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Dr. Shai D. Silberberg: Curriculum Vitae

1. PERSONAL DETAILS

Name:
Shai D. Silberberg

2. EDUCATION

1978-1981	B.Sc. - Jerusalem; Biology; Summa cum laude. Received Summer Research Scholarship for academic achievements
1982	M.Sc. - Hebrew University-Hadassah Medical School, Jerusalem; Department of Physiology. Advisor: Prof. Rami Rahamimoff. Accepted to the "direct path" program for Ph.D.
1982-1987	Ph.D. - Hebrew University-Hadassah Medical School, Jerusalem; Department of Physiology. Advisor: Prof. Rami Rahamimoff. Title of Thesis: Depression - Frequency modulation at the neuromuscular junction of the frog. Received Bird Award for academic and research achievements.

3. EMPLOYMENT HISTORY

1982-1985	Teaching Assistant in the "General Physiology" course for medical students and in the "Biophysics and Physiology of Excitable Tissue" lab course. Hebrew University Hadassah Medical School, Jerusalem.
1985-1987	Instructor in the "General Physiology" course for medical students. Hebrew University Hadassah Medical School, Jerusalem.
1987-1989	Research Associate, Department of Physiology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas.
1989-1990	Research Associate, Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida.
1990-1993	Research Assistant Professor, Dept. of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida.
1992-1993	Research Assistant Professor, Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida.
1993-1998	Lecturer, Dept. of Life Sciences, Ben Gurion University, Beer Sheva, Israel.
1998-present	Senior Lecturer, Dept. of Life Sciences, Ben Gurion University, Beer Sheva, Israel
1999	Tenure

3. Courses Taught

1999	“Animal physiology” course for B.Sc. students. Ben Gurion University, Beer Sheva. (Joint teaching).
1996	"Physiology lab course" course for B.Sc. students. Ben Gurion University, Beer Sheva. (Joint teaching).
1995-1998	"The cardiovascular system" course for B.Sc. and M.Sc. students. Ben Gurion University, Beer Sheva. (Joint teaching).
1995	"Ion channels: Structure, Function, and Regulation" course for B.Sc. and M.Sc. students. Ben Gurion University, Beer Sheva
1994-1995	"Principals of Biochemistry B" course for B.Sc. students. Ben Gurion University, Beer Sheva. (Joint teaching).
1990-1992	"Medical Pharmacology"; Medical students; University of Miami, Florida. (Joint teaching).
1985-1987	Instructor in the "General Physiology" course for medical students. Hebrew University, Jerusalem. (Joint teaching).
1982-1985	Assistant in the "General Physiology" course for medical students. Hebrew University, Jerusalem. (Joint teaching).
1983-1984	Assistant in the "Biophysics and Physiology of Excitable Tissue" lab course. B.Sc. and M.Sc. students. (Joint teaching).

Memberships in professional / scientific societies

Biophysical Society.

Israel Society for Neurosciences.

srael Society for Physiology and Pharmacology.

4. Scientific Publications

(a) Chapters in collective volumes - conference proceedings

1. Abdul-Ghani, M.A., Silberberg, S.D., Johnston, M.F., Kravitz, E.A., Meiri, H. and Rahamimoff, R. (1986). The role of peptides released by small cell carcinoma of the lung on neuromuscular transmission: Calcitonin. In: Calcium, Neuronal Function and Transmitter Release, eds. R. Rahamimoff and B. Katz, Martinus Nijhoff Publishing, U.S.A., pp. 593-601.

2. Rahamimoff, R., Silberberg, S.D., Nussinovitch, I. and Ginsburg, S. (1986). Cellular basis of plasticity in synaptic transmission. In: Sensorimotor Plasticity: Theoretical, Experimental and Clinical Aspects, eds. S. Ron, R. Schmid and M. Jeannerod, Les Edition Inserm, Paris, pp. 17-44.

3. Rahamimoff, R., Silberberg, S.D. and Ginsburg, S. (1987). The role of calcium ions in the regulation of transmitter release. In: Current Advances in Skeleto-genesis Vol. 3. eds. S. Horovitz and J. Sela, Jerusalem, Heiliger Publishing Co., pp. 3-12.

4. Rahamimoff, R., Abdul-Ghani, M., DeRiemer, S.A., Ginsburg, S., Sakmann, B., Shapira, R., Silberberg, S.D., Stadler, H. and Yakir, N. (1988). Regulation of acetylcholine release: calcium, peptide channels and vesicle. In: Neuromuscular Junction, eds. L.C. Sellin, R. Libelius and S. Thesleff, Elsevier Science Publishers (Biomedical Division), pp. 125-136.

5. *Silberberg, S.D., Korngreen, A., Ma, W., Uzlaner, N. and Priel, Z. (2001). Modulation of ciliary motility by Na⁺. In: Cilia, Mucus, and Mucociliary Interactions, eds. M. Salathe, P. Satir, K.B. Adler and R.C. Boucher, Marcel Dekker Inc. in Press (accepted September, 2000).

(b) Refereed articles in scientific journals

1. Silberberg, S.D., Ginsburg, S. and Rahamimoff, R. (1986). Neuromuscular depression. Rev. Clin. Basic Pharmacol., 6, 15s-21s.

2. Shapira, R., Silberberg, S.D., Ginsburg, S. and Rahamimoff, R. (1987). Activation of Protein kinase C augments evoked transmitter release. Nature 325, 58-60.

3. Silberberg, S.D., Poder, T.C. and Lacerda, A.E. (1989). Endothelin increases single-channel calcium currents in coronary arterial smooth muscle cells. FEBS Lett. 247, 68 72.

4. Silberberg, S.D. and van Breemen, C. (1990). An ATP, calcium and voltage sensitive potassium channel in porcine coronary artery smooth muscle cells. Biochem. Biophys. Res. Com. 172, 517-522.

5. Gelband, C.H., Silberberg, S.D., Groschner, K., and van Breemen, C. (1990). ATP inhibits smooth muscle Ca2+-activated K+ channels. Proc. R. Soc. Lond. B 242, 23-28.

6. Groschner, K., Silberberg, S.D., Gelband, C.H. and van Breemen, C. (1991). Ca2+-activated K+ channels in airway smooth muscle are inhibited by ATP. Pflügers Arch. 417, 517-522.

7. Poder, T.C., Silberberg, S.D. and Rampe, D. (1991). Contraction of reptile, amphibian and fish blood vessels by endothelin-1. Can. J. Physiol. Pharmacol. 69, 215-217.

8. Silberberg, S.D. and van Breemen, C. (1992). A potassium channel activated by lemakalim and metabolic inhibition in rabbit mesenteric artery. Pflügers Arch. 420, 118-120.

9. Silberberg, S.D. and Magleby, K.L. (1993). Preventing errors when estimating single channel properties from the analysis of current fluctuations. Biophys. J. 65, 1570-1584.

10. Silberberg, S.D. Lagrutta, A., Adelman, J.P., and Magleby, K.L. (1996). Wanderlust kinetics and variable Ca2+ sensitivity of dSlo, a large conductance Ca2+-activated K+ channel, expressed in oocytes. Biophys. J. 70, 2640-2651.

11. Silberberg, S.D. and Magleby, K.L. (1997). Voltage-induced slow activation and deactivation of mechanosensitive channels in Xenopus oocytes. J. Physiol. 505, 551-569.

12. Korngreen, A., Ma, W., Priel, Z. and Silberberg, S.D. (1998). Extracellular ATP directly gates a cation-selective channel in rabbit airway ciliated epithelial cells. J. Physiol. 508, 703-720.

13. *Moss, B. L., Silberberg, S. D., Nimigean, C. M. and Magleby, K. L. (1999). Ca²⁺-dependent gating mechanisms for dSlo, a large conductance Ca²⁺-activated K⁺ channel. Biophys. J. 76, 3099-3117.

14. *Gil, Z., Magleby, K. L., and Silberberg, S. D. (1999). Membrane-pipette interactions underlie delayed voltage activation of mechanosensitive channels in Xenopus oocytes. Biophys. J. 76, 3118-3127.

15. *Ma, W., Korngreen, A., Uzlaner, N., Priel, Z. and Silberberg S. D. (1999). Extracellular Na⁺ regulates airway ciliary motility by inhibiting a P2X receptor. Nature, 400, 894-897.

16. *Gil, Z., Silberberg, S.D., and Magleby, K.L. (1999). Voltage-induced membrane displacement in patch pipettes activates mechanosensitive channels. PNAS, 96, 14594-14599.

17. *Braiman, A., Silberberg, S. D., and Priel, Z. (2000). Purinergic stimulation of ciliary activity in mucociliary systems. Drug Dev. Res., 50, 550-554.

18. *Gincel, D., Silberberg, S.D., and Shoshan-Barmatz, V. (2000). Brain synaptosomal voltage-dependent anion channel: purification, permeability, and subcellular localization. J. Bioenerg. Biomembr., 32, 571-583.

19. *Ruppelt, A., Ma, W., Borchardt, K., Silberberg S.D. and Soto F. (2001). Genomic structure, developmental distribution and functional properties of the chicken P2X₅ receptor. J. Neurochem., 77, 1256-1265.

20. *Gil, Z., Magleby, K. L. and Silberberg S. D. (2001). Two-dimensional kinetic analysis suggests non-sequential gating of mechanosensitive channels in Xenopus oocytes. Biophys. J., in press.

*Silberberg, S.D. and Magleby, K.L. (1999). Beating the Odds with Big K. Science, 285, 1859-1860. (Invited Editorial Comment).

5. RESEARCH GRANTS

1991	Granting Institution: American Heart Association Florida Affiliate. Grantees: Shai D. Silberberg. Subject: Calcium activated potassium channel of vascular smooth muscle. Period of grant: two years; $71,000
1994	Granting Institution: United States - Israel Binational Science Foundation. Grantee: Shai D. Silberberg (Karl L. Magleby, U.S. Collaborating Investigator). Subject: Identification of molecular structures involved in BK channel gating. Period of grant: three years, $111,500.
1994	Granting Institution: The Ministry of Science and the Arts. Grantee: Shai D. Silberberg. Subject: Identification of cellular factors involved in BK channel gating. Period of grant: three years, approximately $35,000.
1995	Granting Institution: The Israel Science Foundation. Grantee: Shai D. Silberberg (PI) and Zvi Priel. Subject: Involvement of membrane conductances in muco-ciliary activation and regulation. Period of grant: three years, $134,550.
1995	Granting Institution: The Israel Science Foundation. Grantee: Shai D. Silberberg (PI) and Zvi Priel. Subject: An integrated system for simultaneous, high resolution, ciliary motility measurement and patch clamp recording. Period of grant: Equipment grant, $25,000 from the ISF and $45,000 matching from BGU.
1998	Granting Institution: The Israel Science Foundation. Grantee: Shai D. Silberberg (PI) and Zvi Priel. Subject: Reconstruction of the biochemical pathways underlying purinergic regulation of mucociliary activity using the patch-clamp technique Period of grant: three years, $105,000.
2000	Granting Institution: The Israel Science Foundation. Grantee: Zvi Priel (PI), Michael Danilenko (PI), and Shai D. Silberberg (CI). Subject: Interplay between protein phosphorylation and intracellular calcium in ciliary stimulation. Period of grant: four years, first year- $79,490 ($60,000 + $19,490 for equipment).
2002	Granting Institution: German-Israeli Foundation for Scientific Research and Development. Grantee: Shai D. Silberberg and Florentina Soto (German collaborator). Subject: Elucidation the molecular structure of the ATP-activated channel in airway ciliated cells. Period of grant: three years, EURO 194,100.

6. RESEARCH STUDENTS

1995	Jasmin Fisher, Research project.
1996-1998	Jasmin Fisher, M.Sc.
1996	Noga Burstein, Research project.
1997	Elya Levi, Research project.
1997	Amit Nehushtan, Research project.
1997	Weiyuan Ma, Ph.D. (in collaboration with Prof. Zvi Priel).
2000	Avi Priel, M.Sc.
2000	Enbal Ben-tal, M.Sc.
2000	Noga Hermoni, Research project.
2000	Sharon Jessen , Research project.
2000	Irit Ya’acobovich, Research project.

Instructed and supervised in my laboratory the research of the following Ph.D. students on ion channel physiology and Biophysics, using the patch-clamp technique:

1994-1997	Alon Korngreen (see publications 12 and 15)
1997-2000	Ziv Gil (see publications 14,16 and 20)

7. PRESENT ACTIVITIES

Involvement of membrane conductances in mucociliary activation and regulation.

The mucociliary system is responsible for maintaining the airways clean of inhaled particles and pathogens. This immense task is performed by ciliated cells, which transport the mucus from the lungs to the upper airways. Ciliary Beat Frequency (CBF) is strongly regulated by hormones and neurotransmitters, thus providing fine control over the efficiency of mucus transport. In collaboration with Prof. Zvi Priel from the Department of Chemistry we aim to elucidate the biochemical mechanisms underlying the stimulation of mucociliary beating by extracellular nucleotides. To this end, we are using the patch-clamp technique to control the composition of the intracellular environment of single freshly dissociated rabbit airway ciliated cells, and then monitor the effects of ATP and UTP on membrane conductances. We are also simultaneously measuring ciliary activity in the same cell. The combination of patch-clamp recording with CBF measurements provides a unique means to investigate the relationship between the transduction pathway and the end biological effect in the same cell.

Elucidate the molecular structure and subunit composition of the P2X_cilia receptor.

The unraveling physiological importance of purinergic receptors in airway mucociliary function, has promoted interest in the mechanisms underlying stimulation of mucociliary clearance by ATP, and has led to the development of new strategies to treat obstructive airway disorders such as cystic fibrosis (CF). Thus, inhalants containing either UTP or UTP analogs, which target a P2Y receptor in the ciliated cells, are being developed. Our recent discovery that airway ciliated cells express an UTP-insensitive P2X receptor (P2X_cilia receptor), which is modulated by Na⁺, lends way to the development of novel treatments targeting this P2X pathway. The rational development of such drugs, and the unraveling of the mechanism of Na⁺ inhibition, would be greatly facilitated if the molecular structure of P2X_cilia receptor were known. Hence, in collaboration with Dr. Soto from the Department of Molecular Biology of Neuronal Signals, Max-Planck Institute for Experimental Medicine, Göttingen, we are attempting to elucidate the molecular structure and subunit composition of the P2X_cilia receptor.

Regulation of mechanosensitive channels by voltage.

Mechanosensitive (MS) channels are implicated in a variety of cellular functions including volume regulation and mechanoreception. MS channels activated by membrane stretch typically activate rapidly (within ms) and deactivate rapidly when the stretch is removed. Using the patch clamp technique, we found that MS channels in Xenopus oocytes can have an uncommonly slow response to step changes in voltage in the absence of applied stretch. The mechanisms underlying this slow cooperative activation of MS channels by voltage and the steady state voltage-dependence of the MS channels are being investigated.

Last Updated: 20/12/2005