Guy M Benian, MD

Muscle Cell Biology

Professor
Pathology & Laboratory Medicine

Other Appointments/Positions

Associate Professor, Department of Cell Biology, Emory University

Pathology Division(s):
Experimental Pathology

Email Address:
pathgb@emory.edu

Education:

B.S.   University of Michigan, Ann Arbor, MI, high honors, - 1976

M.D.   Wayne State University School of Medicine, Detroit, MI, - 1980

Resident   Laboratory Medicine, Barnes Hospital and Washington University, St. Louis, MO, 1980 - 1985

Postdoc Fellow   Department of Genetics, Washington University, St. Louis, MO, supervisor R.H Walter, 1981 - 1986

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Research Interests:

- Using C. elegans to understand the assembly and maintenance of the muscle contractile apparatus
The sarcomere performs the work of muscle contraction and is a "nano"-machine consisting of a highly ordered assemblage of many proteins. Despite increasing knowledge of the components and functions of sarcomeric proteins (indeed new ones are discovered each year!), we still dont understand how sarcomeres are assembled, and maintained in the face of muscle contraction. Understanding sarcomere assembly / maintenance is important for two reasons: (1) it will help us understand the pathogenesis of many types of human muscle diseases, including muscular dystrophies and cardiomyopathies; and (2) it should lead to discovery of common principles that govern the assembly of other complex cellular structures. Our lab is studying these questions in the model genetic organism, C. elegans. We have two main projects: (1) the study of proteins (UNC-98, UNC-96, UNC-97) that are crucial for the attachment of myofibrils to the muscle cell membrane, and (2) the study of giant polypeptides (>700,000 Da) that have key roles in sarcomere assembly and signaling (twitchin, UNC-89, TTN-1). The giant proteins consist primarily of multiple copies of immunoglobulin (Ig) and fibronectin type 3 (Fn3) domains, and one or even two protein kinase domains. One focus is determining the identity of proteins that interact with these giants that permits them to carry out their functions. Another focus is to learn the substrates of the protein kinase domains, and to understand how the normally "autoinhibited" kinase domains become activated.

Honors / Awards:

Outstanding Service Award, Emorys Graduate Program in Genetics and Molecular Biology, 2005-2006

Established Investigator Award, American Heart Association, 1991-1996

Muscular Dystrophy Association Postdoctoral Fellow, 1982 & 1983

B.S. w/ high honors, University of Michigan, 1976

Selected Publications:

Published and Accepted Research Articles -

Zastrow, MS, Flaherty, DB, Benian, GM, Wilson, KL: Nuclear titin interacts with A- and B-type lamins in vitro and in vivo, J. Cell Sci. 119: 239-249, 2006.

Mercer, KB, Miller, RK, Tinley, TL, Sheth, S, Qadota, H, Benian, GM: C. elegans UNC-96 is a new component of M-lines that interacts with UNC-98 and paramyosin and is required in adult muscle for assembly and/or maintenance of thick filaments. Mol. Biol. Cell 17: 3832-3847, 2006.

Ayanaful, A, Dolan-Livengood, JM, Lewis, T, Sheth, S, DeZalia, Sherman, MA, MN, Kalman, LV, Benian, GM, Kalman, D: Paralysis and killing of C. elegans by enteropathogenic E. coli requires the bacterial tryptophanase gene, Mol. Microbiol. 57(4): 988-1007, 2005

Small, TM, Gernert KM, Flaherty DB, Mercer KB, Borodovsky M, Benian GM: Three new isoforms of C. elegans UNC-89 containing MLCK-like protein kinase domains. J. Mol. Biol.342: 91-108, 2004

Mercer KB, Flaherty DB, Miller RK, Qadota H, Tinley TL, Moerman DG, and Benian GM: C. elegans UNC-98, a C2H2 Zn finger protein, is a novel partner of UNC-97 / PINCH in muscle adhesion complexes. Mol. Biol Cell 14: 2492-2507, 2003.

Ono K, Parast M, Alberico C, Benian GM, and Ono S: Specific requirements of two ADF/cofilin isoforms in distinct actin-dependent processes in C. elegans. J. Cell Sci. 116: 2073-2085, 2003

Flaherty DB, Gernert KM, Shmeleva N, Tang X, Mercer KB, Borodovsky M, and Benian GM: Titins in C. elegans with unusual features: coiled-coil domains, novel regulation of kinase activity and two new possible elastic regions. J. Mol. Biol. 323(3): 533-549, 2002

Edens WA, Sharling L, Cheng G., Shapira R, Kinkade JM, Lee T, Edens HA, Tang X, Flaherty DB, Benian GM, and Lambeth JD: Tyrosine cross-linking of extracellular matrix is catalyzed by duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox, J. Cell Biol. 154(4): 879 -891, 2001

Ono S, McGough A, Pope BJ, Tolbert VT, Bui A, Pohl J, Benian GM, Gernert KM, and Weeds AG. The C-terminal tail of UNC-60B (ADF/cofilin) is critical for maintaining its stable association with F-actin and is implicated in the second actin-binding site, J. Biol. Chem. 276(8):5952-5958, 2001

Ono S, Baillie DL and Benian GM: UNC-60B, an ADF/cofilin family protein, is required for proper assembly of actin into myofibrils in C. elegans body wall muscle, J. Cell Biol. 145(3): 491-502, 1999

Ono S, and Benian GM: Two C. elegans actin depolymerizing factor/cofilin proteins, encoded by the unc-60 gene, differentially regulate actin filament dynamics, J. Biol Chem. 273: 3778-3783, 1998

Fong S, Hammill SJ, Proctor M, Freund SMV, Benian GM, Chothia C, Bycrott M, and Clarke J: Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode C. elegans, J. Mol. Biol. 264: 624-639, 1996

Heierhorst J, Tang X, Lei J, Kemp B, Weiss K, and Benian GM: Substrate requirements, inhibition by naphthylene sulfonates, and distinct calmodulin affinities of twitchin kinases, Eur. J. Biochem. 242: 454-459, 1996

Kobe B, Heierhorst J, Feil SC, Parker MW, Benian GM, Weiss KR, and Kemp BE: Giant protein kinases: domain interactions and structural basis of autoregulation, EMBO J. 24: 6810-6821,1996

Hardman WJ, Benian GM, Howard T, McGowan JE, Metchock B, and Murtagh JJ: Inflammatory necrotizing granulomas that are acid fast stain and culture negative for Mycobacteria but positive by PCR in formalin-fixed paraffin embedded tissue with CP follow-up. Am. J. Clin. Path. 106: 384-389, 1996

Heierhorst J, Kobe B, Feil SC, Parker MW, Benian GM, Weiss KR, and Kemp BE: Ca+2/S100 regulation of giant protein kinases. Nature 380: 636-639, 1996

Benian GM, Tinley TL, Tang X, and Borodovsky M: The C. elegans gene unc-89, required for muscle M-line assembly, encodes a giant modular protein containing Ig & signal transduction domains. J. Cell Biology 132(5): 835-848, 1996

Ayme-Southgate A, Southgate R, Saide JD, Benian GM, and Pardue ML: Both synchronous and asynchronous muscle isoforms of projectin, the Drosophila bent locus product, contain functional kinase domains. J. Cell Biology 128(3):393-403, 1995

Lei J, Tang X, Chambers T, Pohl J, and Benian GM: The protein kinase domain of twitchin has protein kinase activity and an autoinhibitory region. J. Biol. Chem. 269(33):21078-21085, 1994

Hu S-H, Parker MW, Lei J, Wilce MCJ, Benian GM and Kemp BE: Intrasteric regulation of protein kinases: insights from the crystal structure of twitchin kinase. Nature 369:581-584, 1994

Hu S-H, Lei J, Wilce MCJ, Valenzuela MRL, Benian GM, Parker MW, and Kemp BE: Crystallization and preliminary x-ray analysis of the auto-inhibited twitchin kinase. J. Mol. Biol. 236:1259-1261, 1994

Schein JE, Marra MA, Benian GM, Fields C, and Baillie DL: The use of deficiencies to determine essential gene content in the let-56-unc-22 region of C. elegans. Genome 36:1148-1156, 1993

Benian GM, L'Hernault SW, and Morris ME, Additional sequence complexity in the muscle gene, unc-22, and its encoded protein, twitchin, of C. elegans. Genetics 134:1097-1104, 1993

L'Hernault SW, Benian GM, and Emmons RB: Genetic and molecular characterization of the Caenorhabditis elegans spermatogenesis defective gene spe-17. Genetics134:769-780, 1993

Ayme-Southgate A, Vigoreaux J, Benian G, and Pardue ML: Drosophila has a twitchin/titin-related gene that appears to encode projectin. Proc. Nat. Acad. Sci. USA 88:7973-7977, 1991

Benian GM, Kiff JE, Neckelmann N, Moerman DG, Waterston RH: The sequence of twitchin: An unusually large protein implicated in regulation of myosin activity in C. elegans. Nature 342:45-50, 1989

Mori I, Benian GM, Moerman DG, and Waterston RH: The transposon Tcl of C. elegans recognizes specific target sequences for integration. Proc. Nat. Acad. Sci. USA 85:861-864, 1988

Moerman DG, Benian GM, Barstead RJ, Schriefer L, and Waterston RH: Identification and intracellular localization of the unc-22 gene product of C. elegans. Genes and Development 2:93-105, 1988

Moerman DG, Benian GM, and Waterston RH: Molecular cloning of the muscle gene unc-22 in C. elegans by Tcl transposon tagging. Proc. Nat. Acad. Sci. USA 83:2579-2583, 1986

Benian GM and Murray P: Practical modification of conventional blood culture systems for recovery of mycobacteria. Diagn. Microbiol. Infect. Dis. 4:351-353, 1986

Totty WG, Romano T, Benian GM, Gilula LA, and Sherman LA: Serum sickness following streptokinase therapy - brief report. Am. J. of Roentgenol. 138:143-144, 1982

Rittenhouse HG, Benian GM, Rittenhouse JW, Hansen ER, and Boyd LE: Heterogeneity of concanavalin A receptors on Ehrlich tumor cells, In: Membranes and Neoplasia: New Approaches and Strategies, Marchessi VT (ed) pp 203-213, 1976

Other Publications -

Ferrara TM, Flaherty DB, and Benian GM: Titin / connectin-related proteins in C. elegans: A review and new findings, J. Mus. Res. and Cell Motil. 26: 435-447, 2005.

Chamberlain JS and Benian GM: Muscular dystrophy: The worm turns to genetic disease, Current Biology 10: R795-R797, 2000.

Benian GM, Ayme-Southgate A, and Tinley TL: The genetics and molecular biology of titin/connectin-like proteins in invertebrates, Reviews of Physiology, Biochemistry and Pharmacology 138: 235-268, 1999.

Benian GM, Tang X, and Tinley TL: Twitchin and related giant Ig superfamily members of C. elegans and other invertebrates (In: Muscle Elastic Proteins), Advances in Biophysics 33:183-197, 1996.