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Faculty Detail    
Name WILLIAM E GRIZZLE
Professor of Pathology
Head, Pathology Program for Translational Research in Neoplasia
Director, Tissue Collection and Banking Facility
Senior Scientist, UAB Comprehensive Cancer Center, Center for Aging, Metabolic Bone Disease Research Center, Cystic Fibrosis Center
Senior Editor, Clinical Cancer Research
 
Campus Address ZRB 426 Zip 0007
Phone  205-934-4214
E-mail  wgrizzle@uabmc.edu
Other websites
     

Education
Undergraduate  Harvard University    1965  A.B. Chemistry and Physics 
Graduate  Johns Hopkins University    1975  Ph.D. in Biophysics 
Medical School  Johns Hopkins University School of Medicine    1977  M.D. 
Residency  Vanderbilt University    1979  Anatomic Pathology 
Residency  University of Alabama at Birmingham    1981  Clinical Pathology 

Certifications
American Board of Pathology, Anatomical and Clinical, Diplomate  1982 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Anatomic Pathology Professor
Center  General Clinical Research Center  Center for Outcomes & Effectiveness Res & Educ Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor
Center  Medicine  Ctr Cardiovasc Bio (Org Ret) Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Professor

Graduate Biomedical Sciences Affiliations
Integrative Biomedical Sciences 
Molecular and Cellular Pathology Program 

Biographical Sketch 
After college, I served (1970-1975) in the US Navy in the Division of Naval Reactors and the Atomic Energy Commission. Subsequently, I completed a Ph.D. and then entered medical school. Since 1981, I have been on the faculty of the University of Alabama at Birmingham (UAB) with a primary appointment in the Department of Pathology. My career at UAB has involved teaching medical students, pre-doctoral students, but primarily post-doctoral students, research, and service in anatomic pathology (surgical pathology, cytopathology, and autopsy pathology)and clinical pathology (endocrinology and clinical chemistry). I headed autopsy pathology from 1990-2000 and then became the head of the Program in Translational Research in Pathology (2000-current).

Society Memberships
Organization Name Position Held Org Link
Alabama Society for Histotechnology (ASH)  Honorary  http://www.alhistology.org/ 
American Association for Cancer Research (AACR)  Senior Editor, Clinical Cancer Research  http://www.aacr.org/ 
Biological Stain Commission (BSC)  Trustee, Past Vice-President, Past President  http://www.biologicalstaincommission.org/ 
College of American Pathologists (CAP)  Past Elected Member  http://www.cap.org/apps/cap.portal 
Endocrine Society  Past Elected Member  https://www.endocrine.org/ 
International Society for Biological and Environmental Repositories (ISBER)  Past President, Member of Publications Committee, Science Policy Committee  http://www.isber.org/ 

Research/Clinical Interest
Title
Biomarkers; Anatomic and Clinical Pathology; Tissue Resources; Immunomodulation of Cancer and Exosomes; Post-transcriptional Processing; Non-coding RNAs; Epigenetics of Cancer; Molecular Imaging
Description
Our laboratory has worked to increase the understanding of molecular features of epithelial cancers including prostate, pancreas, mammary, colorectal and ovarian adenocarcinomas as well as squamous cell lesions of oral cavity, esophagus, lung, cervix and skin. Our goal has been to identify biomarkers associated either with early pre-invasive neoplastic lesions or with advanced stage malignant lesions, especially metastatic lesions. Of special interest are biomarkers that can be used to aid in determining prognosis and risk assessment and in predicting successful therapy. Also, we collaborate to improve the biomathematic/statistical approaches to evaluating biomarkers and multiplex methods of analysis and on the identification of how bias in collecting, processing, and storing tissue samples may affect multiplex assays. We have reported molecules that are differentially expressed in prostatic intraepithelial neoplasia, ductal carcinoma of the breast, and adenomatous polyps of the colorectum and have identified multiple biomarkers associated with the prognosis of the colorectal cancer and breast cancer. In addition, we have evaluated racial differences in biomarkers; racial disparities in cancer research are a major interest. Besides epithelial neoplasia, we have a broad interest in diffuse pulmonary diseases including pulmonary arterial hypertension and cystic fibrosis. Thus, in general, our studies are on the molecular epidemiology of epithelial neoplasia. New interests include characterizations of the molecules involved in mitosis and cilia, especially proteins of the centriole and centrosome, post-transcriptional processing (e.g., microRNA and IRES), exosomes, and genes controlling metastasis (e.g., KISS). More recent collaborative studies with Dr. Lacey McNally at the University of Louisville have been on molecular imaging using multispectral optoacoustic tomography (MSOT) and the correlation of MSOT signals with tissue morphology. For the last three 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) and the Pulmonary Hypertension Breakthrough Initiative (PHBI), we have introduced to biorepositories the utilization of quality control of the specific tissues provided for research, database development, and biorepository sciences. In this area, we have expertise in how different types of fixation of tissues interacts with the stages of tissue processing to affect immunorecognition and other molecular assays.

Selected Publications 
Publication PUBMEDID
Stanley J, Klepczyk L, Keene K, Wei S, Li Y, Forero A, Grizzle W, Wielgos M, Brazelton J, LoBuglio AF, Yang ES. PARP1 and phosphor-p65 protein expression is increased in human HER2-positive breast cancers. Breast Cancer Res Treat 2015; 150(3):569-79.  4396624 
Forero-Torres A, Varley KE, Abramson VG, Li Y, Vaklavas C, Lin NU, Liu MC, Rugo HS, Nanda R, Storniolo AM, Traina TA, Patil S, Hayes DF, Van Poznak CH, Nangia JR, Irvin Jr WJ, Krontiras H, De Los Santos JF, Haluska P, Grizzle W, Meyers RM, Wolff AC. TBCRC 019: phase II trial of nab-PAC with/without the anti-death receptor 5 monoclonal antibody tigatuzumab in patients with triple negative breast cancer. Clin Can Res 2015; 21(12):2722-9.   
Yin W, Kimbrough Cw, Gomez-Gutierrez JG, Burns CT, CHuong P, Grizzle WE, McNally LR. Tumor specific liposomes improve detection of pancreatic adenocarcinoma in vivo using optoacoustic tomography. J Nanobiotechnol 2015;13(1):90. doi: 10.1186/s12951-015-0139-8.  4665906 
Vaklavas C, Meng Z, Choi H, Grizzle WE, Zinn KR, Blume SW. Small molecule inhibitors of IRES-mediated translation. Cancer Biol Ther 2015;16(10);1471-1485 doi: 10.1080/15384047.201.1071729.   
Yin W, Kimbrough Cw, Gomez-Gutierrez JG, Burns CT, CHuong P, Grizzle WE, McNally LR. Tumor specific liposomes improve detection of pancreatic adenocarcinoma in vivo using optoacoustic tomography. J Nanobiotechnol 2015;13(1):90. doi: 10.1186/s12951-015-0139-8.  4665906 
Kimbrough CW, Khanal A, Zeiderman M, Khanal BR, Burton NC, McMasters KM, Vickers S, Grizzle WE, McNally LR. Targeting acidity in pancreatic adenocarcinoma: multispectral optoacoustic tomography detects pH-low insertion peptide probes in vivo. Clin Can Res 2015 Oct 15:21(20):4576-85. doi: 10.1158/1078-0432.CCR-15-0314.   4609270 
Li H, Hsu HC, Wu Q, Yang P, Li J, Oukka M, Steele CH, Cua DJ, Grizzle WE, Mountz JD. IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORγt. Nature Comm 2014; 8(5):4259.  4136447 
Theodore SC, Davis M, Zhou F, Wang H, Chen D, Rhim J, Dean-Colomb W, Turner T, Ji W, Zeng G, Grizzle W, Yates C. MicroRNA profiling of novel African American and Caucasian prostate cancer cell lines reveals a reciprocal regulatory relationship of miR-152 and DNA methyltranferase-1. Oncotarget 2014; 5(11):3512-25.  4116499 
Varley KE, Gertz J, Roberts BS, Davis NS, Bowling KM, Kirby MK, Nesmith AS, Oliver PG, Grizzle WE, Forero A, Buchsbaum DJ, LoBuglio AF, Myers RM. Recurrent read-through fusion transcripts in breast cancer. Breast Cancer Res Treat 2014; 146(2):287-97.  4085473 
Devine DJ, Rostas JW, Metge BJ, Das S, Mulekar MS, Tucker JA, Grizzle WE, Buchsbaum KJ, Shevde LA, Samant RS. Loss of N-Myc interactor promotes epithelial-mesenchymal transition by activiation of TGF-β/SMAD signaling. Oncogene 2014; 33(20):2620-8.  4267223 
Birket SE, Chu KK, Liu L, Houser GH, Diephuis BJ, Wilsterman EJ, Dierksen G, Mazur M, Shastry S, Li Y, Watson JD, Smith AT, Schuster BS, Hanes J, Grizzle WE, Sorscher EJ, Tearney GJ, Rowe SM. A functional anatomic defect of the cystic fibrosis airway. Am J Respir Crit Care Med 2014;190(4):421-32.  4214131 
Kerr EH, Frederick PJ, Egger ME, Stockard CR, Sellers J, DellaManna D, Oelschlager D, Amm HM, Eltoum IE, Straughn JM, Buchsbaum DJ, Grizzle WE, McNally LR. Lung resistance-related protein (LRP) expression in malignant ascetic cells as a prognostic marker for advanced ovarian serous carcinoma. Annals of Surgical Oncology PLoS ONE Epub 2013 Jan 23 doi: 10.1371/journal.pone.0054473.  3553101 
Gurpinar E, Grizzle WE, Shacka JJ, Mader B, Li N, Piazza NA, Russo S, Keeton AB, Piazza GA. A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy. Molecular Cancer Ther 2013;12(5):63-74.  3651802  
Deng ZB, Zhuang X, Ju S, Xiang X, Mu J, Liu Y, Jiang H, Zhang L, Mobley J, McClain C, Feng W, Grizzle W, Yan J, Miller D, Dronenberg M, Zhang HG. Exosome-like nanoparticles from intestinal mucosal cells carry prostaglandin E2 and suppress activation of liver NKT cells. J Immunol 2013; 90(7):3579-89. (PMCID not required; no federal funding)   
Grizzle WE, Srivastava S, Manne U. Translational Pathology of Cancer. In: Translational Pathology of Early Cancer. (Eds. S. Srivastava, WE Grizzle) IOS Press BV, Amsterdam. 2012;7-20   
Grizzle WE, Bell WC, Sexton KC. Issues in collecting, processing and storing human tissues and associated information to support biomedical research. In: Translational Pathology of Early Cancer. (Eds. S Srivastava, WE Grizzle), IOS Press BV, Amsterdam. 2012;531-549.   
Katayama H, Wang J, Treekitkarnmongkol W, Kawai H, Sasai K, Zhang H, Wang H, Adams HP, Jiang S, Chakratory SN, Suzuki F, Arlinghaus RB, Liu J, Mobley JA, Grizzle WE, Wang H, Sen S. Aurora Kinase-A inactivates DNA damage induced apoptosis and spindle assembly checkpoint response functions of p73. Cancer Cell 2012;21(2):196-211  22340593 
Singh AP, Arora S, Bhardwaj A, Srivastava SK, Kadakia MP, Wang B, Grizzle WE, Owen LB, Singh S. CXCL12/CXCR4 signaling axis induces SHH expression in pancreatic cancer cells via ERK- and Akt- mediated activation of NF=κB: implications for bidirectional tumor-stromal interactions. J Biological Chem 2012;287(46):39115-24  3493952 
Srivastava SK, Bhardwaj A, Singh S, Arora S, McClellan S, Grizzle WE, Reeed E, Singh AP. Mb overexpression overrides androgen depletion-induced cell cycle arrest and apoptosis in prostate cancer cells, and confers aggressive malignant traits: potential role in castration resistance. Carcinogenesis 2012;33(6):1149-57  3514863 

Keywords
epithelial cancers, proteomics, biomarkers, molecular imaging, molecular staging, immune modulation, post-transcriptional processing, microRNA, metastases, extracellular vesicles, exosomes, centrosomal & centriolar proteins, biorepositories