The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Paul J. Simmons, Ph.D.

Paul J. Simmons, Ph.D.

Adjunct Professor

Paul.J.Simmons@uth.tmc.edu

713-500-3427

Dr. Simmons serves as Adjunct Professor for the Stem Cell Research at the Brown Foundation Institute of Molecular Medicine. He is also President of the International Society for Stem Cell Research (ISSCR) www.isscr.org.

Education & Training: Dr. Simmons graduated from Queen Elizabeth College, University of London, UK with a B.Sc Hons majoring in Cell Biology. In 1985 he received his Ph.D. from the University of Manchester, UK where his research focused on understanding the nature of the stromal cell microenvironment responsible for regulating the growth and differentiation of hematopoietic cells in long-term bone marrow cultures. These studies were guided by Drs. Terry Allen and Mike Dexter, FRS. Postdoctoral research (1985-86) was initially in the lab of Dr RK Humphries, Department of Molecular Genetics, Terry Fox Laboratory, BC Cancer Research Center, Vancouver, BC, Canada and subsequently (1986-1990) in the Department of Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA in the lab of Dr Beverly Torok-Storb.

Professional Experience: Dr Simmons began his academic career as the inaugural R.L. Clifford Fellow in Experimental Haematology (1990-94) in the Division of Haematology, Hanson Center for Cancer Research (HCCR), IMVS, Adelaide, Australia. He was appointed a Member (Professorial equivalent) of the HCCR and promoted to the position of Chief Hospital Scientist (tenured) from 1995-1999. In 1999 Dr Simmons was recruited to the Peter MacCallum Cancer Center (Peter Mac) in Melbourne Australia as Program Head in Stem Cell Biology. From 2003 until his recruitment to the Brown Foundation Institute of Molecular Medicine, UTHSC-Houston in December 2006, Dr Simmons also held the position of Director of the Adult Stem Cell Platform of the Australian Stem Cell Center (ASCC).

Editorial Boards & Committees. Dr. Simmons is or has served as Associate Editor on multiple journals in the field of stem cell biology including Experimental Hematology, Cytotherapy and Stem Cell Research and is on the editorial boards of Cell, Stem Cell, Blood and Stem Cells. Dr. Simmons serves regularly as a reviewer for PNAS, Science, Journal of Clinical Investigation and various of the Nature periodicals amongst others. He is currently Scientific Advisor to the Spinal Cord Society of Australia (SCSA; stepahead.org.au). Prior to his appointment at the IMM, Dr Simmons was a member of Gene and Related Therapies Advisory Panel (GTRAP), an expert committee of the National Health and Medical Research Council (NHMRC) that provides advice to the Australian Government on human cellular therapies, gene and related therapies and xenotransplantation.

Current Research Projects. The major focus of Dr Simmons' research for many years has been to utilise the paradigm of the hematopoietic system as a model to understand the mechanisms that contribute to the extrinsic regulation of stem cells in adult organs by the tissue microenvironment (stem cell niche) in which the stem cells reside. Dr Simmons has received international recognition for his pioneering contributions to basic haemopoiesis research and has an unbroken track record of excellence in this field. Current studies in his lab 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 lung as a means to develop novel cellular therapies for treatment of the many disorders that currently affect the respiratory system and the application of MSC as a cell therapy for the treatment of spinal cord injury. 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.

Selected Publications. The following are taken from a list of over 120 papers and chapters and 10 issued US and International patents:

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.

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

Levesque J-P., Leavesley D.I., Niutta S., Vadas M., Simmons P.J (1995). Cytokines increase human haemopoietic cell adhesiveness by activation of VLA-4 and VLA-5 integrins. J. Exp. Med. 181: 1805-1815.

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.

Li A, Simmons PJ, Kaur P (1998). Identification and isolation of candidate human keratinocyte stem cells based on surface phenotype. Proc. Natl. Acad. Sci. (USA) 95: 3902 - 3907.

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.

Buhring H-J, Simmons PJ, Pudney M, Muller R, Jarrossay D, van Agthoven A, Brugger W, Valent P, Kanz L (1999). The monoclonal antibody 97A6 defines a novel surface antigen expressed on human basophils and their multi- and unipotent progenitors. Blood 94: 2343 - 2356.

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.

Corbeil D, Roper K, Hellwig A, Tavian M, Miraglia S, Watt S, Simmons PJ, Peault B, Buck DW, Huttner W (2000). Human AC133 hematopoietic stem cell antigen, like mouse prominin, is expressed on plasma membrane protrusions of epithelial and non-epithelial cells. J. Biol. Chem 275: 5512 - 5520.

Simmons PJ, Levesque J-P, Haylock DN (2001). Mucin-like molecules as modulators of the survival and proliferation of primitive hematopoietic cells. Ann NY Acad Sci 938:196-206.

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

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.

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.

Winkler IG, Snapp KR, Simmons PJ, Lévesque J-P (2004). Adhesion to E-selectin promotes growth inhibition and apoptosis of human and murine hematopoietic progenitor cells independent of PSGL-1. Blood 103:1685-92.

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 106:1232-1239

Lepore DA, Jokubaitis VJ, Simmons PJ, Roeszler KN, Rossi R, Bauer K, Thomas PQ (2006) A role for angiotensin-converting enzyme in the characterization, enrichment and proliferation potential of adult murine pituitary colony-forming cells. Stem Cells 24:2382-2390.

Haylock DN, Williams B, Johnston HM, Liu MC, Rutherford KE, Whitty GA, Simmons PJ, Bertoncello I, Nilsson SK (2007). Hemopoietic stem cells with higher hemopoietic potential reside at the bone marrow endosteum. Stem Cells. 2007 Apr;25(4):1062-1069.

Zambidis E, Sinka L, Tavian M, Jokubaitis V, Park TS, Simmons PJ, Peault B (2007). Emergence of human angio-hematopoietic cells in normal development and from cultured embryonic stem cells. Ann N Y Acad Sci. Mar 14; [Epub ahead of print]