Robert M. Strieter

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Primary Appointment

Professor, Medicine

Research Interests

Cytokine and Chemokine Biology As Related to Human Diseases

Research Description

Our laboratory is interested in cytokine and chemokine biology as it relates to a variety of human diseases. We are currently investigating the role of a variety of cytokines (i.e., early response, Th1, and Th2) and CXC, CC, C, and CX 3C chemokines in mediating inflammatory and immunologically mediated disease processes. Our laboratory is interested in the mechanisms of how CXC chemokines modulate angiogenesis and metastases of cancer; and promotes vascular remodeling in fibroproliferative disorders. Our laboratory was the first to discover that the CXC chemokine family can behave as either promoters or inhibitors of angiogenesis. We have determined that on a structural/functional basis the domain of three amino acids (Glu-Leu-Arg; ELR motif) that immediately precedes the first cysteine amino acid residue of the primary structure of these cytokines, dictates their function in regulating angiogenesis. Members of the CXC chemokine family that contain the ELR motif (ELR+) are angiogenic, whereas members that lack the ELR motif (ELR-) and are induced by interferons inhibit the angiogenic activity induced by either ELR+ CXC chemokines, bFGF, or VEGF. Furthermore, others and we have determined that specific chemokine receptors are involved in this disparate angiogenic activity. Our laboratory is interested in mesenchymal progenitor cell trafficking during inflammation and resolution of injury. We are one of the first groups to show that these cells can contribute to the fibroproliferative phase of lung injury. We are expanding these findings to include understanding mechanisms of mesenchymal stem cell plasticity that may be relevant for pathogenesis of obesity. We have found that a circulating progenitor epithelial cell is necessary for repair of injury related to the airway or lung parenchyma epithelium. Our laboratory is interested in the role of cytokines/chemokines in mediating acute and chronic lung allograft rejection. We are one of the few laboratories in the country that has operative an orthotopic single lung transplantation model in rat. Our laboratory uses a variety of strategies that include molecular, cellular, animal models, and human tissue specimens to examine the biology of chemokines in the regulation of innate and adaptive immunity, angiogenesis, and progenitor cell trafficking in a variety of model systems relevant to human disease.

Personal Statement

Our laboratory is interested in cytokine and chemokine biology as it relates to a variety of human diseases. We are currently investigating the role of a variety of cytokines (i.e., early response, Th1, and Th2) and CXC, CC, C, and CX 3C chemokines in mediating inflammatory and immunologically mediated disease processes. Our laboratory is interested in the mechanisms of how CXC chemokines modulate angiogenesis and metastases of cancer; and promotes vascular remodeling in fibroproliferative disorders. Our laboratory was the first to discover that the CXC chemokine family can behave as either promoters or inhibitors of angiogenesis. We have determined that on a structural/functional basis the domain of three amino acids (Glu-Leu-Arg; ELR motif) that immediately precedes the first cysteine amino acid residue of the primary structure of these cytokines, dictates their function in regulating angiogenesis. Members of the CXC chemokine family that contain the ELR motif (ELR+) are angiogenic, whereas members that lack the ELR motif (ELR-) and are induced by interferons inhibit the angiogenic activity induced by either ELR+ CXC chemokines, bFGF, or VEGF. Furthermore, others and we have determined that specific chemokine receptors are involved in this disparate angiogenic activity. Our laboratory is interested in mesenchymal progenitor cell trafficking during inflammation and resolution of injury. We are one of the first groups to show that these cells can contribute to the fibroproliferative phase of lung injury. We are expanding these findings to include understanding mechanisms of mesenchymal stem cell plasticity that may be relevant for pathogenesis of obesity. We have found that a circulating progenitor epithelial cell is necessary for repair of injury related to the airway or lung parenchyma epithelium. Our laboratory is interested in the role of cytokines/chemokines in mediating acute and chronic lung allograft rejection. We are one of the few laboratories in the country that has operative an orthotopic single lung transplantation model in rat. Our laboratory uses a variety of strategies that include molecular, cellular, animal models, and human tissue specimens to examine the biology of chemokines in the regulation of innate and adaptive immunity, angiogenesis, and progenitor cell trafficking in a variety of model systems relevant to human disease.

Selected Publications

Hou Y, Wu Y, Farooq SM, Guan X, Wang S, Liu Y, Oblak JJ, Holcomb J, Jiang Y, Strieter RM, Lasley RD, Arbab AS, Sun F, Li C, Yang Z, A critical role of CXCR2 PDZ-mediated interactions in endothelial progenitor cell homing and angiogenesis., 2015; Stem cell research. 14(2) 133-43. PMID: 25622052

Choi YH, Burdick MD, Strieter BA, Mehrad B, Strieter RM, CXCR4, but not CXCR7, discriminates metastatic behavior in non-small cell lung cancer cells., 2013; Molecular cancer research : MCR. 12(1) 38-47. PMID: 24025971 | PMCID: PMC4262747

Mehrad B, Strieter RM, Fibrocytes and the pathogenesis of diffuse parenchymal lung disease., 2012; Fibrogenesis & tissue repair. 5() S22. PMID: 23259468 | PMCID: PMC3368792

Keeley EC, Mehrad B, Strieter RM, The role of fibrocytes in fibrotic diseases of the lungs and heart., 2011; Fibrogenesis Tissue Repair. 4(0) 2.0. PMID: | PMCID: PMC3027110

Dengel LT, Norrod AG, Gregory BL, Clancy-Thompson E, Burdick MD, Strieter RM, Slingluff Jr, Mullins DW, Interferons induce CXCR3-cognate chemokine production by human metastatic melanoma., 2010; J Immunother. 33(9) 965-74. PMID: | PMCID: NIHMS253549

Crawford MA, Burdick MD, Glomski IJ, Boyer AE, Barr JR, Mehrad B, Strieter RM, Hughes MA, Interferon-inducible CXC chemokines directly contribute to host defense against inhalational anthrax in a murine model of infection., 2010; PLoS Pathog. 6(11) e1001199. PMID: | PMCID: PMC2987825

Keeley EC, Mehrad B, Strieter RM, Chemokines as mediators of tumor angiogenesis and neovascularization., 2010; Exp Cell Res. 0(0) null. PMID:

Choi YH, Burdick MD, Strieter RM, Human circulating fibrocytes have the capacity to differentiate osteoblasts and chondrocytes., 2010; Int J Biochem Cell Biol. 42(5) 662-71. PMID: | PMCID: PMC2835809

Keeley EC, Mehrad B, Strieter RM, Fibrocytes: bringing new insights into mechanisms of inflammation and fibrosis., 2010; Int J Biochem Cell Biol. 42(4) 535-42. PMID: | PMCID: PMC2835833

Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, Strieter RM, Rosin DL, Okusa MD, IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury., 2010; J Clin Invest. 120(1) 331-42. PMID: | PMCID: PMC2798679

Keeley EC, Mehrad B, Strieter RM, The role of circulating mesenchymal progenitor cells (fibrocytes) in the pathogenesis of fibrotic disorders., 2009; Thromb Haemost. 101(4) 613-8. PMID:

Mehrad B, Burdick MD, Strieter RM, Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis., 2009; Int J Biochem Cell Biol. 41(8) 1708-18. PMID: | PMCID: PMC2681415

Wallace KL, Marshall MA, Ramos SI, Lannigan JA, Field JJ, Strieter RM, Linden J, NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-gamma and CXCR3 chemokines., 2009; Blood. 114(3) 667-76. PMID: | PMCID: PMC2713467

Park SJ, Hughes MA, Burdick M, Strieter RM, Mehrad B, Early NK cell-derived IFN-{gamma} is essential to host defense in neutropenic invasive aspergillosis., 2009; J Immunol. 182(7) 4306-12. PMID:

Crawford MA, Zhu Y, Green CS, Burdick MD, Sanz P, Alem F, O'Brien AD, Mehrad B, Strieter RM, Hughes MA, Antimicrobial effects of interferon-inducible CXC chemokines against Bacillus anthracis spores and bacilli., 2009; Infect Immun. 77(4) 1664-78. PMID: | PMCID: PMC2663164

Keeley EC, Mehrad B, Strieter RM, Chemokines as mediators of neovascularization., 2008; Arterioscler Thromb Vasc Biol. 28(11) 1928-36. PMID: | PMCID: PMC2735456

Strieter RM, Out of the shadows: CXC chemokines in promoting aberrant lung cancer angiogenesis., 2008; Cancer Prev Res (Phila). 1(5) 305-7. PMID: | PMCID: PMC2614299

Strieter RM, What differentiates normal lung repair and fibrosis? Inflammation, resolution of repair, and fibrosis., 2008; Proc Am Thorac Soc. 5(3) 305-10. PMID: | PMCID: PMC2645241

Mehrad B, Keane MP, Gomperts BN, Strieter RM, Circulating progenitor cells in chronic lung disease., 2007; Expert Rev Respir Med. 1(1) 157-65. PMID:

Mehrad B, Keane MP, Strieter RM, Chemokines as mediators of angiogenesis., 2007; Thromb Haemost. 97(5) 755-62. PMID:

Strieter RM, Gomperts BN, Keane MP, The role of CXC chemokines in pulmonary fibrosis., 2007; J Clin Invest. 117(3) 549-56. PMID: | PMCID: PMC1804376

Mehrad B, Burdick MD, Zisman DA, Keane MP, Belperio JA, Strieter RM, Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease., 2007; Biochem Biophys Res Commun. 353(1) 104-8. PMID:

Strieter RM, Keeley EC, Burdick MD, Mehrad B, The role of circulating mesenchymal progenitor cells, fibrocytes, in promoting pulmonary fibrosis., ; Trans Am Clin Climatol Assoc. 120(0) 49-59. PMID: | PMCID: PMC2744511

Lapar DJ, Burdick MD, Emaminia A, Harris DA, Strieter BA, Liu L, Robbins M, Kron IL, Strieter RM, Lau CL, Circulating fibrocytes correlate with bronchiolitis obliterans syndrome development after lung transplantation: a novel clinical biomarker., ; Ann Thorac Surg. 92(2) 470-7. PMID:

Keeley EC, Moorman JR, Liu L, Gimple LW, Lipson LC, Ragosta M, Taylor AM, Lake DE, Burdick MD, Mehrad B, Strieter RM, Plasma chemokine levels are associated with the presence and extent of angiographic coronary collaterals in chronic ischemic heart disease., ; PLoS One. 6(6) e21174. PMID: | PMCID: PMC3120847

Lapar DJ, Burdick MD, Emaminia A, Harris DA, Strieter BA, Liu L, Robbins M, Kron IL, Strieter RM, Lau CL, Circulating fibrocytes correlate with bronchiolitis obliterans syndrome development after lung transplantation: a novel clinical biomarker., ; Ann Thorac Surg. 92(2) 470-7. PMID:

Keeley EC, Mehrad B, Strieter RM, CXC chemokines in cancer angiogenesis and metastases., ; Adv Cancer Res. 106(0) 91-111. PMID: