Professor Rebecca Sitsapesan
Fellow and Tutor in Pharmacology and Medicine
University Lecturer in Pharmacology
Rebecca Sitsapesan holds a BSc in Pharmacology (Aberdeen), an MSc in Cardiovascular Studies (Leeds) and a PhD in Cardiac Physiology and Pharmacology (Strathclyde). Her post-doctoral research into ion-channel biophysics began at the University of Glasgow and continued at the National Heart & Lung Institute at Imperial College, London. In 1991 she was awarded a British Heart Foundation Basic Science Lectureship to investigate the function of cardiac intracellular Ca2+-release channels and a University Lectureship at Imperial College. Rebecca Sitsapesan moved to Bristol in 2001 and was promoted to Professor of Pharmacology in 2011. In August 2013, she became Professor of Pharmacology at the University of Oxford.
Research in the Sitsapesan lab focuses on the biophysical properties and putative physiological roles of ion-channels present on intracellular Ca2+-stores. Although we are particularly interested in their relevance in the heart, these ion-channels are also crucial to the normal physiology of many other organs, including the lungs, kidney, brain, vascular smooth muscle and skeletal muscle. We are studying not only Ca2+-release channels, such as the ryanodine receptor (RyR) found in the sarcoplasmic/endoplasmic reticulum (SR), and the two-pore channel, type 2 (TPC2, collaboration with Antony Galione, Oxford) present on acidic lysosomal Ca2+-stores, but also other ion-channels that support the process of Ca2+-release but whose exact physiological roles have not been fully identified. These include the two sub-types of trimeric intracellular cation channel (TRIC-A and TRIC-B) that are present in the SR of most cells. Deficiency in TRIC-A and/or TRIC-B is associated with severe disease including embryonic heart failure, respiratory failure and hypertension. We are working closely with Hiroshi Takeshima (Kyoto, Japan) to examine the relationships between structure and function of the TRIC channels and to relate our understanding of the gating and conducting properties of the channels to their physiological roles in the heart and in skeletal and vascular smooth muscle. We expect our investigations to expose many novel sites on intracellular Ca2+-stores as targets for therapeutic intervention.
(selected recent papers)
Venturi, E., Matyjaszkiewicz, A., Pitt, S.J., Tsaneva-Atanasova, K., Nishi, M., Yamazaki, D., Hiroshi Takeshimi, H. & Sitsapesan, R. (2013). TRIC-B channels display labile gating: evidence from the TRIC-A knockout mouse model. Pflugers Arch. 465, 1135-48.
Venturi, E., Sitsapesan, R., Yamazaki, D. & Takeshima, H. (2012). TRIC channels supporting efficient Ca2+ release from intracellular stores. Pflugers Arch. 465, 187-195.
Galfré, E., Pitt, S. J., Venturi, E., Sitsapesan, M, Zaccai, N.R., Tsaneva-Atanasova, K., O’Neill, S. & Sitsapesan, R. (2012). FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6. PLoS ONE, 7, Issue 2, e31956.
Venturi,V., Mio, K., Nishi, M., Ogura, T., Moriya, T., Pitt, S.J., Okuda, K., Sitsapesan, R., Sato, C. & Takeshima, H. (2011). Mitsugumin23 forms a massive bowl-shaped assembly and cation-conducting channel. Biochemistry. 50, 2623-32.
Carter, S., Pitt, S.J., Colyer, J. & Sitsapesan, R. (2011). Ca2+-dependent phosphorylation of RyR2 can uncouple channel gating from direct cytosolic Ca2+-regulation. J. Membr. Biol. 240, 21-33.
Pitt, S.J., Funnell, T., Sitsapesan, M., Venturi, E., Reitdorf, K., Ruas, M., Ganesan, A., Gosain, R., Churchill, R.C., Zhu, M.X., Parrington, J., Galione, A. & Sitsapesan, R. (2010). TPC2 is a novel NAADP-sensitive Ca2+-release channel, operating as a dual sensor of luminal pH and Ca2+. JBC, 285, 35039-35046.
Venturi, E., Pitt, S., Galfré, E. & Sitsapesan, R. (2010). From eggs to hearts: What is the link between cyclic ADP-ribose and ryanodine receptors? Cardiovascular Therapeutics. 30, 109–116.
Pitt, S.J., Park, K.-H., Nishi, M., Urashima, T., Aoki, S., Yamazaki, D., Ma, J., Takeshima, H. & Sitsapesan, R. (2010). Charade of the SR K+-channel: Two ion-channels, TRIC-A and TRIC-B, masquerade as a single ion channel. Biophys.J. 99, 417-426.
Sigalas, C., Mayo-Martin, M.B., Jane, D.E. & Sitsapesan, R. (2009). Ca2+-calmodulin increases RyR2 open probability yet reduces ryanoid association with RyR2. Biophys.J. 97, 1907-1916.
Sitsapesan, R. (2009). In pursuit of ryanodine receptors gating in the plasma membrane of RINm5F pancreatic b-cells. Islets, 1, 84-86.
Song, L., Carter, S.M., Chen,Y. & Sitsapesan, R. (2009). Diadenosine pentaphosphate is a potent activator of cardiac ryanodine receptors revealing a novel high-affinity binding site for adenine nucleotides. Br. J. Pharmacol. 156, 857-67.
Sigalas, C., Bent, S., Kitmitto, A., O'Neill, S. & Sitsapesan R. (2009). Ca2+-calmodulin can activate and inactivate cardiac ryanodine receptors. Br J Pharmacol. 156, 794-806.