METHODOLOGYThe Research and Education Newsletter of Houston Methodist

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.

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SPRING/SUMMER 2015

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

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

by Maitreyi Muralidhar

Houston Methodist RNACore Awarded $4.8 Mill ion for RNA Therapeutics and Research by the Cancer Prevention and Research Institute of Texas

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 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

valve replacement (TAVR) technology and a neuroprotective drug called T-817MA to manage

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

Chang and Jaime Mejia to simplify the process of collaborative clinical trials with Weill Cornell

Medical College, Emory University, the University of Utah and Thomas Jefferson University.

Our researchers are pushing the boundaries of medicine – Dr. Alessandro Grattoni is

harnessing the power of nanotechnology for designing controlled drug release devices and

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

this year for testing in preclinical models aboard the International Space Station.

Dr. John Cooke has received a CPRIT grant to expand our RNACore to produce RNA

Therapeutics for cancer, in addition to the constructs it currently produces for heart disease in

partnership with the National Heart, Lung & Blood Institute – read more about both initiatives

in this issue.

I would like to announce several key Houston Methodist recruitments this year that are central

to continuing our legacy of innovation and expanding our academic mission and strategic initiatives.

Dr. Tanya Burkholder has joined us from the Division of Veterinary Resources at the National

Institutes of Health to lead our Comparative Medicine Program. Dr. Phil Horner has joined

us from the University of Washington to lead our Neuroregeneration research program. Please

welcome them to our team when you meet them in the halls and on shared committees.

This issue of Methodology also celebrates the founding of the Sherrie and Alan Conover

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 –

together we are leaders in medicine.

Mauro Ferrari, Ph.D.

Ernest Cockrell Jr. Distinguished Endowed ChairPresident and CEO, Houston Methodist Research InstituteProfessor of Biomedical Engineering in MedicineDirector, Institute for Academic MedicineExecutive Vice President, Houston Methodist

Senior Associate Dean and Professor of MedicineWeill Cornell Medical College, New York, NY

Read more online: HoustonMethodist.org/hmrinews

Contents

FROM THE PRESIDENT

by xxxxxxxxxxxxxxxxFeatured News

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

Research Highlights

In Orbit or on Earth, Implantable Device to Release Therapeutic Drugs Remotely .......................................6

Reprogrammed Cells Grow Into New Blood Vessels .........................8

Creating Unsafe Neighborhoods for Cancer Cells ...........................10

Houston Methodist Researcher at the Forefront of Immunology Research ......................................11

Gene Appears to “Skew” Production of Helper T Cells .......11

Brain Tumor Cells Decimated by Mitochondrial “Smart Bomb” .....13

Clinical Research Highlights

Transcatheter Alternative for Aortic Valve Replacement...........14

Slowing Brain Deterioration: The NOBLE Study ........................16

CARE Consortium for Cancer .....17

Education News

Houston Methodist, Imperial College London Discuss Future Scientific Collaboration, Joint Training Programs .......................18

Revolutionary Platform of Robotic Technology for Cardiac Arrhythmias ................................20

Of Interest

Mauro Ferrari Honored With The Stodola Award .....................23

John Cooke Receives Stanford University’s Outstanding Inventor Award ..........................................23

Contents

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.

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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.

>> CONT. FROM PAGE ONE

RECRUITMENT UPDATE

Houston Methodist Research Institute Gets New Director for Comparative Medicine Program

4

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.”

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”.

by David Bricker

Breast cancer vaccines may work better with sil icon microparticles

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

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.

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.

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– Haifa Shen, M.D., Ph.D. Assistant Professor of Nanomedicine Institute for Academic Medicine

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.

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.

HOUSTON METHODIST RECEIVES $6.5 MILLION GIFT TO NAME LIVER CENTER

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

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.

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.

for drugs and a silicon membrane housing

615,342 channels as small as 2.5 nm.

The channels are sized and shaped to

control drug release, and the exactness of

the design is achieved using nanotechnology

techniques developed by Grattoni and Ferrari.

Drug movement through the channels is

controlled by surface electrodes that “tune”

the rate of drug delivery. Below the drug

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

Grattoni, Ph.D. “If we are able to show the

technology works in vivo and is safe, it could

have an enormous impact on drug delivery

and patient care.” Houston Methodist

Research Institute President and CEO and

Ernest Cockrell Jr. Presidential Distinguished

Chair, Mauro Ferrari, Ph.D., is the project’s

co-principal investigator and will help

supervise the project.

Grattoni’s device, called a nanochannel

delivery system or “nDS,” is an 18 mm-wide

squat cylinder. It contains a reservoir

The device’s effectiveness will be tested

aboard the International Space Station

and on Earth’s surface. Austin-based

NanoMedical Systems Inc. and the

Houston Methodist Research Institute

are also supporting the five-year project,

bringing total funding to $1.92 million.

“The prospect of developing and

demonstrating a remotely controlled

drug delivery implant excites us,” said

principal investigator and Assistant

Professor of Nanomedicine Alessandro

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)

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Research Highlights

by David Bricker

Grattoni has also received close to $600,000

from the National Institute of General Medical

Sciences to further develop this nanochannel-

based technology to enable the in vivo analysis

of investigational drugs and dosing regimens.

Logo design by: Matthew Landry

microchip-based devices may not be

suitable for long term treatments –

despite their large volume, they have

limited drug storage capacity.

Doctors may want to have control over

the rate of drug delivery for several

reasons. Some drug regimens work

better or are better tolerated when

delivered at regularly timed bursts,

while some drugs have been shown

to be more effective when delivered

at specific times of day. In addition,

doctors may also want to be able to

stop or start drug delivery quickly in

response to changes in patients’

health. With Grattoni’s nDS, this could

be done remotely – potentially saving

time and improving medical outcomes

for patients.

via radio-frequency remote control. The

device will be tested in preclinical

models aboard the International Space

Station.

There are three technologies available

today that allow a patient to receive

drug infusions without having to visit a

hospital or clinic. Among these are

wearable external pumps, implantable

multi-layered polymers that release drugs

as they erode, and implantable, metal-

gated devices. In Grattoni’s view, all

three types of devices have limitations.

External pumps may carry risk of infection

around transdermal catheters and can be

inconvenient. Drug-lined polymers may

cause an initial burst in drug release and

are not tunable once implanted. Current

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

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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.

Research Highlights

“

”– 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

Reprogrammed cells grow into new blood vesselsby David Bricker

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Other research groups have managed to generate endothelial

cells using infectious virus particles specially engineered to

deliver gene-manipulating DNA to cells. The DNA encodes

proteins called transcription factors to alter gene expression

patterns in such a way that cells behave more like endothelial

cells. “There are problems with using viruses to transfer

genes into cells,” Cooke said. “This gene therapy approach

is more complicated, and using viral vectors means a

possibility of causing damage to the patient’s chromosomes.

We believe a small-molecule approach to transforming the

cells will be far more feasible and safer for clinical therapies.”

The new method described by Cooke and his coauthors

starts with exposing fibroblasts to poly I:C (polyinosinic:

polycytidylic acid), a small segment of double-stranded

RNA that binds to the host cell receptor TLR3 (toll-like

receptor 3), tricking the cells into reacting as if attacked

by a virus. Cooke and coauthors reported to Cell in 2012

that fibroblasts’ response to a viral attack — or, in this case,

a fake viral attack — appears to be a vital step in diverting

fibroblasts toward a new cell fate. After treatment with poly I:C,

the researchers observed a reorganization of nuclear

chromatin, allowing previously blocked-off genes to be

expressed. The fibroblasts were then treated with factors,

such as VEGF, that are known to compel less differentiated

cells into becoming endothelial cells.

Cooke and his colleagues reported to Circulation that

about 2 percent of the fibroblasts were transformed from

fibroblasts into endothelial cells, a rate comparable to what

other research groups have accomplished using viruses

and gene therapy. But Cooke said preliminary, as-yet-

unpublished work by his group suggests they may be able

to achieve transformation rates as high as 15 percent.

That’s about where we think the yield of transformed cells

needs to be,” Cooke said. “You don’t want all of the

fibroblasts to be transformed as fibroblasts perform a

number of important functions, including making proteins

that hold tissue together. Our approach will transform some

of the scar cells into blood vessel cells that will provide

blood flow to heal the injury.”

In a second part of the study, the scientists introduced the

transformed human cells into immune-deficient mice that

had poor blood flow to their hind limbs. The human blood

vessel cells increased the number of vessels in the mouse

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.

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Creating unsafe neighborhoods for cancer cellsby James J. Mancuso

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.

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.

Cell populations were sorted from normal and tumor lungs based on specific

cell surface markers and subjected to single cell RNA sequencing; this way they

could see comprehensively how tumors change their neighbors and vice versa.

The findings, expand a new front in the fight against cancer based on precision

medicine that creates a hostile environment for cancer, based on patient and

cancer specific simulation.

Cancer’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 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.

Research Highlights

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.

QUICK FACTSHOUSTON METHODIST

71,931

789,74895,651

4,000+18,000

Hospitals

Operating beds

Outpatient visits

Admissions

Physicians

Employees

5691,460

360 37

74448

Faculty

Credentialed researchers

Trainees (residents, postdoctoral fellows & students)

ACGME-accredited training programs

GMEC-sponsored fellowship programs

Regularly scheduled CME activities

Live programs educating 10,071 physicians

440,000

100,000

Sq.ft. dedicated research building with 12 stories and 150 lab benches

TOP 20$130 M

U.S. domestic hospital based research institutes

Annual research expenditures

Additional sq.ft. research space embedded throughout the hospital

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.

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.

Houston Methodist researcher at the forefront of immunology research

These studies will provide new insight into the associations of alloantibody and increased 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

Gene appears to “skew” production of helper T cellsby David Bricker

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.

“ “

- Rongfu Wang, Ph.D. Professor of Inflammation and Epigenetics Institute for Academic MedicineLi 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.

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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.”

Research HighlightsResearch Highlights

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.

For the second consecutive year, Houston Methodist hosted the Multiscale Systems Biology Symposium on April 16 and 17.

HOUSTON METHODIST HOSTS THE MULTISCALE SYSTEMS BIOLOGY SYMPOSIUM

INNOVATIONS IN MEDICAL RESEARCH: CONTRIBUTING TO FEDERAL INITIATIVES

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

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

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.

by Veronica Custer Karam

12

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.

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 kil l them.

Brain tumor cells decimated by mitochondrial “smart bomb”

by David Bricker & Gale Smith

As reported on the cover of the April 2015

ChemMedChem, Kenneth R. Peak

Presidential Distinguished Chair David

S. Baskin, M.D., and Associate Research

Professor of Neurosurgery Martyn Sharpe,

Ph.D., designed a drug called MP-MUS that

destroyed malignant glioma cells. In other

experiments however, it did not seem to

adversely affect healthy human brain cells

in vitro. This compliments a soon to be

published extensive study showing that

the same drug can treat human brain cancer

grown in the brains of murine models.

Researchers hope to begin testing the drug

in human clinical trials in 2016 or 2017.

“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

where we want it to, leaving healthy brain

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

new approach to brain cancer.”

Medical options for brain tumor patients

are woeful, Baskin said. Gliomas a type of

brain tumor, develop from brain cells called

astrocytes. Gliomas account for 20 to 30

percent of all tumors of the brain and

central nervous system.

Mitochondria are often referred to as the

“powerhouses” of cells — including misbehaving

cancer cells — because they help cells create

energy. In cancer cells, this feature is partially

switched off, causing cells to rely on other

systems that generate energy. The numerous

pill-shaped mitochondria in each cell perform

a number of other crucial functions, and even

cancer cells cannot grow and divide without

healthy mitochondria.

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

their mitochondria are only exposed to low

levels of MP-MUS, Baskin says. On the other

hand, in tumor cells the vast majority of the

pro-drug is converted into P+-MUS, which

essentially traps the drug inside their

mitochondria where it attacks the mitochondrial

DNA.

“ “

- David Baskin, M.D. Kenneth R. Peak Presidential Distinguished Chair Department of Neurosurgery

Sharpe M, Han J, Baskin A, Baskin DS. Design and synthesis of a MAO-B-selectively activated prodrug based on MPTP:

a mitochondria-targeting chemotherapeutic agent for treatment of human malignant gliomas. ChemMedChem. 2015

Apr;10(4):621-8.

13

Clinical Research Highlights

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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.

Transcatheter Alternative for Aortic Valve Replacementby Maitreyi Muralidhar

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.

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Reprise III - Repositionable Percutaneous Replacement of Stenotic

Aortic Valve Through Implantation of Lotus™ Valve System - Randomized

Clinical Evaluation trial, is a new TAVR study sponsored by Boston Scientific.

In addition to Houston Methodist, this trial is being conducted at 60 centers

across the US, Canada, Western Europe and Australia. The study will

evaluate the safety and effectiveness of the Lotus™ Valve System in

symptomatic patients with severe aortic stenosis who are deemed

extreme or high risk for surgical valve replacement.

“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.

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.

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 lagreen2@houstonmethodist.org

for more information on these studies.

The SURTAVI trial, also known as the Surgical

Replacement and Transcatheter Aortic Valve

Implantation trial is designed to evaluate the safety

and efficacy of the Medtronic CoreValve® System

in the treatment of symptomatic, severe aortic

stenosis. Patients in this study are at intermediate

risk for the traditional surgical aortic valve

replacement procedure. SURTAVI is a follow-up

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

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 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.

“

”– Michael J Reardon, M.D. Allison Family Distinguished Chair in Cardiovascular Research Houston Methodist DeBakey Heart & Vascular Center

Clinical Research Highlights

16

Slowing Brain Deterioration:

The NOBLE Study

Patients must have been taking donepezil

(“Aricept”) or rivastigmine (“Exelon”), single

or combined with memantine (“NamendaTM”),

for at least four months before enrollment

in the trial, for symptom management. Study

participants will be randomized to T-817MA

or placebo.

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

initial symptoms develop. In previous studies,

T-817MA has been shown to mitigate

amyloid-induced learning deficits in

experimental Alzheimer’s disease models.

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.

The NOBLE study is sponsored by Toyama Chemical Co., Ltd., FUJIFILM Group.

Approximately 50 sites nationwide are offering this study to patients with mild to

moderate Alzheimer’s disease. Houston Methodist is the only study location in Texas.

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

Graham Family Distinguished Chair for Neurological Sciences and the

principal investigator of this study at Houston Methodist. “Our goal

is to find out if this drug is a viable option for our patients.

“

”

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.

by Gale Smith

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.

Consortium Members: 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)

TEAL Study for Breast CancerThis 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 CancerThe 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.

CARE CONSORTIUM FOR CANCER by Maitreyi Muralidhar

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.

CARE Consortium Open & Enrolling Clinical Trials

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Education News

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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.

Houston Methodist, Imperial College London discuss Future Scientific Collaboration, Joint Training Programsby David Bricker

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).

“

“– Mauro Ferrari, Ph.D. President and CEO Ernest Cockrell, Jr. Presidential Distinguished Chair Houston Methodist Research Institute

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Ferrari said the joint programs could also broaden

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

into health and wealth improvements,” said

Gann, Imperial College London Vice President of

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

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.”

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: •PostdoctoralFellows,ClinicalFellows/Residents - 1st place: $ 1,000 – CARLY FILGUEIRA - 2nd place: $ 750 – BRANDON LIEBELT

• Graduate/Undergraduatestudents - 1st place: $ 1,000 – FRANK OSPINO

Poster Presentations: • PostdoctoralFellows,ClinicalFellows/Residents - 1st place: $ 750 – JIA FAN - 2nd place: $ 500 – JACLYN JERZ

• Graduate/Undergraduatestudents - 1st place: $ 1,000 – THOMAS GENINATTI - 2nd place: $ 500 – STEFANO PERSANO - 3rd place: $ 500 – LAURA PANDOLFI - 3rd place: $ 500 – FRANK OSPINO

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

ideas about their research projects with fellow colleagues at the

Texas Medical Center.

Mapping the Road to Success in Academia

Education News

20

“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.

FOR CARDIAC ARRHYTHMIAS

REVOLUTIONARY PLATFORM OF

ROBOTIC TECHNOLOGY

Houston Methodist offers two laboratories that feature Hansen Medical’s robotic system for application and development of advanced, cutting-edge, catheter-based cardiovascular procedures.

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.

“

“

Miguel Valderrábano, M.D., positioning the robotic arm in place.

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

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FOR CARDIAC ARRHYTHMIAS

It is the fifth time the Houston Methodist Research Institute

has hosted the event, part of the NanoDays festival launched

by the Nanoscale Informal Science Education initiative (NISE)

in 2008 and funded by the National Science Foundation.

The event is designed to engage the public and spark interest

in the science of nanotechnology and its use in everyday life.

The number of institutions participating nationwide has

grown to more than 250.

With a record attendence of over 425 children and members

of their families, this years event was designed to spark

interest in the science of nanotechnology. Children

participated in activities like the “MedMyst,” a game

designed and sponsored by the Rice Center for Technology

in Teaching and Learning; “Nano Fabric,” a hands-on activity

showing how nano-sized whiskers can protect clothing

from stains by changing surface properties; “Diet Coke &

Mentos,” in which kids create a fountain by tossing candies

into a soda-containing vessel; and “Thin Films,” a hands-on

activity in which kids create a dynamic, colorful bookmark

using a super thin layer of nail polish on water.

Future medical scientists ages 4 to 12 joined Houston Methodist Research Institute staff on Saturday, April 25, to celebrate NanoDays 2015.

NANODAYS 2015 - Making Science Education Fun at Houston Methodist

OF INTEREST

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2015 George and Angelina Kostas Research Center for Cardiovascular Nanomedicine Annual International MeetingThe 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.

Save the Date: September 14-15, 2015

Marialuisa Lectureship for Life

The Marialuisa Lectureship award was

established at The Ohio State University

Comprehensive Cancer Center - Arthur

G. James Cancer Hospital and Richard

J. Solove Research Institute in 2000 by

the Ferrari family in memory of Marialuisa

Ferrari. This annual event educates

researchers, physicians, nurses, caregivers,

and the community about the importance

of symptom and pain management for

cancer patients.

This year’s awardee, Sir Thomas

Hughes-Hallett, is the Imperial

College London David and Susan

Heckerman Professor of Pediatrics

and of Microbiology and Immunology,

and Executive Chair of the Institute of

Global Health Innovation. Sir Hughes-

Hallett is Chair of the End-of-Life Care Implementation Advisory Board

and Commissioner of Royal Hospital Chelsea. The upcoming 2015

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.

Visit houstonmethodist.org/hmrievents for more information on

the upcoming event.

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Joseph C. “Rusty” Walter and Carole

Walter Looke Presidential Distinguished

Chair in Cardiovascular Disease Research,

John Cooke, M.D., Ph.D., has been bestowed

with the “Outstanding Inventor Award” by

Stanford University. The award is given to

those who have at least 7 technologies

that have in aggregate, generated over

$500,000 in royalties. Dr. Cooke who

joined Houston Methodist in 2013 from

Stanford University, is an inventor on

30 patent filings by Stanford and most of

his issued patents have been licensed by

biotechnology companies. On May 15,

2015, the Stanford University Office of

Technology Transfer, recognized 27 new

prolific inventors including Dr. Cooke,

whose technological discoveries were

successfully transferred to industry.

At Houston Methodist, fostering innovations

with the potential for clinical application is

at the very heart of what we do. Integrated

into one of the nation’s finest hospitals, the

Research Institute is designed to streamline

the process of translating laboratory research

into treatments and cures for our patients.

Dr. Cooke and his research team have further

strengthened Houston Methodist’s mission

of fostering translational research through

their experience and expertise of transferring

early research insights and inventions to

industry for further development.

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

scientists because he is a “globally recognized expert” in his

area. According to the department, the annual Stodola Medal

and Lecture “commemorate the personality and the seminal

contributions to the field of mechanical engineering of its former

faculty member Aurel Stodola.” Stodola is best known for helping

perfect the steam turbine. He may have been the first engineer

to collaborate with a doctor — to invent a dynamic prosthetic

hand and arm. Stodola died in 1942.

Ferrari is an expert in the use of nanotechnology in medicine,

such as the use of nanometer-sized discs that seek out and

bind to cancer cells before delivering bursts of toxic chemotherapy

drugs where they are most needed — and only there. Ferrari is

also an expert in “transport oncophysics,” an abstract approach

to modeling the movement of small molecules into and out of

cancer cells, as well as the flow of energy. In 2011, Ferrari

co-wrote the much cited “What does physics have to do with

cancer?” for the journal Nature, that explained the different

ways in which physics can contribute breakthroughs to cancer

biology.

Past Stodola awardees include atmospheric chemist John

Seinfeld of CalTech (2008), metabolic engineer Greg

Stephanopoulos of MIT (2009), and fluid mechanics expert

Nobuhide Kasagi of the University of Tokyo (2013).

Mauro Ferrari Honored with the Stodola Medal

John Cooke receives Stanford University’s Outstanding Inventor Award

Houston Methodist Research Institute

6670 Bertner Ave.Houston | TX 77030

Editor-in-Chief Rebecca Hall, Ph.D.

Managing Editor and Writer Maitreyi Muralidhar, MS

Design & Creative Lead Doris T. Huang

METHODOLOGYThe Research and Education Newsletter of Houston Methodist

Contributing Writers David Bricker James J. Mancuso Gale Smith Veronica Custer Karam Colleen Kelly

Public Relations Contact David Bricker 832.667.5811 dmbricker@houstonmethodist.org

Read more online: houstonmethodist.org/hmrinews

Office of Communications and External RelationsInstitute for Academic MedicineHouston MethodistEmail: news@houstonmethodist.org

IAMNEWS-004 | 06.2015 | 2090

SAVE THE DATE July 6 MITIE - Microsurgery Mini-Fellowship (4 Day Course)

September 14-15 Marialuisa Lectureship for Life Awardee: Sir Thomas Hughes-Hallett

September 26 Emerging Topics in Liver Disease Conference CME credit available

October 9-11 6th Annual Multi-Modality Cardiovascular Imaging for the Clinician CME credit available

October 12 2015 George and Angelina Kostas Research Center for Cardiovascular Nanomedicine

Annual International Meeting

October 13-14 National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium (PCBC) Meeting

December 7 Pumps & Pipes 9: Discovery Pathways

UPCOMING MAJOR CONFERENCES

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Go to houstonmethodist.org/hmrievents for more information.