Paul J. Simmons, Ph.D. 1985, University of Manchester UT-Houston Institute of Molecular Medicine Center for Stem Cell Research Contact Information Biographical Sketch

Research Interests: stem cell biology; mesenchymal stem cells; hematopoiesis; cell adhesion molecules; stem cell mobilization; skeletal biology; monoclonal antibodies

The research in my laboratory is directed at studying the fundamental properties of stem cells and to translate their unique biological properties into novel cellular therapies for graft engineering and tissue regeneration for currently intractable disorders. Current studies focus on the characteristics and biological properties of hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) and in defining the cell and molecular composition of the respective niches for these two stem cell populations during ontogeny and in the adult skeleton. Additional studies focus on the identification of stem cells in the adult kidney, heart and lung as a means to develop novel cellular therapies for treatment of the many disorders that currently affect these organ systems. The laboratory makes extensive use of flow cytometry, microarray-based transcriptional profiling, the development of specific monoclonal antibodies and novel transplant assays as the means to identify and characterize stem cells in adult tissues.

A tutorial in my laboratory would provide experience in the isolation and characterization of stem cells from a range of adult tissues. This would incorporate use of multi-colour flow cytometric analysis and cell sorting; in vitro clonogenic assays; in vivo transplant models in mouse models; the development and application of monoclonal reagents to phenotypically and functionally dissect tissues as a means to identify stem cell populations.

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Selected Publications from a list of over 100 [journal impact factor; number times cited]:

Simmons, Przepiorka D, Thomas ED, Torok-Storb G (1987) Host origin of marrow stromal cells following allogeneic bone marrow transplantation. Nature, 328: 429-432. [30.979; 196]

Simmons PJ, Kaushansky K, Torok-Storb B (1990) Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells Proc. Natl. Acad. Sci. USA, 87: 1386-1390. [10.272; 142]

Simmons PJ, Torok-Storb B (1991) Identification of stromal cell precursors by a novel monoclonal antibody, STRO-1. Blood 78: 55-62. [10.120; 226]

Simmons PJ, Mazinovsky B, Longenecker BM, Berenson R, Torok-Storb B, Gallatin WM (1992) VCAM-1 expressed by bone marrow stromal cells mediates the binding of haemopoietic progenitor cells. Blood 80: 388-395. [10.120; 257]

Haylock DN, To LB, Dowse TL, Juttner CA, Simmons PJ (1992) Ex-vivo Expansion and maturation of peripheral blood CD34+ cells into the myeloid lineage. Blood 80: 1405-1412. [10.120; 307]

Lopez AF, Shannon MF, Barry S, Phillips JA, Cambareri B, Dottore M, Simmons P, Vadas MA (1992) A human interleukin-3 analog with increased biological and binding activities. Proc. Natl.Acad. Sci. ( USA), 89: 11842-11846. [10.272; 29]

Gronthos S, Ohta S, Graves S, Simmons PJ (1994) The STRO-1 + fraction of adult human bone marrow contains the osteoprogenitors. Blood 84: 4164-4173. [10.120; 131]

Gronthos S, Simmons PJ (1995) The growth factor requirements of STRO-1 + stromal precursors under serum-deprived conditions. Blood 85: 929-940. [10.120; 79]

Levesque J-P, Leavesley DI, Niutta S, Vadas M, Simmons PJ (1995) Cytokines increase human haemopoietic cell adhesiveness by activation of VLA-4 and VLA-5 integrins. J. Exp. Med. 181: 1805-1815. [4.012; 195]

Zannettino A, Raynor JA, Ashman LK, Gonda TJ, Simmons PJ (1996) A powerful new technique for isolating genes encoding cell surface antigens using retroviral expression cloning. J. Immunol. 156: 611-620. [6.702; 27]

Baird PN, Simmons PJ (1997) Expression of the Wilm’s tumour gene (WT1) in normal haemopoiesis. Exp. Hematol. 25: 312 - 320. [4.012; 59]

Haylock DN, Horsfall MJ, Dowse TL, Ramshaw HS, Niutta S, Protopsaltis S, Peng L, Burrel C, Rapold I, Buhring H-J, Simmons PJ (1997) Increased recruitment of haemopoietic progenitor cells underlies the ex vivo expansion potential of FLT3 ligand. Blood 90: 2260 - 2272. [10.120; 61]

To LB, Haylock DN, Simmons PJ, Juttner CA (1997) The Biology and clinical uses of blood stem cells. Blood 89: 2233 - 2258. [10.120; 342]

Filshie RJA, Zannettino, ACW, Gronthos S, Makrynikola V, Henniker AJ, Bendall LJ,Gottlieb DJ, Simmons PJ (1998) MUC-18, a member of the immunoglobulin superfamily is expressed by bone marrow fibroblasts and a subset of haematological malignancies. Leukaemia 12: 414 - 421. [5.116; 15]

Watt SM, Buhring H-J, Rappold I, Chan JY-H, Lee-Prudhoe J, Jones T, Zannettino ACW, Simmons PJ, Doyonnas R, Sheer D, Butler LH (1998) CD164, a novel sialomucin on CD34+ and erythroid subsets is located on human chromosome 6q21. Blood 92: 849 - 866. [10.120; 31]

Zannettino ACW, Buhring H-J, Niutta S, Watt S, Benton A, Simmons PJ (1998) The sialomucin CD164 (MGC-24v) is an adhesive glycoprotein expressed by human hematopoietic progenitors and bone marrow stromal cells which serves as a potent negative regulator of hematopoiesis. Blood 92: 2613 - 2628. [10.120; 53]

Gronthos S, Zannettino ACW, Graves SE, Ohta S, Hay SJ, Simmons PJ (1999) Differential cell surface expression of the STRO-1 and alkaline phosphatase antigens on discrete developmental stages in primary cultures of human bone cells. J. Bone Min. Res 14:47-56. [6.225; 52]

Levesque J-P, Zannetino ACW, Pudney M, Haylock DN, Niutta S, Kansas GS, Snapp KR, Berndt MC, Simmons PJ (1999) PSGL-1 mediated adhesion of human haemopoietic progenitors to P-selectin results in the suppresion of haemopoiesis. Immunity 11: 369 - 378. [16.016; 50]

Chan JY, Lee-Prudhoe JE, Jorgensen B, Ihrke G, Doyonnas R, Zannettino AC, Buckle VJ, Ward CJ, Simmons PJ, Watt SM (2001) Relationship between novel isoforms, functionally important domains and subcellular distribution of CD164/endolyn. J. Biol. Chem. 276:2139-2152. [6.482; 13]

Levesque J-P, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ (2001) VCAM-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood 98:1289-1297 [10.120; 21]

Ramshaw HS, Haylock DN, Swart B, Gronthos S, Horsfall MJ, Niutta S, Simmons PJ (2001) Monoclonal antibody BB9 raised against marrow stromal cells identifies a cell surface glycoprotein expressed by primitive human haematopoietic progenitors. Exp Hematol 29:981-992 [4.012; 0]

Short B, Brouard N, Driessen R, Simmons PJ (2001) Prospective isolation of stromal progenitor cells from mouse compact bone. Cytotherapy 3:407-408. [0.832: 1]

Lévesque J-P, Bendall LJ, Hendy J, Williams B, Simmons PJ (2003) Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 111:187-196. [14.30, 60]

Nilsson SK, Haylock DN, Johnston HM, Occhiodoro-Scott T, Simmons PJ (2003) Hyaluronan is synthesised by primitive hemopoietic cells, participates in their lodgement at the endosteum following transplantation and is involved in the regulation of their proliferation and differentiation in vitro. Blood 101:856-862. [10.120; 10]

Lévesque J-P, Hendy J, Winkler IG, Takamatsu Y, Simmons PJ (2003) Granulocyte colony-stimulating factor induces the release in the bone marrow of proteases that cleave c-KIT receptor (CD117) from the surface of hematopoietic progenitor cells. Exp Hematol. 31:109-117. [4.012; 12]

Gronthos S, Zannettino AC, Hay SJ, Shi S, Graves SE, Kortesidis A, Simmons PJ (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci. 116: 1827-1835. [7.250; 32]

Prince HM, Simmons PJ, Whitty G, Wall DP, Barber L, Toner GC, Seymour JF, Richardson G, Mrongovius R, Haylock DN (2004) Improved haematopoietic recovery following transplantation with ex vivo-expanded mobilized blood cells. Br J Haematol. 126: 536–545. [3.267; 0]

Nilsson SK, Simmons PJ (2004) Transplantable stem cells: home to specific niches. Curr Opin Hematol. 11:102-106. [4.449; 3]

Levesque J-P, Liu F, Simmons PJ, Betsuyaku T, Senior RM, Pham C, Link DC (2004) Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood 104: 65-72. [10.120; 5]

Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN (2005) Osteopontin, a key component of the hematopoietic stem cell niche and negative regulator of primitive hematopoietic progenitor cells. Blood (prepublished online April 21, 2005; DOI 10.1182/blood-2004-11-4422)). [10.120; 0]