We study the cellular events and signaling dynamics that control the heterogeneous cell fate response of individual cells in time. Specifically, how internal cycling factors, such as the circadian clock, the cell cycle, and the p53 protein dynamics interact with the DNA damage response pathway to determine the response of cancer cells to perturbations.
The Granada Lab develops methods that combine long-term live single-cell microscopy with time series analysis, non-linear dynamics and mathematical modeling to track the evolving internal cellular state and the outcome cell fate. Gaining understanding on the internal state and dynamics of cell fate decision of individual tumor cells will help to identify sensitive cellular states and to design optimal schedules for future cancer treatments.
Much of the work in our lab is focused on a subtype of breast cancer known as triple negative breast cancer (TNBC). TNBC affects 15-20% of all breast cancer patients, and is one of the most heterogeneous and aggressive subtypes of breast cancer with high rates of mortality. TNBC have an unmet medical need and effective treatments are urgently required. Currently, we can not predict which treatment will be the most effective for the different TNBC patients. The Granada Lab seeks to develop tools to quantitatively understand the sources of heterogeneity in time and space within TNBC tumors.
The Granada Lab is part of the translational research unit from the Charité Comprehensive Cancer Center (CCCC) in Berlin, Germany.
Lab spiritual guide
Mathematician, theoretical physicist, engineer, and philosopher of science.
Adrián E. Granada, Alba Jiménez, Jacob Stewart-Ornstein, Nils Blüthgen, Simone Reber, Ashwini Jambhekar, and Galit Lahav (2020). The effects of proliferation status and cell cycle phase on the responses of single cells to chemotherapy. Mol. Biol. Cell. Vol. 31, Issue 8. PDF
Christian H. Gabriel, Marta del Olmo, Amin Zehtabian, Silke Reischl, Hannah van Dijk, Barbara Koller, Astrid Grudziecki, Bert Maier, Helge Ewers, Hanspeter Herzel, Adrian E. Granada, Achim Kramer (2020). Live-cell imaging of circadian clock protein dynamics in CRISPR-generated knock-in cells. Preprint biorXiv. PDF
Gregor Mönke, Frieda A. Sorgenfrei, Christoph Schmal, Adrián E. Granada (2020). Optimal time frequency analysis for biological data - pyBOAT. Preprint biorXiv. PDF and PyBOAT software Github repository.
Granada AE, Herzel H, Kramer A, Abraham U. (2017). Information Transfer in the Mammalian Circadian Clock. Book chapter. Information and Communication Theory in Molecular Biology. Springer. PDF
Bordyugov G, Abraham U, Granada AE, Rose P, Imkeller K, Kramer A, Herzel H (2015). Tuning the phase of circadian entrainment. Journal of the Royal Society Interface. 6;12(108). PDF
Erzberger A, Hampp G, Granada AE, Albrecht U, Herzel H (2013). Genetic redundancy strengthens the circadian clock leading to a narrow entrainment range. Journal of the Royal Society Interface 10(84):20130221.
Granada AE, Bordyugov G, Kramer A, Herzel H (2013). Human chronotypes from a theoretical perspective. PLoS One 8(3):e59464.
Bordyugov G*, Granada AE*, and Herzel H (2011). How Coupling Determines the Entrainment of Circadian Clocks. European Physical Journal B.
Granada AE, Cambras T, Diez-Noguera A, Herzel H (2011). Circadian desynchronization. Journal of the Royal Society Interface 1:153-166.
Granada AE (2011). Transients and bifurcations of the mammalian circadian system: From synchronization to desynchronization mechanisms. Book. Logos-Verlag. ISBN-13: 978-3-8325-2966-6.
Abraham U*, Granada AE*, Westermark PO*, Heine M*, Kramer A, and Herzel H (2010) Coupling governs entrainment range of circadian clocks. Molecular Systems Biology, 6:438.
Granada AE, Herzel H (2009) How to achieve fast entrainment? The timescale to synchronization. PLoS One 4: e7057.
Granada AE, Hennig RM, Ronacher B, Kramer A, Herzel H (2009) Phase response curves elucidating the dynamics of coupled oscillators. Methods in Enzymology 454:1–27.
Granada AE, Gabitto M, García G, Alliende J, Méndez J, Trevisan M, Mindlin GB (2006). The generation of respiratory rhythms in birds. Physica A. 371:84–87.
What we are looking for:
We are setting up our team and we are looking for students and scientists with diverse backgrounds. Interested graduate students, postdocs, physicians, technicians, and undergraduates are welcome to inquiry for positions. Regardless of your education, we are looking for people who are motivated to learn and develop new tools to tackle tough research problems with their feet in basic science and a perspective on future cancer treatments.
What you can expect:
We offer a diverse, supportive and collaborative research environment in a top cancer research institute. There are many opportunities for you to gain training in both single-cell experimental, computational and theoretical skills.
As your advisor Adrian’s role is to help you work towards your research and career goals, regardless if you are in the lab for a very short internship or a 5-year stay. Joining the lab is a training opportunity for you and we will work together to make the best out of it.
We are part of the Charité Comprehensive Cancer Center (CCCC), which is supported by the German Cancer Aid as a center of excellence in oncology and is the first oncological center certified through the German Cancer Society.
Link to the official calls for each position will appear here soon.
In the meantime, write Adrián an email if you're interested.
Videos and images from our work
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