Elizabeth O. Davis, Ph.D.
Department of Pediatrics
Section of Hematology-Oncology,
Baylor College of Medicine
Ph.D., University of Rochester, Rochester, NY
Dr. Olmsted-Davis’s research program encompasses the design of a cell based gene therapy system for targeted production of bone. One of the therapeutic goals for this system is to enhance bone repair both in long bone fractures, as well as offer a potential treatment for critical size defects resulting from bone trauma. These clinical problems are difficult challenges to orthopedic surgeons resulting in the need to introduce additional hardware or bone graft, and often in the case of trauma, result in the loss of the limb altogether. Our system is designed to rapidly form bone within two weeks after a single injection of our gene therapy system, thus significantly reducing both complications from potential infection as well as overall recovery time. This work is currently supported by the DOD-orthopedic trauma research program.
A second approach for the treatment of critical size defects is to tissue engineer the bone within a bioreactor which could then later be engrafted into the defect area. This work is a collaborative effort between our laboratory and several others within the Center for Cell and Gene Therapy, and Baylor College of Medicine. Our contribution to this project is to characterize the normal physiological processes of de novo bone formation. Using our gene therapy model, we have identified a novel stem cell population and characterized the micro-environmental signals that eventually lead to stem cell differentiation into cartilage and bone. This work is currently funded by the NIBIB.
The third focus of the laboratory is to develop a non-invasive approach for spine fusion. This project has been ongoing over the past three years and has resulted in an efficacious injectable system that results in fusion of the vertebral bones. We are currently completing the efficacy testing in rodent models. Once animal testing is completed, we propose to translate this project into a tentative clinical trial. This work is supported by the DOD-PRMRP.
Dr. Olmsted-Davis has also been involved with establishing a Vector Development Laboratory, a non-profit core facility at Baylor College of Medicine, which provides gene therapy vectors for use as gene delivery systems for preclinical and basic research. This organization has aided researchers in both the Texas Medical Center as well as the global research community.
- Bikram M, Fouletier-Dilling C, Hipp JA, Gannon F, Davis AR, Olmsted-Davis EA, West JL. Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells. Ann Biomed Eng. 2007 May;35(5):796-807.
- Fouletier-Dilling CM, Gannon FH, Olmsted-Davis EA, Lazard Z, Heggeness MH, Shafer JA, Hipp JA, Davis AR. Efficient and rapid osteoinduction in an immune-competent host. Hum Gene Ther. 2007 Aug;18(8):733-45.
- Olmsted-Davis E, Gannon FH, Ozen M, Ittmann MM, Gugala Z, Hipp JA, Moran KM, Fouletier-Dilling CM, Schumara-Martin S, Lindsey RW, Heggeness MH, Brenner MK, Davis AR. Hypoxic adipocytes pattern early heterotopic bone formation. Am J Pathol. 2007 Feb;170(2):620-32.
- Shafer J, Davis AR, Gannon FH, Fouletier-Dilling CM, Lazard Z, Moran K, Gugala Z, Ozen M, Ittmann M, Heggeness MH, Olmsted-Davis E. Oxygen tension directs chondrogenic differentiation of myelo-monocytic progenitors during endochondral bone formation. Tissue Eng. 2007 Aug;13(8):2011-9.
- Fouletier-Dilling CM, Bosch P, Davis AR, Shafer JA, Stice SL, Gugala Z, Gannon FH, Olmsted-Davis EA. Novel compound enables high-level adenovirus transduction in the absence of an adenovirus-specific receptor. Hum Gene Ther. 2005 Nov;16(11):1287-97.
- Dacquin R, Mee PJ, Kawaguchi J, Olmsted-Davis EA, Gallagher JA, Nichols J, Lee K, Karsenty G, Smith A. Knock-in of nuclear localised beta-galactosidase reveals that the tyrosine phosphatase Ptprv is specifically expressed in cells of the bone collar. Dev Dyn. 2004 Apr;229(4):826-34.
- Gugala Z, Olmsted-Davis EA, Gannon FH, Lindsey RW, Davis AR. Osteoinduction by ex vivo adenovirus-mediated BMP2 delivery is independent of cell type. Gene Ther. 2003 Aug;10(16):1289-96.
- Olmsted-Davis EA, Gugala Z, Camargo F, Gannon FH, Jackson K, Kienstra KA, Shine HD, Lindsey RW, Hirschi KK, Goodell MA, Brenner MK, Davis AR. Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15877-82.
- Olmsted EA, Kaplan FS, Shore EM. Bone morphogenetic protein-4 regulation in fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 2003 Mar;(408):331-43.
- Olmsted-Davis EA, Gugala Z, Gannon FH, Yotnda P, McAlhany RE, Lindsey RW, Davis AR. Use of a chimeric adenovirus vector enhances BMP2 production and bone formation. Hum Gene Ther. 2002 Jul 20;13(11):1337-47.
- Olmsted EA, Blum JS, Rill D, Yotnda P, Gugala Z, Lindsey RW, Davis AR. Adenovirus-mediated BMP2 expression in human bone marrow stromal cells. J Cell Biochem. 2001 Apr 2-27;82(1):11-21.
- Yeh GL, Mathur S, Wivel A, Li M, Gannon FH, Ulied A, Audi L, Olmstead EA, Kaplan FS, Shore EM. GNAS1 mutation and Cbfa1 misexpression in a child with severe congenital platelike osteoma cutis. J Bone Miner Res. 2000 Nov;15(11):2063-73.
- Lanchoney TF, Olmsted EA, Shore EM, Gannon FA, Rosen V, Zasloff MA, Kaplan FS. Characterization of bone morphogenetic protein 4 receptor in fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 1998 Jan;(346):38-45.
- Olmsted EA, Gannon FH, Wang ZQ, Grigoriadis AE, Wagner EF, Zasloff MA, Shore EM, Kaplan FS. Embryonic overexpression of the c-Fos protooncogene. A murine stem cell chimera applicable to the study of fibrodysplasia ossificans progressiva in humans. Clin Orthop Relat Res. 1998 Jan;(346):81-94.
- Gannon FH, Kaplan FS, Olmsted E, Finkel GC, Zasloff MA, Shore E. Bone morphogenetic protein 2/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva. Hum Pathol. 1997 Mar;28(3):339-43.
- Mauro LJ, Olmsted EA, Davis AR, Dixon JE. Parathyroid hormone regulates the expression of the receptor protein tyrosine phosphatase, OST-PTP, in rat osteoblast-like cells. Endocrinology. 1996 Mar;137(3):925-33.
- Mauro LJ, Olmsted EA, Skrobacz BM, Mourey RJ, Davis AR, Dixon JE. Identification of a hormonally regulated protein tyrosine phosphatase associated with bone and testicular differentiation. J Biol Chem. 1994 Dec 2;269(48):30659-67.