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Faculty Detail     Name JOANNE MURPHY-ULLRICH   Campus Address VH 668B Zip 0019 Phone 205-934-0415 E-mail murphy@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Pathology   Molecular & Cellular Pathology Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor Center  Pathology   Cell Adhesion & Matrix Research Center Professor Center  Center for Metabolic Bone Disease  Center for Metabolic Bone Disease Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  Medicine  Comprehensive Diabetes Ctr Professor Center  Medicine  Ctr Cardiovasc Bio Professor Center  Medicine  Nephrology Res & Trng Ctr Professor

Graduate Biomedical Sciences Affiliations Cancer Biology  Cell, Molecular, & Developmental Biology  Medical Scientist Training Program  Pathobiology and Molecular Medicine  Waiting to be Seated

Biographical Sketch  Dr. Murphy-Ullrich received her BS from Marquette University in Medical Technology and her Ph.D. from the University of Wisconsin in Pathology. She did post-doctoral work at Wisconsin with Dr. Deane Mosher. She joined the Department of Biochemistry at UAB as a Research Associate and then she joined the faculty in the Department of Pathology. She is a past Established Investigator of the American Heart Association, Secretary/Treasurer of the American Society for Matrix Biology, and Co-Director of the UAB BioMatrix Engineering and Regenerative Medicine Center. She has serves on the editorial boards of the Journal of Biological Chemistry and Matrix Biology and on peer review panels including NIH, the American Cancer Society, and the Arthritis Foundation. She is co-Chair of the American Heart Association Established Investigator Peer Review panel. Her work has been funded by the AHA, including an Established Investigator Award, the American Cancer Society, the Juvenile Diabetes Research Foundation, the Arthritis Foundation, and by the NIH.

Society Memberships Organization Name Position Held Org Link American Society for Biochemistry and Molecular Biology  member    American Society for Cell Biology  member    American Society for Investigative Pathology  member    American Society for Investigative Pathology  member    American Society for Matrix Biology  Council member 2001-2002; Secretary/Treasurer 2008-13  http://www.asmb.net  TERMIS-NA

Research/Clinical Interest Title Extracellular Matrix Control of Cell and Growth Factor Function Description Our research seeks to understand how the extracellular environment—matrix molecules and growth factors—regulate cellular processes such as growth, death, motility, and differentiation. We focus on a complex protein thrombospondin 1 (TSP1) which is made by cells in response to injury and stress. Our lab made the seminal discovery that TSP1 as a major regulator of activation of the pleiotrophic cytokine, TGF-beta. TGF-beta is a key factor that drives the development of fibrotic organ failure due to scarring. TSP1 is a key player in regulating the inappropriately high levels of TGF-beta activity in diabetes and hypertension and in vivo studies showed that a peptide antagonist of TSP1-dependent TGF-beta activation can reduce scarring and improve organ function in diabetic cardiomyopathy and nephropathy and in the tumor microevironment. Ongoing studies are evaluating the utility of these peptides as therapeutics for the treatment of diabetic complications in the kidney and the heart and cancer. We are pursuing therapeutic development of antagonists of the TSP1-TGF-beta pathway for treatment of fibrotic disease and for treatment of bone marrow cancers. Recent work is focused on establishing a link between endoplasmic reticulum (ER) stress as occurs in diabetes and fibrotic complications. Our lab has demonstrated that the ER stress protein calreticlin regulates production of the extracellular matrix and that it is required for the ability of TGF-beta to signal extracellular matrix transcription. This occurs through calreticulin's calcium regulatory functions. In separate studies, we have identified a novel function for the N-terminal domain of TSP1 that stimulates collagen deposition in an in vivo model of the foreign body response through TGF-beta-independent stimulation of collagens. We are currently developing novel biomaterial scaffolds of this sequence of TSP1 which could be used to support cell survival and matrix production during transplantation or tissue engineering of mesenchymal stem cells. We are working with BERM Center members to develop 3D scaffolds composed ot biocompatible materials and ECM molecules to develop "organoids" which can be used to predict cellular and tissue responses to drugs during the drug development process.

Selected Publications  Publication PUBMEDID Bailey DuBose K, Zayzafoon M, Murphy-Ullrich JE. Thrombospondin1 inhibits osteogenic differentiation of human mesenchymal stem cells through latent TGF-beta activation. Biochem Biophys Res Commun. 2012 422488-493  22583901  Sweetwyne MT, Pallero MA, Lu A, Graham LV, Murphy-Ullrich JE. The calreticulin-binding sequence of thrombospondin1 regulates collagen expression and organization during tissue remodeling. Am. J Pathol 177: 1710-24.  20724603  Van Duyn Graham L, Sweetwyne MT, Pallero MA, Murphy-Ullrich JE. Intracellular calreticulin regulates multiple steps in fibrillar collagen expression,trafficking, and processing into the extracellular matrix. J Biol Chem. 2010 285: 7067-78  20044481  Pallero MA, Talbert Roden M, Chen YF, Anderson PG, Lemons J, Brott BC,Murphy-Ullrich JE. Stainless Steel Ions Stimulate Increased Thrombospondin-1-Dependent TGF-Beta Activation by Vascular Smooth Muscle Cells: Implications for In-Stent Restenosis. J Vasc Res. 2009 Dec 16;47(4):309-322. [Epub ahead of print]   20016205  Gold LI, Eggleton P, Sweetwyne MT, Van Duyn LB, Greives MR, Naylor SM,Michalak M, Murphy-Ullrich JE. Calreticulin: non-endoplasmic reticulum functions in physiology and disease. FASEB J. 2010 24:665-83   19940256  Liu A, Garg P, Yang S, Gong P, Pallero MA, Annis DS, Liu Y, Passaniti A, Mann D, Mosher DF, Murphy-Ullrich JE, Goldblum SE. The EGF-like repeats of thrombospondins activate phospholipase C gamma and increase epithelial cell migration through indirect epidermal growth factor receptor activation. J Biol Chem. 2009 284: 6389-6402  19129184   Zhou Y, Koli K, Hagood JS, Miao M, Mavalli M, Rifkin DB, Murphy-Ullrich JE. Latent transforming growth factor-beta-binding protein-4 regulates transforming growth factor-beta1 bioavailability for activation by fibrogenic lung fibroblasts in response to bleomycin. Am J Pathol. 2009 Jan;174(1):21-33. Epub 2008 Dec 4.   19056849  Pallero MA, Elzie CA, Chen J, Mosher DF, Murphy-Ullrich JE. Thrombospondin 1 binding to calreticulin-LRP1 signals resistance to anoikis. FASEB J. 2008 Nov;22(11):3968-79. Epub 2008 Jul 24.   18653767  Belmadani S, Bernal J, Wei CC, Pallero MA, Dell'italia L, Murphy-Ullrich JE,Berecek KH. A Thrombospondin-1 Antagonist of Transforming Growth Factor-{beta} Activation Blocks Cardiomyopathy in Rats with Diabetes and Elevated Angiotensin II. Am J Pathol. 2007 Sep;171(3):777-89. Epub 2007 Jul 19.   17640965  Zhou Y, Poczatek MH, Berecek KH, Murphy-Ullrich JE. Thrombospondin 1 mediates angiotensin II induction of TGF-beta activation by cardiac and renal cells under both high and low glucose conditions.Biochem Biophys Res Commun. 2006 Jan 13;339(2):633-41. Epub 2005 Nov 18.  16310163  First Prev   1 2 of  2  Next Last

Keywords atherosclerosis,restenosis, diabetic complications, pulmonary fibrosis, tumor microenvironment, tissue engineering, cell adhesion and motility, fibrosis, TGF-beta, thrombospondin, tissue engineering

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