Make your own free website on Tripod.com
   

Aldrin V. Gomes, Ph.D.

Cardiovascular Research Laboratory
Departments of Physiology and Medicine/Cardiology
David Geffen School of Medicine
University of California, Los Angeles (UCLA)
Room 1609, MRL Building
675 Charles E. Young Drive South
Los Angeles, CA 90095
Tel (310) 267-5624
Fax (310) 267-5623

e-mail: avgomes@mednet.ucla.edu


  Curriculum Vitae
Ph.D. Biochemistry University of the West Indies, St. Augustine, Trinidad 1998
Postdoctoral Fellow University of Miami School of Medicine 1999-2004
Assistant Research Physiologist University of California, Los Angeles 2004-Present
 
 

RESEARCH


I am interested in basic molecular mechanisms of signal transduction, particularly in muscle contraction and cardiovascular disease.



PROTEIN DEGRADATION

Most proteins are degraded by the Proteasome. However, the role of the Proteasome in cardiac physiology and pathophysiology is not well understood. Molecular signals present in the primary amino acid sequence of proteins contain regions rich in proline (P), glutamic acid (E), serine (S) and threonine (T), called PEST regions, which are believed to be putative signals for rapid intracellular degradation. Other proteins also contain sequences biochemically related to the pentapeptide sequence KFERQ, which is known to target proteins for lysosomal proteolysis. How these possible signal sequences are involved in degradation of these proteins, if at all, is not known but is of great interest to the entire scientific community.

Gomes, A.V. Zong, C., Edmondson, R., Li, X., Stefani, E., Zhang, J., Jones, R.C., Thyparambil, S., Wang, G.W., Qiao, X., Bardag-Gorce, F., Ping, P. (2006) Mapping the Murine Cardiac 26S Proteasome Complexes. Circulation Research 99:362-71.

Zong, C., Gomes, A.V. Drews, O., Li, X., Young, G.W., Berhane, B., Qiao, X., French, S.W., Bardag-Gorce, F., Ping, P. (2006) Regulation of Murine Cardiac 20S Proteasomes: Role of Associating Partners. Circulation Research 99:372-80.

Gomes, A.V. Zong, C., Ping, P. (2006) Protein Degradation by the 26S Proteasome System in the Normal and Stressed Myocardium. Antioxidants & Redox Signaling 9/10:1677-1691.

Gomes, A.V. et al., (2005) Murine Cardiac 26S Proteasome: An Organelle Awaiting Exploration. Ann N Y Acad Sci. 1047, 197-207.

Barnes, J.A,, Singh, S., Gomes, A.V. (2005) Protease activated receptors in cardiovascular function and disease. Mol. Cell Biochem. 263, 227-39.

Barnes, J.A,, Gomes, A.V. (2002) Proteolytic signals in the primary structure of annexins. Mol. Cell Biochem. 231, 1-7.

Cuervo A.M., Gomes A.V., Barnes J.A., Dice J.F. (2000) Selective Degradation of Annexins by Chaperone-mediated Autophagy. J. Biol. Chem. 275, 33329-33335.

Ca2+ Regulation of Muscle Contraction

Previous studies have suggested that the primary role for troponin T (TnT) is to interact with and anchor the complex of troponin I (TnI) and troponin C (TnC) to the thin filaments through TnT's interaction with tropomyosin (Tm). Recent results from Dr. James D. Potter Lab suggest that in addition to this role, TnT may have two additional functions that have important physiological consequences. The first is that the carboxy-terminus of TnT appears to play a direct role in the Ca2+-dependent regulation of contraction through its interaction with TnC. The second is that the hypervariable NH2-terminal region of TnT appears to play a role in determining the level of potentiation of actomyosin ATPase activity, and would be expected to affect the contractile properties of muscle as well.

Gomes, A.V., Liang, J., Potter J.D. (2005). Mutations in human cardiac troponin I that are associated with restrictive cardiomyopathy affect basal ATPase activity and the calcium sensitivity of force development. J. Biol Chem. 280, 30909-15.

Gomes, A.V., Harada, K., Potter J.D. (2005). A Hypertrophic Cardiomyopathy Mutation in the N-terminal of Troponin I affects the Ca2+-Sensitivity, Phosphorylation Kinetics and Proteolytic Susceptibility of Troponin. J. Mol. Cell. Cardiol. 39, 754-65.

Venkatraman, G., Gomes, A.V., Kerrick, W.G., Potter J.D. (2005) Characterization of troponin T dilated cardiomyopathy mutations in the fetal troponin isoform. J. Biol Chem. 280, 17584-92.

Gomes, A.V., Venkatraman, G., Davis, J.P., Tikunova, S.B., Engel, P., Solaro, R.J., Potter J.D. (2004) Cardiac troponin T isoforms affect the Ca2+ sensitivity of force development in the presence of slow skeletal troponin I: Insights into the role of troponin T isoforms in the fetal heart. J. Biol Chem. 279, 49579-87.

Venkatraman, G., Harada K., Gomes, A.V., Kerrick, W.G., Potter, J.D. (2003) Different functional properties of troponin T mutants that cause dilated cardiomyopathy. J. Biol Chem. 278, 41670-6.

Gomes, A.V., Guzman, G., Zhao, J., Potter, J.D. (2002) Cardiac troponin T isoforms affect the Ca2+-sensitivity and inhibition of force development: insights into the role of troponin T isoforms in the heart. J. Biol Chem. 277, 35341-35349.

Lang, R., Gomes, A.V., Zhao, J., Housmans, P.R., Miller, T., Potter, J.D. (2002) Functional Analysis of a Troponin I (R145G) Mutation Associated with Familial Hypertrophic Cardiomyopathy. J. Biol. Chem. 277, 11670-11678.

Miller, T., Szczesna, D., Housmans, P.R., Zhao, J., de Freitas, F., Gomes, A.V., Culbreath, L., McCue, J., Wang, Y., Xu, Y., Kerrick, W.G. and Potter, J.D. (2001) Abnormal Contractile Function in Transgenic Mice Expressing an FHC-Linked Troponin T (I79N) Mutation. J. Biol. Chem. 276, 3743-3755.

Szczesna, D., Ghosh, D., Li, Q., Gomes, A.V., Guzman, G., Arana, C., Zhi, G., Stull, J.T., Potter, J.D.(2001) Abnormal Familial hypertrophic cardiomyopathy mutations in the regulatory light chains of myosin affect their structure, Ca2+ binding and phosphorylation. J. Biol. Chem. 276, 7086-7092.

Recent Reviews

Gomes, A.V., Venkatraman, G., Potter, J.D. (2005) The miscommunicative cardiac cell: when good proteins go bad. Ann N Y Acad Sci. 1047, 30-7.

Gomes, A.V., Potter, J.D. (2004) Cellular and molecular aspects of familial hypertrophic cardiomyopathy caused by mutations in the cardiac troponin I gene. Mol Cell Biochem. 163, 99-114

Gomes, A.V., Barnes, J.A., Harada, K., Potter, J.D. (2004) Role of troponin T in disease. Mol. Cell. Biochem. 263, 115-129

Gomes, A.V., Potter, J.D. (2004) Molecular and cellular aspects of troponin cardiomyopathies. Ann N Y Acad Sci. 1015, 214-24.

Gomes, A.V., Keita, H., and Potter, J.D. (2002) Cation signaling in Striated Muscle Contraction. In Molecular Control Mechanisms in Striated Muscle Contraction Eds. Solaro, R.J., and Moss, R.L. Kluwer Academic Publishers, Netherlands, 163-197.

Gomes, A.V., Potter, J.D., Szczesna, D. (2002) Role of Troponin in Muscle Contraction. IUBMB Life. 54, 323-333.

Calcium-binding Proteins

The isolation and characterization of calcium-binding proteins (such as calmodulin and troponin c) and investigation of how these proteins interact with calcium. Although more than 70 calmodulin-binding proteins are known, less than half of these proteins are characterized. Calmodulin is a ubiquitous calcium-binding protein which is critical for many cellular processes including memory and growth. Understanding the mechanism by which intracellular calmodulin is regulated is vital to the overall understanding of the second messenger function of calcium.

Yuan, T., Gomes, A.V., Barnes, J.A., Hunter, H.N. and Vogel, H.J. (2004) Spectroscopic characterization of the calmodulin-binding and autoinhibitory domains of calcium/calmodulin-dependent protein kinase I. Arch. Biochem. Biophys. 421, 192-206.

Gutierrez-Ford, C., Levay, K., Gomes, A.V., Perera, E.M., Som, T., Kim, Y.M., Benovic J.L., Berkovitz G.D., Slepak V.Z. (2003) Characterization of Tescalcin, a Novel EF-Hand Protein with a Single Ca2+-Binding Site: Metal-Binding Properties, Localization in Tissues and Cells, and Effect on Calcineurin. Biochemistry 42, 14553-14565.

Gomes A.V., Barnes J.A., Vogel H.J. (2000) Spectroscopic characterization of the interaction between calmodulin-dependent protein kinase I and calmodulin. Arch Biochem Biophys. 379, 28-36.

Related links

Calmodulin
Calcium-binding Database
- Basic information on more than 30 EF-hand Calcium-binding proteins
Prof. H. J. Vogel (University of Calgary)
Prof. B. Sykes (University of Alberta)
Prof. J.D. Potter (University of Miami)

                                               
Protein gel electrophoresis troubleshooting guide

All you need to know about Biochemistry
 

Bioinformatics Troponin Recent Abstracts

Students that I Supervise
Lab Pictures
Former Research Projects
My links to Fun Sites

                
July 2006