William E. Grizzle - US grants

DESCRIPTION: (Applicant?s Description) The Southern Division (SD) of the Cooperative Human Tissue Network (CHTN) at UAB has participated enthusiastically and effectively in all CHTN cooperative operations since its inception. The policies and guidelines that have been established have resulted in a dependable source of human tissues, with associated histopathologic and demographic data, that has had a major impact on cancer research. It is anticipated that the current advances in cancer research and technology will result in an increased demand on the supply of tissues and more sophisticated demands on diagnosis and processing. To meet these demands the SD proposes to continue its leading roles in: I) the design and modernization of the computerized data management system of the CHTN to support increased networking of tissues; 2) publicizing the availability of human tissues to the research community and promoting communication between the scientists receiving the tissues and the CHTN; 3) the development of regulatory policies including positions on confidentiality and informed consent, guidelines for implementation of new and modified federal regulations, and guidelines to protect against biohazards involved in use of human tissues; and 4) facilitating the development of tissue resources at multiple institutions through outreach and education. At the local level, the SD proposes to continue to focus on providing reliable high quality human research tissues obtained under optimal conditions from surgical procedures and autopsies performed at the UAB associated hospitals and subcontractor institutions. In response to requests from investigators, the SD has already established the procedures and has in place the equipment and expertise to provide tissues frozen within 15 minutes of recovery and preneoplastic lesions, as well as microdissection, tissue matrix arrays, mRNA/DNA samples, and clinical follow-up. In this funding cycle (1996-2000), the SD, which primarily serves researchers in the Southern United States but also serves investigators throughout the US and Canada through networking, has provided over 25,000 fresh, frozen and fixed human tissue specimens to over 450 investigators. In the next funding cycle, consortium agreements with participating institutions that will provide access to tissues from more than 150,000 surgical procedures with a goal of supplying 48,000 samples.

tissue resource /registry; neoplasm /cancer diagnosis; early diagnosis; human tissue; biopsy;

tissue resource /registry; neoplasm /cancer diagnosis; early diagnosis; human tissue; biopsy;

Oral cancer is a major health problem in the United States; it is a disease of high mortality and severe morbidity. While risk factors include alcohol and tobacco usage, some oro-pharyngeal tumors develop without a defined pattern of alcohol or tobacco abuse. In fact, the increased use of alcohol based mouth washes in the United States may be a risk factor. Although it has been reported that consumption of fresh fruits and vegetables is associated with protective effects on the development of oro-pharyngeal tumors in high risk groups, identification of specific nutritional components such as one specific antioxidant that protects against the development of this type of tumor has not been successful. The inability to isolate a protective effect of a specific vitamin (e.g., beta-carotene) might be secondary to synergistic protective effects of multiple dietary components or to inadequate previous study of methyl supplying components such as folate or vitamin B-12. Localized folate and vitamin B-12 deficiencies may be especially relevant to the development of these tumors since levels of active folate and vitamin B-12 in tissues may be decreased by exposure to components of tobacco or alcohol usage. We hypothesize that the normal proliferative homeostasis of basal cells of the oral epithelium is dysregulated by localized deficiencies of folate and vitamin B-12 and that the resulting abnormality in basal cell proliferation is exacerbated by exposure to alcohol and tobacco products. Ultimately, increased cellular proliferation increases immature cells at intermediate and higher layers (i.e., above the basal cell layer) in the oral epithelium and leads to the development of histologically recognizable pre-malignant characteristics in the epithelium (e.g., dysplasia). These changes can be identified by decreased regional vitamin levels and by changes in the expression of intermediate endpoint biomarkers (IEBs) in the proliferating or dysplastic epithelium. We will select tissues for evaluation based on standard epidemiological methods in order to validate our hypothesis. We will evaluate the relation of folate and vitamin B-12 levels geographically within the epithelium and their correlation with the development of neoplastic changes and with expression of the following IEBs: TGFalpha, EGF-R, EGF, p185/crbB-2, TGF-beta, fatty acid synthetase, markers of proliferation and p53. This proposal is strengthened by nesting state-of- the-art biochemical, molecular, and pathological assessments of normal, pre-malignant and squamous cell cancers within a sound epidemiological investigation of well characterized patients.

DESCRIPTION: (Applicant's Description) UAB has extensive experience in collecting, processing, storing, and supplying a wide range of human tissues to support research. Fresh, frozen, and paraffin preparations of tissues can be supplied , as well as unstained tissue slides and other histology services. We will expand our current tissue resource services as part of the Ovarian SPORE to: 1) establish a bank of well characterized ovarian tumor specimens and matching normal specimens from patients who have given specific informed consent for their tissues to be used in genetic and other types of research so tissue can be supplied to investigators along with clinical data including outcome. 2) offer microdissected specimens for investigators wishing to use sensitive PCR based technologies on pure samples of ovarian neoplasia or normal ovarian tissue. This core also will offer investigators access to methods of morphological analysis that are too complex for individual projects to support efficiently. Primarily the core will provide light microscopic and immunocytochemical interpretation of animal and human tissues and cytologic materials and will offer methods to detect gene products within tranfected cells and adjacent tissues. Investigators will have access to sophisticated techniques usually available only for human pathology, including tissue microdissection, immunoelectron microscopy, special histology services, in situ hybridization, and flow cytometry. Advantages are that the core will enable unified purchase, characterization and utilization of a shared set of reagents. Centrally performed procedures will free investigators from duplication of basic work, allowing more productive work with the available resources and acceleration of experimental timetables.

This goal of this application is to establish a Biomarker Validation laboratory (BVL) at the University of Alabama at Birmingham, which will provide both the expertise and sufficient quantities of high quality resources to act as an efficient referral center within the Early Detection Research Network (EDRN) of the NCI. The P.I. Investigator, William B. Grizzle, MD, PhD, has assembled a group of investigators with expertise in biomarker evaluation and with a commitment to translational research. The UAB-BVL will offer a broad range of validation systems, as indicated in the RFA, and clinical and research expertise in tumors of various organ systems, including breast, prostate, colorecturn, lung, head and neck, and gynecologic. The major focus of the UAB-BVL will fulfill the requests for the development of well-characterized tissue resources, including urine and serum, that have been collected and stored according to standard procedures; the development of high through-put immunohistochemical techniques that have been characterized according to specificity, sensitivity, and reproducibility; and the molecular characterization of lesions that are currently defined histologically or morphologically. A Development Proposal entitled Molecular Markers to Characterize Aggressive PIN lesions addresses the issue of molecular characterization of PIN lesions in prostate cancer using tissue matrix technology. The BVL leverages the considerable expertise of the investigators and will provide access to established tissue resources, standard operating procedures, and quality control systems as well as equipment. The Core Facilities of the UAB Comprehensive Cancer Center together with other Centers of Excellence at UAB further enhances the available resources. The existing collaborations among the investigators at UAB and the associated institutions and prior participation in national networks (CHTN, EDRN) will ensure rapid and effective responses to the needs of the EDRN. An organizational structure has been developed that defines lines of authority and communication to ensure both high quality performance and effective and timely communication. The research objectives of all of the investigators in this proposal match those of the EDRN: to rapidly translate basic research findings into a full understanding of the pathogenesis of neoplasia such that cancer patients can benefit from early detection, improved prognostic tools, and rapid development of more effective therapeutic and preventive strategies through the use of surrogate end- point markers.

[unreadable] DESCRIPTION (provided by applicant): Confocal DNA cytometry uses 3D images of nuclei stained quantitatively for DNA; nuclear DNA content, size, shape, and chromatin texture are measured and used to derive a quantitative nuclear grade (QNG). QNG measures abnormalities in cancer nuclei, and changes in QNG have been correlated to increasing genomic instability and more aggressive tumor behavior. QNG provides significant and independent prognostic information when compared to established markers of risk such as the Gleason Score. With respect to prostate adenocarcinoma (PCa), this information may be most useful in describing PCa with more prevalent intermediate Gleason scores (6 and 7). If the biology of PCa varies with age, race and ethnicity, QNG should detect such changes. Three areas might be useful in different clinical scenarios unique to the age or racial/ethnic groups of the affected individuals: 1) Detection. Analysis of malignancy associated changes in normal appearing nuclei adjacent to carcinomas might enhance the usefulness of core needle biopsies. 2) Diagnosis. QNG might provide additional independent information to supplement Gleason grades and pathologic stages. 3) Prognosis. QNG might allow greater sensitivity for the prediction of occult extraprostatic extension, recurrence and/or responsiveness to therapy. Malignancy associated changes are important in understanding progressive changes in normal appearing cells with the development of neoplasia and with age, race, and ethnicity. More careful surveillance, delineation of high-risk cohorts for chemoprevention studies, and detection of clinically insignificant cancer might all be different for elderly vs. younger men and in different racial/ethnic groups; these issues must be explored thoroughly. The ability of QNG to detect biological changes with age, race and ethnicity also should be complemented by phenotypic expression of selected molecular markers which correlate with proliferation, apoptosis and/or prognosis. In all age groups, predicting the biological aggressiveness and stage of tumors, based on needle biopsy findings and/or on the results of radical specimens, is critical for clinical decision making. We will use the levels of QNG and molecular markers to predict the aggressiveness of PCa based on age/race and ethnicity. We will test the negative hypothesis that age and ethnic groups, with all other prognostic variables being equal, will have no correlation with tumor aggressiveness.

DESCRIPTION (provided by applicant): The Tissue Resource, Molecular Analysis and Immunopathology Core Facility has extensive experience in collecting, processing, storing/banking, and distributing a wide range of tissues and controls to support the research of the Skin Diseases Research Core Center (SDRC) members. Fresh, frozen and paraffin preparations of tissues can be supplied as well as unstained tissue slides, tissue matrix arrays, microdissected tissue components, as well as histology services. The Core also can provide investigators with access to methods of morphological and molecular analysis that are difficult for individual projects to support efficiently. Primarily the Core provides light microscopic and immunocytochemical interpretation of animal and human tissues and cytologic materials including methods to detect gene products within transfected cells and adjacent tissues. Investigators have access to sophisticated techniques usually available only for human pathology, including immunoelectron microscopy and special histology services such as computerized morphometric analysis (CAS200 and BLISS systems) and in situ hybridization. The involvement of dedicated diagnostic pathologists ensures that all assays are performed on optimally collected, processed and diagnosed tissue components. Centrally performed procedures free investigators from duplication of basic work, allowing more productive work with the available resources and acceleration of experimental timetables. The Core works closely with the biostatistical personnel so that clinical/demographic information can be linked easily with tissue specimens. The Core will support all projects of the SDRC and its services will be available to all SDRC members. In addition, its costs will be waived for all pilot projects and for the collection of preliminary data to support grant applications. Depending on demands for services and remaining resources, the current resources requested will permit about a 30% discount below costs of services to SDRC members.

[unreadable] DESCRIPTION (provided by applicant): The goal of this application is to establish a Biomarker Reference Laboratory (BRL) at the University of Alabama at Birmingham that will function within the EDRN to develop, modify and trouble-shoot potential methods of early detection prior to their entry into validation studies. Components of development will include conversion of methodologies to high-throughput methods, analysis of limitations, and development of standard-operating-procedures. As the core group of investigators has been drawn from the Program in Translational Research in Neoplasia in the Department of Pathology at UAB, all of these investigators are committed to, and have expertise in, the analysis of biomarkers. The group includes pathologists and basic researchers with expertise in neoplastic processes of the skin, head and neck, lung, colorectum, pancreas, breast, ovary and cervix, as well as technical expertise in, and resources for, surface- enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS), multidimensional gel analysis protein purification, high-throughput ELISA, multiplex immunoassays, construction of tissue matrix arrays (spotted and tissue cylinders), computerized cytomorphometric analysis, immunohistochemistry (bright field fluorescent, confocal microscopy), in situ hybridization, single and multiplex real time quantitative PCR, other PCR techniques, immunomagnetic separations, tissue resources, and experimental design of validation studies. A key resource is expertise in analysis of the effects of patient characteristics (age, sex, race nutritional status, etc.) on disease progression. The expertise of the core investigators is complemented by the resources available though the UAB Comprehensive Cancer Center and the Center for Human Genetics as well as the four UAB SPORES. A network of extramural consultants and resources, both academic and commercial, also is described. The ability of the investigators to work collaboratively and as a resource is demonstrated in their publications. The ability of the UAB-BRL to act as a key resource within the EDRN is demonstrated by the fact that UAB has functioned successfully as a Biomarker Validation Laboratory in the current EDRN. In this role, UAB worked in the design and protocol development of the validation study of using microsatellite analysis of urine sediment in the early detection of transitional cell carcinoma of the bladder and as the primary validation laboratory of the Validation Study of the use of SELDI-TOF-MS to identify protein signatures in serum that predict the presence of adenocarcinoma of the prostate. A developmental project is proposed in which the effects of fixatives and antigen retrieval techniques on real time quantitative PCR will be determined; the ability to perform such analyses on fixed biopsy specimens and archival material would greatly enhance the development of markers of early detection. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The Tissue Resource, Molecular Analysis and Immunopathology Core Facility has extensive experience in collecting, processing, storing/banking, and distributing a wide range of tissues and controls to support the research of the Skin Diseases Research Core Center (SDRC) members. Fresh, frozen and paraffin preparations of tissues can be supplied as well as unstained tissue slides, tissue matrix arrays, microdissected tissue components, as well as histology services. The Core also can provide investigators with access to methods of morphological and molecular analysis that are difficult for individual projects to support efficiently. Primarily the Core provides light microscopic and immunocytochemical interpretation of animal and human tissues and cytologic materials including methods to detect gene products within transfected cells and adjacent tissues. Investigators have access to sophisticated techniques usually available only for human pathology, including immunoelectron microscopy and special histology services such as computerized morphometric analysis (CAS200 and BLISS systems) and in situ hybridization. The involvement of dedicated diagnostic pathologists ensures that all assays are performed on optimally collected, processed and diagnosed tissue components. Centrally performed procedures free investigators from duplication of basic work, allowing more productive work with the available resources and acceleration of experimental timetables. The Core works closely with the biostatistical personnel so that clinical/demographic information can be linked easily with tissue specimens. The Core will support all projects of the SDRC and its services will be available to all SDRC members. In addition, its costs will be waived for all pilot projects and for the collection of preliminary data to support grant applications. Depending on demands for services and remaining resources, the current resources requested will permit about a 30% discount below costs of services to SDRC members.

UAB has extensive experience in collecting, processing, storing, and supplying a wide range of human breast tissues to support Breast SPORE research. Fresh, frozen, and paraffin preparations of tissues can be supplied as well as histology services. The Breast SPORE 1) has established a bank of well characterized breast tumor specimens and matching uninvolved specimens from patients who have given specific informed consent for their tissues to be used in genetic and other types of research. Through October 2005, the Core has obtained research specimens from 1,168 patients with surgically resected diseases of the breast;over 4,000 specimens of breast or related tissues, including about 1,500 specimens of breast neoplasia, have been stored in a bank of frozen solid tissues;2) has processed to paraffin blocks over 3,000 breast specimens, including 1,300 carcinoma specimens. Tissue arrays have been constructed from these blocks as well as from diagnostic paraffin blocks;3) has provided frozen, paraffin processed and/or microdissected specimens for SPORE intramural as well as extramural investigators. The Core also offers investigators access to multiple experimental methods including light microscopic and immunocytochemical interpretation of animal and human tissues and cytologic materials and methods to detect gene products within cells and adjacent tissues. Investigators have access to techniques usually available only for human diagnostic pathology, including tissue microdissection, tissue arrays, antibody arrays, immunoelectron microscopy, computerized cytomorphometric analysis, special histology services, in situ hybridization, proteomic techniques including multidimensional electrophoresis, ELISA, multiplex immunoassay (Luminex), SELDI/MALDI-mass spectroscopy and flow cytometry. The Core permits the utilization of a shared set of reagents and centrally performed procedures that permits cross project comparisons of research on the same cases of breast cancer. Investigators are freed from duplication of basic work, allowing more productive work with the available resources and acceleration of experimental timetables. In summary, this Core aids investigators to reach their goals in breast cancer research;specifically, it provides samples of human tissues needed to complete research projects and aids in the research by providing methodological support for the research of SPORE investigators.

The Tissue Resource and Molecular Pathology Core Facility has extensive experience in collecting, processing, storing/banking, and distributing a wide range of tissues and controls to support the research of the Skin Diseases Research Center (SDRC) members. Fresh, frozen and paraffin preparations of tissues can be supplied as well as unstained tissue slides, tissue matrix arrays, microdissected tissue components, as well as histology services. The Core also can provide investigators with access to methods of morphological and molecular analysis that are difficult for individual projects to support efficiently. Primarily the Core provides light micrscopic and immunocytochemical interpretation of animal and human tissues and cytologic materials including methods to detect gene products within transfected cells and adjacent tissue. Investigators have access to sophisticated techniques usually available only for human pathology, including immunoelectron microscopy and special histology services such as computerized morphometric analysis (CAS200 and BLISS) systems, in situ hybridization, and flow cytometry. Analytical methods available to the SDRC include high throughput ELISA assays and Western, Southern and Northern blotting. Both multiplex RT-Q-PCR and immunoassays are also available. The involvement of dedicated diagnostic pathologists ensures that all assays are performed on optimally collected, processed and diagnosed tissue components. Centrally performed procedures free investigators from duplication of basic work, allowing more productive work with the available resources and acceleration of experimental timetables. The Core works closely with biostatistical personnel so that clinical/demographic information can be linked easily with tissue specimens. The Core will support all projects of the SDRC and its services will be available to all SDRC members. In addition, its costs will be waived for Pilot and Feasibility Studies, as appropriate, for the collection of preliminary data to support grant applications. Depending on demands for services, the current resources requested will permit about a 50% discount below costs of services to SDRC members.

PROJECT SUMMARY (See instructions): UAB has extensive experience in collecting, processing, storing, and supplying a wide range of human tissues to support research. Fresh, frozen, and paraffin preparations of tissues can be supplied as well as unstained tissue slides and other histology services. We will expand our current tissue resource services as part of the Pancreatic SPORE and join with our partners at the University of Minnesota (UMN) to establish a seamless tissue resource. We will 1) optimize pancreatic tissue collections so that specimens are snap frozen in liquid nitrogen in less than 15 minutes and the number of pancreatic tissues collected are greatly increased; 2) expand our bank of well characterized pancreatic pre-invasive and invasive neoplastic specimens and matching uninvolved specimens from patients who have consented for their tissues to be used in genetic and other research along with clinical data/ outcome; 3) provide microdissected specimens for sensitive technologies requiring pure samples of pancreatic neoplasia; 4) establish uniform collection procedures with UMN and other SPORES 5) develop tissue matrix arrays of samples of pre-invasive and invasive pancreatic neoplasia to permit the concomitant study of many different specimens; and 5) to receive, store and distribute primary pancreatic xenograft cells from the collaboration with Johns Hopkins. This Core also will provide access to methods of morphological analysis that are difficult for individual projects to support efficiently, including quantitative light microscopic and immunocytochemical interpretation of tissues and cytologic materials and will offer methods to detect gene products within transfected cells and adjacent tissues. Investigators will have access to sophisticated techniques usually available only for human pathology, including multiplex immunoassays, tissue microdissection, special histology services, in situ hybridization, confocal laser microscopy, quantitative cytomorphometric analysis and flow cytometry. The core will enable unified purchase, characterization and utilization of shared sets of reagents; centrally and expertly performed procedures will free investigators from duplication of research methods, allowing more productive work with the available resources and acceleration of experimental timetables.

DESCRIPTION (provided by applicant): Pulmonary Arterial Hypertension (PAH) is a heterogeneous group of diseases with high mortality, difficult diagnosis, limited available treatment, and no cure. The Pulmonary Hypertension Breakthrough Initiative (PHBI) is dedicated to comprehensive biobanking of human lungs with PAH and controls, supported by a detailed clinical annotation of the accrued specimens. Having started in 2006, the PHBI successfully developed a novel and unique infrastructure, whose success relied on the active participation of a highly integrated network of university-based sites with extensive expertise in each of the spheres of competency: excellence in clinical care of PAH (including patient accruals), lung transplantation, pathology, genetics, genomics, and cell isolation. The goal of this application is to leverage these unparalled resources and unique expertise into an R24-supported initiative to direct the bank to accrue specimens of disease-specific groups, which will be highly integrated with pathologic, genetic, and genomic subphenotypes pertaining to not only lung and blood specimens, but now expanding to the failing PAH heart. This proposal will be highly synergistic with the presently supported initiatives by the NHLBI in the field. The flexibilty of our infrastructure and governance will allow us to be decidedly responsive and integrated with any future NHLBI initiatives. We propose that this unique infrastructure will serve the pressing roles of advancing the translation of key discoveries to the patients with PAH and to aid in new discoveries that will have a long lasting impact in the field. The following specific aims will be pursued: Specific Aims of the Proposal 1) To establish a comprehensive biorepository of the specimens from subjects with pulmonary arterial hypertension and failed donor controls. 2) To provide the infrastructure to support human tissue based research in PAH via integrated cores devoted to Administration, Tissue Handling and Pathology, Cell Line Development, and Genomic Characterization and Cataloging. 3) To develop and implement an interface for consultation of research design and analysis to enhance broader scientific investigation.

DESCRIPTION (provided by applicant): The Collaborative Human Tissue Network is a continuation of a successful program to increase the supply and quality of human tissues to support research in cancer. The University of Alabama at Birmingham (UAB), as the Southern Division (SD) of the CHTN, has participated effectively in all CHTN operations at the national level since 1987. The policies and guidelines that have been established have resulted in a dependable source for cancer researchers of a wide range of expertly processed, well-characterized and high quality human tissues with associated histopathologic and demographic data. New challenges to biorepository operations are emerging, however. The current advances in cancer research, including the issues surrounding research into personalized medicine, have resulted in an increase in demand for tissue samples and more complex requests. Concurrently, changes in medical care, such as preoperative therapy, use of high resolution imaging instead of tissue diagnoses, as well as a changing regulatory environment are affecting tissue collections. The leadership team of the SD has taken a proactive stance to meet the future needs of cancer investigators. (1) Enhancement of operations through recruitment of additional participating sites; increased use of archival paraffin blocks for metastatic lesions and untreated primary tumors; use of novel techniques, including nitrocellulose blots, for obtaining aliquots of small tissue specimens; and development of a rapid autopsy program. These are accompanied by increased education of investigators as to use of alternative tissues (e.g., autopsy, paraffin blocks) and to specimen limitations; (2) Enhancement of quality assurance and quality control through participation in external accreditation processes; and (3) Enhancement of the ethical and regulatory stance through expansion of utilization of patient advocates. The informatics system is critical to all biorepository functions and the SD proposes development of an Investigators' IT system that utilizes new-era interoperability and linked big-data systems. It als proposes an increased emphasis on training and proficiency testing in IT systems, coupled with greater utilization of the Web for access to and training in SOPs. The SD reaffirms its commitment to the operations of the CHTN as a whole. In addition to ongoing involvement at the leadership level, it continues significant collaborative efforts with individual divisions, including supplying tissues for microarrays and beta-testing of modifications of the current IT system. Since 2008, the SD has provided 20,287 fresh, frozen and fixed human aliquots to 264 investigators. Notably, within the CHTN network it provides complex specimens including aliquots of tissue processed within 30 minutes of collection; macrodissected paraffin and frozen tissues and mRNA/DNA samples as well as detailed clinical information and follow-up to investigators. It is one of the leading providers of fresh tissue samples and body fluids and the leading provider of samples from African-American patients.

PROJECT SUMMARY The involvement of skilled bioethicists is necessary for the success of research in the basic and translational sciences. In particular, research that is conducted to reduce the burdens caused by the racial disparities in cancer incidence requires bioethical guidance. For these reasons, the Bioethics Shared Resource (BESR) is an integral component of this Partnership. For full/pilot projects, the BESR provides consultation and collaborative support regarding ethical issues from design to implementation and assists in the development of grant proposals, abstracts, and manuscripts. In addition to its work supporting the research of Partnership investigators, the BESR enhances the bioethical capabilities of the Partnership participants. This is accomplished by providing education in bioethics to investigators, junior faculty, post-doctoral fellows, medical residents, graduate/undergraduate and medical students, community health advisors, navigators, partners, and other Partnership personnel regarding sound applications of bioethical principles in cancer research. The BESR provides bioethical education through the Research Education Core of the Partnership and, at TU, collaborates in teaching the graduate/undergraduate courses in bioethics in research, health disparities, and health policy. Bioethics support is essential for enhancing of the basic and translational research of the MSM/TU/UAB CCC Partnership.

CLINICAL RESEARCH GROUP TISSUE PROCUREMENT SHARED FACILITY (TPSF) ABSTRACT The goal of the UAB Comprehensive Cancer Center Tissue Procurement Shared Facility (TPSF) is to promote the research undertaken by UAB-CCC investigators by ensuring the availability of relevant, high quality human tissues. The TPSF accomplishes this through the collection, processing, storage, and distribution of a wide range of human tissues. Neoplastic and control tissues are supplied as fresh, frozen, paraffin-processed specimens or tissue sections. Bodily fluids and fluid components also can be provided. Pathologists evaluate all solid tissues supplied for research for quality and diagnostic accuracy. The supplementary services provided, including specialized histology, macrodissection and customized clinical data, are of demonstrable significance to the UAB-CCC investigators as are the ability of the TPSF to work effectively with other UAB- CCC Shared Facilities and affiliates. The TPSF leadership provides expert individual guidance to the UAB- CCC investigators in experimental design and the effective use of emerging methodologies in basic and translational research, as well as ensuring compliance in the changing regulatory environment. The leadership's expertise is based on active research in the area of tissue processing and banking as well as their participation in educational and outreach programs at the local, national and international levels. Strategic planning has been used to harness institutional and philanthropic resources to expand the capabilities of the Facility while improving the cost-effectiveness of its operations. Initiatives that have been undertaken since 2011 include extensive renovations, updating of equipment and harmonization of standard-operating- procedures for accreditation by the College of American Pathologists; continued improvements in information technology applications that will enhance research capabilities while reducing labor costs; and establishment of the CCC Tissue Bank. Institutional support has permitted targeted recruitment of an additional pathologist, an informatics specialist, and a pathology physician's assistant to aid the TPSF. The TPSF serves investigators in all six UAB-CCC programs and since 2011 its involvement in clinical trials has tripled. It plays a central role in promoting the mission of the Cancer Center in terms of providing tissues from African-American patients that support their inclusion in early translational studies. From March 2011 to March 2015 the TPSF has supported requests from 57 UAB-CCC investigators and has supported 32 clinical trials. Between January and December 2014 the facility provided 38 UAB-CCC investigators with 919 fresh or frozen human tissue samples, 754 paraffin blocks, and 12,925 slides. TPSF-supported research has been reported in over 120 publications during this time period. Since 1978, the facility has provided approximately 212,000 tissue specimens, blocks, and slides to investigators at UAB. These have been used in a total of 1,295 publications.