Karen M. Lyons, Ph.D.

Biography

Research Interest: Growth Factor Signaling in Mammalian Development and Disease Many of the inductive events associated with vertebrate development are mediated by diffusible signals. The involvement of members of the transforming growth factor ß family of growth regulatory molecules in aspects of cell cycle control, gene expression, and cell-cell interactions is well established. Members of the Bone Morphogenetic Protein (BMP) subgroup of TGFß-related molecules have been implicated in many key signalling events in vertebrates and invertebrates. We are using the mouse as a model organism to study the roles of these regulatory factors during vertebrate development. We are interested in identifying the cellular targets of action of TGFß-related genes in a developmental context. Our approach is to take advantage of the genetic capabilities the mouse system offers, including transgenic and gene targeting technologies. We are also using organ and cell culture strategies to define the molecular mechanism of action of TGFß-related molecules in a biologically relevant context. These efforts have been facilitated by the recent identification of receptors for specific BMPs. We are currently developing cell culture systems and in vivo models to study BMP-mediated receptor signalling.

Publications

A selected list of publications:

Hall-Glenn Faith, Aivazi Armen, Akopyan Lusi, Ong Jessica R, Baxter Ruth R, Benya Paul D, Goldschmeding Roel, van Nieuwenhoven Frans A, Hunziker Ernst B, Lyons Karen M   CCN2/CTGF is required for matrix organization and to protect growth plate chondrocytes from cellular stress Journal of cell communication and signaling, 2013; .
Merrill Amy E, Sarukhanov Anna, Krejci Pavel, Idoni Brian, Camacho Natalia, Estrada Kristine D, Lyons Karen M, Deixler Hannah, Robinson Haynes, Chitayat David, Curry Cynthia J, Lachman Ralph S, Wilcox William R, Krakow Deborah   Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling American journal of human genetics, 2012; 90(3): 550-7.
Hall-Glenn Faith, De Young R Andrea, Huang Bau-Lin, van Handel Ben, Hofmann Jennifer J, Chen Tom T, Choi Aaron, Ong Jessica R, Benya Paul D, Mikkola Hanna, Iruela-Arispe M Luisa, Lyons Karen M   CCN2/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis PloS one, 2012; 7(2): e30562.
Ascenzi Maria-Grazia, Blanco Christian, Drayer Ian, Kim Hannah, Wilson Ryan, Retting Kelsey N, Lyons Karen M, Mohler George   Effect of localization, length and orientation of chondrocytic primary cilium on murine growth plate organization Journal of theoretical biology, 2011; 285(1): 147-55.
Chien Wenwen, O’Kelly James, Lu Daning, Leiter Amanda, Sohn Julia, Yin Dong, Karlan Beth, Vadgama Jay, Lyons Karen M, Koeffler H Phillip   Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis International journal of oncology, 2011; 38(6): 1741-7.
Hall-Glenn Faith, Lyons Karen M   Roles for CCN2 in normal physiological processes Cellular and molecular life sciences : CMLS, 2011; 68(19): 3209-17.
Estrada Kristine D, Retting Kelsey N, Chin Alana M, Lyons Karen M   Smad6 is essential to limit BMP signaling during cartilage development Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011; 26(10): 2498-510.
Suwanwela Jaijam, Farber Charles R, Haung Bau-Lin, Song Buer, Pan Calvin, Lyons Karen M, Lusis Aldons J   Systems genetics analysis of mouse chondrocyte differentiation Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011; 26(4): 747-60.
Stevens Jennifer R, Miranda-Carboni Gustavo A, Singer Meredith A, Brugger Sean M, Lyons Karen M, Lane Timothy F   Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2010; 25(10): 2138-47.
Retting Kelsey N, Song Buer, Yoon Byeong S, Lyons Karen M   BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation Development (Cambridge, England), 2009; 136(7): 1093-104.
Nishida Takashi, Kondo Seiji, Maeda Azusa, Kubota Satoshi, Lyons Karen M, Takigawa Masaharu   CCN family 2/connective tissue growth factor (CCN2/CTGF) regulates the expression of Vegf through Hif-1alpha expression in a chondrocytic cell line, HCS-2/8, under hypoxic condition Bone, 2009; 44(1): 24-31.
Crawford Maureen, Guney Maureen, Oh Maureen, Deyoung Maureen, Valenzuela Maureen, Murphy Maureen, Yancopoulos Maureen, Lyons Maureen, Brigstock Maureen, Economides Maureen, Gannon Maureen   Connective Tissue Growth Factor (CTGF) Inactivation Leads to Defects in Islet Cell Lineage Allocation and {beta} Cell Proliferation During Embryogenesis Molecular endocrinology (Baltimore, Md.), 2009; 94(2): .
Lyons Karen, Ezaki Marybeth   Molecular regulation of limb growth The Journal of bone and joint surgery. American volume, 2009; 91 Suppl 4(8): 47-52.
Sengle Gerhard, Ono Robert N, Lyons Karen M, Bächinger Hans Peter, Sakai Lynn Y   A new model for growth factor activation: type II receptors compete with the prodomain for BMP-7 Journal of molecular biology, 2008; 381(4): 1025-39.
Kawaki Harumi, Kubota Satoshi, Suzuki Akiko, Lazar Noureddine, Yamada Tomohiro, Matsumura Tatsushi, Ohgawara Toshihiro, Maeda Takeyasu, Perbal Bernard, Lyons Karen M, Takigawa Masaharu   Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2008; 23(11): 1751-64.
Pala Daphne, Kapoor Mohit, Woods Anita, Kennedy Laura, Liu Shangxi, Chen Shioqiong, Bursell Laura, Lyons Karen M, Carter David E, Beier Frank, Leask Andrew   Focal adhesion kinase/Src suppresses early chondrogenesis: central role of CCN2 The Journal of biological chemistry, 2008; 283(14): 9239-47.
Laurencin Cato T, Einhorn Thomas A, Lyons Karen   Fracture repair: challenges and opportunities The Journal of bone and joint surgery. American volume, 2008; 90 Suppl 1(2): 1-2.
Kawaki Harumi, Kubota Satoshi, Suzuki Akiko, Yamada Tomohiro, Matsumura Tatsushi, Mandai Toshiko, Yao Mayumi, Maeda Takeyasu, Lyons Karen M, Takigawa Masaharu   Functional requirement of CCN2 for intramembranous bone formation in embryonic mice Biochemical and biophysical research communications, 2008; 366(2): 450-6.
Nishida Takashi, Kawaki Harumi, Baxter Ruth M, Deyoung R Andrea, Takigawa Masaharu, Lyons Karen M   CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes Journal of cell communication and signaling, 2007; 1(1): 45-58.
Kennedy Laura, Liu Shangxi, Shi-Wen Xu, Chen Yunliang, Eastwood Mark, Sabetkar Mojhgan, Carter David E, Lyons Karen M, Black Carol M, Abraham David J, Leask Andrew   CCN2 is necessary for the function of mouse embryonic fibroblasts Experimental cell research, 2007; 313(5): 952-64.
Huang Bau-Lin, Dornbach Lisa M, Lyons Karen M   The 5′ untranslated regions (UTRs) of CCN1, CCN2, and CCN4 exhibit cryptic promoter activity Journal of cell communication and signaling, 2007; 1(1): 17-32.
Pogue, R. and Lyons, K.M.   BMP signaling in the cartilage growth plate, Curr Top Dev Biol, 2006; 76: 1-48.
Pogue Robert, Lyons Karen   BMP signaling in the cartilage growth plate Current topics in developmental biology, 2006; 76(2): 1-48.
Yoon Byeong S, Pogue Robert, Ovchinnikov Dmitri A, Yoshii Isaac, Mishina Yuji, Behringer Richard R, Lyons Karen M   BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways Development (Cambridge, England), 2006; 133(23): 4667-78.
Yoon, B.S., Pogue, R. Ovchinnikov, D. A., Yoshii, I., Mishina, Y., Behringer, R.R. and Lyons, K.M.   BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways, Development, 2006; 133(23): 4667-78.
Shi-wen Xu, Stanton Lee Anne, Kennedy Laura, Pala Daphne, Chen Yunliang, Howat Sarah L, Renzoni Elisabetta A, Carter David E, Bou-Gharios George, Stratton Richard J, Pearson Jeremy D, Beier Frank, Lyons Karen M, Black Carol M, Abraham David J, Leask Andrew   CCN2 is necessary for adhesive responses to transforming growth factor-beta1 in embryonic fibroblasts The Journal of biological chemistry, 2006; 281(16): 10715-26.
Gamradt Seth C, Abe Nobuhiro, Bahamonde Matthew E, Lee Yu-Po, Nelson Scott D, Lyons Karen M, Lieberman Jay R   Tracking expression of virally mediated BMP-2 in gene therapy for bone repair Clinical orthopaedics and related research, 2006; 450(23): 238-45.
Yoon BS, Ovchinnikov DA, Yoshii I, Mishina Y, Behringer RR, Lyons KM   Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo Proceedings of the National Academy of Sciences of the United States of America. , 2005; 102(14): 5062-7.
Yoon Byeong S, Ovchinnikov Dmitry A, Yoshii Isaac, Mishina Yuji, Behringer Richard R, Lyons Karen M   Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo Proceedings of the National Academy of Sciences of the United States of America, 2005; 102(14): 5062-7.
Murali D, Yoshikawa S, Corrigan RR, Plas DJ, Crair MC, Oliver G, Lyons KM, Mishina Y, Furuta Y   Distinct developmental programs require different levels of Bmp signaling during mouse retinal development Development (Cambridge, England) , 2005; 132(5): 913-23.
Lee Nathan V, Rodriguez-Manzaneque Juan Carlos, Thai Shelley N-M, Twal Waleed O, Luque Alfonso, Lyons Karen M, Argraves W Scott, Iruela-Arispe M Luisa   Fibulin-1 acts as a cofactor for the matrix metalloprotease ADAMTS-1 The Journal of biological chemistry, 2005; 280(41): 34796-804.
Kim Joon, Wu Hsiao-Huei, Lander Arthur D, Lyons Karen M, Matzuk Martin M, Calof Anne L   GDF11 controls the timing of progenitor cell competence in developing retina Science (New York, N.Y.), 2005; 308(5730): 1927-30.
Chen Yunliang, Abraham David J, Shi-Wen Xu, Pearson Jeremy D, Black Carol M, Lyons Karen M, Leask Andrew   CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin Molecular biology of the cell, 2004; 15(12): 5635-46.
Chen Y, Abraham DJ, Shi-Wen X, Pearson JD, Black CM, Lyons KM, Leask A   CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin Molecular biology of the cell. , 2004; 15(12): 5635-46.
Chuva de Sousa Lopes SM, Feijen A, Korving J, Korchynskyi O, Larsson J, Karlsson S, ten Dijke P, Lyons KM, Goldschmeding R, Doevendans P, Mummery CL   Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction Developmental dynamics : an official publication of the American Association of Anatomists. , 2004; 231(3): 542-50.
Andl T, Ahn K, Kairo A, Chu EY, Wine-Lee L, Reddy ST, Croft NJ, Cebra-Thomas JA, Metzger D, Chambon P, Lyons KM, Mishina Y, Seykora JT, Crenshaw EB, Millar SE   Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development Development (Cambridge, England) , 2004; 131(10): 2257-68.
Nakamura Kotoka, Kennedy Matthew A, Baldán Angel, Bojanic Dragana D, Lyons Karen, Edwards Peter A   Expression and regulation of multiple murine ATP-binding cassette transporter G1 mRNAs/isoforms that stimulate cellular cholesterol efflux to high density lipoprotein The Journal of biological chemistry, 2004; 279(44): 45980-9.
Yoon BS, Lyons KM   Multiple functions of BMPs in chondrogenesis Journal of cellular biochemistry. , 2004; 93(1): 93-103.
Yoon Byeong S, Lyons Karen M   Multiple functions of BMPs in chondrogenesis Journal of cellular biochemistry, 2004; 93(1): 93-103.
Wine-Lee Lara, Ahn Kyung J, Richardson Rory D, Mishina Yuji, Lyons Karen M, Crenshaw E Bryan   Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord Development (Cambridge, England), 2004; 131(21): 5393-403.
Wine-Lee L, Ahn KJ, Richardson RD, Mishina Y, Lyons KM, Crenshaw EB   Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord Development (Cambridge, England) , 2004; 131(21): 5393-403.
Wu HH, Ivkovic S, Murray RC, Jaramillo S, Lyons KM, Johnson JE, Calof AL   Autoregulation of neurogenesis by GDF11 Neuron. , 2003; 37(2): 197-207.
Wu Hsiao-Huei, Ivkovic Sanja, Murray Richard C, Jaramillo Sylvia, Lyons Karen M, Johnson Jane E, Calof Anne L   Autoregulation of neurogenesis by GDF11 Neuron, 2003; 37(2): 197-207.
Délot Emmanuèle C, Bahamonde Matthew E, Zhao Manxu, Lyons Karen M   BMP signaling is required for septation of the outflow tract of the mammalian heart Development (Cambridge, England), 2003; 130(1): 209-20.
D??lot EC, Bahamonde ME, Zhao M, Lyons KM   BMP signaling is required for septation of the outflow tract of the mammalian heart Development (Cambridge, England) , 2003; 130(1): 209-20.
Ivkovic Sanja, Yoon Byeong S, Popoff Steven N, Safadi Fayez F, Libuda Diana E, Stephenson Robert C, Daluiski Aaron, Lyons Karen M   Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development Development (Cambridge, England), 2003; 130(12): 2779-91.
Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM   Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development Development (Cambridge, England) , 2003; 130(12): 2779-91.
Nishimura Ichiro, Drake Thomas A, Lusis Aldons J, Lyons Karen M, Nadeau Joseph H, Zernik Joseph   ENU large-scale mutagenesis and quantitative trait linkage (QTL) analysis in mice: novel technologies for searching polygenetic determinants of craniofacial abnormalities Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists, 2003; 14(5): 320-30.
Schneider MD, Gaussin V, Lyons KM   Tempting fate: BMP signals for cardiac morphogenesis Cytokine & growth factor reviews. , 2003; 14(1): 1-4.
Daluiski A, Engstrand T, Bahamonde ME, Gamer LW, Agius E, Stevenson SL, Cox K, Rosen V, Lyons KM   Bone morphogenetic protein-3 is a negative regulator of bone density Nature genetics. , 2001; 27(1): 84-8.
Yi SE, LaPolt PS, Yoon BS, Chen JY, Lu JK, Lyons KM   The type I BMP receptor BmprIB is essential for female reproductive function Proceedings of the National Academy of Sciences of the United States of America. , 2001; 98(14): 7994-9.
Yi SE, Daluiski A, Pederson R, Rosen V, Lyons KM   The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb Development (Cambridge, England) , 2000; 127(3): 621-30.
Engstrand T, Daluiski A, Bahamonde ME, Melhus H, Lyons KM   Transient production of bone morphogenetic protein 2 by allogeneic transplanted transduced cells induces bone formation Human gene therapy. , 2000; 11(1): 205-11.