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Faculty Detail    
Name JOANNE MURPHY-ULLRICH
 
Campus Address VH G001 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  Biomedical Engineering  Biomatrix Eng Regen Med (BERM) Ctr Professor
Center  Pathology   Cell Adhesion & Matrix Research Center Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering 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
Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP, Bouck N. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell. 1998 Jun 26;93(7):1159-70.  9657149 
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 
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A,
Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.
Cell. 2005 Oct 21;123(2):321-34. 
16239148 
Zhou Y, Hagood JS, Murphy-Ullrich JE. Thy-1 expression regulates the ability of rat lung fibroblasts to activate transforming growth factor-beta in response to fibrogenic stimuli. Am J Pathol. 2004 Aug;165(2):659-69.   15277239 
Young GD, Murphy-Ullrich JE. Molecular interactions that confer latency to transforming growth factor-beta. J Biol Chem. 2004 Sep 3;279(36):38032-9. Epub 2004 Jun 18.   15208302 
Wang S, Skorczewski J, Feng X, Mei L, Murphy-Ullrich JE. Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2. J Biol Chem. 2004 Aug 13;279(33):34311-22. Epub 2004 Jun 07.   15184388 
Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, Murphy-Ullrich JE. Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly.J Cell Biol 2003 Jun 23; 161(6):1179-89.  12821648 
Orr AW, Elzie CA, Kucik DF, Murphy-Ullrich JE. Thrombospondin signaling through the calreticulin/LDL receptor-related protein co-complex stimulates random and directed cell migration. J Cell Sci 2003 Jul 15; 116(Pt 14): 2917-27.  1280819 
Murphy-Ullrich JE. The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state? J Clin Invest. 2001 Apr;107(7):785-90. Review.  11285293 

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