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Cores at a Glance Houston Methodist Research Institute


At

the

Houston

Institute, the

Methodist

fostering

potential

for

Research

innovations clinical

with

application

is at the very heart of what we do. Integrated

into

one

of

the

nation’s

finest hospitals, the Research Institute is committed to streamlining the process of translating laboratory research into treatments and cures for our patients. Translating laboratory discoveries into novel treatments for patients requires specialized research and development infrastructure, along with regulatory knowledge, technical expertise, and specialized facilities. Houston Methodist supports translational research with on-site capabilities for Federal Drug Administration (FDA) approved current good manufacturing practice (cGMP) and good laboratory practice (GLP) studies, and early phase (I and II) clinical trials. Our commitment to the full translational cycle from discovery to cure is how we deliver on our mission of leading medicine.


Houston Methodist Research Institute

Research cores

To support the unique technological needs inherent to conducting translational research, the Houston Methodist Research Institute has built over 20 core facilities that provide our investigators and external researchers access to exceptional scientific technology. Whether an investigator is in the initial phase of discovery or is developing, testing, or validating a new drug or device, the Research Institute has a core facility ready to assist in every step with technical expertise and state-of-the-art equipment.

01 03 04 Central Support Services Clinical Research Services & Support

Translational Research Cores & Services Translational research cores facilitate moving preclinical discoveries into the clinical phase of development. At the Houston Methodist Institute for Technology, Innovation & Education or MITIESM, researchers are accelerating the discovery and delivery of better care by fostering new medical technologies and techniques using advanced imaging systems, minimal access technologies, and robotics. Translational research cores also include the FDA compliant cGLP facilities to perform safety and risk assessments in preclinical models, and cGMP facilities designed to produce clinical grade radiopharmaceuticals, nanoparticles or biologicals for preclinical and clinical studies.

2 | Houston Methodist Research Institute

Translational Research Cores & Services

02 Research Cores & Services

Research Cores & Services The research cores & services provide platform technologies comprising of instruments and techniques, and services that are foundational to basic laboratory research. Clinical Research Services & Support The clinical research cores offer clinical research infrastructure to support investigators in the design, initiation, management, and reporting of clinical trials. Central Support Services The central support service cores provide scientific and technical expertise related to a broad range of areas such as bioinformatics, library services, scientific writing and editing, and grant application services through the Office of Strategic Research Initiatives.


cGMP Manufacturing Core..............................................................................4

Cyclotron and Radiopharmaceutical Core....................................................6

Translational Imaging Core................................................................................8

Magnetic Resonance Imaging Facility

Preclinical Imaging Facility

Positron Emission Tomography (PET) Facility

Houston Methodist Institute for Technology,

Innovation & Education (MITIESM)................................................................. 10

Machine Shop Core......................................................................................... 14

Comparative Medicine.................................................................................... 15

Preclinical Catheterization Laboratory Core.............................................. 16

Biorepository Core........................................................................................... 18

Research Pathology Core.............................................................................. 19

Research Cores & Services Cellular and Molecular Services

Biomicrofluidics Core......................................................................... 20

Flow Cytometry Core......................................................................... 22

Molecular Diagnostics Core............................................................. 23

Nanoengineering Core....................................................................... 24

Peptidomics Nanoengineering Core.............................................. 25

RNAcore................................................................................................ 26

Microscopy Services

Advanced Cellular and Tissue Microscopy Core........................ 28

Electron Microscopy Core................................................................ 29

Clinical Research Services & Support

Clinical Research Services............................................................................ 30

Academic Office of Clinical Trials

Clinical Research Support............................................................................. 32

Cockrell Centers for Advanced Therapeutics

Central Support Services

Biomedical Informatics Services................................................................... 34

Center Grant Proposals Support................................................................. 35

Scientific Writing & Editing Support............................................................ 35

Library Services................................................................................................ 36

content

Translational Research Cores & Services


cGMP Manufacturing Core The current Good Manufacturing Practices (cGMP) Manufacturing Core is an FDA-approved facility that provides a controlled cleanroom and aseptic processing environment for manufacturing molecular, nanotech, and cellular therapies.

Houston Methodist has two cGMP cores on-site offering investigators unparalleled opportunities for generating novel, clinical grade therapeutics.

4 | Houston Methodist Research Institute


• Exposed surfaces and floors designed for rigorous cleaning and high sanitation standards that ensure product purity and patient safety

• HEPA filter and air handling units to provide particulate-free air at a positive air pressure

• Continuous monitoring of critical parameters like temperature, pressure, and humidity

• H  igh capacity, ultra-pure water system with environmental monitoring system to assure microbiological control

• In-house waste treatment system to neutralize wet bench waste streams

• Manufacturing equipment and utilities validated to meet biopharmaceutical standards (IQ/OQ/PQ)

• C  ontrolled access facility with designated gowning areas, preparatory labs, shipping and receiving stations, storage areas, and clean rooms

• R  obust sample identification, traceability systems, and electronic document control systems are part of the centralized quality infrastructure

Equipment

• Wet bench

• Tissue culture hoods

• RIE-1700 plasma etcher

• Wafer spin rinse dryers

• Room temperature and cold storage (4 °C, -20 °C, and -80 °C)

• Biological safety cabinets (class 1,000)

• Centrifuges and microscopes

• CO2 incubators

• Stainless steel work surfaces

houstonmethodist.org/cgmpmanufacturing Core Director: Glenn Winnier, PhD Email: gewinnier@houstonmethodist.org Phone: 713.441.2049

Cores At A Glance | 5

TRANSLATIONAL RESEARCH CORES & SERVICES

Special Features


Cyclotron and Radiopharmaceutical Core The Cyclotron and Radiopharmaceutical Core is a cGMP-compliant facility that produces clinical grade and rare custom radiopharmaceuticals for research and medical purposes. The applications for these tracers include Positron Emission Tomography (PET) imaging of prostate, renal, and brain tumors, diagnosis of Alzheimer’s disease and other dementias, locating epilepsy seizure foci prior to surgery, detecting coronary artery disease, and measuring the in vivo biodistribution and pharmacokinetic profiles of experimental drugs.

The on-site facility enables production of multiple doses of PET tracers for a patient in a single day. The half-lives of these tracers range from 2 to110 minutes. 6 | Houston Methodist Research Institute


The facility produces [18F] Fludeoxyglucose on a daily basis and other compounds given below on request:

• [13N] Ammonia (Cardiac perfusion)

• [11C] Acetate (Cardiac oxygen metabolism)

• [18F] F-AV-1451 (Alzheimer’s Tau imaging)

• [18F] FHBG (Gene therapy imaging)

• [18F] Fluoro-L-DOPA (Brain tumor imaging, over 96% sensitivity)

• [11C] Choline (Prostate cancer imaging)

• [11C] PIB (Beta-amyloid plaque imaging for Alzheimer’s disease) • [11C] Raclopride (Dopamine D2 receptor-imaging for motor and cognitive function) • [11C] PBR28 (Neuroinflammation imaging) • [18F] GE180 (Neuroinflammation imaging) • [18F] Fluorothymidine (Cancer proliferation imaging)

Services

• Nuclear pharmacy for radiopharmaceuticals preparation and dispensing

• Integrated rapid transport delivery system to research imaging suite for short half-life isotopes

• GMP production of various 18F, 15O, 13N, 11 C, and 64Cu compounds

• Consultation for research studies involving radioisotopes

Equipment

• GE PETrace 16.5 MeV negative ion isochronous cyclotron

• Seven automated and customized synthesis modules, including a solid target system for 64Cu

• Nine ventilated hot cells

• Aseptic preparation laminar airflow hood

• Two Class 100 telemanipulator dispensing hot cells

houstonmethodist.org/cyclotron Core Director: Meixiang (Max) Yu, PhD Email: myu@houstonmethodist.org Phone: 713.441.2921

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TRANSLATIONAL RESEARCH CORES & SERVICES

Available PET Radiopharmaceuticals


Translational Imaging Core The Translational Imaging Core provides access to advanced high-performance Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) for use with preclinical and clinical research studies.

MRI Facility

• Houses a state-of-the-art 70 cm wide-bore 3.0 Tesla whole-body human MRI scanner

• Offers support for imaging research studies (including functional MRI) by a team of imaging experts utilizing advanced MRI pulse sequences and image analysis software

• Provides dedicated areas for human and preclinical research with separate access to the scanner room

PET Imaging Facility

• Includes a dedicated nuclear and PET imaging clinic, a cyclotron facility, and a cGMP-compliant laboratory for the production of clinical grade radiopharmaceuticals

• Operates latest generation scanners for advanced scintigraphic imaging of shortand long-lived radioisotopes

• Provides full support for Investigational New Drug (IND) filing, imaging protocol development, and optimization for clinical trials

8 | Houston Methodist Research Institute


• Enables imaging of preclinical study models

• Imaging modalities available: PET, SPECT, CT, MRI/MRS, ultrasound, and optical imaging

• End-user training (depending on the application)

• Assistance with experimental design, image acquisition, and image analysis

• Troubleshooting and optimization of experiments

• Ongoing consultation and support

Key Equipment

• 70 cm wide-bore, 3.0 Tesla, whole-body human MRI scanner

• Inveon dedicated PET system

• Inveon multimodality SPECT/CT system

• Caliper IVIS-200 system

• Maestro in vivo fluorescence imaging system

MRI Director: Christof Karmonik, PhD Email: ckarmonik@houstonmethodist.org houstonmethodist.org/mri-core Phone: 713.441.7979

PET Director: Daniel Y. Lee, MD, PhD Email: dlee@houstonmethodist.org houstonmethodist.org/pet_facilities Phone: 713.441.0806

MRI Medical Director: Steve H. Fung, MD Email: shfung@houstonmethodist.org

Preclinical Imaging Director: Zheng-Zheng Shi, MD, PhD Email: zshi@houstonmethodist.org houstonmethodist.org/preclinicalimaging Phone: 713.441.9601 Cores At A Glance | 9

TRANSLATIONAL RESEARCH CORES & SERVICES

Preclinical Imaging Facility


Houston Methodist Institute for Technology, Innovation & Education The pace of technological change in medicine is unprecedented -- making it a challenge for surgeons and proceduralists to stay abreast of the latest innovations in their fields. Medical care and research has also become a team effort, requiring interdisciplinary skills, rehearsal of complex interventions, and coordinated communication among multiple team members. In 2007, Houston Methodist addressed these challenges by building a world-leading institute for medical education and research called the Houston Methodist Institute for Technology, Innovation & Education or MITIESM.

One of the largest and most comprehensive education and research facilities in the world, MITIE is defining a revolutionary platform for the ongoing training of physicians and health care providers. 10 | Houston Methodist Research Institute


MITIE is a comprehensive, state-of-the-art education and research institute at Houston Methodist. It was developed to foster novel training programs in procedurebased medicine and as a platform for research and development. In addition to a sophisticated physical space, MITIE provides a world-class team of curriculum design experts, event managers, and laboratory specialists to assist in the development and implementation of any training or research program.

MITIE encompasses more than 40,000 square feet of education and research space and serves thousands of health care providers each year from all around the world.

Cores At A Glance | 11 Glance | 15

TRANSLATIONAL RESEARCH CORES & SERVICES

About MITIE


FOUR core components of MITIE

sm

1 2 3

Procedural Skills Lab for hands-on procedural training

• Fifteen operating rooms and endoscopy suites

• State-of-the-art models for teaching procedures in any specialty

• Full complement of surgical tools equivalent to clinical operating rooms

an immersive viewing environment Medical Presence Suite finorthe operating room or procedure suite

• Seats 24; customizable viewing experience

• Panoramic video wall with HD streaming

• Real-time two-way communication with any operating room or procedure area

Virtual Hospital for team training in simulated patient care environments

• Simulation technology to recreate any patient care environment

• Sophisticated full-body human patient simulators that breathe, blink, talk, and respond to medications

• Audiovisual recording capabilities that facilitate team-based debriefings

• Six debrief conference rooms

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TRANSLATIONAL RESEARCH CORES & SERVICES

4

Experimental Operating Rooms for research and development

• Two fully equipped operating rooms modifiable for any specialty set-up

• Computer tomography (CT) equipped operating room

• MRI equipped operating room

• Robotically guided fluoroscopic imaging operating room (Hybrid Suite)

Key Equipment Within the Operating Suites

Siemens MAGNETOM Aera 1.5 Tesla Wide Bore MRI

Siemens Artis Zeego

• For intraoperative MRI (iMRI) Provides robotically guided fluoroscopy for:

• Traditional 2D X-ray images

• Advanced fluoroscopic (“live X-ray”) images/video, including 360-degree X-ray view

• DynaCT for CT-like scans

• 3D anatomical reconstructions

Hansen Medical Magellan Robotic System

Intuitive da Vinci Si HD Surgical Systems

• For robotically guided minimally invasive surgery

• Equipped with virtual reality simulators (“backpacks”) for skills rehearsal

Volcano Intravascular Ultrasound (IVUS) System

• Robotically guided endovascular catheter system

• Catheter-based system that allows for acquisition of ultrasound images from within the vessel itself

mitietexas.com Houston Methodist Institute for Technology, Innovation & Education (MITIESM) Operations Manager: Angela Mitchell Medical Director: Brian J. Dunkin, MD, FACS Email: almitchell@houstonmethodist.org Email: mitie@houstonmethodist.org Phone: 713.441.3998 Phone: 713.441.7912

Cores At A Glance | 13


Machine Shop Core The Machine Shop develops prototypes of medical devices and other instruments by providing concept creation, product design, and precision machining services. A broad range of materials are available for device fabrication, including polymer, carbon-steel, stainless steel, brass, copper, titanium, polycarbonate, peek, and delrin. Prototype devices developed in the Machine Shop include the DeBakey rotary blood pump, preclinical model holder, Nedo pump, and infant tongue depressor.

Services

• Design consultation

• Developing prototypes for medical devices

• Fabricating custom laboratory equipment

• Implementing improvements to device designs

• Device repair

Equipment

• 13” Colchester lathe

• Precision Hardinge toolroom lathe

• Knee mills

• CNC Benchman mill

• Vertical and horizontal saws

• Shear and brake metal fabricator

• Table saw

• Silver soldering capabilities

houstonmethodist.org/machineshop Core Director: Juan A. Fernandez Email: jafernandez@houstonmethodist.org Phone: 713.441.6399

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The Houston Methodist Comparative Medicine program conducts studies in both large and small preclinical models. The program has:

• 65,000 square feet of dedicated state-of-the-art facilities

• Housing space for a variety of preclinical models, individual ventilated caging for rodents, and flexible housing configurations for larger preclinical models

• Rodent space managed as a strict barrier, specialized space for imaging and an ABSL2 isolation suite

• Two fully equipped operating rooms and an ABSL3 suite for infectious agents

The program also offers good laboratory practices or GLP services for conducting risk, safety, and efficacy assessment studies in compliance with current FDA guidelines. Veterinary pathologist services and expertise for interpretation of preclinical study data is also available.

GLP Services

• Writing IACUC protocols

• Consultation for GLP protocols

• Assistance for device-related procedures

• Performing preclinical model procedures including injections, blood draws, catheter placements, clinical observations, equipment calibrations, monitoring, and necropsy

• Consultation on study design and tissue collection for studies with pathology end points

• Routine processing and slide generation

• Staining with routine and special stains, including immunohistochemistry

• Reporting pathology findings

• Necropsy

Veterinary Pathology Services

houstonmethodist.org/comparativemedicine Core Director: Tanya Burkholder, DVM, DACLAM Email: thburkholder@houstonmethodist.org Phone: 713.441.8685

Veterinary Pathologist: Judit Markovits, DVM, PhD Email: jemarkovits@houstonmethodist.org Phone: 713.441.8404

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TRANSLATIONAL RESEARCH CORES & SERVICES

Comparative Medicine


Preclinical Catheterization Laboratory Core The Preclinical Catheterization Laboratory Core offers investigators and industry with a state-of-the-art environment to train physicians, nurses, and technologists in the use of medical devices in preclinical or inanimate models. The core is supported by the Houston Methodist Research Institute’s Comparative Medicine Program. The core offers a Seimens Axiom Artis fluoroscopic C-arm for use with preclinical studies and physician training for approved and preapproved devices.

The core personnel perform many cardiovascular surgical procedures such as vessel access and cath lab surgical procedures, and have extensive experience operating simulators for cardiovascular surgery.

16 | Houston Methodist Research Institute


these images to the Seimens Syngo® workstation allows for the production of 3D images. The core also has a conference room for didactic training sessions, and a large control room for viewing procedures out of the field of radiation.

Services

• Cardiac and peripheral interventions

• Electrophysiology studies

• Radiofrequency and laser ablations

• Endovascular interventions

• Robotic catheter studies

• Pacemaker implants

• Transseptal puncture

Training

• Hansen robotic catheter

• Cardiac and peripheral intervention

• Chronic total occlusion intervention

• Carotid stent implantation with distal filter protection

• Epicardial puncture

houstonmethodist.org/pccl Core Director: Daryl Schulz Email: dgschulz@houstonmethodist.org Phone: 713.441.3318

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TRANSLATIONAL RESEARCH CORES & SERVICES

The fluoroscopic C-arm is capable of producing images known as Dyna-CT®. Transferring


BIOREPOSITORY Core The Biorepository Core is a large, general-purpose sample bank of solid tissue samples, blood, serum, plasma and, other body fluids for use by Houston Methodist researchers and their collaborators. All sample collection activities are conducted in a manner that ensures patient confidentiality, accurate pathologic annotation, and high ethical standards before, during, and after sample collection.

Services

• Collection, processing and storage in a timely, quality driven manner of fresh, snap-frozen, solid tissues from surgical pathology specimens, and blood and other body fluids from patients

• Provision of relevant controls including normal solid tissues from same or other patients, and/or blood from healthy patients/volunteers

• Paraffin embedding, Immunohistochemical and H&E staining, and pathology review services provided in conjunction with Research Pathology service

• Protocol-specific collection, processing, and storage for biospecimens • Maintenance of a clinical database with basic clinical data elements for all samples in the repository • Round-the-clock monitoring of freezers with adequate backup and disaster recovery protocols in place • Current global bio-banking standards followed to ensure research relevance of stored specimens

houstonmethodist.org/biorepository Core Director: Rajeev Singh, MD, MBA Email: rsingh2@houstonmethodist.org 713.441.0777

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Core Manager: Pam McShane Email: pmcshane@houstonmethodist.org 713.441.2113


The Research Pathology Core assists with routine histology techniques such as embedding tissue, sectioning tissue blocks, and staining sections. Custom tissue blocks can be prepared by the core staff, including multi-tissue arrays. Immunohistochemistry services offered include antibody characterization and optimization, and immunohistochemical and immunofluorescence staining. The core handles both preclinical tissue samples and patient samples with required approvals.

Services

• Specimen processing and embedding

• Titration/optimization of antibodies

• Microtomy

• Design and creation of tissue microarrays

• Immunofluorescence (antibodies provided by investigator)

• Cryostat training and technical support

• Consultation with a pathologist upon request

• Tissue staining (H&E, Gram, GMS, Iron, Von Kossa)

• Provide supplies e.g. cassettes, formalin, slides, molds, and slide boxes

• Immunohistochemistry (antibodies provided by core or investigator)

• Rush service available for an additional fee

houstonmethodist.org/researchpathology Core Director: Andreana Rivera, MD Email: alrivera@houstonmethodist.org Phone: 713.441.2662

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TRANSLATIONAL RESEARCH CORES & SERVICES

Research Pathology Core


Biomicrofluidics Core The Biomicrofluidics Core creates custom designed microfluidic molds and chips, fabricates pre-made biomicrofluidic chips, and provides consultation services in the biomicrofluidics field.

Services • Consultation for building your own biomicrofluidic chips • Fabrication of the following: − Replica molds used for soft lithography − Microfluidic PDMS/Glass chips − Pre-made microfluidic chips:

V-chip is a microfluidic device that quickly measures the concentration of a biomarker in a biological sample and allows for the analysis of up to 50 samples in parallel. The quantitative results are displayed directly on the device in the form of ink bar graphs. The V-chip is a cheap and easy-to-use device that does not rely on optical or electronic components.

Cell separation chip has a micropost array structure and is able to separate cells by size and deformability in a high-throughput manner. This chip is being used for probing cellular heterogeneity and identifying more invasive phenotypes in cancer cells.

20 | Houston Methodist Research Institute


mesenchymal-mode migration and screen for anti-metastatic drugs that specifically inhibit mesenchymal migration. The small size of samples used with the M-chip allows detection and analysis of the metastatic potential of primary or rare cells.

Single-cell analysis chip uses a live-cell printing technique (Block-Cell-Printing) to deposit single cells on a PS/glass substrate in order to create functional single-cell arrays. These single-cell arrays may be used to screen cell heterogeneity and function, including cell protrusion, cell-cell communication, and patterning.

Single-cell pipette tip can transfer and deposit live single cells directly from a cell suspension to any container for single cells. The tip is compatible with the commonly used air displacement pipette (ADP). It provides for low cost, rapid, controllable, single-cell manipulation with high cell viability, high efficiency, and operational simplicity.

Equipment

• OAI model 200 mask aligner

• Self-built UV exposure system

• Nikon Eclipse LV100ND microscope

• Plasma Etch PE50 and Harrick plasma cleaners

• Thermoscientific Super-Nuova single-position digital stirring hotplates

• Dongda engraving machine

• Schmidt Tech holes puncher

houstonmethodist.org/biomicrofluidics

Core Director: Lidong Qin, PhD Email: lqin@houstonmethodist.org Phone: 713.441.7328

Core Manager: Erkuan Wang, MS Email: ewang3@houstonmethodist.org Phone: 713.441.9633

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Research Cores & Services: Cellular and Molecular Services

M-chip is a high-throughput microfluidic device with 3120 ultra-miniaturized chambers to monitor


Flow Cytometry Core The Flow Cytometry Core provides investigators with state-of-the-art equipment and support for flow cytometric analysis and high-speed cell sorting. Analytical applications can be performed directly by the end user or by facility staff members. End-user training in various types of applications, as well as software support, is also provided.

Services

• Experimental design

• Sample preparation

• Proper controls

• Excitation and detection

• Data interpretation

• Manuscript preparation

Equipment

• BD FACS LSRII – Five lasers with 355, 405, 488, 561, and 630 nm excitation; 14 color analysis

• BD FACS Fortessa – Four lasers with 405, 488, 561, and 630 nm excitation; 13 color analysis; forward scatter PMT; FSC photodiode

• NIR BD FACS Ariall – Six lasers with 355, 405, 488, 550, 635, and 785 nm excitation; 18 color analysis; forward scatter PMT; FSC photodiode; high-speed sample sorting; temperature controlled sample and collection chambers; four-way and single-cell deposition

• SORP BD FACS Ariall – Four lasers with 405, 488, 550, and 635 nm excitation; 13 color detection; high-speed sample sorting; temperature controlled sample and collection chambers; four-way and single-cell deposition

• A Millipore Guava 8-HT – Two lasers with 488 and 635 nm excitation; 6 color detection; 96-well handling capability

houstonmethodist.org/flowcytometry Core Director: David L. Haviland, PhD, C. Cy. Email: dlhaviland@houstonmethodist.org Phone: 713.441.9233

22 | Houston Methodist Research Institute


The Molecular Diagnostics Core provides access to advanced instrumentation for gene expression analysis, SNP genotyping, capillary electrophoresis, and other molecular assays. Core instrumentation is available for self-use by trained investigators.

Services

• End-user training for the use of instrumentation

• Experimental design

• Consultation and support

Equipment

• Affymetrix GeneChip® Instrument System

− Microarray platform for gene expression analysis − Dell Precision 490 workstation with Affymetrix software

• Aligent 2100

− Microfluidics-based platform for capillary electrophoresis of DNA, RNA, proteins, and cells

• NanoDrop® ND-1000 UV-Vis Spectrophotometer

− Highly accurate analysis of nucleic acid and protein concentration

houstonmethodist.org/molecular-diagnostics Core Director: Randall J. Olsen, MD, PhD Email: rjolsen@houstonmethodist.org Phone: 713.441.6802

Core Staff: Dilzi Mody Email: dfmody@houstonmethodist.org Phone: 713.441.1771

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Research Cores & Services: Cellular and Molecular Services

Molecular Diagnostics Core


Nanoengineering Core The Nanoengineering core develops and produces state-of-the-art silicon-based bio-nanotechnology using microfabrication techniques. Scalability, precision, and reproducibility are characteristics of the silicon microfabrication processes which are extremely valuable for clinical applications. The core has developed a series of silicon-based nanomedicine platforms including Porous Silicon Particles (PSPs) and other 3 dimensional nanostructures. Owing to their biodegradability and readily modified surface properties, PSPs are emerging as promising injectable drug delivery carriers.

Services

• Develop and produce silicon-based nanoparticles

- Routine: 1 μm x 400 nm discs with 30 nm or 60 nm pores, 2.5 μm x 700 nm discs with 60 nm pores, and 600 nm x 400 nm discs with 30 nm pores.

- Available by request: 7 μm x 2 μm discs, 3.2 μm hemisphere, 1 μm x 200 nm discs, 600 nm x 200 nm discs, 1 μm x 400 nm discs with larger pores, and 2.5 μm x 700 nm discs with larger pores

houstonmethodist.org/nanoengineering Core Director: Xuewu Liu, PhD Email: xliu@houstonmethodist.org Phone: 713.441.7322

24 | Houston Methodist Research Institute

• Design and fabricate PSPs featuring precisely tailored size, shape, and porous structure • Develop multistage delivery system comprising several nested nanocomponents, each of which is designed to negotiate one or more biological barriers • Fabricate stage 1 PSPs in a non-spherical geometry to enable superior blood margination and cell surface adhesion • Design and fabricate 3 dimensional nanostructures for biomedical application


The Peptidomics NanoEngineering Core is a facility that designs and fabricates customized NanoTraps for protein/peptide biomarker discovery and specific biomarker detection. As an active research laboratory, the core is continuously developing new methods to improve results.

Services

• NanoTrap design and fabrication

• On-chip sample fractionation and data analysis

• Nanoparticle insertion

• Peptides and proteins identification

• Unknown low molecular weight protein/ peptide biomarker discovery • Targeted peptide biomarker extraction and quantification (e.g. Hepcidin-25)

Equipment

• Bruker Microflex LRF MALDI-TOF mass spectrometer

• Brewer Science Cee 200X automatic spin coater

• Thermo Scientific Velos Pro ion trap mass spectrometer

• Thermo Scientific programmable oven

• Thermo Scientific Dionex Ultimate 3000 system

• Lindberg BLUE M vacuum oven

• J.A. Woollam Co. M-2000VI spectroscopic ellipsometers

• Nordson AP-600 March asher • Thermo Speedvac SPD 111V with RVT 4104 trap and OFP400 pump • Fisher Scientific sonic dismembrator

houstonmethodist.org/peptidomicsnanoengineering Core Director: Tony Hu, PhD Email: yhu@houstonmethodist.org Phone: 713.441.5530

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Research Cores & Services: Cellular and Molecular Services

Peptidomics NanoEngineering Core


RNACore The core serves as the RNAcore for the Progenitor Cell Biology Consortium of the National Heart, Lung and Blood Institute. The core produces research and clinical grade RNA, including modified mRNA (mmRNA) of any gene of interest, microRNA cassettes and noncoding RNA. The mRNA/mmRNA constructs produced by this core have higher fidelity because of the use of error-free plasmid templates for in vitro transcription rather than polymerase chain reaction (PCR)-generated templates.

Services

• Expert assistance with plasmid design

• Synthesis of high fidelity research and clinical grade:

− mRNA

– modified mRNA (mmRNA)

− mRNA cassettes

− noncoding RNA

− piRNA clusters

− non-coding RNA including single-guided RNA (sgRNA)

− customized polycistronic mRNA/mmRNA constructs with a reporter gene

26 | Houston Methodist Research Institute


RNA IMMEDIATELY AVAILABLE

RNA ON DEMAND

Reporter Proteins eGFP

Flus

nGFP

b-Gal

RNA ON DEMAND Lineage Factors

Signaling Pathways IL-6

Reprogramming Factors

STAT3

MAPK/JNK

MAPK/JNK

NF-kB

AP1

IFNA2

STAT1

OCT4

cMYC

TGF-b

STAT2

SOX2

LIN28

PKR

SMAD3

KLF4

NANOG

PKC

SMAD4

Beta-Cell

Blood Progenitors

Cardiomyocyte

ETV2

Recombinase

Cas9

GATA2

RUNX1c

Zinc-Finger Nuclease

hCas9 D10A Nickase

TALEN

dCas9-CatInact (dead)

Others H1FOO

IL12

Neuron

Others CREB

RHOA

NFAT

PAX7

SRF

YAP1

P53

MECP2

HSF1

SERPINA1 (AAT)

HIF1A

F9 (Coagulation Factor)

MBD3

DNA damage

TCF3 (E2A)

Heat shock

Hypoxia

GATA1

GATA4

TBX5

MESP1

HNF1F

FOXA2

HNF4A

FOXA3

FOXA1

TCR and CAR constructs

PRKACA/PRKACB

UL48 (VP16)

MYEF2

Genome Editing

FLI1

MAF1

PDX1

GATA3

Hepatocytes

Endothelium Lineage

NGN3

Osteoclast

BRN2

NEUROD1

ASCL1

NEUROD2

NGN2

LHX3

MNX1

FOXA2

ISL1

ZIC1

ASCL1Â

-

FOS

TFE3

MITF Myocytes

MYOD1

All RNAs may be produced for human and mouse species and are synthesized as modified mRNAs with 5-methyl-CTP, pseudo-UTP, bearing an anti-reverse cap analog (ARCA) and long 150 nt poly-A tail.

houstonmethodist.org/rnacore R&D Director: Eduard Yakubov, PhD Email: eyakubov@houstonmethodist.org Phone: 713.441.5053

Clinical Director: Ivone Bruno, PhD Email: igbruno@houstonmethodist.org Phone: 713.441.7292

Cores At A Glance | 27

Research Cores & Services: Cellular and Molecular Services

RNA available from RNAcore


Advanced Cellular and Tissue Microscopy Core The core provides access to high performance microscopy for cell biology and tissue pathology studies. The core staff will assist with experimental design, sample preparation, advanced microscope image acquisition, and software for quantitative data analysis.

Services

• Brightfield, phase contrast, differential interference contrast (DIC), and fluorescence imaging

• Widefield and confocal live-cell imaging

• Darkfield and reflected imaging

• Laser scanning and spinning disk confocal

• Multispectral imaging (Cri)

• Total internal reflection fluorescence (TIRF) imaging

• Laser capture microdissection

• High content screening

• 2D/3D deconvolution

Equipment

• ImagestreamX imaging cytometer high content screening system

• IncuCyte™ live-cell imaging – a microscope within an incubator

• ImageXpress micro high content screening system

• Total internal reflection fluorescence microscopy

• Nikon A1 confocal imaging system

• Live cell spinning disk confocal imaging system

• Laser capture microdissection (LCM, Arcturus)

• FluoView™ FV1000 confocal microscope

• Inverted/upright fluorescent microscopes

• CRI nuance multispectral imaging system

houstonmethodist.org/tissue-cellular-imaging Core Manager: Kemi Cui, MD, PhD Email: kcui@houstonmethodist.org Phone: 713.441.7270

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The Electron Microscopy Core is equipped to perform scanning electron microscopy, transmission electron microscopy, fluorescent microscopy, and atomic force microscopy.

Equipment • Biocatalyst Atomic Force Microscope − High-resolution optical imaging, life science atomic force microscope − MIRO software integrates fluorescent and atomic force microscopy − Compatible with coverslips, petri dishes, and perfusing stage incubator for live cell imaging

• Multimode Atomic Force Microscope − Ultra high-resolution material science microscope for imaging in air or fluid medium − Equipped with ScanAsyst, PeakForce Quantitative Nanomechanical imaging modes, and Peak Force Tapping technology

• Nova NanoSEM 230 − Ultra high-resolution scanning electron microscope for generating nanoscale images of material and biological specimens − High and low vacuum may be used for imaging in the presence of non-conducting and contaminating materials − Secondary and backscattered electron in-lens detection and beam deceleration • Transmission Electron Microscopes (TEM) Jeol JEM - 1400 Electron microscope − Ultra High Resolution TEM for clinical work (tissue and cellular imaging) Nova Nano 230 SEM with STEM detector − H  igh resolution TEM imaging function for research work (function materials, tissues and cellular imaging)

houstonmethodist.org/SEM Core Director: Jianhua (James) Gu, PhD Email: jgu@houstonmethodist.org Phone: 713.441.9955

Cores At A Glance | 29

Research Cores & Services: Microscopy Services

Electron Microscopy Core


CLINICAL RESEARCH Services The Academic Office of Clinical Trials supports programs and physicians by providing investigators with experienced and certified research coordinators, regulatory personnel, and financial infrastructure to support internally and externally sponsored clinical research. By serving as a liaison between investigators and industry sponsors, the Academic Office of Clinical Trials facilitates the integration of clinical research operations throughout Houston Methodist. The Academic Office of Clinical Trials is also responsible for all components of the Clinical Trials Management System (CTMS) at Houston Methodist.

Clinical Research Services provide leadership for clinical trials operations by providing investigators with experienced and certified staff to promote innovative clinical research.

26 | Houston Methodist 30 | Houston MethodistResearch ResearchInstitute Institute


Regulatory Support

• IRB submissions and amendments

• Informed consent preparation

• Regulatory document preparation and management

Research Coordinator Support

• Study feasibility and initiation

• Data collection

• Investigator meetings

• Case Record Form (CRF) completion

• Subject screening, enrollment, and follow-up

• Specimen collection

• IP accountability

Financial Support

• Cost assessment

• Financial reporting

• Study budget preparation and negotiation

• Invoicing

• Reconciliation of the study cost center

• Investigational New Devices (IND) and Investigational Device Exemptions (IDE) applications

• CTMS entry • Study closeout

houstonmethodist.org/clinical-research-services Academic Office of Clinical Trials Director: Pauline Todd, MBA, BSN, RN Email: ptodd@houstonmethodist.org Phone: 713.441.3242 Clinical Research Services Mainline: 713.441.3250

Manager: Lenis Sosa, MSN, BSN, RN, OCN Email: lsosa@houstonmethodist.org Phone: 713.441.3245

Cores At A Glance | 31

Clinical Research Services & Support

Resources


CLINICAL RESEARCH Support Clinical research support at Houston Methodist enables rapid translation of a potential treatment or technology from the preclinical stage into early phase clinical trials. The Cockrell Centers for Advanced Therapeutics offer six sites throughout the Houston metro area and a Phase 1 Unit in the heart of the Texas Medical Center (TMC) for clinical research support. The Centers provide a full range of outpatient clinical care and study management services, including regulatory submissions and budget management support for all phases of clinical trials.

C  ockrell Centers for Advanced Therapeutics The Cockrell Centers for Advanced Therapeutics promote and support clinical research operations at Houston Methodist. They offer more than 7000 sq. ft. of clinical research space throughout the greater Houston area to support clinical trials closer to study participant homes or workplaces. The Centers are staffed by research nurses, coordinators, and regulatory personnel to support internally and externally sponsored clinical research.

Resources

• Exam rooms for outpatient studies

• Private rooms for infusion services

• Semiprivate room for infusion services and/or serial blood sampling

• Fully equipped specimen processing laboratory

32 | Houston Methodist Research Institute

• Adjacent state-of-the-art inpatient services, including critical care monitoring • Secure storage, preparation, and dispensing services for investigational products with 24/7 temperature monitoring


Clinical Research Phase 1 Unit

The Phase 1 Unit is located in the Houston Methodist Hospital’s Main Six Southeast wing. It is involved with early-phase and proof-of-concept clinical trials, and conducting advanced pharmacokinetic or pharmacodynamic evaluations. The unit is conveniently located adjacent to inpatient units for inpatient studies and to a radiology facility dedicated to clinical trials.

Services

• Early-phase clinical trials

• Research outpatient services

• Regulatory and budget management

• Pharmacokinetic and pharmacodynamic sampling (extended hours) • Infusion services for investigational drugs, biologics, and cell products

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1 HOUSTON METHODIST RESEARCH INSTITUTE

Cockrell Centers for Advanced Therapeutics

2 CLINICAL RESEARCH PHASE 1 UNIT - TMC HOUSTON METHODIST HOSPITAL

4

3 SUGAR LAND HOUSTON METHODIST SUGAR LAND HOSPITAL 1

4 WEST HOUSTON Houston Methodist West Hospital

2

Pearland 5 Houston Methodist Primary Care Group

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6

3

5

The Woodlands (coming soon) HOUSTON METHODIST WOODLANDS HOSPITAL

houstonmethodist.org/ccat Cockrell Centers for Advanced Therapeutics Director: Pauline Todd, MBA, BSN, RN Email: ptodd@houstonmethodist.org Phone: 713.441.3242

Cockrell Centers for Advanced Therapeutics Clinical Research Phase 1 Unit Director: Eileen Dickman, PhD, MBA, CCRC Email: edickman@houstonmethodist.org Phone: 713.441.9777 Cores At A Glance | 33

Clinical Research Services & Support

Cockrell Center for Advanced Therapeutics


Biomedical Informatics Service Core The Biomedical Informatics Service Core offers computational support for enhancing a variety of scientific disciplines, including molecular biology, genetics, protein chemistry, biochemistry, and clinical research. The core facilitates translational research by providing expertise in bioinformatics, bioimaging, database development, image analysis, and clinical informatics. The core services range from DNA, RNA, and protein sequence analysis to database searching, genomic prediction, and molecular modeling.

Services

• Bioinformatics – Microarray, RNAseq, Fluidigm, next-generation sequencing, and other platforms

• Data analysis – Genomic, transcriptomic, epigenomic, proteomic, metabolomic, clinical, and image data analysis

• Image and data acquisition, processing, analysis, retrieval, and management • Machine learning, data mining, and outcome studies • Proposal planning • In vitro and in vivo quantitative imaging

• Cluster computing solutions

• Experimental design and evaluation

• Statistical analysis – Sample size and power estimation, basic and advanced analyses

• Gene/target/disease analysis

• Web portal and database programming

houstonmethodist.org/biomedical-informatics Core Director: Jon Xue, PhD Email: zxue@houstonmethodist.org Phone: 713.441.2577

34 | Houston Methodist Research Institute

Core Manager: Tian Ding, PhD Email: tding@houstonmethodist.org Phone: 713.441.7266


Center Grant Proposals Support The Office of Strategic Research Initiatives (OSRI) increases institutional competitiveness for large grant opportunities. The office staff work directly with investigators throughout Houston Methodist to develop multi-institutional extramural funding proposals.

Services

• Develop and submit center grant proposals

• Budget development for center grant proposals

• Guide investigators through the administrative processes and requirements for grants and contracts, technology transfer and intellectual property, regulatory compliance and research protections, and clinical trial services

StrategicResearchOSRI@houstonmethodist.org Manager: Hanh H. Hoang, PhD | Email: hhhoang@houstonmethodist.org | Phone: 713.441.8227

Scientific Writing & Editing Support Houston Methodist researchers, clinicians, and staff have on-site access to a fee-for-service scientific editing, writing, and consulting support through BioScience Writers, LLC. To assist with the growing pressures to publish and secure funding, BioScience Writers offers a variety of concierge services to meet the needs of native and non-native English speaking scientists.

Services

• Consulting on large grants

• Language translation

• Academic/medical writing and editing

• Journal submission

• Overlapping text detection

• Writing workshops

Email: hm-onsite@biosciencewriters.com Cores At A Glance | 35

CENTRAL SUPPORT SERVICES

other SupportServices


other SupportServices Library Services The Houston Methodist Library serves as a rich resource for meeting the requested and anticipated information needs of faculty, researchers, residents, fellows, students and other affiliated health care professionals. In addition to the subscription to more than 9000 books and journals and access to over 40 publication databases, the library offers access to:

Scientific Literature Databases & Reference Management Software • Cochrane - Database of Abstracts of Reviews of Effects

• Cochrane NHS Economic Evaluation Database

• Scopus

• Cochrane Database of Systematic Reviews

• IEEE Xplore

• PubMed

• Web of Science

• Cochrane - Health Technology Assessments

• RefWorks

• Health Business Elite

• Browzine

• Medline

Clinical Trial and Methodology Databases

• Cochrane Central Register of Controlled Trials

• Cochrane Methodology Register

Funding Databases

• SciVal Funding

Trainings & Workshops

• Introduction to Electronic Materials

• Assembling the Relevant Literature

• RefWorks

Hospital Librarian: Linné Girouard, MLIS, AHIP Email: lgirouard@houstonmethodist.org | Phone: 713.441.2229

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Houston Methodist Research Institute 6670 Bertner Street Houston, TX 77030

houstonmethodist.org/research HMRI Office of Communications & External Relations | HMRI-101 | MM | DH | 05.2015

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