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Yinghua Zhang M.D., Ph.D.

Academic Title: Research Associate
Primary Appointment: Physiology
yzhan004@umaryland.edu
Location: HSF1, 546
Phone: 410-706-6028
Fax: 410-706-8341

Personal History:

I completed my MD degree at the Sun Yat-sen University of Medical Sciences, P.R. China and my PhD degree in Molecular Biology and Genetics at Kyoto Prefectureal University of Medicine in Japan. Then I got my postdoctoral traning in cancer biology at Lombardi cancer center of Georgetown University.

Research Interests:

Spectrin is an actin-binding protein composed of a 280 kDa α-subunit and a 246 kDa beta-subunit, which associate laterally to form an elongated heterodimer. Two such dimers self-associate, head to head, to form a heterotetramer. Spectrin and its associated proteins function to stabilize membranes and organize proteins and lipids into microdomains in intracellular organelles and at the plasma membrane. In cardiac muscle, these proteins bind to and stabilize the t-tubular and SR membranes. We have studied intracellular spectrins in the heart to test the hypothesis that separate spectrin cytoskeletal structures stabilize t-tubules and SR, and that their association with these membranes is regulated by phosphorylation. My research has examined two alternatively spliced forms of αII-spectrin, one with a 20 amino acid insert in the SH3 domain just C-terminal to repeat 10 (termed SH3i+), and a 21 amino acid insert close to the C-terminus, in the nucleation site for binding to the beta-subunit (termed â?ocardi+). My studies show that both alternatively spliced forms of these proteins are developmentally regulated, that their expression is independent of other alternatively spliced sequences, and that their solubility and membrane association is regulated by phosphorylation. The SH3i+ form appears to associate preferentially with the SR, where it binds to ankyrin B, RyR and SERCA. Dissociation of the SH3i+ form of the protein from membranes and its appearance in the soluble fraction is promoted by calyculin A (which inhibits dephosphorylation) and alters EC-coupling in cardiomyocytes. Inclusion of the alternatively spliced, cardi+ sequence into αII-spectrin has no significant effect on binding to either betaI- or betaII-spectrin, but it does appear to limit the amount of αII-spectrin that is available for binding. I am still testing the possibility that the cardi+ form associates preferentially with the t-tubule, where it may associate preferentially with the Na,K-ATPase and the Na,Ca-exchanger and the physiological consequences of its phosphorylation.


Publications:

Selected Publications

Su Y-A., Bittner M.L., Chen Y., Tao L., Jiang Y., Zhang Y., Stephan D.A., TrentJ.M., Identification of Tumor Suppressor Genes using Human Melanoma Cell Lines UACC903, UACC903 (+6), and SRS3 by comparison of expression profiles, Mol. Carcino. 28 (2): 119-27, 2000.

Naimuddin M., Kurazono T., Zhang Y., Watanabe T., Yamaguchi M. and Nishigaki K., Species Identification Dots: A Potent Tool for Developing Genome Microbiology. Gene 261 (2): 243-250, 2000.

Wong L-J. C., Wang J., Zhang Y., Hsu E., Heim R.A., Bowman C.M., Woo M., Improved Mutation Detection of CFTR in Southern California Hispanic CF Patients, Hum. Mutat. 18(4): 296-307, 2001.

Zhang Y., Ji H., Zheng W., and Sandberg K., Translational Control of the Rat Angiotensin Type 1a Receptor by Alternative Splicing, Gene. 2004 Oct 27;341:93-100

Ji H., Zhang Y., Zheng W. and Sandberg K., Translational Regulation of Angiotensin Type 1A Receptor Expression and Signaling by Upstream AUGS in the 5-Leader Sequence, J Biol Chem. 2004 Oct 29;279(44):45322-8

Ji H., Pesce C., Zheng W., Kim J., Zhang Y., Menin S., Haywood J.R. and Sandberg K., Sex Differences in Renal Injury and Nitric Oxide Production in Renal Wrap Hypertension, Am J Physiol Heart Circ Physiol, 2005 Jan;288(1):H43-7.

Hassan A, Ji H, Zhang Y, Sandberg K. Splice variant-specific silencing of angiotensin II type 1a receptor messenger RNA by RNA interference in vascular smooth muscle cells, Biochem Biophys Res Commun. 2006 Jan 13;339(2):499-505.

Ruiz-Perez F, Henderson IR, Leyton DL, Rossiter A, Zhang Y, Nataro JP.  Roles of Periplasmic Chaperone Proteins in the Biogenesis of Serine Protease Autotransporters of Enterobacteriaceae. J Bacteriol. November 2009, p. 6571-6583, Vol. 191, No. 21.  PMCID: PMC2795308

Zhang Y, Resneck GW, Lee C, Randall RW, Bloch JR, and Ursitti AJ. Characterization and expression of a heart-specific alternatively spliced variant of áII-spectrin, cardi+, during development in the rat. JMCC 48 (2010) 1050-1059.  PMCID: PMC3537504

Weinman EJ, Steplock D, Zhang Y, Biswas R, Bloch RJ, Shenolikar S.  Cooperativity between the phosphorylation of Thr95 and Ser77 of NHERF-1 in the hormonal regulation of renal phosphate transport. J Biol Chem. 2010 Aug 13;285 (33):25134-8. Epub 2010 Jun 22.  PMCID: PMC2919075

Ackermann MA, Ziman AP, Strong J, Zhang Y, Hartford AK, Ward CW, Randall WR, Kontrogianni-Konstantopoulos A, Bloch RJ. Integrity of the network sarcoplasmic reticulum in skeletal muscle requires small ankyrin 1. J Cell Sci. 2011 Nov 1;124 (Pt 21):3619-30. Epub 2011 Nov 1.  PMCID: PMC3215573

Lund LM, Kerr JP, Lupinetti J, Zhang Y, Russell MA, Bloch RJ, Bond M. Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes. FASEB J. 2012 Jan; 26(1):137-48. Epub 2011 Oct 7.  PMCID: PMC3250239