LEUVEN RESEARCH INSTITUTE FOR NEUROSCIENCE & DISEASE
GEERT BULTYNCK, PHD
contact address:
KU Leuven, Laboratory of Molecular and Cellular Signaling
Department Cellular and Molecular Medicine
Campus Gasthuisberg O/N-I bus 802
Tel: +32 16 330215
Fax: +32 16 345991
E-mail: geert.bultynck@med.kuleuven.be
Web: http://gbiomed.kuleuven.be/english/research/50000618/50753344/
EDUCATION AND PROFESSIONAL TRAINING
1997
Master Biochemistry, KU Leuven
1997-2001
PhD Medical Sciences, KU Leuven (IWT fellow)
2001-2002
Post-doctoral fellow (BOF-PDM), Physiology, KU Leuven
2002-2008
Post-doctoral fellow (FWO), Physiology, KU Leuven
2003-2006
Post-doctoral fellow (BAEF-D. Collen Foundation), Stanford University, CA
2006
Internship at Agilent Laboratories, Santa Clara, CA
2008-2012
Assistant Professor LMCS, Dep. Molecular and Cellular Biology, KU Leuven
2013-present Associate Professor LMCS, Dep. Cellular and Molecular Medicine, KU Leuven
RESEARCH TOPICS
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Intra- and intercellular Ca2+ signaling in health and disease
Cell survival/death proteins (Bcl-2, Beclin 1, Bax Inhibitor-1,…) controlling intracellular Ca2+release channels (IP3Rs and RyRs) in apoptosis, autophagy, unfolded protein response,…
Bcl-2-family members, Ca2+ signaling and disease: chronic lymphocytic leukemia, diffuse large Bcell lymphoma, Alzheimer’s disease
RESEARCH AREAS
Research at LMCS is focused on the role of intra- and intercellular Ca2+ signaling in health and disease
with a strong focus on the endoplasmic reticulum (ER), the main intracellular Ca2+ stores. Intracellular
Ca2+-release channels play a pivotal role in determining fundamental cellular processes, including
metabolism, bio-energetics, proliferation and cell death. Many cell survival/death proteins also act at
the ER membranes and modulate Ca2+ signaling often by directly targeting ER-resident channels, like
IP3Rs and RyRs. In a variety of diseases, including hematological cancers and neurodegenerative
diseases, aberrant IP3R and RyR-channel activity has been implicated.
Our team aims to understand i) how these proteins control the functional properties of these channels
at the molecular and ii) how complex formation and functional regulation occur in normal/healthy
conditions and are affected in disease conditions and models. These insights are exploited to develop
innovative tools to modulate the aberrant IP3R/RyR-channel activity by targeting these complexes, e.g.
stimulating Ca2+ release in cancer cells to promote apoptosis or inhibit excessive Ca2+ release in neurons
to promote survival. We have applied this strategy to develop and apply novel peptide tools, like i) “TATIDP”, which selectively targets Bcl-2 via its BH4 domain, triggering pro-apoptotic Ca2+ signals in CLL and
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LEUVEN RESEARCH INSTITUTE FOR NEUROSCIENCE & DISEASE
DL-BCL but not in normal lymphocytes and ii) “TAT-L2”, which selectively inhibits Cx43 hemichannels but
not gap junctions, erasing fear memory consolidation upon injection in the basal amygdala.
Finally, our team has a keen interest in assessing the “Ca2+-signaling profile” of a variety of
pharmacological tools with a focus on anti-cancer drugs, but suggestions by others and collaborative
projects are warmly welcomed. In particular, disturbing intracellular Ca2+-homeostasis or dynamics may
be a “toxic” side effect or may actually contribute to the mode of action of the drugs. Hence,
pharmacological compounds are assessed in a standardized work flow using permeabilized cells single
cells and cell populations (including plasmalemmal Ca2+ fluxes), thereby providing integrated insights on
their effect on ER Ca2+ uptake, ER Ca2+ leak, IP3-induced Ca2+ release in unidirectional Ca2+-flux conditions
and on plasmalemmal Ca2+ fluxes, including store-operated Ca2+ influx.
For these studies, we make use of different molecular, biophysical and cellular approaches (including
SPR, pull-downs, Ca2+ imaging in single cells and cell populations, 45Ca2+ fluxes, confocal microscopy,
cytometry-based analysis).
MAJOR SCIENTIFIC AWARDS
- FK506 Award (Fujisawa GmbH, Munchen, Germany), 2001
- Physiology Award (Royal Academy for Medicine of Belgium), 2003
- Octaaf Dupont Award (Royal Flemish Academy of Belgium for Science), 2010
- J.B. Van Helmont Award for pathophysiology (Royal Academy for Medicine of Belgium), 2011
- Best Talk at the Signal Transduction Society meeting (Weimar, Germany), 2012
- Galenus Award for fundamental pharmacology (ActuaMedica/Artsenkrant), 2013
SELECTED PUBLICATION
1. Jensen LE, Bultynck G, Luyten T, Amijee H, Bootman MD, Roderick HL. (2013) Alzheimer's diseaseassociated peptide Aβ42 mobilizes ER Ca2+ via InsP3R-dependent and -independent mechanisms.
Frontiers in Molecular Neuroscience. 6:36. (PMID: 24204331)
2. Akl H, Bultynck G. (2013) Altered Ca2+ signaling in cancer cells: proto-oncogenes and tumor
suppressors targeting IP3 receptors. Biochim Biophys Acta - Reviews on Cancer. 1835(2):180-93.
(PMID: 23232185)
3. Akl H, Monaco G, La Rovere R, Welkenhuyzen K, Kiviluoto S, Vervliet T, Molgó J, Distelhorst CW,
Missiaen L, Mikoshiba K, Parys JB, De Smedt H, Bultynck G. (2013) IP3R2 levels dictate the apoptotic
sensitivity of diffuse large B-cell lymphoma cells to an IP3R-derived peptide targeting the BH4
domain of Bcl-2. Cell Death and Disease. 4:e632. (PMID: 23681227)
4. Monaco G, Decrock E, Akl H, Ponsaerts R, Vervliet T, Luyten T, De Maeyer M, Missiaen L, Distelhorst
CW, De Smedt H, Parys JB, Leybaert L, Bultynck G. (2012) Selective regulation of IP3-receptormediated Ca2+ signaling and apoptosis by the BH4 domain of Bcl-2 versus Bcl-Xl. Cell Death and
Differentiation. 19(2):295-309. (PMID: 2181811) Faculty of 1000.
5. Decuypere JP, Welkenhuyzen K, Luyten T, Ponsaerts R, Dewaele M, Molgó J, Agostinis P, Missiaen L,
De Smedt H, Parys JB, Bultynck G. (2011) Ins(1,4,5)P3 receptor-mediated Ca2+ signaling and
autophagy induction are interrelated. Autophagy. 7(12):1472-89. (PMID: 2208287) Faculty of 1000.
6. Ponsaerts R, De Vuyst E, Retamal M, D'hondt C, Vermeire D, Wang N, De Smedt H, Zimmermann P,
Himpens B, Vereecke J, Leybaert L, Bultynck G. (2010) Intramolecular loop/tail interactions are
essential for connexin 43-hemichannel activity. FASEB Journal. 24(11):4378-95. (PMID: 2063435)
Faculty of 1000.
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