Mary C. Farach-Carson, Ph.D.

Research Interests

Research in Dr. Farach-Carson's laboratory relates to the role of extracellular matrix in the progression of cancer following metastasis from primary sites, such as prostate or breast, to bone. In many cases, primary tumors are fairly slow growing and do not become life-threatening until they form tumors in bone. The growth factors sequestered in bone matrix provide a very rich environment to promote the growth of cancer cells that invade there. Many of these growth factors are bound to a class of proteoglycans that contain heparan sulfate which regulate their bioactivity. Studies in the laboratory are aimed at identifying and isolating the growth factors responsible for cancer growth and progression with the long term aim of developing "molecular drugs" to combat cancer metastasis. Three dimensional models are used to study the behavior of cancer cells and to test their susceptibility to anti-cancer drugs that reduce cancer growth and progression. Industrial partnerships support the development of novel cancer diagnostics based on the principle that cancer biomarkers are created by cancer growth in bone.

A multidisciplinary project involves the use of proteoglycans, particularly those bearing heparan sulfate chains such as perlecan, in engineering of connective tissues such as bone, cartilage or salivary gland. Cell and molecular engineering strategies are being developed that facilitate controlled tissue growth and differentiation. Growth factor binding and delivery by engineered proteoglycans is being used in oral surgery and orthopaedic applications. Several engineering partnerships both within and outside the university exist to support these studies.

A trainee doing research in this laboratory would be exposed to a variety of techniques including cell culture, recombinant and natural protein purification and analysis, cloning and molecular biology, microRNAs, immunodetection and immunohistochemistry, and various pre-clinical cancer models.

Current Projects

• NIH, Heparan Sulfate Proteoglycans in Bone Stromal Metastasis (with Leland Chung, Cedars Sinai).
• NIH, Perlecan and Heparanase in Cartilage Growth and Healing (with Catherine Kirn-Safran)

Research Group

• Chu Zhang, Ph.D. - Research Associate III (Ph.D., University of Delaware). Studying the biological function of perlecan in apoptosis of prostate cancer cells and biological interactions between osteoblasts and prostate cancer cells at sites of bony metastases; using microarray analysis to characterize phenotypic changes in prostate cancer cells at sites of bony metastasis. (Research Coordinator, CTCR)
• Lisa Gurski, B.S. - Graduate Student (B.S., Boston College). Development of 3-D systems for study of metastatic cancer cells (with Dr. Kenneth van Golen).
• Swati Pradhan, B.S. - Graduate Student (B.S., University of Delaware). Tissue engineering of a human salivary gland (with Dr. Robert Witt).
• William Thompson, B.S. - Graduate Student (B.S., Lee University). Studying the role of perlecan and other candidate extracellular matrix molecules in the transmission of mechanical stimuli among osteocytes in bone.

Selected Publications

• Alcorn JL, Merritt TM, Farach-Carson MC, Wang HH, Hecht JT. Ribozyme-mediated reduction of wild-type and mutant cartilage oligomeric matrix protein (COMP) mRNA and protein. RNA. 2009;15(4):686–695.
• Chung S-W, Miles FL, Sikes RA, Cooper CR, Farach-Carson MC, Ogunnaike BA. Quantitative modeling and analysis of the transforming growth factor beta signaling pathway. Biophys J. 2009;96(5):1733–1750.
• Gurski LA, Jha AK, Zhang C, Jia X, Farach-Carson MC. Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells. Biomaterials. 2009;30(30):6076–6085.
• Hartman O, Zhang C, Adams EL, et al. Microfabricated Electrospun Collagen Membranes for 3-D Cancer Models and Drug Screening Applications. Biomacromolecules. 2009:in press.
• Kirn-Safran C, Farach-Carson MC, Carson DD. Multifunctionality of extracellular and cell surface heparan sulfate proteoglycans. Cell Mol Life Sci. 2009:in press.
• O'Connor RD, Zayzafoon M, Farach-Carson MC, Schanen NC. Mecp2 deficiency decreases bone formation and reduces bone volume in a rodent model of Rett syndrome. Bone. 2009;45(2):346–356.
• Opdenaker LM, Farach-Carson MC. Rapamycin selectively reduces the association of transcripts containing complex 5' UTRs with ribosomes in C4-2B prostate cancer cells. J Cell Biochem. 2009;107(3):473–481.
• Oristian DS, Sloofman LG, Zhou X, Wang L, Farach-Carson MC, Kirn-Safran CB. Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice. J Orthop Res. 2009;27(1):28–35.
• Pradhan S, Zhang C, Jia X, Carson D, Witt RL, Farach-Carson MC. Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro. Tissue Eng Part A. 2009:in press.
• Shao Y, Czymmek KJ, Jones PA, et al. Dynamic interactions between L-type voltage sensitive calcium channel (VSCC) Cav1.2 ({alpha}1C) subunits and ahnak in osteoblastic cells. Am J Physiol Cell Physiol. 2009;296(5):C1067–C1078.
• Sisson K, Zhang C, Farach-Carson MC, Chase DB, Rabolt JF. Evaluation of Cross-Linking Methods for Electrospun Gelatin on Cell Growth and Viability. Biomacromolecules. 2009:in press.
• Brown AJ, Alicknavitch M, D'Souza SS, et al. Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation. Bone. 2008;43(4):689–699.
• Cooper CR, Graves B, Pruitt F, et al. Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha. J Cell Biochem. 2008;104(6):2298–2309.
• D'Souza S, Yang W, Marchetti D, Muir C, Farach-Carson MC, Carson DD. HIP/RPL29 antagonizes VEGF and FGF2 stimulated angiogenesis by interfering with HS-dependent responses. J Cell Biochem. 2008;105(5):1183–1193.
• D'Souza SS, Fazleabas AT, Banerjee P, et al. Decidual heparanase activity is increased during pregnancy in the baboon (Papio anubis) and in in vitro decidualization of human stromal cells. Biol Reprod. 2008;78(2):316–323.
• Farach-Carson MC, Brown AJ, Lynam M, Safran JB, Carson DD. A novel peptide sequence in perlecan domain IV supports cell adhesion, spreading and FAK activation. Matrix Biol. 2008;27(2):150–160.
• Casper CL, Yang W, Farach-Carson MC, Rabolt JF. Coating electrospun collagen and gelatin fibers with perlecan domain I for increased growth factor binding. Biomacromolecules. 2007;8(4):1116–1123.
• Chen Q, Sivakumar P, Barley C, et al. Potential role for heparan sulfate proteoglycans in regulation of transforming growth factor-beta (TGF-beta) by modulating assembly of latent TGF-beta-binding protein-1. J Biol Chem. 2007;282(36):26418–26430.
• D'Souza SS, Daikoku T, Farach-Carson MC, Carson DD. Heparanase expression and function during early pregnancy in mice. Biol Reprod. 2007;77(3):433–441.
• Farach-Carson MC, Carson DD. Perlecan--a multifunctional extracellular proteoglycan scaffold. Glycobiology. 2007;17(9):897–905.
• O'Connor JC, Farach-Carson MC, Schneider CJ, Carson DD. Coculture with prostate cancer cells alters endoglin expression and attenuates transforming growth factor-beta signaling in reactive bone marrow stromal cells. Mol Cancer Res. 2007;5(6):585–603.
• Rohe B, Safford SE, Nemere I, Farach-Carson MC. Regulation of expression of 1,25D3-MARRS/ERp57/PDIA3 in rat IEC-6 cells by TGF beta and 1,25(OH)2D3. Steroids. 2007;72(2):144–150.
• Yeo H, Beck LH, Thompson SR, et al. Conditional disruption of calcineurin B1 in osteoblasts increases bone formation and reduces bone resorption. J Biol Chem. 2007;282(48):35318–35327.