Research in Dr. Trackman’s laboratory is focused on the regulation of extracellular matrix accumulation in mineralized and non-mineralized normal tissues, and in pathologies in which extracellular matrix accumulation is affected. Studies, which utilize cell culture, animal models, and human tissues, encompass a wide range of experimental approaches derived from the disciplines of biochemistry, enzymology, cell biology, and quantitative biology. Goals of these studies are to obtain a greater understanding of the molecular and cellular basis for gingival overgrowth and other fibrotic diseases, and to understand mechanisms of osteopenia that occurs as a complication of type I diabetes. Recent important findings show that oral fibroblasts are resistant to the effects of certain inflammatory factors, and that this resistance contributes to the elevated expression of connective tissue growth factor (CCN2/CTGF). This growth factor, in turn, contributes to gingival overgrowth and oral fibrosis. In addition, the biological process of epithelial to mesenchymal transition has been identified as a contributor to gingival overgrowth. These understandings provide new avenues for therapeutic approaches to prevent and treat gingival overgrowth.
The mechanism by which lysyl oxidase acts as a tumor suppressor is under investigation. Dr. Trackman’s laboratory has made the novel discovery that the tumor suppressor function of lysyl oxidase resides in the propeptide (LOX-PP) region of a proenzyme precursor. This propeptide is released from the proenzyme by extracellular proteolytic processing, and the released propeptide inhibits growth of tumor cells and tumor formation. A focus of the laboratory is to identify mechanisms by which the lysyl oxidase propeptide can suppress tumor formation or tumor growth and tumor metastasis. A major target of LOX-PP was found to be the fibroblast growth factor receptor-1 (FGFR1). Intracellular targets are now under investigation. A polymorphism in LOX-PP was found to have impaired ability to suppress tumors in mice, and is a risk factor for breast cancer in estrogen receptor-negative breast tumors in humans. rLOX-PP is effective as an inhibitor of tumor growth in xenograft models. Dr. Trackman’s laboratory works on this project in collaboration with the laboratories of Dr. Gail Sonenshein (Tufts University School of Medicine) and Dr. Kathrin Kirsch of Boston University School of Medicine, Department of Biochemistry. The potential use of LOX-PP as a pharmacologic agent has been submitted and is pending in the U.S. patent office; and preclinical studies continue.
- Director of Graduate Programs, Molecular & Cell Biology, Molecular & Cell Biology, Boston University Henry M. Goldman School of Dental Medicine
- Research Assistant Professor, Biochemistry, Boston University School of Medicine
- Mentor for Graduate Medical Students, Boston University School of Medicine, Division of Graduate Medical Sciences
- Boston University, PhD
- College of Wooster, BA
- Published on 7/3/2018
de la Cueva A, Emmerling M, Lim SL, Yang S, Trackman PC, Sonenshein GE, Kirsch KH. A polymorphism in the lysyl oxidase propeptide domain accelerates carcinogen-induced cancer. Carcinogenesis. 2018 Jul 03; 39(7):921-930. PMID: 29579155.
- Published on 5/1/2018
Saxena D, Mahjour F, Findlay AD, Mously EA, Kantarci A, Trackman PC. Multiple Functions of Lysyl Oxidase Like-2 in Oral Fibroproliferative Processes. J Dent Res. 2018 May 01; 22034518775971. PMID: 29787337.
- Published on 1/12/2018
Herzog CR, Berzins DW, DenBesten P, Gregory RL, Hargreaves KM, Messer RLW, Mina M, Mooney MP, Paine ML, Phillips C, Presland RB, Quivey RG, Scannapieco FA, Sheridan JF, Svoboda KKH, Trackman PC, Walker MP, Walker SG, Wang CY, Hu JCC. Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016. J Dent Res. 2018 May; 97(5):483-491. PMID: 29328868.
- Published on 10/30/2017
Trackman PC. Functional importance of lysyl oxidase family propeptide regions. J Cell Commun Signal. 2018 Mar; 12(1):45-53. PMID: 29086201.
- Published on 10/28/2017
Trackman PC, Bais MV. Measurement of lysyl oxidase activity from small tissue samples and cell cultures. Methods Cell Biol. 2018; 143:147-156. PMID: 29310775.
- Published on 7/22/2017
Bais MV, Kukuruzinska M, Trackman PC. Corrigendum to "Orthotopic non-metastatic and metastatic oral cancer mouse models" [Oral Oncol. 51(5) (2015) 476-482]. Oral Oncol. 2017 09; 72:201. PMID: 28743466.
- Published on 5/1/2017
Kim D, Mecham RP, Trackman PC, Roy S. Downregulation of Lysyl Oxidase Protects Retinal Endothelial Cells From High Glucose-Induced Apoptosis. Invest Ophthalmol Vis Sci. 2017 May 01; 58(5):2725-2731. PMID: 28538980.
- Published on 4/25/2017
Sánchez-Morgan N, Kirsch KH, Trackman PC, Sonenshein GE. UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells. J Cell Biochem. 2017 Aug; 118(8):2347-2356. PMID: 28106301.
- Published on 1/1/2017
Trackman PC, Saxena D, Bais MV. TGF-ß1- and CCN2-Stimulated Sirius Red Assay for Collagen Accumulation in Cultured Cells. Methods Mol Biol. 2017; 1489:481-485. PMID: 27734398.
- Published on 3/3/2016
Trackman PC. Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer. Expert Opin Ther Targets. 2016 Aug; 20(8):935-45. PMID: 26848785.
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