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Faculty Detail    
Name JAY M MCDONALD
 
Campus Address WP P210 Zip 7331
Phone 205-996-2808
E-mail mcdonald@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Pathology Gen Administration Professor Emeritus

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Jay M. McDonald, M.D. is Professor, Department of Pathology at The University of Alabama at Birmingham (UAB) Medical Center, Schools of Medicine and Dentistry. He is currently principal investigator on one VA grant. Dr. McDonald is board certified in Anatomic and Clinical Pathology. His academic career has spanned 30 years and includes Directorship of the Division of Laboratory Medicine in the Departments of Pathology and Medicine at Washington University School of Medicine in St. Louis for ten (10) years prior to his recruitment to UAB in 1990 to Chair its Department of Pathology. He served as Chair of UAB Pathology from 1990-2008 and was Editor-in-Chief of the primary pathology research journal, The American Journal of Pathology, from 2003-2008. In addition, he was Director of an NIH funded Center for Metabolic Bone Disease (one of five in the United States) from 1996-2010.

Society Memberships
Organization Name Position Held Org Link
American Association for Cancer Research, Inc.     
American Association for Clinical Chemistry     
American Diabetes Association     
American Society for Bone and Mineral Research     
American Society for Investigative Pathology  Editorial Board   
American Society of Clinical Pathology  Editorial Board   
Association of Pathology Chairs     
College of American Pathologists     
Medical Association for the State of Alabama     

Research/Clinical Interest
Title
Cellular Life and Death Signals in Cancer, Aids and Bone Disease.
Description
Research is focused upon understanding intracellular signal transduction pathways that transfer key information from the extracellular to the intracellular environment, resulting in coordinated cellular responses. More specifically, the role of calcium, the calcium receptor protein, calmodulin, and related protein kinases and phosphatases in 1) osteoporosis and metabolic bone disease, 2) the pathogenesis of AIDS and AIDS-related bone disease, and 3) malignant transformation and tumorigenesis are being studied. A combination of biochemistry, cell biology, and molecular biology techniques are used to elucidate the critical signal transduction pathways involved in each of the diseases with the ultimate goal of modulating key signal transduction pathways as potential new avenues for therapy. 1. In osteoporosis, a disease in which the metabolic balance between bone production and bone destruction is altered resulting in decreased bone mass and an increased incidence of life threatening fractures, research is focused on the intracellular signal transduction mechanisms that regulate the number and activity of osteoclasts and osteoblasts. Osteoclasts are highly specialized cells that are responsible for degrading bone while osteoblasts produce bone. Specific emphasis is being placed on the role of calcium and calmodulin. Furthermore, zero gravity simulation cultures are being used to dissect osteoblast differentiation signals. This zero gravity simulation system represents a drug discovery screening system for anabolic agents. 2. In AIDS, T-lymphocytes are rapidly destroyed resulting in the life threatening immunodeficiency to which the patients ultimately succumb. Research is focused on understanding the mechanisms by which T-lymphocytes are killed. This killing (apoptosis) involves complex signal transduction mechanisms initiated by external stimuli. The unique intracellular signal transduction pathways for HIV-mediated killing that involve calmodulin interaction with the death receptor Fas are being explored and new potential avenues of therapy are being tested. Also, the molecular mechanism of AIDS-related osteopenia and osteoporosis are being investigated. Specifically AZT, which is used in highly active antiviral therapy, stimulates osteoclastogenesis in vitro and in mouse models. 3. In carcinogenesis, the focus is on the cellular mechanisms of cell death and their effects on tumorigenesis. The primary models for study are unique human-derived cholangiocarcinoma cell lines, which heterogeneously express the death receptor, Fas, providing the opportunity to investigate key underlying intracellular molecular events and design new anticancer therapeutics. The mechanism involves Fas binding to calmodulin. These studies have led to a recent application for an NIH sponsored clinical trial for cholangiocarcinoma involving interferon-gamma and tamoxifen.

Selected Publications 
Publication PUBMEDID
Pawar P, Ma L, Byon CH, Liu H, Ahn E-Y, Jhala N, Arnoletti JP, McDonald JM, Chen Y. Molecular mechanisms of tamoxifen therapy for cholangiocarcinoma: Role of calmodulin. Clin Cancer Res 2009;15(4):1288-1296.   19228732 
Mamaeva O, Kim J, Feng G, McDonald JM. Calcium/calmodulin-dependent kinase II regulates Notch-1 signaling in prostate cancer cells. J Cell Biochem 2009;106(1):25-32.   19021144 
Suever J, Chen Y, McDonald JM, Song Y. Conformation and free energy analyses of the complex of Ca2+-bound calmodulin and the Fas death domain. Biophys J 2008;95(12):5913-5921.   18820240 2599819 
Chen Y, Wang X, Di L, Fu G, Chen Y, Bai L, Liu J, Feng X, McDonald JM, Michalek S, He Y, Yu M, Fu YX, Wen R, Wu H, Wang D. Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis. J Biol Chem 2008;283(43):29593-29601.   18728019 2570883 
Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, McDonald JM, Chen Y. Oxidative stress induces vascular clacification through modulation of the osteogenic transcription factor RUNX-2 by AKT signaling. J Biol Chem 2008;283:15319-15327.   18378684 2397455 
Pawar P, Micoli KJ, Ding H, Cook WJ, Kappes JC, Chen Y, McDonald JM. Calmodulin binding to cellular FLICE-like inhibitory protein modulates Fas-induced signaling. Biochem J 2008;412:459-468.   18257744 
Yeo H, Beck LH, Thompson SR, Farach-Carson MC, McDonald JM, Clemens TL, Zayzafoon M. Conditional disruption of calcineurin B1 in osteoblasts increases bone formation and reduces bone resorption. J Biol Chem 2007;282:35318-35327.   17884821 
Pan G, Ahn E-Y, Chen Y, Feng G, Reddy V, Jhala NC, McDonald JM. Reciprocal co-expression of Fas and Fas ligand in human cholangiocarcinoma. Int J Oncol 2007;31:843-850.   17786316 
Chen Y, Pawar P, Pan G, Ma L, Liu H, McDonald JM. Calmodulin binding to the Fas-mediated death-inducing signaling complex in cholangiocarcinoma cells. J Cell Biochem 2008;103:788-799.   17654480 
Yeo H, Beck LH, McDonald JM, Zayzafoon M. Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation. Bone 2007;40:1502-1516,   17392048 1974856 
Pan G, Kilby M, McDonald JM. Modulation of osteoclastogenesis induced by nucleoside reverse transcriptase inhibitors. AIDS Res Hum Retroviruses 2006;22:1131-1141 (doi: 10.1089/aid.2006.22.1131).   17147500 1994207 

Keywords
AIDS, apoptosis, bone, cancer