Major Equipment:

The Salem research laboratory contains class II cell culture facilities, chemical hoods, incubated plate shakers, wet chemistry equipment, microfabrication equipment, particle technology equipment, DNA preparation equipment, gel electrophoresis apparatus, luminometer, high performance liquid chromatography equipment, a lyophilizer and a fluorescent/luminescent plate reader. The lab also contains individual desk-space and computers (Dell Dimensions) for graduate students and postdoctoral fellows. Specific equipment in the lab includes:

 

 

Scientific Environment

The University of Iowa Colleges of Pharmacy and Medicine and the University of Iowa Hospitals and Clinics are located on the Health Sciences campus, which is part of the 1,300 acre main campus of the University. The facilities and organizational environment available to the investigators and staff are described below.

 

The University of Iowa College of Pharmacy:

The College of Pharmacy receives support through the general fund of the University. The Pharmacy Building is located in the health center complex on the University’s main campus, in close proximity to the College of Medicine and the Health Sciences Library. The College offers the Pharm.D. as its single entry-level degree and three Ph.D.-granting graduate programs. The College is comprised of two departments. Dr. Salem is a faculty member and the Bighley Chair and Professor of Pharmaceutical Sciences.

 

Teaching and practitioner faculty sites include General Medicine, Family Practice, Cardiology, Oncology, Neurology, Obstetrics and Gynecology, Burn and Wound Care, Pediatrics, and Infectious Disease. Facilities include The University of Iowa Hospitals and Clinics and the Veterans Administration Medical Center, as well as various other sites throughout the state.

 

The University of Iowa Carver College of Medicine:

 

UI Carver College of Medicine faculty members are some of the most productive when measured by NIH dollars. Many College faculty members are internationally renowned for their research. Four faculty members are Howard Hughes Medical Institute Investigators, 22 are members of the Institute of Medicine and two are members of the National Academies of Sciences.

 

Dr. Salem has served as a program leader in the Holden Comprehensive Cancer Center (HCCC) http://www.uihealthcare.org/holdencomprehensivecancercenter/ and is a member. The Holden Cancer Center is Iowa’s only NCI-designated comprehensive cancer center and has held that designation since 2000. The NCI designation recognizes our cancer center, and its research scientists, physicians and other health care professionals, for their roles in advancing cancer research that impacts on our ability to prevent, detect and treat our patients with cancer. The Holden Comprehensive Cancer Center provides Center members with access to the services and resources of our core facilities. The facilities provide quality products and services that enhance the research efforts of Cancer Center investigators to foster basic and translational research. Members of the Cancer Center with peer-reviewed, funded projects are the primary beneficiaries of these core resources. The core facilities within the Holden Comprehensive Cancer Center are funded by a combination of funding from the Cancer Center Support Grant, Institutional support, other University of Iowa sources and charge-back for services. Available shared resources include: Bioinformatics Core, Biostatistics Core, Central Microscopy Research Facility, Clinical Trials Support Core, DNA Core, Flow Cytometry Core, Gene Transfer Vector Core, Population Research Core, Radiation and Free Radical Research Core, Small Animal Imaging and Tissue Procurement Core.

 

Dr. Salem is a faculty member in the Institute for Clinical and Translational Science (CTSA).  The University of Iowa created the CTSA to serve as the University’s overarching, academic structure for all clinical and translational research and training. The Institute establishes a multidisciplinary matrix to facilitate and support all clinical and translational science across the University’s colleges. The Institute and its structure were formally approved by the State of Iowa Board of Regents in December 2006. The Institute is now recognized as a unique organization (org 21) with the University of Iowa with the Director reporting directly to the University Provost. Funding for the Institute will come from the Colleges of Medicine, Public Health, Liberal Arts, Pharmacy, Dentistry, Nursing, the Office of the Vice President for Research, community healthcare organizations, and the NIH CTSA grant. The Institute was made possible through a $33.8 million NIH Clinical and Translational Science Award.

 

Laboratory:

Dr. Salem has 4500 sq ft laboratory space adjacent to his office in the College of Pharmacy. In addition, there are University of Iowa and VA Core facilities that include:  Flow Cytometry, Tissue Culture/Hybridoma, Biostatistics, Gene Vector, Small Animal Imaging, Central Microscopy, and DNA.  Excellent administrative and secretarial help is available.

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Animal:

Office of Animal Resources (http://research.uiowa.edu/animal/) 

Transgenic Animal Facility (http://www.physiology.uiowa.edu/transgenic/)

The university maintains excellent AAALAC animal facilities supervised by a senior veterinarian, Dr. Paul Cooper, and his staff.  It consists of space in the Medical Laboratories, the Bowen Science Building, the Biology Building, and on the University of Iowa Research Park campus.  There are also substantial animal care facilities in the Veterans Administration Hospital.  At the present time, the University of Iowa has an approved assurance with the Public Health Service for the care and use of laboratory animals.  There is an animal care review committee that is charged with the responsibility of reviewing all applications for animal research and making certain that the care of all animals involved in research protocols meets with the standards set forth by the American Physiological Society, Department of Agriculture, NIH, etc.  MERF houses the specific pathogen-free AALAC-approved animal care facility on the lower level.  The University of Iowa provides caretakers for day-to-day animal care, weaning, and colony maintenance. Therefore, mice are in close proximity and readily available. 

 

Computer:

Dell Computers are available in both offices and laboratories of the investigators. All computers are connected to the internet and are used for data searching, storage, analysis, and presentation and word-processing.

 

 

Office:

Dr. Salem’s office is located at the College of Pharmacy in room S452 CPB. 

 

3D Printing Capabilities:

3D printing is the rapid prototyping or additive manufacturing technique which has huge potential for its application in biomedical and Tissue Engineering research. The facility hosts several 3D printers which work on different principles, hence to deliver unique and customized applications.

 

Prusa i3 MK3:

It is a Fused Deposition Modeling (FDM) based 3D printer which works with a wide range of polymers with melting temperatures in the range of 120 – 280 °C. The printer was equipped with multi-material print head that can print different polymers simultaneously. The printer is best suited to print hard surgical tools, anatomic prototypes, implants of different shapes and structures.

 

Bio X:

A multi-head extrusion based 3D bioprinter is equipped with a heating bed and UV light source that can facilitate crossliking of thermosensitive and UV curable biopolymers. The bioprinter has the capability to print multiple biopolymers with different cells simultaneously. The printer helps in development of biocompatible organ-specific hydrogel scaffolds for full organ regeneration. 

 

Sparkmaker:

A unique compact SLA based 3D printer that can print high resolution models using UV curable resin. The printer is equipped with a UV Backlight of 400 nm. The resolution of the printer is 20-100 µm which can deliver precise structural details of the printed models.

 

Nanoscribe:

The sophisticated high resolution 3D printer will facilitate printing wide variety of structures and shapes at micrometer size range (1-100 µm). The printer works on the principle of Two Photon Polymerization technique that cross-link a resin. The printer print micron sized structures in a single drop of resin. The printer benefits to a great deal of research in drug delivery and delivery systems for pharmaceutics.

 

Other:

 

Hardin Library for the Health Sciences.

Hardin Library serves the health science colleges as well as the University.  It maintains books, periodicals, electronic services and educational resources related to health and medicine. Currently there are 389,184 volumes available and 3,447 periodicals received. OASIS, the University Libraries automated library system, includes LCAT, which contains records for all books cataloged since 1980, a significant number of older books, and all journal titles currently received. The card catalog should be consulted for older materials not found in LCAT.  OASIS also includes periodical indexes and provides access to other libraries' catalogs. OASIS is accessible through workstations located throughout the buildings or by remote access.  Healthnet is the Hardin Library's information system, which provides campus-wide access to Medline and other health-related databases. Healthnet workstations are located by the Information Desk. Users may also access Healthnet through the web, modem/dial-up, and the campus network.

Library facilities are provided by the Health Science Library. The Holden Comprehensive Cancer Center’s dedicated Core Research Facilities include Gene Transfer Vector, Small Animal Imaging, Central Microscopy, Flow Cytometry, and DNA Cores.  Information about the cores can be found at http://www.uihealthcare.com/depts/cancercenter/research/cores.html.  Additional core facilities are available through the Carver College of Medicine that includes the Biomedical Research Store, Biochemistry Store, Comparative Pathology, and others.  Information about these cores can be found at http://www.healthcare.uiowa.edu/corefacilities/index.html.

 

The Medical Education Research Facility building is connected via skywalk to an adjacent research buildings that houses the Central Microscopy Core facility (location of the Xenogen IVIS imaging system used for bioluminescent imaging of tumor-bearing mice), Small Animal Imaging, and Flow Cytometry Core Facility (location of the two BD LSR multi-parameter flow cytometers, and high-speed FacsDiva cell sorter). 

 

 

The University of Iowa and Its Administration

 

One of three universities operated by the State of Iowa, the University of Iowa was established in 1847 in Iowa City.  It has a faculty exceeding 1,700 in number and 13,000 staff, serving a student body of about 29,000.  A single State Board of Regents is appointed by the Governor, and each university has a President who reports to the Board of Regents. Each of the colleges of the University of Iowa has its own dean who reports to the Vice President for Health Sciences. The University has a central Business Office. The chief financial officer is the Vice President for Finance and University Services, who coordinates all financial operations. A central Research Office coordinates all research administration under the direction of the Vice President for Research.

 

 

Institutional Core Resources

 

Additional Core facilities on the University of Iowa campus of relevance to the proposal that are available to our research group include:

 

Central Microscopy Research Facility (CMRF) (http://cmrf.research.uiowa.edu/)

The Facility provides instrumentation and technical assistance to research programs involving the use of scanning and transmission electron microscopy, light microscopy and confocal microscopy, freeze fracture and x-ray microanalysis. The CMRF also provides all solutions, supplies, and training necessary for investigators involving microtomy, including specialized staining and embedding techniques, negative staining, metal coating, autoradiography, cryo-fixation, and cryomicrotomy, enzyme cytochemistry, immuno-cytochemistry, morphometry and stereology, the preparation of material science samples for both TEM and SEM including x-ray microanalysis and other procedures.  A library containing texts and a review of various applications of transmission and scanning electron microscopy is also available. The CMRF serves both the experienced and novice investigator, and provides training for those in need. Alternatively, all or parts of a project can be handled by the staff. The facility is available 24 hours a day and 7 days a week. 

 

Flow Cytometry Facility (http://www.healthcare.uiowa.edu/corefacilities/flowcytometry/)

The Holden Cancer Center Flow Cytometry Facility is directed by Dr. Zuhair Ballas, who oversees the facility and its three full time staff members. The 1,200-square Flow Cytometry Facility is located in the Eckstein Medical Research Building (EMRB). The Facility has one magnetic-based and ten laser-based instruments whose major purpose is the identification and isolation of various cell populations. The laser-based instruments accomplish this by the use of antibodies to which various colors or dyes have been attached and are directed at molecules known to exist on the cell surface or in the cytoplasm. By using several colors attached to different antibodies, one can identify and purify cells that express any given configuration of various molecules. In addition to identification and isolation of various cell populations using antibodies, flow cytometry can analyze:

 

Cell proliferation response to drugs or treatments, such as those used in chemotherapy
Cell physiological properties, such as calcium flux and pH
DNA content and integrity
Transfection markers such as GFP and mCherry
Quantification of cytokines, gene expression, micro RNA

 

The Facility provides scientific and technical personnel who are available for consultation in designing experimental protocols and training in the use of bench-top instruments and software programs for the interpretation and analysis of data. Cell preparation protocols and publication quality output are available upon request.

 

Offline data analysis using FlowJo™, Cellquest™, and ModFIT™ can be done through the Facility’s system of networked computers. Investigators can perform analysis at their laboratories or offices by accessing data through the Facility’s dedicated file server. Data are archived on a separate server and stored for at least ten years.

 

A secure, web-based reservation system allows investigators to schedule instrument time. The Facility is staffed M-F, 8am to 6pm and is available 24/7 following training.

 

DNA Core Facility (http://www.medicine.uiowa.edu/humangenetics/genomics/)

The purpose of the DNA Facility is to provide a centralized resource for access to state-of-the-art equipment used in DNA sequence and transcript analysis. The DNA Facility strives to provide high quality services with a rapid turnaround and support their services with well-trained personnel that are able to consult with users on how they may best utilize the services. The services offered by the facility are:

 

Microarrays

Affymetrix GeneChip System
Illumina iScan Microarray System

Real-time PCR

Applied Biosystems Model 7900HT
Applied Biosystems Model 7000
Applied Biosystems Model 7500

Sanger Sequencing

Applied Biosystems Model 3730 (48-capillary)
Applied Biosystems Model 373oxl (96-capillary)

Genome Sequencing including custom and whole exome sequence target capture, RNA-Seq (quantification of transcript, i.e., expression analysis), smRNA discovery and quantification, DNA-Seq (Resequencing), ChIP-Seq, Methyl-Seq, De novo Sequencing
Synthetic Oligonucleotide productions
Quality control and support instrumentation

 

Small Animal Imaging Core (http://www.medicine.uiowa.edu/saic/)

This facility provides a comprehensive service for non-invasive anatomical and physiological imaging of mice and rats. The ultimate product of the core involves spatial imaging (high resolution pictures) and temporal imaging (longitudinal studies) related to cancer biology, drug development, and assessment of therapeutic intervention. The core instrumentation consists of several imaging modalities which have been specifically purchased or modified for scanning small rodents include: microPET, microSPECT, microCT, high resolution X-ray radiography, optical imaging, planar radionuclide imaging, autoradiography, whole tissue biodistribution assays and cell assays. Full time staff members are also available to consult and/or assist in the use of core equipment.

 

Comparative Pathology Laboratory (http://www.medicine.uiowa.edu/cpl/)

This core provides veterinary pathology support and interpretation of changes at the gross and/or microscopic level in animal models of disease, including professional consultation with a pathologist. Additional services include: (1) comprehensive services for labor intensive techniques such as cryo- and paraffin sectioning (2) access to specialized equipment, including cryostats, paraffin microtomes, and tissue processing and embedding equipment; and (3) consultation and instruction in specialized morphological techniques, including immunocytochemistry and in situ hybridization, and methods of image analysis.

 

Proteomics Facility (http://www.medicine.uiowa.edu/proteomics/)

Services currently available in the facility include:

 

Protein identification and mapping
Protein expression profiling
Accurate weight determination for intact macromolecules and conjugates
Development of quantitative MRM assays (e.g. “multiplexed ELISA” w/o antibodies)
Characterization of PTM status
Rapid biotyping to determine bacterial strains
MALDI and nano LC-MS/MS analyses of digests performed either in-gel or in-solution
MASCOT, SEQUEST and SpectrumMill data analyses with final reporting in Scaffold or Excel format

 

High Throughput Screening Facility at the University of Iowa:

(http://pharmacy.uiowa.edu/high-throughput-screening-facility)

The University of Iowa High Throughput Screening Facility (UIHTS) is a high throughput platform that integrates robotics, detection systems and chemical /biologics libraries. UIHTS enables scalable screening approaches, not only to foster hit and lead generation for drug discovery and development through screening of systematic, unbiased large chemical/biologics libraries; but also to facilitate molecular probe discovery for mechanism of action (MOA) studies of chemical biology through screening of focused intellectually-designed compound collections. As a university core facility, UIHTS provides highly flexible screening services, project management, and assay/technology development for investigators across campus as well as off-campus.

 

UIHTS is equipped to perform high throughput screening (HTS) in 96, 384 and 1536-well formats with plate reader detection (Perkin-Elmer EnVision) using absorbance, fluorescence and luminescence, including advanced FRET and BRET techniques. UIHTS is also equipped to perform high content screening (HCS, Perkin-Elmer Operetta Confocal Imaging System) to detect and quantify phenotypic changes, i.e. cell differentiation, cell migration, neurite outgrowth, and target trafficking; or by fluorescence intensities for target protein expression, transcription factor or signaling pathway analysis. HTS and HCS systems are integrated with robotics for plate handling and assay execution, suitable for small- or large-scale compound library screens with “walk-away” levels of automation.

 

UIHTS holds two “small molecule” libraries. The Spectrum Library from MicroSource consists of 2320 structurally diverse compounds including marketed and experimental drugs as well as natural products. This array of test compounds provides a rigorous platform for assay validation and testing. The larger collection is from Chembridge, the Diverset, a collection of 50,000 small molecules representing a wide swath of chemical space, optimized to be “drug like,” considering factors such as partition coefficient and Lipinski-like rules. UIHTS is also building a UI legacy library with pure natural products and medicinal chemistry-focused compounds. In addition, UIHTS are also in the process of determining the need and feasibility of obtain a biologics library, i.e. genome-wide siRNA, antibodies, and diverse cell lines.

 

Overall, UIHTS is a laboratory core focused on scalable screening approaches for drug discovery and development and molecular probe discovery for mechanism of action (MOA) studies of chemical biology for investigators across campus and beyond.

 

 

The Prostate Cancer Research Program at the University of Iowa:

 

Another aspect of the environment for prostate cancer research at the University of Iowa is the Prostate Cancer Research Program.  Salem is a member of the prostate cancer research program at the University of Iowa. Opened in 1991, as a result of common research interests, 17 members of the University of Iowa’s Departments of Anatomy, Biochemistry, Internal Medicine, Pathology, Pediatrics, Pharmacy, Preventive Medicine and Environmental Health, Radiology, and Urology, met to organize a Prostate Cancer Research Group.  Each investigator either had previous research experience in prostate cancer or had expressed an interest in forging collaborations in a new field.  Under the direction of our collabarator, Dr. Lubaroff, the group began meeting on a monthly basis to discuss the development of research collaborations.  The research backgrounds of the investigators at that time included immunology, genetics, molecular biology, epidemiology, chemoprevention, radiation research, clinical urology, and chemotherapy.  Monthly journal club meetings were also initiated to discuss pertinent papers in the field of prostate cancer.  Support for the efforts of this group was strong from its inception.

 

The success of the Prostate Cancer Research Group has depended upon the interdisciplinary collaborations that have been forged in the eight years of its existence.  There has been, and continues to be, a commitment from members of the group to maintain an active and productive research group in prostate cancer.  Each member has contributed his or her expertise and insight into the problems associated with prostate cancer.  The interest and direction of the group is predominantly that of laboratory research, although there is a significant clinical research component.

 

The environment created by the collaborations among members of the Prostate Cancer Research Program is one of support, collaborations, critical evaluations of research programs, and shared expertise.  All of these factors aid in the continued success of prostate cancer research at the University of Iowa.

 

The Cancer Immunotherapy Group at the University of Iowa:

 

The Cancer Immunotherapy Group was founded to foster collaborations and translational science among the large number of investigators in the Holden Comprehensive Cancer Center whose research is devoted to cancer immunotherapies.  There are 45 members from two colleges and 8 departments.  The group meets monthly with informal presentations of immunotherapy research in the laboratories of members as well as discussion of new clinical trials, funding opportunities, and, of course the formation of new collaborations among members with diverse expertise in the field.  At least two new grants have been submitted and approved as a result of the new collaborations.