Francesco Tombola, Ph.D.
Education
| 2003 – 2008 | Postdoctoral | University of California, Berkeley | Biophysics |
| 2001 – 2003 | Postdoctoral | University of Padua, Italy | Biophysics |
| 2001 | Ph.D. | University of Padua, Italy | Molecular & Cellular Biology & Pathology |
| 1994 | B.S. – M.S. | University of Padua, Italy | Chemistry |
Positions and Employment
| 2023 – | Assoc. Dean for Graduate and Postdoctoral Studies, UCI School of Medicine |
| 2023 – | Professor of Physiology and Biophysics, UC Irvine |
| 2021 – 2023 | Vice-Chair, Dept. of Physiology & Biophysics, UC Irvine |
| 2018 – 2021 | Graduate Faculty Advisor, Dept. of Physiology & Biophysics, UC Irvine |
| 2015 – 2023 | Associate Professor of Physiology and Biophysics, UC Irvine |
| 2008 – 2015 | Assistant Professor of Physiology and Biophysics, UC Irvine |
| 2005 – 2008 | Research Specialist, UC Berkeley |
| 2005 | Instructor of Neurobiology, University of Padua, Italy |
| 2003 – 2005 | Postdoctoral Fellow, UC Berkeley |
| 2002 | Lecturer of Biochemistry, University of Bologna, Italy |
| 2001 – 2003 | Postdoctoral Fellow, University of Padua, Italy |
Honors
| 2017 | Paul F. Cranefield Award from the Society of General Physiologists |
| 2004 – 2006 | American Heart Association WSA Postdoctoral Fellowship |
| 2002 | University of Padua Postdoctoral Fellowship |
| 2001 | Young Investigator Award, University of Padua |
| 2001 | Italian National Research Council Fellowship |
| 1997 – 2000 | Doctoral Fellowship of the Italian Ministry of Education |
| 1996 | Italian Telethon Fellowship |
Publications
55. C. Zhao, P.D. Webster, A. De Angeli, F. Tombola (2023) Mechanically-primed voltage-gated proton channels from angiosperm plants. Nature Commun. 14:7515.
54. S. Noh, F. Tombola, P. Burke (2023) Allostery: Nanowire biosensors with olfactory proteins: towards a genuine electronic nose with single molecule sensitivity and high selectivity. Nanotechnology 34: 465502.
53. C. Zhao, L. Hong, S. Riahi, V.T. Lim, D.J. Tobias, F. Tombola (2021) A novel Hv1 inhibitor reveals a new mechanism of inhibition of a voltage-sensing domain. J. Gen. Physiol. 153(9): e202012833.
52. C. Zhao, L. Hong, J.D. Galpin, S. Riahi, V.T. Lim, P.D. Webster, D.J. Tobias, C.A. Ahern, F. Tombola (2021) HIFs: new arginine mimic inhibitors of the Hv1 channel with improved VSD-ligand interactions. J. Gen. Physiol. 153(9): e202012832.
51. C. Zhao & F. Tombola (2021) Voltage-gated proton channels from fungi highlight role of peripheral regions in channel activation. Commun. Biol. 4: 261.
50. V.T. Lim, J.A. Freites, F. Tombola, D.J. Tobias (2021) Thermodynamics and Mechanism of the Membrane Permeation of Hv1 Channel Blockers. J. Membr. Biol. 254: 5-16.
49. V.T. Lim, A.D. Geragotelis, N.M. Lim, J.A. Freites, F. Tombola, D. Mobley, D. Tobias (2020) Insights on small molecule binding to the Hv1 proton channel from free energy calculations with molecular dynamics simulations. Sci. Rep. 10: 13587.
48. A.D. Geragotelis, M.L. Wood, H. Göddeke, L. Hong, P.D. Webster, E.K. Wong, J.A. Freites, F. Tombola, D.J. Tobias (2020) Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations. Proc. Nat. Acad. Sci. USA 117 (24) 13490-13498.
47. R. Kautz, L. Phan, J. Arulmoli, A. Chatterjee, J.P. Kerr, M. Naeim, J. Long, A. Allevato, J.E. Leal-Cruz, L. Le, P. Derakhshan, F. Tombola, L.A. Flanagan, A.A. Gorodetsky (2020) Growth and Spatial Control of Murine Neural Stem Cells on Reflectin Films. ACS Biomater. Sci. Eng. 6(3): 1311-1320.
46. K.L. Ellefsen, J.R. Holt, A.C. Chang, J.L. Nourse, J. Arulmoli, A.H. Mekhdjian, H. Abuwarda, F. Tombola, L.A. Flanagan, A.R. Dunn, I. Parker, M.M. Pathak (2019) Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca2+ flickers. Commun. Biol. 2: 298.
45. M.L. Wood, J.A. Freites, F. Tombola, and D.J. Tobias (2017) Atomistic Modeling of Ion Conduction through the Voltage-Sensing Domain of the Shaker K+ Ion Channel. J. Phys. Chem. B. 121(15):3804-3812.
44. M.M. Pathak, T. Tran, L. Hong, B. Joós, C.E. Morris, and F. Tombola (2016) The Hv1 proton channel responds to mechanical stimuli. J. Gen. Physiol. 148(5): 405-418.
43. L. Phan, R. Kautz, J. Arulmoli, I.H. Kim, D-T.T. Le, M.A. Shenk, M.M. Pathak, L.A. Flanagan, F. Tombola, A.A. Gorodetsky (2016) Reflectin as a material for neural stem cell growth. ACS Appl. Mater. Interfaces 8(1): 278-284.
42. L. Hong & F. Tombola, (2016) Allostery: A lipid two-step Nat. Chem. Biol. 12(4): 202-3.
41. L. Hong, V. Singh, H. Wulff, F. Tombola (2015) Interrogation of the intersubunit interface of the open Hv1 proton channel with a probe of allosteric coupling. Sci. Rep. 5: 14077.
40. J. Arulmoli, M.M. Pathak, L. McDonnell, J.L. Nourse, F. Tombola, J. Earthman, L.A. Flanagan (2015) Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner Sci. Rep. 5: 8499.
39. M.M. Pathak, J.L. Nourse, T. Tran, J. Hwe, J. Arulmoli, D-T.T. Le, E. Bernardis, L.A. Flanagan, F. Tombola (2014) Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc. Nat. Acad. Sci. USA 111(45):16148-53.
38. I.H. Kim, P. Hevezi, C. Varga, M.M. Pathak, L. Hong, D. Ta, C.T. Tran, A. Zlotnik, I. Soltesz, F. Tombola (2014) Evidence for functional diversity between the voltage-gated proton channel Hv1 and its closest related protein HVRP1. PLoS One Aug 28;9(8):e105926.
37. L. Hong, I.H. Kim, F. Tombola (2014) Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives. Proc. Nat. Acad. Sci. USA 111(27):9971-6.
36. J.L. Nourse, J.L. Prieto, A.R. Dickson, J. Lu, M.M. Pathak, F. Tombola, M. Demetriou, A.P. Lee, L.A. Flanagan (2014) Membrane biophysics define neuron and astrocyte progenitors in the neural lineage. Stem Cells 32(3):706-16.
35. L. Hong, M.M. Pathak, I.H. Kim, D. Ta, F. Tombola (2013) Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains. Neuron 77(2): 274-286.
34. M.L. Wood, E.V. Schow, J.A. Freites, S.H. White, F. Tombola, D.J. Tobias (2012) Water wires in atomistic models of the Hv1 proton channel. Biochim. Biophys. Acta 1818(2): 286-93.
33. F. Tombola, M.H. Ulbrich, S.C. Kohout, E.Y. Isacoff (2010) The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity. Nat. Struct. Mol. Biol. 17(1) 44-50.
32. F. Tombola, M.H. Ulbrich and E.Y. Isacoff (2009) Architecture and gating of Hv1 proton channels. J. Physiol. 587, 5325–5329.
31. F. Tombola, M.H. Ulbrich E.Y. Isacoff (2008) The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron 58: 546-56.
30. M.M. Pathak, V. Yarov-Yarovoy, G. Agarwal, B. Roux, P. Barth, S. Kohout, F. Tombola E.Y. Isacoff (2007) “Closing in” on the resting state of the Shaker K+ channel. Neuron 56: 124-40.
29. P. Ruggiero, G. Rossi, F. Tombola, L. Pancotto, L. Lauretti, G. Del Giudice, M. Zoratti (2007) Red wine and green tea reduce H. pylori- or VacA-induced gastritis in a mouse model. World J. Gastroenterol. 13: 349-54.
28. F. Tombola, M.M. Pathak, P. Gorostiza, E.Y. Isacoff (2007) The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445: 546-9.
27. P. Ruggiero, F. Tombola, G. Rossi, L. Pancotto, L. Lauretti, G. Del Giudice, M. Zoratti (2006) Polyphenols reduce gastritis induced by Helicobacter pylori infection or VacA toxin administration in mice. Antimicrob. Agents Chemother. 50: 2550-2.
26. F. Tombola, M.M. Pathak and E.Y. Isacoff (2006) How does voltage open an ion channel? Annu. Rev. Cell Dev. Biol. 22: 23-52.
25. P. Gorostiza, F. Tombola, A. Verdaguer, S.B. Smith, C. Bustamante, E.Y. Isacoff (2005) Molecular handles for the mechanical manipulation of single membrane proteins in living cells. IEEE Trans. Nanobiosci. 4: 269-76.
24. F. Tombola, M.M. Pathak and E.Y. Isacoff (2005) How far will you go to sense voltage? Neuron 48: 719-25.
23. F. Tombola, M.M. Pathak, E.Y. Isacoff (2005) Voltage-sensing arginines in a voltage-gated channel permeate and occlude cation selective pores. Neuron 45: 379-88.
22. S. Campello, U. De Marchi, I. Szabo, F. Tombola, J.C. Martinou, M. Zoratti (2005) The properties of the mitochondrial megachannel in mitoplasts from human colon carcinoma cells are not influenced by Bax. FEBS Lett. 579: 3695-700.
21. M. Pathak, L. Kurtz, F. Tombola, E. Isacoff (2005) The Cooperative Voltage Sensor Motion that Gates a Potassium Channel. J. Gen. Physiol. 125: 57-69.
20. U. De Marchi, S. Campello, I. Szabo, F. Tombola, J.C. Martinou, M. Zoratti (2004) Bax does not directly participate in the Ca(2+)-induced permeability transition of isolated mitochondria. J. Biol. Chem. 279: 37415-22.
19. F. Tombola, S. Campello, L. De Luca, P. Ruggero, G. Del Giudice, E. Papini, M. Zoratti (2003) Plant polyphenols inhibit VacA, a toxin secreted by the gastric pathogen Helicobacter pylori. FEBS Lett. 543: 184-89.
18. M. Zoratti, F. Tombola, C. Montecucco, L. Debellis and E. Papini (2003) Helicobacter pylori vacuolating toxin VacA. In Pore-Forming Peptides and Protein Toxins. Eds: G. Menestrina, M. Dalla Serra and P. Lazarovici. Taylor and Francis London; 60-75.
17. S. Campello, F. Tombola, G. Cabrini, M. Zoratti (2002) The vacuolating toxin of Helicobacter pylori mimics the CFTR-mediated chloride conductance. FEBS Lett. 532: 237-40.
16. M. Moschioni, F. Tombola, M. de Bernard, A. Coelho, A. Zitzer, M. Zoratti, C. Montecucco (2002). The Vibrio cholerae hemolysin anion channel is required for cell vacuolation and death. Cell. Microbiol. 4: 397-409.
15. I. Szabò, F. Tombola, S. Martinucci, M. Zoratti (2002) DNA interacts with Bacillus subtilis mechanosensitive channels in native membrane patches. Cell. Physiol. & Biochem. 12: 127-34.
14. M. Zoratti and F. Tombola (2001) Physiology of the Permeability Transition Pore. In Mitochondria in Pathogenesis, Lemaster & Nieminen Ed., Kluwer Academic/Plenum Publishers, New York; 125-52.
13. L. Morbiato, F. Tombola, S. Campello, G. Del Giudice, R. Rappuoli, M. Zoratti, E. Papini (2001) Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl- and water. FEBS Lett. 508: 479-83.
12. F. Tombola, C. Pagliaccia, S. Campello, J.L. Telford, C. Montecucco, E. Papini, M. Zoratti (2001) How the loop and middle region influence the properties of Helicobacter pylori VacA channels. Biophys. J. 81: 3204-15.
11. F. Tombola, L. Morbiato, G. Del Giudice, R. Rappuoli, M. Zoratti, E. Papini (2001) The Helicobacter pylori VacA toxin is a urea permease that promotes urea diffusion across epithelia. J. Clin. Invest. 108: 929-37.
10. G. Bàthori, I. Parolini, I. Szabò, F. Tombola, A. Messina, M. Oliva, M. Sargiacomo, V. DePinto, and M. Zoratti (2000) Extramitochondrial porin: facts and hypotheses. J. Bioenerg. Biomembr. 32: 79-89.
9. S. Martinucci, I. Szabò, F. Tombola, M. Zoratti (2000) Ca2+-reversible inhibition of the mitochondrial mega-channel by ubiquinone analogues. FEBS Lett. 480: 89-94.
8. F. Tombola, G. Del Giudice, E. Papini, M. Zoratti (2000) Blockers of VacA provide insights into the structure of the pore. Biophys. J. 79: 863-73.
7. F. Tombola, F. Oregna, S. Brutsche, I. Szabò, G. Del Giudice, R. Rappuoli, C. Montecucco, E. Papini, M. Zoratti (1999) Inhibition of the vacuolating and anion channel activities of the VacA toxin of Helicobacter pylori. FEBS Lett. 460: 221-25.
6. I. Szabò, S. Brutsche, F. Tombola, M. Moschioni, B. Satin, J.L. Telford, R. Rappuoli, C. Montecucco, E. Papini, M. Zoratti (1999) Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity. EMBO J. 18: 5517-27.
5. G. Bàthori, I. Parolini, F. Tombola, I. Szabò, A. Messina, M. Oliva, V. DePinto, M. Lisanti, M. Sargiacomo, M. Zoratti (1999) Porin is present in the plasma membrane where it is concentrated in caveolae and caveolae-related domains. J. Biol. Chem. 274: 29607-12.
4. F. Tombola, C. Carlesso, I. Szabò, M. de Bernard, J.M. Reyrat, J.L. Telford, R. Rappuoli, C. Montecucco, E. Papini, M. Zoratti (1999) Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implication for the mechanism of cellular vacuolation. Biophys. J. 76:1401-9.
3. I. Szabò, G. Bàthori, F. Tombola, A. Coppola, I. Schmehl, M. Brini, A. Ghazi, V. DePinto, M. Zoratti (1998) Double-stranded DNA can be translocated across a planar membrane containing purified mitochondrial porin. FASEB J. 12: 495-502.
2. G. Bàthori, I. Szabò, I. Schmehl, F. Tombola, V. DePinto, M. Zoratti (1998) Novel aspects of the electrophysiology of mitochondrial porin. Biochem. Biophys. Res. Commu. 243: 258-63.
1. I. Szabò, G. Bàthori, F. Tombola, M. Brini, A. Coppola, M. Zoratti (1997) DNA translocation across planar bilayers containing Bacillus subtilis ion channels. J. Biol. Chem. 272: 25275-82.