Pathobiology and Molecular Medicine  http://www.gbs.uab.edu  http://www.uab.edu/graduate  Back to Main

Faculty Detail    
Name JOANNE MURPHY-ULLRICH
  
Campus Address PBMR 408
Phone  (205) 934-0415
E-mail  jmurphy@uabmc.edu
Other websites
     

Education
Undergraduate  Marquette University    1976  B.S. Medical Technology (Honors) 
Graduate  University of Wisconsin    1983  PhD 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Joint Pathology  Molecular & Cellular Pathology Professor Emeritus

Graduate Biomedical Sciences Affiliations
Cancer 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 under Dr. Terry D. Oberley studying autoimmune responses to fibronectin in the kidney. She did post-doctoral work at Wisconsin with Dr. Deane Mosher where she studied thrombospondin-1 binding and degradation by endothelial cells. She joined the Department of Biochemistry at UAB as a Research Associate to work with Magnus Hook to study thrombospondin-heparan sulfate interactions. She joined the faculty in the Department of Pathology in 1991. She is a past Established Investigator of the American Heart Association. She served as Director of the Cell Adhesion and Matrix Research Center and Co-Director of the UAB BioMatrix Engineering and Regenerative Medicine Center. She has served on the editorial boards of the Journal of Biological Chemistry, Matrix Biology, and the Journal of Cellular Communication and Signaling and on peer review panels including NIH, the American Cancer Society, and the Arthritis Foundation. She Chaired 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, The American Society for Hematology, the Department of Defense, and by the NIH. She served on the American Society for Matrix Biology (ASMB) Council, as ASMB Secretary/Treasurer, ASMB President-elect, ASMB president, and as ASMB Past-President. She is currently Editor-in-Chief of Matrix Biology and Matrix Biology Plus.

Society Memberships
Organization Name Position Held Org Link
American Society for Biochemistry and Molecular Biology  member   
American Society for Matrix Biology  Council member 2001-2002; Secretary/Treasurer 2008-13, President-elect 2015-16, President 2017-18, Past-President 2019-21  http://www.asmb.net 
International CCN Society  liaison to ASMB   
International Society for Matrix Biology  member   
 



Research/Clinical Interest
Title
Extracellular Matrix Control of Cell and Growth Factor Function, multiple myeloma, diabetic complications, glaucoma
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 microenvironment. Ongoing studies are developing small molecule antagonists of the TSP1-TGF-beta pathway and evaluating the utility of these small molecules as therapeutics for the treatment of diabetic complications and to reduce osteolytic bone disease and improve immune balance in multiple myeloma. Recent studies showed that blockade of the TSP1-TGF-beta pathway reduces myeloma disease progression and osteolytic bone disease in pre-clinical models. In a collaboration with Southern Research, we are developing lead compounds to antagonize the TSP1-TGF-beta pathway for therapeutic applications in myeloma and other diseases. 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 calreticulin 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. We showed that calreticulin is important for vascular smooth muscle cell control of ECM after acute vascular injury and ongoing studies are addressing calreticulin's role in renal fibrosis in diabetes. We are also collaborating with researchers studying the biomechanical environment of the optic nerve head in glaucoma to explore mechanisms of ECM remodeling through the TSP1-TGF-beta pathway in this disease.

Selected Publications 
Publication PUBMEDID
Murphy-Ullrich JE. Thrombospondin-1 Signaling Through the Calreticulin/LDL
Receptor Related Protein 1 Axis: Functions and Possible Roles in Glaucoma. Front
Cell Dev Biol. 2022 May 27;10:898772. doi: 10.3389/fcell.2022.898772. 		 PMC9185677 
Zhang C, Xu X, Trotter TN, Gowda PS, Lu Y, Suto MJ, Javed A, Murphy-Ullrich
JE, Li J, Yang Y. Runx2 Deficiency in Osteoblasts Promotes Myeloma Resistance to
Bortezomib by Increasing TSP-1-Dependent TGFβ1 Activation and Suppressing
Immunity in Bone Marrow. Mol Cancer Ther. 2022 Feb;21(2):347-358. doi:
10.1158/1535-7163.MCT-21-0310. Epub 2021 Dec 14. 		 PMC8828708 
Lu A, Pallero MA, Owusu BY, Borovjagin AV, Lei W, Sanders PW, Murphy-Ullrich
JE. Calreticulin is important for the development of renal fibrosis and
dysfunction in diabetic nephropathy. Matrix Biol Plus. 2020 Apr 3;8:100034. doi:
10.1016/j.mbplus.2020.100034. PMID: 33543033 		 PMC7852315 
Suto MJ, Gupta V, Mathew B, Zhang W, Pallero MA, Murphy-Ullrich JE.
Identification of Inhibitors of Thrombospondin 1 Activation of TGF-beta. ACS Med
Chem Lett. 2020 May 7;11(6):1130-1136. doi: 10.1021/acsmedchemlett.9b00540.
PMID: 32550992; 		 PMC7294719 
Stenina-Adognravi O, Murphy-Ullrich J. The 2019 FASEB Science Research
Conference on Matricellular Proteins in Inflammation and Tissue Remodeling, July
14-19, 2019, Lisbon, Portugal. FASEB J. 2020 Apr;34(4):4825-4827. doi:
10.1096/fj.202000364. Epub 2020 Mar 13. 		 32167185 
Murphy-Ullrich JE. Thrombospondin 1 and Its Diverse Roles as a Regulator of Extracellular Matrix in Fibrotic Disease. J Histochem Cytochem. 2019 Sep;67(9):683-699.  31116066 
Wang L, Murphy-Ullrich JE, Song Y. Multiscale simulation of the interaction of
calreticulin-thrombospondin-1 complex with a model membrane microdomain. J Biomol
Struct Dyn. 2019 Feb;37(3):811-822. doi: 10.1080/07391102.2018.1433065. Epub 2018
Feb 15 		 29380675 
Prete A, Lo AS, Sadow PM, Bhasin SS, Antonello ZA, Vodopivec DM, Ullas S, Sims
JN, Clohessy J, Dvorak AM, Sciuto T, Bhasin M, Murphy-Ullrich JE, Lawler J,
Karumanchi SA, Nucera C. Pericytes Elicit Resistance to Vemurafenib and Sorafenib
Therapy in Thyroid Carcinoma via the TSP-1/TGFbeta1 Axis. Clin Cancer Res. 2018 Dec
1;24(23):6078-6097. doi: 10.1158/1078-0432.CCR-18-0693. Epub 2018 Aug 3. 		 PubMed PMID: 30076136 
Rebolledo DL, González D, Faundez-Contreras J, Contreras O, Vio CP,
Murphy-Ullrich JE, Lipson KE, Brandan E. Denervation-induced skeletal muscle
fibrosis is mediated by CTGF/CCN2 independently of TGF-β. Matrix Biol. 2019 Feb
1. pii: S0945-053X(18)30455-4. doi: 10.1016/j.matbio.2019.01.002. [Epub ahead of
print] 		 PubMed PMID: 30716392 
Sipes JM, Murphy-Ullrich JE, Roberts DD. Thrombospondins: Purification of
human platelet thrombospondin-1. Methods Cell Biol. 2018;143:347-369. doi:
10.1016/bs.mcb.2017.08.021. Epub 2017 Nov 6.  		 29310787 
Owusu BY, Zimmerman KA, Murphy-Ullrich JE. The role of the endoplasmic reticulum protein calreticulin in mediating TGF-β-stimulated extracellular matrix production in fibrotic disease. J Cell Commun Signal. 2018 Mar;12(1):289-299.  PMID: 29080087 
Murphy-Ullrich JE, Suto MJ. Thrombospondin-1 regulation of latent TGF-beta; activation: A therapeutic target for fibrotic disease. Matrix Biol. 2017 Dec 27. pii: S0945-053X(17)30359-1. doi: 10.1016/j.matbio.2017.12.009. [Epub ahead ofprint]   PMID: 29288716 
Lu A, Pallero MA, Lei W, Hong H, Yang Y, Suto MJ, Murphy-Ullrich JE.Inhibition of Transforming Growth Factor-β Activation Diminishes Tumor Progression and Osteolytic Bone Disease in Mouse Models of Multiple Myeloma. Am JPathol. 2016 Mar;186(3):678-90.  26801735 
Zimmerman KA, Xing D, Pallero MA, Lu A, Ikawa M, Black L, Hoyt KL, Kabarowski JH, Michalak M, Murphy-Ullrich JE. Calreticulin Regulates Neointima Formation and Collagen Deposition following Carotid Artery Ligation. J Vasc Res.
2015;52(5):306-20. 		 26910059 
Murphy-Ullrich JE, Sage EH. Revisiting the matricellular concept. Matrix Biol.
2014 Jul;37:1-14. doi: 10.1016/j.matbio.2014.07.005. Epub 2014 Jul 24.  		 25064829 
Zimmerman KA, Graham LV, Pallero MA, Murphy-Ullrich JE. Calreticulin regulates transforming growth factor-β-stimulated extracellular matrix production. J Biol Chem. 2013 May 17;288(20):14584-98. PMCID: PMC3656311.

 		 23564462 
Wang L, Murphy-Ullrich JE, Song Y. Molecular insight into the effect of lipid
bilayer environments on thrombospondin-1 and calreticulin interactions.
Biochemistry. 2014 Oct 14;53(40):6309-22. doi: 10.1021/bi500662v. Epub 2014 Sep
26.  		 25260145 
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 
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 
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 
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 
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 
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 
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 
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 
 

Keywords
atherosclerosis, diabetic complications, tumor microenvironment, multiple myeloma, osteolytic bone disease, glaucoma, fibrosis, TGF-beta, thrombospondin