MANSOUREH EGHBALI, Ph.D.
Assistant Researcher
Division of Molecular Medicine
Department of Anesthesiology
David Geffen School of Medicine at UCLA
Los Angeles, California.
Los Angeles, California 90095-7115, USA
Phone: (310) 794 7808
Fax: (310) 825 6649
Email: meghbali@ucla.edu
2001 to present: Assistant Researcher, Department of Anesthesiology, UCLA, Los Angeles, California.
Education:
1983 - 1987 Bachelor of Biomedical Engineering, University of Kerman, Iran
1993 - 1995 Master of Biomedical Engineering, University of New South Wales, Sydney, Australia
1996 – 1999 Ph.D, John Curtin School of Medical Research, Australian National University, Canberra, Australia
1999 – 2001 Postdoctoral Fellow, Department of Anesthesiology, UCLA, Los Angeles, California.
Grant Support:
7/2002-6/2004. American Heart Association, Postdoctoral Fellowship
Regulation of ITO current molecular components.
7/2004-6/2008 American Heart Association, Scientist Development Grant
Heart MiRP1 gene regulation: Gender and Age Differences
My main interest is the molecular remodeling of voltage activated K channels during cell function and disease in heart. In the myocardium, outward K currents are major determinants of cardiac repolarization. Several different types of voltage gated K channels, which mediate the different phases of the repolarization process, have been characterized. Among them, Ito currents (transient outward, rapidly activating and inactivating) and IK (delayed outwardly rectifying K currents) are the two broad classes of Kv channels. Ito currents underlie the early phase of repolarization whereas IK underlies the late phase of repolarization. I am investigating:
1. Molecular mechanism of K channel remodeling in heart functional hypertrophy during pregnancy. During pregnancy, there is an increased risk of arrhythmias and the heart develops functional hypertrophy. In the heart, Kv1.4 and Kv4 channels are important molecular components of transient K currents (Ito currents) that regulate the heart action potential duration. Decreased Kv4.3 mRNA levels have been reported under pathological conditions such as heart failure and heart ischemia, suggesting that Kv4.3 plays a role in heart function. During pregnancy, although there is an increased risk of arrhythmias, the heart develops functional hypertrophy and hormone levels dramatically change. I am focusing on the remodeling of putative Ito current molecular components during pregnancy (Kv1.4, Kv4.2 and Kv4.3 genes and regulatory subunits). My main goals are 1. To investigate the genomic and non-genomic regulation of Ito current molecular components by sex hormones in heart (17ß-estradiol (E2) and other steroids progesterone, P4; testosterone) 2. To characterize the action of external K concentration on the voltage dependence of channel opening and inactivation in Kv4 channels and in native heart Ito currents. 3. To define the role of auxiliary subunits on Kv4 trafficking and targeting 4. To investigate the action of c-Src dependent tyrosine phosphorylation on Ito current and the potential colocalization of Kv4 channels and c-Src.
2. The characterization of the KCNE2 gene and search for potential regulatory elements under hormonal control in heart cells. ERG1 (KCNH2) coassembles with the regulatory subunit MiRP1 (KCNE2) in vivo and produce K current similar to native Ikr (rapid component of IK). Mutations in the MiRP1 subunit are associated with arrythmogenesis and long QT syndrome. Since there are gender and age differences in cardiac arrythmogenesis, my main goals are 1. To define the regulatory mechanisms that determine the expression and function of KCNE2 (MiRP1) and 2. To study the sub-cellular distribution and co localization of MiRP1 and its partner ERG1 (KCNH2), in males and females, during aging and pregnancy in cardiac myocytes.
My study involves multidisciplinary approaches, using molecular biology, biochemical, immunocytochemical and functional techniques. I am using real time PCR for accurate quantification of transcript levels and high resolution confocal microscopy with 3D reconstruction for colocalization of various proteins in the cellular compartments.
Publications:
1. Eghbali M., Curmi J.P., Birnir B., & Gage P.W. (1997). Hippocampal GABAA channel conductance increased by diazepam. Nature 388, 71-75.
2. Eghbali M., Gage P.W. & Birnir B. (2000). Pentobarbital modulates g-aminobutyric acid-activated single-channel conductance in rat cultured hippocampal neurons. Mol. Pharmacol 58(3):463-469.
3. Birnir B., Eghbali M., Everitt A.B. & Gage P.W. (2000). Bicuculline, pentobarbital and diazepam modulate spontaneous GABAA channels in rat hippocampal neurons, British Journal of Pharmacology 131: 695-704.
4. Birnir B., Eghbali M., Cox G.B. & Gage P.W. (2001). GABA concentration sets the conductance of delayed GABAA channels in outside-out patches from rat hippocampal neurons. Journal of membrane biology 181(3):171-183.
5. Zarei M.M., Zhu N., Alioua A., Eghbali M., Stefani E. & Toro L (2001). A novel MaxiK splice varient exhibits dominant negative properties. Journal of Biological Chemistry 276(19):16232-16239.
6. Song M., Helguera G., Eghbali M., Zhu N., Zarei M. M., Olcese R., Toro L. & Stefani E (2001). Remodeling of kv4.3 potassium channel gene expression under the control of sex hormones. Journal of Biological Chemistry 276(34):31883-90. In this paper Song, Helguera and Eghbali equally participated.
7. Eghbali M., Olcese R., Zarei M.M., Toro L. & Stefani E. (2002). External pore collapse as an inactivation mechanism for kv4.3 k+ channels. Journal of Membrane Biology 188(1):73-86.
8. Eghbali M., Gage P.W. & Birnir B. (2003). Effects of propofol on GABA(A) channel conductance in rat-cultured hippocampal neurons. Eur J Pharmacol. 468(2):75-82.
9. Eghbali M., Birnir B & Gage P.W. (2003). Conductance of GABAA channels activated by pentobarbitone in hippocampal neurons from newborn rats. Journal of Physiology. 552(1):13-22.
10. Eghbali M., Toro L. & Stefani E. (2003). Diminished surface clustering and increased perinuclear accumulation of large conductance Ca2+-activated K+ channel in mouse myometrium with pregnancy. Journal of Biological Chemistry 278(46): 45311-7.
11. Nishimaru K., Eghbali M., Stefani E. & Toro L.(2004). Function and clustered expression of MaxiK channels in cerebral myocytes remain intact with aging. Exp Gerontol. 39(5):831-839.
12. Zarei M.M., Eghbali M., Alioua A., Song M., Knaus H.G., Stefani E., Toro L. (2004). An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant. Proc Natl Acad Sci U S A. 101(27):10072-10076. In this paper Zarei, Eghbali and Alioua equally participated.
13. Nishimaru K., Eghbali M., Lu R., Marijic J., Stefani E. & Toro L. (2004). Functional and molecular evidence of MaxiK channel β1subunit decrease with coronary artery ageing in the rat. Journal of Physiology 559(3): 849–862.
14. Ropero A.B., Eghbali M., Toro L.& Stefani E. Differential Subcellular Localization of Estrogen Receptor α Isoforms in Ventricular Cardiomyocytes. Submitted (journal of Biological Chemistry).
15. Lu R., Alioua A., Eghbali M., Stefani E. & Toro L. c-Src tyrosine kinase, a primary step for 5-Hydroxytryptamine contractile signaling in aortic myocytes. Submitted (Circulation Research).
16. Eghbali M., Deva R., Alioua A., Wang Y., Toro L. & Stefani E. Molecular Signature of heart hyprretrophy during pregnancy. Submitted (Circulation Research)
In Preparations:
17. Zhu N., Eghbali M., Helguera G., Stefani E. & Toro L. b-Estradiol mediates transcriptional downregulation of a MaxiK channel splice variant confering differential PKA dependent phosphorylation. In Preparation.
18. Eghbali M., Minosyan T., Toro L. & Stefani E. Kv4.3 and c-Src Can Share the Same Membrane Microenvironment with Caveolin in Rat Heart. In preparation.
19. Eghbali M., Toro L. & Stefani E. High External K+ Promotes Faster Inactivation in Kv4.3 Channels and Heart ITO Currents. In Preparation.
20.Toro L., Conti L., Eghbali M., Mahajan A., Tanaka Y., Stefani E., Vandenberg C. &. Alioua A. Inward rectifier K+ channels (Kir) control muscle tone of a rat conduit vessel: Role of Kir2.x. In Preparation.
21. Deva R., Eghbali M., Ropero A.B., Toro L. & Stefani E . Gender differences in heart estrogen receptor alpha and its regulation by estrogen. In Preparation.
22. Deva R., Eghbali M., Ropero A.B., Toro L. & Stefani E. Changes in heart estrogen receptor alpha during pregnancy. In Preparation.
23. Eghbali M., Kundo P., Deva R., Foroughi S., Toro L. & Stefani. Regulation of heart MiRP1 by local estrogen. In Preparation.
24. Marijic J., Lee J.Y., Eghbali M., Song M. Stefani E. & Toro L. Aging alters regional vascular responses to vasopressin. In Preparation.
25. Alioua, A., Eghbali, M., Han S., Kumar Y., Lu R., Foroughi S., Stefani, E. &Toro L. Functional Consequences of the Voltage-and Ca -Activated Potassium (MaxiK) Channel and Caveolin-1 Direct Protein-Protein Interaction. In Preparation.
Review :
L.Toro, A. Alioua, R. Lu, J. Garcia-Valdes, M. Zarei, K. Nishimaru, M. Eghbali, and E. Stefani (2003). Ca2+-activated, voltage-dependent K+ channels. Ion Channels in the Pulmonary Vasculature. Lung Biology in Health and Disease. C. Lenfant and J. X.-J. Yuan, eds. Marcel Dekker, Inc.
1. Eghbali M., Zhu N., Toro L. & Stefani E. (2001). Rattus norvegicus transient voltage dependent potassium channel Kv4.3 long form mRNA, complete cds. Gene Bank, Accession Number AF334791.
2. Garcia-Valdes, J., Eghbali, M., Stefani, E. & Toro, L (2001). Mouse Kcnmb2 subunit of the large conductance calsium activated K+ channel. Complete cds. Gene bank, Accession Number AY062429.
3. Eghbali M., Foroughi S., Toro L. and Stefani E. (2003). Rattus norvegicus inactivating beta 2 subunit of large conductance Ca2+-activated K+ channel mRNA, complete cds. Gene bank, Accession Number AY191836.
Abstracts:
1. Eghbali M., Birnir B., Curmi J.P. & Gage P.W. (1997). Diazepam increases the conductance of hippocampal GABAA channels. Proceedings of A.P.P.S. 28(2), 50.
2. Birnir B., Eghbali M., Curmi J.P., Cox G.B. & Gage P.W. (1998). Modulation of GABAA single channel conductance. Biophysical Journal, M-P327.
3. Eghbali M., Birnir B. & Gage P.W. (1998). Direct activation of GABAA receptors by pentobarbitone in cultured rat hippocampal neurons. Proceedings of A.P.P.S. 29(2), 119p.
4. Birnir B., Eghbali M., Cox G.B. & Gage P.W. (1998). GABAA single channel conductance is determined by the GABA concentration in outside-out patches from cultured rat hippocampal neurons. Proceedings of A.P.P.S. 29(2), 315p.
5. Birnir B., Eghbali M., Everitt A.B., Cox G.B. & Gage P.W. (1999). Non-synaptic GABA-gated receptors exhibit great plasticity in channel conductance. Biophysical Journal, Tu-P357.
6. Birnir B, Eghbali M & Gage P.W. (1999). Channel conductance of GABAA receptors varies with agonist and modulator concentration. Proceedings of A.P.P.S. 30(2), 65P.
7. Song M., Zhu N., Eghbali M., Toro L. & Stefani E. (2000). Changes of expression levels of Kv4.3 K channels during pregnancy, Biophysical Journal, W-P2648.
8. Eghbali M., Olcese R., Zarei M.M., Toro L. & Stefani E. (2001). External k+ increases the rate of inactivation of kv4.3 k+ channels, Biophysical Journal, 1888-P.
9. Zarei M.M., Zhu N., Alioua A., Eghbali M., Stefani E. & Toro L. (2001). A novel MaxiK splice variant exhibits dominant negative properties. Biophysical Journal, 887-P.
10. Stefani E., Song M., Eghbali M., Olcese R., Helguera G. & Toro L. (2001). b-estradiol induces a specific down regulation of Kv4.3 potassium channel protein expression in rat myometrium. The Endocrine Society Meeting. Denver, CO.June 20-23.
11. Birnir B., Eghbali M. & Gage P.W. (2001). The agonist sets the conductance level of GABAA channels. Society for Neuroscience, 460.5 page 237.
12. Stefani E., Song M., Zhu N., Helguera G., Olcese R., Eghbali M., & Toro L. (2001). Hormonal regulation of ion channels. Workshop on genomics vs non-genomic steroid actions. Spain 131-P31.
13. Eghbali M., Olcese R., Zarei M.M., Toro L. & Stefani E. (2002) . External pore collapse as an inactivation mechanism for Kv4.3 K+ channels. Biophysical Journal, 1117-P.
14. Nishimaru K., Eghbali M., Stefani E. & Toro L. (2002). Aging-associated changes in Maxik channel properties in rat coronary artery. Biophysical Journal, 1198-P.
15. Helguera G., Sforza D., Eghbali M., Toro L & Stefani E. (2002). Changes in global gene expression in rat myometrium at the onset of labor. Biophysical Journal, 3056-P.
16. Eghbali M., Song M., Zarei M.M., Helguera G., Stefani E., & Toro L. (2002). Different mechanisms (transcription vs. trafficking) of MaxiK channel surface expression in rat and mouse lead to diminished surface expression in late-pregnant myometrium. The Endocrine Society Meeting, P1-486.
17. Helguera G., Sforza D., Eghbali M., Toro L. & Stefani E. (2002). Changes in global gene expression in rat myometrium at the onset of labor. The Endocrine Society Meeting, P3-193.
18. Sforza D., Helguera G., Eghbali, M., Mahajan A. & Stefani E. (2002). Global Gene Expression in Mouse Ventricle during Pregnancy-Induced Cardiac Hypertrophy: Contribution of Cell Cycling and Cell Division Genes. American Society of Anesthesiology A-612.
19. Alioua A., Mahajan A., Eghbali M., Stefani E. & Toro L. (2002). Functional and Molecular Identification of Inward Rectifier Type 2 Family (Kir2.x) Channels in Rat Aorta Smooth Muscle. American Society of Anesthesiology A-631.
20. Nishimaru K., Eghbali M., Stefani E. & Toro L. (2002). Mechanism of MaxiK Channel Loss during Aging in Coronary Arteries: Transcriptional Downregulation of Both Pore Forming and Regulatory Subunits. American Society of Anesthesiology A-703.
21. Zhu N., Eghbali, M., Helguera G., Stefani E. & Toro L. (2002). -Estradiol Mediates Transcriptional Downregulation of a MaxiK Splice Variant Confering Differential PKA Dependent Phosphorylation. American Society of Anesthesiology A-707.
22. Eghbali, M., Song M., Helguera G., Toro L. & Stefani E. (2002). Different Cellular Mechanisms in Rats and Mice for the Reduction of BK(Ca++) Channel Surface Expression in Myometrium during Late Pregnancy. American Society of Anesthesiology A-1058.
23. Helguera G., Sforza D., Eghbali M., Toro L. & Stefani E. (2002). Global Gene Expression Changes of Rat Myometrium before and during Labor. American Society of Anesthesiology A-1059.
24. Eghbali M., Toro L. & Stefani E. (2003). High External K+ Promotes Faster Inactivation in Kv4.3 Channels and Heart ITO Currents. Biophysical Journal, 371-P.
25. Rueda A. Alioua A., Eghbali M., Song M., Stefani E. &Toro L. (2003). Expression and intracellular localization of sorcin in vascular smooth muscle. Biophysical Journal, 496-P.
26. Zarei M.M., Eghbali M., Song M., Stefani E. & Toro L. (2003). A Novel ER Trafficking Signal Prevents Surface Expression of a MaxiK Splice Variant. Biophysical Journal, 733 Platform.
27. Eghbali M., Minosyan T., Bravo-Zehnder M., Toro L. & Stefani E. (2003). Kv4.3 and c-Src Can Share the Same Membrane Microenvironment with Caveolin in Rat Heart. Biophysical Journal, 738 Platform.
28. Alioua A., Conti L., Eghbali M., Mahajan A., Tanaka Y., Stefani E., Vandenberg C. & Toro L (2003). Inward rectifier K+ channels (Kir) control muscle tone of a rat conduit vessel: Role of Kir2.x. Biophysical Journal, 1094-P.
29. Eghbali M, Alioua A., Toro L. & Stefani E. (2003). Increased c-Src Activity and Transcriptional Downregulation of Kv4.3 and KChIP2 in Heart Functional Hypertrophy During Pregnancy. Biophysical Journal, 2003-P.
30. Marijic J., Lee J.Y., Eghbali M., Song M. & Toro L.(2003). Aging alters regional vascular responses to vasopressin. American Society of Anesthesiology.A-655
31. Eghbali M., Minosyan T., Toro L. & Stefani E. (2003). Kv4.3 Channel, c-Src Tyrosine Kinase and Caveolin Form a Macromolecular Signaling Complex in Rat Heart. American Society of Anesthesiology.A-702
32. Eghbali M., Toro L. & Stefani E. (2003). High External K+ Modulates Activation and Inactivation of Kv4.3 K+ Channels and Heart ITO Currents. American Society of Anesthesiology.A-727
33. Lu R., Eghbali M., Song M., Stefani E. & Toro L. (2003). Coupling of c-Src to MaxiK Channels Mediating Vasoconstriction is Weakened by Age. American Society of Anesthesiology.A-745.
34. Alioua A. , Kumar Y., Eghbali M., Minosyan T. & Toro L. (2003). Maxi-K, c-Src and Caveolin form a Macromolecular Complex and Colocalize in Brain Lipid Rafts. American Society of Anesthesiology.A-800
35. Deva R. , Eghbali M., Toro L. and Stefani E. (2003). Transcriptional Regulation by Estrogen of Myometrium and Cardiac Kv4.3 K+ Channels. American Society of Anesthesiology.A-1167.
36. Minosyan T., Eghbali M., Alioua A., Lu R., & Stefani E. (2003). Macromolecular Signaling Complexes of Myometrium K+ Channels (MaxiK and Kv4.3). American Society of Anesthesiology.A-1219.
37. Eghbali M., Alioua A., Toro L. & Stefani E. (2003). Molecular Signature of Heart Functional Hypertrophy during Pregnancy. American Society of Anesthesiology.A-1560.
38. Zarei M.M. , Eghbali M., Song M., Stefani E. & Toro L. (2003). A new ER Trafficking Signal Identified in a MaxiK Splice Variant Prevents Protein Expression ASCB,43rd Annual Meeting. 1273-P.
39. Alioua A. , Kumar Y., Lu R., Eghbali M., Stefani E. & Toro L. (2004). Arterial MaxiK, c-Src and 5-HT2A Receptors Strategically Colocalize in Lipid Rafts and Form a Macromolecular Complex for Efficient Arterial Tone Control. Biophysical Journal, 49-Platform.
40. Deva R., Eghbali M., Ropero A.B., Toro L. &Stefani E. (2004). Heart Transcript Levels of Estrogen Receptor Alpha but not Beta Are Under Hormonal Control. Biophysical Journal, 255-P.
41. Ropero A.B., Deva R., Eghbali M., Alioua A., Toro L. &Stefani E. (2004). Estrogen Receptor Alpha Localizes In Several Subcellular Compartments In Adult Rat Cardiomyocytes. Biophysical Journal, 256-P.
42. Alioua A., Lu R., Garcia J., Eghbali M., Stefani E. & Toro L. (2004). Diminished MaxiK Channel Expression Alters 5-HT-Induced Contraction in Aged Rat Aorta. Biophysical Journal, 640-P.
43. Kumar Y., Alioua A., Eghbali M., Minosyan T., Stefani E. & Toro L. (2004). Brain MaxiK Channel, c-Src and Caveolin-1 Macromolecular Complex: Lipid raft and Microvessel Localization. Biophysical Journal, 642-P.
44. Lu R., Alioua A., Eghbali M., Stefani E. & Toro L. (2004). Activation of c-Src Tyrosine Kinase as a Primary Step in 5-HT Receptor Mediated Vasoconstriction is Supported by Their Colocalization in Aortic Myocytes. Biophysical Journal, 1193-P.
45. Minosyan T., Eghbali M., Alioua A., Toro L. &Stefani E. (2004). Serotonin Receptors, Caveolin, and c-Src Form Part of the Same Macromolecular Complex in Rat Myometrium and Are Upregulated in Late Pregnancy. Biophysical Journal, 1194-P.
46. Garcia J., Alioua A., Eghbali M., Stefani E. & Toro L. (2004). Different Pattern of Expression and Subcellular Localization of c-Src, Yes, and Fyn in Rat Aortic Myocytes. Biophysical Journal, 2037-P.
47. Eghbali M., Toro L. & Stefani E. (2004). High Resolution Confocal Microscopy and 3D Deconvolution Reveals that Membrane and Cytosolic Proteins Can Be Organized in Distinct Cluster Patterns. Biophysical Journal, 2310-P.
48. Eghbali M., Toro L. & Stefani E. (2004). MaxiK Channel Localizes in Dense Clusters at the Surface of Non-pregnant Mouse Myometrial Cells and Becomes Undetectable in Late Pregnancy. Biophysical Journal, 2705-Platform.
49. Ropero A.B., Eghbali M., Deva R., Toro L. &Stefani E. (2004). A 43kDa form of estrogen receptor alpha (ER) associates with membrane structures in rat male hearts. FASEB meeting.(Steroid Hormone Receptors) P3-2.
50. Zarei M.M, Eghbali M., Alioua A., Stefani E., &Toro L. (2004). A new ER Trafficking Signal Identified in a Smooth Muscle MaxiK Splice Variant Prevents Channel Protein Expression. American Society of Anesthesiology. A-671
51. Alioua A, Garcia J., Eghbali M., Lu R., & Toro L. (2004). c-Src, Yes, and Fyn in Rat Aortic Myocytes: Functional Role, Quantification and Subcellular Localization. American Society of Anesthesiology.A-672
52. Lu R., Alioua A., Eghbali M., Stefani E. & Toro L. (2004). Src Tyrosine Kinase Activation is Critical for 5-Hydroxytriptamine Contractile Signaling in Aortic Myocytes. American Society of Anesthesiology.A-675
53. Alioua A. , Kumar Y., Lu R., Eghbali M., & Toro L. Caveolae Disruption Uncouples 5-HT2A Receptor Contractile Signaling Complex CoAssembled by MaxiK, c-Src and Caveolin-1. American Society of Anesthesiology. A-687.
54. Ropero A.B., Eghbali M., Deva R., Toro L. &Stefani E. (2004). A 43kDa Form of Estrogen Receptor alpha Localizes in Several Subcellular Membrane Compartments In Adult Rat Cardiomyocytes. American Society of Anesthesiology.A-702.
55. Deva R., Eghbali M., Ropero A.B., Toro L. &Stefani E. (2004). Hormonal Regulation of Heart Transcript Levels of Estrogen Receptor Alpha. American Society of Anesthesiology. A-734
56. Minosyan T., Eghbali M., Ph.D., Alioua A., Toro L., & Stefani E., (2004). Regulation During Pregnancy of the Macromolecular Complexes Formed by Serotonin Receptors (5HT2A), Caveolin, and Tyrosine kinase (c-Src). American Society of Anesthesiology.A-1182.
57. Eghbali M., Deva R., Alioua A., Wang Y., Toro L. & Stefani E. (2005). Molecular Signature of Heart Hypertrophy in Mice During Pregnancy. Biophysical Journal, 585-P
58. Ropero A.B., Eghbali M., Toro L. &Stefani E. (2005). Different Subcellular Localization but Similar Downregulation Regulation by Estrogen of the Two Estrogen Recetpor alpha Isoforms of 66 and 43 kDa in Adult Rat Cardiomyocytes. Biophysical Journal, 1512-P
59. Stefani E., Grabarchuk V., Eghbali M., Ropero A.B. &Toro L. (2005). Discrete Protein-Protein Proximity (“Colocalization”) Analysis in Microscopic Images. Biophysical Journal, 1674-P
60. Gomes P.B., Crosso C., Eghbali M., Ropero A.B., Alioua A., Toro L. &Stefani E. (2005). Upregulation of Kv4.3 channel activity by c-Src tyrosine kinase dependent phosphorylation. Biophysical Journal, 2235-P