Ralph and Dorothy Looney Professor of Biochemistry and Cell Biology
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, calcium imaging, cloning and molecular biology, microRNAs, immunodetection and immunohistochemistry, and various pre-clinical cancer models.
Chen, J., Lobachev, K.S., Grindel, B.J., Farach-Carson, M.C., Olivares-Navarrette, R., Doroudi, M., Boyan, B.D., Schwartz, Z. Chaperone properties of Pdia3 participate in rapid plasma membrane associated actions of 1α,25-dihydroxyvitamin D3 . Molecular Endocrinology, 27 2013 Jul: 1065-77
Fong, E.L.S., Lamhamedi-Cherradi, S.E., Burdett, E., Ramamoorthy, V., Lazar, A.,
Kasper, F.K., Farach-Carson, M.C., Vishwamitra, D., Demicco, E.G., Menegaz, B.A.,
Amin, H.M., Ludwig, J.A., Mikos, A. Modeling Ewing's sarcoma tumors in vitro with 3D scaffolds
. Proc. Natl. Acad. Sci. 2013 April: doi: 10.1073/pnas.1221403110
Chung, S.-W., Cooper, C.R., Farach-Carson, M.C., and Ogunnaike, B.A. A control engineering approach to understanding the TGF-β paradox in cancer. Journal of the Royal Society Interface, 9(71) 2012: 1389-97
Fomin, P., Lowe, D., Lepori-Bui, N., Sloofman, L., Zhou, X., Farach-Carson, M.C., Wang, L., Kirn-Safran, C. Deficiency of perlecan/HSPG2 during cartilage growth plate development enhances osteogenesis and decreases quality of adult bone in mice. Calcified Tissue Int. 2012
Sisson, K., Zhang, C., Chase, D.B., Rabolt, J.F., Farach-Carson, M.C. Effect of various crosslinking methods of electrospun gelatin on biocompatibility and osteoblastic cell migration and differentiation. 2012
Gurski, L.A., Xu, X., Labrada, L.N., Nguyen, N.T., Xiao, L., van Golen, K.L., Jia, X., Farach-Carson, M.C. Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels. PLoS One, 7(11) 2012: e50075
Xu, X., Jha, J., Harrington, D.A., Farach-Carson, M.C., Jia, X. Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks. Soft Matter, 8(12) 2012: 3280-3294
Bhatt, S.P., Harrington, D.A., Duncan, R.L., Jia, X., Witt, R.L. Farach-Carson, M.C. Implantable three-dimensional salivary spheroid assemblies demonstrate fluid and protein secretory responses to neurotransmitters. Tissue Engineering 2012
Lukianova-Hleb E.Y., Ren X., Constantinou P.E., Danysh B.P., Shenefelt D.L., Carson D.D., Farach-Carson M.C., Kulchitsky V.A., Wu X., Wagner D.S., Lapotko D.O. Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems. PLoS One, 7(4) 2012: e34537
Srinivasan, P.P., McCoy, S.Y., Jha, A.K., Yang, W., Jia, X., Farach-Carson, M.C. and Kirn-Safran, C.B. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis. Biomedical Materials, 7(2) 2012: 024109
Delk,N., Farach-Carson, M.C. Interleukin-6: A bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells. Autophagy, 8(4) 2012
Xu, X., Gurski, L.A., Zhang, Z., Harrington, D.A., Farach-Carson, M.C., Jia, X. Recreating the Tumor Microenvironment in a Bilayer, Hyaluronic Acid-Hydrogel Construct for Growth of Prostate Cancer Spheroids. Biomaterials, 33(35) 2012: 9049-60
Warren, C.R. Ali-Khan Catts, Z., Farach-Carson, M.C. A new assay for functional screening of BRCA2 linker region mutations identifies variants that alter chemoresistance to cisplatin. Exp. Cell Res., 317(15) 2011: 2099-109
Thompson, W.R., Majid, A.S., Czymmek, K.J., Ruff, A.L., Garcia, J., Duncan, R.L., Farach-Carson, M.C. Association of the α2δ1 Subunit with Cav3.2 enhances membrane expression and regulates mechanically induced ATP release in MLO-Y4 osteocytes. J. Bone Min. Research, 26(9) 2011: 2125-39
Boggs, M.E., Thompson, W.R., Farach-Carson, M.C., Duncan, R.L., Beebe. T.P. Co-culture of osteocytes and neurons on a unique patterned surface. Biointerfaces, 6(4) 2011: 200
Zhang, C., Soori, M., Sikes, R.A., Carson, D.D., Chung, L.L.W., Farach-Carson, M.C. Paracrine factors produced by bone marrow stromal cells induce apoptosis and neuroendocrine differentiation in prostate cancer cells. The Prostate, 71(2) 2011: 157-67
Thompson, W.R., Modla, S., Grindel, B.J., Czymmek, K., Kirn-Safran, C.B., Wang, L. Duncan, R.L., Farach-Carson, M.C. Perlecan/Hspg2 deficiency alters the pericellular space of the lacuno-canalicular system surrounding osteocytic processes in cortical bone. J. Bone Min. Research, 26(3) 2011: 618-629. (Top 2% article by Faculty of 1000)
Lukianova-Hleb E.Y., Oginsky A.O., Shenefelt D.L., Drezek R.A., Hafner J.H., Farach-Carson M.C., Lapotko D.O. Rainbow plasmonic nanobubbles: Synergistic activation of gold nanoparticle clusters. J Nanomed Nanotechnol , 2(104) 2011: 1-8
Grindel, B.J., Rohe, B., Safford, S.E., Bennett, J.J., Farach-Carson, M.C. Tumor necrosis factor-α treatment of HepG2 cells mobilizes a cytoplasmic pool of ERp57/1,25D₃-MARRS to the nucleus. J. Cell Biochem., 112(9) 2011: 2606-15
Lukianova-Hleb, E.Y., Oginsky, A.O., Samaniego, A.P., Shenefelt, D.L., Wagner, D.S., Hafner, J.H., Farach-Carson, M.C., Lapotko, D.O. Tunable plasmonic nanoprobes for theranostics of prostate cancer. Theranostics, 1 2011: 3-17
Wang, X. Gurski, L.A., Zhong, S. Xu, X., Pochan, D.J., Farach-Carson, M.C., Jia, X. Amphiphilic block copolyesters bearing pendant cyclic ketal groups as nanocarriers for controlled release of camptothecin. Journal of Biomaterials Science: Polymer Edition , Epub ahead of print 2010
Hartman, O. Zhang, C., Adams, E.L., Farach-Carson, M.C., Petrelli, N.J., Chase, B.D. Rabolt, J.F. Biofunctionalization of electrospun PCL-based scaffolds with perlecan domain IV peptide to create a 3-D pharmacokinetic cancer model. Biomaterials, 31(21) 2010: 5700-18
Sloofman L.G., Verdelis K., Spevak L., Zayzafoon M., Yamauchi M., Opdenaker L.M., Farach-Carson M.C., Boskey A.L., Kirn-Safran C.B. Effect of HIP/ribosomal protein L29 deficiency on mineral properties of murine bones and teeth. Bone, 47(1) 2010: 93-101
Thompson, W.R., Farach-Carson, M.C. Effects of 1,25-dihydroxyvitamin D3 on voltage sensitive calcium channels in osteoblast differentiation and morphology. Vitamin D, Third Edition 2010
Sisson, K., Zhang, C., Farach-Carson, M.C., Chase, D.B., Rabolt, J.F. Fiber diameter controls osteoblastic cell migration and differentiation in electrospun gelatin. Journal of Biomedical Materials Research Part A, 94(4) 2010: 1312-20
O'Connor, R.D., Farach-Carson, M.C., Schanen, N.C. Genetic and Epigenetic Aspects of Bone Development. Topics in Bone Biology, 6 2010
Jha, A.K. Malik, M.S., Farach-Carson, M.C., Duncan, R.L., Jia, X. Hierarchically structured, hyaluronic acid-based hydrogel matrices via the covalent integration of microgels into macroscopic networks. Soft Matter, 6(20) 2010: 5045-55
Richard C.L., Farach-Carson M.C., Rohe B., Nemere I., Meckling K.A. Involvement of 1,25D3MARRS (membrane associated, rapid response steroid-binding), a novel vitamin D receptor, in growth inhibition of breast cancer cells. Exp. Cell Res., 316(5) 2010: 695-703
Pradhan, S., Liu, C., Zhang, C., Jia, X., Farach-Carson, M.C., Witt, R. Lumen formation in 3D cultures of salivary acinar cells. Otolaryngology & Head and Neck Surgery, 142(2) 2010: 191-5
Pradhan, S. and Farach-Carson M.C. Mining the extracellular matrix for tissue engineering applications. Regen Med., 5(6) 2010: 961-70
Wu W., Beilhartz G., Roy Y., Richard C.L., Curtin M., Brown L., Cadieux D., Coppolino M., Farach-Carson M.C., Nemere I., Meckling K.A. Nuclear translocation of the 1,25D3-MARRS (membrane associated rapid response to steroids) receptor protein and NFB in differentiating NB4 leukemia cells.. Exp. Cell Res., 316(7) 2010: 1101-8
Zhang, C., Soori, M., Miles F.L., Sikes, R.A., Carson, D.D., Chung, L.L.W., Farach-Carson, M.C. Paracrine factors produced by bone marrow stromal cells induce apoptosis and neuroendocrine differentiation in prostate cancer cells. Prostate 2010 Jul 21
Wagner, D.S., Delk, N., Lukianova-Hleb, K.U., Hafner, J.H., Farach-Carson, M.C., Lapotko, D.O. The in vivo performance of plasmonic nanobubbles as cell theranostic agents in zebrafish hosting prostate cancer xenografts. Biomaterials, 31(29) 2010: 7567-74
Gurski, L. A., Petrelli, N.J., Jia,X., Farach-Carson, M.C. Three-dimensional matrices for anti-cancer drug testing and development. Association of Community Cancer Centers Oncology Issues: New Technologies, Jan/Feb 2010: 20-25
Witt, R.L., Jia, X., Liu, C., Zhang, C., Farach-Carson, M.C., Pradhan, S. Engineering an artificial salivary gland . Otolaryngology - Head and Neck Surgery , 141 2009 September : P50
Sisson, K., Zhang, C., Farach-Carson, M.C., Chase, D.B., Rabolt, J.F. Evaluation of Cross-Linking Methods for Electrospun Gelatin on Cell Growth and Viability. Biomacromolecules, 10 2009
Shao, Y., Czymmek, K., Fomin, V., Duncan, R.L., Farach-Carson, M.C. "Fluorescence resonance energy transfer (FRET) reveals dynamic interactions between L-type voltage sensitive calcium channel (VSCC) Cav 1.2 (alpha1C) subunits and ahnak in osteoblastic cells." AJP-Cell Physiol 296 (2009) C1067-1078.
Gurski, L., Jha, A.K., Zhang, C., Jia, X., Farach-Carson, M.C. Hyaluronic acid hydrogel as a scaffold for chemotherapeutic drug selection with poorly adherent cells. Biomaterials, 30 2009: 6076-6085
O'Connor, R.D., Zayzafoon, M., Farach-Carson, M.C., Schanen, N.C. Mecp2 deficiency decreases bone formation and reduces bone volume in a rodent model of Rett Syndrome. Bone, 45 2009: 346-356
Hartman O, Zhang C, Adams EL, Farach-Carson MC, Petrelli NJ, Chase BD, Rabolt JF Microfabricated electrospun collagen membranes for 3-D cancer models and drug screening applications. Biomacromolecules, 10 2009 Aug 10: 2019-32
Kirn-Safran, C., Farach-Carson, M.C., Carson, D.D. Multifunctionality of extracellular and cell surface heparan sulfate proteoglycans. Cellular and Molecular Life Sciences , 66 2009: 3421-3434
Pradhan, S.S., Zhang, C., Jia, X., Carson, D.D., Witt, R.L., Farach-Carson, M.C.
Perlecan Domain IV Peptide Stimulates Salivary Gland Cell Assembly In Vitro. Tissue Engineering Part A 2009 November : 3309-3320
Chung, S.-W., Miles, F.L., Sikes, R.A., Cooper, C.R., Farach-Carson, M.C., and Ogunnaike, B.A. Quantitative modeling and analysis of the transforming growth factor beta signaling pathway. Biophys J , 96 2009: 1733-1750
Opdenaker, L.M., Farach-Carson, M.C. Rapamycin selectively reduces the association of transcripts containing complexes of 5' UTRs with the ribosome in prostate cancer cells . J Cell Biochem, 107 2009: 473-481
Oristian, D.S., Sloofman, L.G., Zhou, X., Wang, L., Farach-Carson, M.C., Kirn-Safran, C.B. Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice. J Orthop Res (cover), 27 2009: 28-35
Alcorn, J.L., Merritt, T.M., Farach-Carson, M.C., Wang, H.H., Hecht, J.T. Targeted reduction of mutant cartilage oligomeric matrix protein (COMP) using a COMP-specific ribozyme: a new strategy for gene therapy. RNA, 15 2009: 686-695
D’Souza, S.S., Yang, W., Marchetti, D., Muir, C., Farach-Carson, M.C., and Carson, D.D. HIP/RPL29 antagonizes VEGF and FGF2 stimulated angiogenesis by interfering with HS-dependent responses. J Cell Biochem, 105(5) 2008: 1183-1193
Farach-Carson, M.C., and Grindel, B. HSPG2 (heparan sulfate proteoglycan 2). Atlas Genet Cytogenet Oncol Haematol 2008 October
Brown, A.J., Alicknavitch, M., D’Souza, S.S., Daikoku, T., Kirn-Safran, C., Marchetti, D., Carson, D.D., and Farach-Carson, M.C. Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation. Bone, 43(4) 2008: 689-699
Farach-Carson, M.C., Brown, A.J., Lynam, M., Safran, J.B., and Carson, D.D. A novel peptide sequence in perlecan domain IV supports cell adhesion and spreading. Matrix Biology, 27 2007: 150-160
O’Connor, J.C., Farach-Carson, M.C., Schneider, C.J., and Carson, D.D. "Co-culture of bone marrow stromal cells with prostate cancer cells alters endoglin expression and attenuates TGF-β signaling in reactive bone stroma." Mol Cancer Res, 5(6) (2007) : 585-603.
Casper, C. L., Yang, W., Farach-Carson, M.C., Rabolt, J.F. Coating electrospun collagen and gelatin fibers with perlecan domain I for increased growth factor binding . Biomacromolecules, 8(4) 2007: 1116-1123
Farach-Carson, M.C. and Carson, D.D. Perlecan: A multifunctional extracellular proteoglycan scaffold in embryo implantation and placentation. Glycobiology, 17 2007: 897-905
Huang, W.C., Wu, D., Xie, Z., Zhau, H.E., Nomura, T., Zayzafoon, M., Pohl, J., Hsieh, C.L., Weitzmann, M.N., Farach-Carson, M.C., Chung, L.W. "β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis." Cancer Res, 66(18) (2006) : 9108-9116.