William E. Grizzle, MD, PhD

Grizzle_William_E-smallProfessor of Pathology



Address: Ziegler Building, room 408
UAB
Birmingham, AL 35294
Telephone: (205) 934-4214
Email: wgrizzle@uab.edu

Publications

 

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Education


B.A. (Chemistry & Physics), Harvard University
Ph.D. (Biophysics), Johns Hopkins University
M.D., Johns Hopkins University



Research Interests


Our laboratory is focused on understanding the molecular features of epithelial cancers such as prostate, pancreas, mammary, colorectal and ovarian adenocarcinomas as well as squamous cell lesions of oral cavity, esophagus, lung, cervix and skin in order to identify biomarkers associated either with early pre-invasive neoplastic lesions or with advanced stage malignant lesions. Of special interest are biomarkers that can be used to aid in determining prognosis or risk assessment or in predicting therapy. For example, the earliest putative pre-invasive lesion of the prostate is prostatic intraepithelial neoplasia (PIN); we have demonstrated the phenotypic expression of molecular markers in PIN is similar to the phenotypic expression of these same molecular markers in prostatic adenocarcinomas. We study the escape of PCa from the requirement for androgens, i.e., development of androgen resistance. We use the human xenograft tumor models CWR22, LNCaP, DU145 and PC-3 in nude mice to investigate androgen effects on prostate tumors and the development of androgen resistance in these tumors. These data are supplemented by in vitro studies. In colorectal adenocarcinoma (CRCs), we have identified six molecular markers that aid in identifying aggressive subgroups of CRCs. These are p53, Bcl-2, p27kip-1, Suppressin, MUC-1 and MUC-2. We have identified differences in prognostic usefulness of biomarkers based on the anatomic location of CRCs. Our studies also have focused on the racial differences in the expression of these molecular markers as well as racial differences in the clinical importance of the expression of these biomarkers. Our studies of breast neoplasia also have emphasized racial differences in molecular features of ductal carcinoma. Besides our interests in epithelial neoplasia, we have a broad interest in diffuse pulmonary diseases including pulmonary arterial hypertension as well as tissue reparative processes leading to granulation tissues and neovascularity. In general our laboratory utilizes proteomic techniques but also has capabilities in molecular biology. In addition to quantitative immunohistochemistry (fluorescent or bright field), Western blotting, high throughput ELISA, multiplex immunoassays (Luminex and MESO), we have a SELDI-TOF-MS system for identification of unique proteomic patterns and we collaborate using other mass spectrometry systems in the early detection of cancers by determining the proteins of specific cancers in biological fluids such as serum. We also have automated cytomorphometric instrumentation and tissue arrays that can be used in multi-tissue analyses. Similarly, we can use gene chip (affymetrix) and spotted array analysis in gene discovery. Of great interest are collaborative efforts to improve the biomathematic/statistical approaches to evaluating biomarkers and multiplex methods of analysis and how bias in collecting and processing tissue samples may affect multiplex assays. Also, for the last two decades we have provided human tissues to support the research of biomedical investigators throughout North America. In this effort, sponsored primarily by the Cooperative Human Tissue Network (CHTN), we have introduced to tissue resources the utilization of quality control of tissues provided for research and we have been involved in database development for tissue resources. We also have great expertise in how fixation of tissues interacts with the stages of tissue processing to affect immunorecognition and other molecular assays. 

Grant Support (P.I.)

  1. Biomarker Reference Laboratory – Early Detection Research Network (EDRN)
  2. Tissue Resource and Molecular Pathology Core of the Breast SPORE
  3. Tissue Research and Molecular Pathology Core of the Pancreatic SPORE
  4. Cooperative Human Tissue Network (CHTN)
  5. Pulmonary Hypertension Breakthrough Initiative (PHBI)

EDRN

Goals – Multiplex Assays in Early Detection, Risk Assessment and Prognosis.