Rachelle Crosbie-Watson, Ph.D.

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A Short Biography:

In 1994, Dr. Crosbie-Watson completed her Ph.D. research in the laboratory of Professor and Dean Emeritus Emil Reisler in the Department of Biochemistry at University of California, Los Angeles (UCLA). She is one of a few graduate students to receive Departmental Awards for Excellence in both teaching and research. Her dissertation project focused on investigating the structural alterations in skeletal muscle actin filaments that affect actomyosin ATPase activity and in vitro motility and resulted in five first-author publications. As a postdoctoral fellow, she was awarded the Robert Sampson Named Postdoctoral Fellowship by the Muscular Dystrophy Association to work with Professor and Chair Kevin P. Campbell at the Howard Hughes Medical Institute, University of Iowa College of Medicine. During her postdoctoral research, she investigated the muscle proteins associated with dystrophin, the causative disease gene for Duchenne muscular dystrophy. Dr. Crosbie-Watson’s work lead to the isolation and characterization of a 25kDa core component of the dystrophin-glycoprotein complex (DGC) that eluded identification for nearly ten years. She named this protein 'sarcospan' based on its multiple sarcolemma-spanning domains. Using several complementary biochemical and genetic approaches, she demonstrated that sarcospan is a bona fide component of the DGC, but is undetectable in the sarcolemma of dystrophin-deficient mdx mice, Duchenne muscular dystrophy patients, and in sarcolgycan-deficient forms of limb-girdle muscular dystrophy. This work culminated in thirteen publications. Dr. Crosbie-Watson is currently a Professor in the Department of Integrative Biology and Physiology with a joint appointment in the Department of Neurology. In 2013, Dr. Crosbie-Watson was one of six faculty members at UCLA to be awarded the “UCLA Distinguished Teaching Award." Dr. Crosbie-Watson serves as the Education Liaison for the Center of Duchenne Muscular Dystrophy. Over the last ten years, her research group has made several important contributions to the field of muscle biology and muscular dystrophy. Our new findings reveal the importance of structural and signaling molecules in the prevention of muscular dystrophy.
Work Titles
UCLA Professor, Integrative Biology and Physiology Professor, Neurology Professor, Brain Research Institute Education Liaison, Center for Duchenne Muscular Dystrophy Member, Biochemistry, Biophysics & Structural Biology GPB Home Area Member, Cell & Developmental Biology GPB Home Area Member, Molecular, Cellular & Integrative Physiology GPB Home Area
Education:
Degrees:
B.S., Texas A&M University
Ph.D., UCLA

Contact Information:

Email Address:

rcrosbie@physci.ucla.edu


Lab Number:

(310) 794-2107

Office Phone Number:

(310) 794-2103

Work Address:

Laboratory
Dept. Integrative Biology & Physiology
610 Charles E Young Drive East
Los Angeles, CA 90095

Office
610 Charles E Young Dr East
Dept Integrative Biology & Physiology
Los Angeles, CA 90095


Detailed Biography:

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.

Publications:

A selected list of publications:

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.
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.
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, 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.
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.
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.
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.
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.
Peter Angela K, Ko Christopher Y, Kim Michelle H, Hsu Nigel, Ouchi Noriyuki, Rhie Suhn, Izumiya Yasuhiro, Zeng Ling, Walsh Kenneth, Crosbie Rachelle H   Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy Human molecular genetics, 2009; 18(2): 318-27.
Peter Angela K, Marshall Jamie L, Crosbie Rachelle H   Sarcospan reduces dystrophic pathology: stabilization of the utrophin-glycoprotein complex The Journal of cell biology, 2008; 183(3): 419-27.
Bekker Janine M, Colantonio Jessica R, Stephens Andrew D, Clarke W Thomas, King Stephen J, Hill Kent L, Crosbie Rachelle H   Direct interaction of Gas11 with microtubules: implications for the dynein regulatory complex Cell motility and the cytoskeleton, 2007; 64(6): 461-73.
Peter Angela K, Miller Gaynor, Crosbie Rachelle H   Disrupted mechanical stability of the dystrophin-glycoprotein complex causes severe muscular dystrophy in sarcospan transgenic mice Journal of cell science, 2007; 120(Pt 6): 996-1008.
Miller Gaynor, Wang Emily L, Nassar Karin L, Peter Angela K, Crosbie Rachelle H   Structural and functional analysis of the sarcoglycan-sarcospan subcomplex Experimental cell research, 2007; 313(4): 639-51.
Colantonio Jessica R, Bekker Janine M, Kim Sarah J, Morrissey Kari M, Crosbie Rachelle H, Hill Kent L   Expanding the role of the dynein regulatory complex to non-axonemal functions: association of GAS11 with the Golgi apparatus Traffic (Copenhagen, Denmark), 2006; 7(5): 538-48.
Peter Angela K, Crosbie Rachelle H   Hypertrophic response of Duchenne and limb-girdle muscular dystrophies is associated with activation of Akt pathway Experimental cell research, 2006; 312(13): 2580-91.
Miller Gaynor, Peter Angela K, Espinoza Erica, Heighway Jim, Crosbie Rachelle H   Over-expression of Microspan, a novel component of the sarcoplasmic reticulum, causes severe muscle pathology with triad abnormalities Journal of muscle research and cell motility, 2006; 27(8): 545-58.
Yi Christopher E, Bekker Janine M, Miller Gaynor, Hill Kent L, Crosbie Rachelle H   Specific and potent RNA interference in terminally differentiated myotubes The Journal of biological chemistry, 2003; 278(2): 934-9.
Crosbie Rachelle H, Dovico Sherri A, Flanagan Jason D, Chamberlain Jeffrey S, Ownby Charlotte L, Campbell Kevin P   Characterization of aquaporin-4 in muscle and muscular dystrophy The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2002; 16(9): 943-9.
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.
Crosbie Rachelle H, Barresi Rita, Campbell Kevin P   Loss of sarcolemma nNOS in sarcoglycan-deficient muscle The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2002; 16(13): 1786-91.
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.
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 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.
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.
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, 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.
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, 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, 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, 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.

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