integrated
Walter Looke Presidential Distinguished
his issued patents have been licensed by
into one of the nation’s finest hospitals, the
Chair in Cardiovascular Disease Research,
biotechnology companies. On May 15,
Research Institute is designed to streamline
John Cooke, M.D., Ph.D., has been bestowed
2015, the Stanford University Office of
the process of translating laboratory research
with the “Outstanding Inventor Award” by
Technology Transfer, recognized 27 new
into treatments and cures for our patients.
Stanford University. The award is given to
prolific inventors including Dr. Cooke,
Dr. Cooke and his research team have further
those who have at least 7 technologies
whose technological discoveries were
strengthened Houston Methodist’s mission
that have in aggregate, generated over
successfully transferred to industry.
of fostering translational research through
$500,000 in royalties. Dr. Cooke who joined Houston Methodist in 2013 from Stanford University, is an inventor on
At Houston Methodist, fostering innovations with the potential for clinical application is
their experience and expertise of transferring early research insights and inventions to industry for further development.
Houston Methodist Research Institute 6670 Bertner Ave. Houston | TX 77030
UPCOMING MAJOR CONFERENCES SAVE THE DATE
MITIE - Microsurgery Mini-Fellowship (4 Day Course)
Marialuisa Lectureship for Life Awardee: Sir Thomas Hughes-Hallett
Emerging Topics in Liver Disease Conference CME credit available
6th Annual Multi-Modality Cardiovascular Imaging for the Clinician CME credit available
2015 George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Annual International Meeting
National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium (PCBC) Meeting
Pumps & Pipes 9: Discovery Pathways
Go to houstonmethodist.org/hmrievents for more information.
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 James J. Mancuso Gale Smith Veronica Custer Karam Colleen Kelly Public Relations Contact David Bricker 832.667.5811 email@example.com
Read more online: houstonmethodist.org/hmrinews Office of Communications and External Relations Institute for Academic Medicine Houston Methodist Email: firstname.lastname@example.org IAMNEWS-004 | 06.2015 | 2090