Rachelle H. Crosbie-Watson, Ph.D.

Work Address:
Dept. Integrative Biology & Physiology
610 Charles E Young Drive East
Los Angeles, CA 90095 610 Charles E Young Dr East
Dept Integrative Biology & Physiology
Los Angeles, CA 90095

Professor, Integrative Biology and Physiology, Neurology, Brain Research Institute
Education Liaison, Center for Duchenne Muscular Dystrophy
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, Cell & Developmental Biology GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Research Interests
My research program focuses on determining the pathogenetic mechanisms of muscular dystrophy. Members of the lab are examining the muscle function using biochemical, molecular, and cellular approaches. There are many forms of muscular dystrophy caused by primary genetic mutations within different muscle genes. For instance, mutations in dystrophin are responsible for causing Duchenne muscular dystrophy (DMD) while mutations in any of the four sarcoglycan genes cause limb-girdle muscular dystrophy. Congenital and Emery-Dreyfus muscular dystrophies are caused by mutations in laminin and emerin, respectively. These muscle diseases differ based on the types of muscles that are affected, clinical progress of the disease, and mode of inheritance. My lab is interested in 1) determining why these proteins are critical for normal muscle function 2) creating animal models for specific forms of muscular dystrophy using transgenic and knockout mouse technology and 3) developing new therapeutic agents. We are in the process of testing FDA-approved compounds in mouse models of muscular dystrophy. In addition, we are developing novel animal models for muscle proteins that are known to rescue muscular dystrophy.

Dr. Crosbie-Watson has pioneered work on the function of sarcospan within the dystrophin-glycoprotein complex. Introduction of sarcospan into dystrophin-deficient mice ameliorates muscular dystrophy in a me. The Crosbie lab has generated all the molecular tools and reagents for the study of sarcospan, which are not available elsewhere. Building on expertise in sarcospan and the dystrophin-glycoprotein complex, the Crosbie lab is collaborating with the Baum lab in development of HTS assays to detect alteration in sarcospan expression as a therapy for Duchenne Muscular Dystrophy. Dr. Crosbie has also collaborated with the Spencer group at UCLA to develop and characterize novel methodologies for creating mouse models of muscle disease. In addition to her research, Dr. Crosbie is a dedicated educator. She has trained several HHMI, Beckman, and Dean's undergraduate and graduate scholars. She successfully mentored a successful recipient of the prestigious Marshall Scholarship. This student was one of only thirteen students to be awarded the Marshall in UCLA?s history. Based on her excellence in classroom instruction, Dr. Crosbie was nominated for a Teaching Distinction Award at UCLA and she is Faculty Director of the Beckman Undergraduate Scholars Program.


A selected list of publications:

Crosbie RH, Dovico SA, Flanagan JD, Chamberlain JS, Ownby CL, Campbell KP   Characterization of aquaporin-4 in muscle and muscular dystrophy FASEB J. , 2002; 16(9): 943-9.
Crawford GC, Faulkner JA, Crosbie RH, Campbell KP, Froehner SC, Chamberlain JS   Assembly of the Dystrophin Associated Protein Complex Does Not Require the Dystrophin C-terminal Domain, J. Cell Biol, 2000; 150: 1411-1422.
Crosbie RH et al.   Molecular and Genetic Characterization of Sarcospan:Insights into Sarcoglycan-Sarcospan Domains Hum. Mol. Genet, 2000; 9: 2019-2027.
Crosbie RH   News and Views: NO Vascular Control in Duchenne Muscular Dystrophy, Nature Med, 2000; 7: 27-29.
Holt KH, Crosbie RH, Venzke DP, Campbell KP   Biosynthesis of dystroglycan: processing of a precursor propeptide FEBS letters. , 2000; 468(1): 79-83.
Crosbie RH, Lebakken CS, Holt KH, Venzke DP, Straub V, Lee JC, Grady RM, Chamberlain JS, Sanes JR, Campbell KP   Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan subcomplex J. Cell Biol. , 1999; 145(1): 153-65.
Crosbie RH, Yamada H, Venzke DP, Lisanti MP, Campbell KP   Caveolin-3 is Not an Integral Component of the Dystrophin-Glycoprotein Complex, FEBS Lett, 1998; 427: 279-282.
Crosbie RH, Straub V, Yun HY, Lee JC, Rafael JA, Chamberlain JS, Dawson VL, Dawson TM, Campbell KP   mdx muscle pathology is independent of nNOS perturbation Hum. Mol. Genet, 1998; 7(5): 823-9.
Duclos F, Straub V, Moore SA, Venzke DP, Hrstka RF, Crosbie RH, Durbeej M, Lebakken CS, Ettinger AJ, van der Meulen J, Holt KH, Lim LE, Sanes JR, Davidson BL, Faulkner JA, Williamson R, Campbell KP   Progressive Muscular Dystrophy in alpha-Sarcoglycan Deficient Mice, J. Cell Biol, 1998; 142: 1461-1471.
Crosbie RH, Heighway J, Venzke DP, Lee JC, Campbell KP   Sarcospan: The 25kDa Transmembrane Component of the Dystrophin-Glycoprotein Complex, J. Biol. Chem, 1997; 272: 31221-31224.
Campbell KP, Crosbie RH   NEWS AND VIEWS: Utrophin to the Rescue, Nature, 1996; 384: 308-309.
Crosbie RH, Chalovich JM, Reisler E   Flexation of caldesmon: effect of conformation on the properties of caldesmon J. Muscle Res. Cell Mot. , 1995; 16(5): 509-18.
Crosbie RH, Miller C, Cheung P, Goodnight T, Muhlrad A, Reisler E   Structural connectivity in actin: effect of C-terminal modifications on the properties of actin Biophysical J. , 1994; 67(5): 1957-64.
Crosbie RH, Miller C, Chalovich JM, Rubenstein PA, Reisler E   Caldesmon, N-terminal yeast actin mutants, and the regulation of actomyosin interactions Biochemistry. , 1994; 33(11): 3210-6.
Crosbie RH, Chalovich JM, Reisler E   Interaction of caldesmon and myosin subfragment 1 with the C-terminus of actin Biochem. Biophys. Res. Comm. , 1992; 184(1): 239-45.
Crosbie R, Adams S, Chalovich JM, Reisler E   The interaction of caldesmon with the COOH terminus of actin J. Biol. Chem. , 1991; 266(30): 20001-6.
Nelson Stanley F, Crosbie Rachelle H, Miceli M Carrie, Spencer Melissa J   Emerging genetic therapies to treat Duchenne muscular dystrophy Current opinion in neurology, 2009; 22(5): 532-8.
Kim Michelle H, Kay Danielle I, Rudra Renuka T, Chen Bo Ming, Hsu Nigel, Izumiya Yasuhiro, Martinez Leonel, Spencer Melissa J, Walsh Kenneth, Grinnell Alan D, Crosbie Rachelle H   Myogenic Akt signaling attenuates muscular degeneration, promotes myofiber regeneration and improves muscle function in dystrophin-deficient mdx mice Hum. Mol. Genet, 2011; 20(7): 1324-38.
Merveille Anne-Christine, Davis Erica E, Becker-Heck Anita, Legendre Marie, Amirav Israel, Bataille Géraldine, Belmont John, Beydon Nicole, Billen Frédéric, Clément Annick, Clercx Cécile, Coste André, Crosbie Rachelle, de Blic Jacques, Deleuze Stephane, Duquesnoy Philippe, Escalier Denise, Escudier Estelle, Fliegauf Manfred, Horvath Judith, Hill Kent, Jorissen Mark, Just Jocelyne, Kispert Andreas, Lathrop Mark, Loges Niki Tomas, Marthin June K, Momozawa Yukihide, Montantin Guy, Nielsen Kim G, Olbrich Heike, Papon Jean-François, Rayet Isabelle, Roger Gilles, Schmidts Miriam, Tenreiro Henrique, Towbin Jeffrey A, Zelenika Diana, Zentgraf Hanswalter, Georges Michel, Lequarré Anne-Sophie, Katsanis Nicholas, Omran Heymut, Amselem Serge   CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs Nature genetics, 2011; 43(1): 72-8.
Solares-Pérez Alhondra, Alvarez Rocío, Crosbie Rachelle H, Vega-Moreno Jesús, Medina-Monares Joel, Estrada Francisco J, Ortega Alicia, Coral-Vazquez Ramón   Altered calcium pump and secondary deficiency of gamma-sarcoglycan and microspan in sarcoplasmic reticulum membranes isolated from delta-sarcoglycan knockout mice Cell calcium, 2010; 48(1): 28-36.
Marshall Jamie L, Holmberg Johan, Chou Eric, Ocampo Amber C, Oh Jennifer, Lee Joy, Peter Angela K, Martin Paul T, Crosbie-Watson Rachelle H   Sarcospan-dependent Akt activation is required for utrophin expression and muscle regeneration J. Cell Biol, 2012; 197(7): 1009-27.
Rutkowski Anne, Bonnemann Carsten, Brown Susan, Thorsteinsdattir Salveig, Dominov Janice, Ruegg Markus A, Matter Michelle L, Guttridge Denis, Crosbie-Watson Rachelle H, Kardon Gabrielle, Nagaraju Kanneboyina, Girgenrath Mahasweta, Burkin Dean J   Report on the Myomatrix Conference April 22-24, 2012, University of Nevada, Reno, Nevada, USA Neuromusc. Dis. : NMD, 2012; .
Marshall Jamie L, Chou Eric, Oh Jennifer, Kwok Allan, Burkin Dean J, Crosbie-Watson Rachelle H   Dystrophin and utrophin expression require sarcospan: loss of alpha7 integrin exacerbates a newly discovered muscle phenotype in sarcospan-null mice Hum. Mol. Genet, 2012; .
Cabrera Paula V, Pang Mabel, Marshall Jamie L, Kung Raymond, Nelson Stanley F, Stalnaker Stephanie H, Wells Lance, Crosbie-Watson Rachelle H, Baum Linda G   High throughput screening for compounds that alter muscle cell glycosylation identifies new role for N-glycans in regulating sarcolemmal protein abundance and laminin binding J. Biol. Chem, 2012; 287(27): 22759-70.
Marshall Jamie L, Crosbie-Watson Rachelle H   Sarcospan: a small protein with large potential for Duchenne muscular dystrophy Skeletal Muscle, 2013; 3(1): 1.
Marshall Jamie L, Kwok Yukwah, McMorran Brian J, Baum Linda G, Crosbie-Watson Rachelle H   The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy The FEBS journal, 2013; 280(17): 4210-29.