Location: DIBIT2 A2, Floor 4, Room 43
Research associate, Chromatin dynamics Unit
Associate professor, Vita-Salute San Raffaele University
After getting his degree in theoretical physics at Complutense University, Madrid (2003), Samuel Zambrano got a Ph. D in Nonlinear Dynamics and Complex Systems between Madrid (King Juan Carlos University), Italy (National Institute of Applied Optics, Florence) and USA (University of Maryland). After serving as Assistant Professor of Physics in Madrid until 2011, and interested by the potential applications of his background to life sciences, he joined San Raffaele in 2011 thanks to the SR International Postdoctoral Programme. In close collaboration with Alessandra Agresti and Marco E. Bianchi he combines live-cell imaging, automatic image analysis, microfluidics and mathematical modelling to gain insights on the role of the oscillatory dynamics of NF-κB, a transcription factor that plays a key role in inflammation and that is often de-regulated in related diseases. More recently, he aims to apply the same quantitative approaches also to understand how other transcription factors exploit dynamics to activate gene expression programs that underpin cell fate decisions and, more broadly speaking, to understand the dynamical principles of fundamental processes in cell biology.
NF-κB is a transcription factor that plays a key role inflammatory response, coordinating the response of hundreds of genes in response to a variety of stimuli. Hence, its derangement can lead to a number of inflammation-related pathologies including cancer. NF-κB is also a paradigmatic example of a biological oscillator: in resting cells it is localized in the cytoplasm, but different external stimuli produce oscillations of its nuclear concentration with a period of 1.5 hours whose role that is still far from being completely understood.
In close collaboration with Alessandra Agresti and Marco E. Bianchi we combine live-cell imaging, automatic image analysis, microfluidics and mathematical modelling to gain insights on the role of NF-κB dynamics in healthy and pathological conditions.
Our main research lines are currently the following:
- NF-κB driven transcription in single cells: NF-κB tightly regulates transcription dynamics but it is known that single-cell transcription dynamics is stochastic. In collaboration with Davide Mazza (SR) and Nacho Molina (IGBMC, France), we are studying NF-κB driven gene expression in single cells to understand how this delicate balance is achieved.
- NF-κB dynamics at tissue level: Mathematical models suggest that NF-κB dynamics can contribute to propagate signals during the inflammatory response. We are characterizing this process in vitro using microfluidics but we also aim to use intra-vital microscopy to observe it in living tissues (with M. Iannacone from SR).
- Systems Biology of NF-κB dynamics: NF-κB is tightly regulated by different negative feedbacks that are themselves stochastic. We are developing tools to simulate this system in order to better understand how this regulation contributes to provide the adequate specificity in the response to different stimuli. From this we generate hypotheses that we can test experimentally through live cell imaging.
Kizilirmak C, Bianchi ME* and Zambrano S* (*equal contribution). Insights on the NF-kB system using live cell imaging: recent developments and future perspectives. Front Immunol. 2022;13: 886127. doi: 10.3389/fimmu.2022.886127 PMID: 35844496
Samuel Zambrano*, A. Loffreda, E. Carelli, G. Stefanelli, F. Colombo, E. Bertrand, A. Agresti, M. E. Bianchi N. Molina, D. Mazza. “First responders shape an NF-κΒ-mediated prompt and sharp transcriptional response to TNF-α”. iScience 23(9), 101529 (2020).
G. Careccia, F. Colombo, M. Tirone, A. Agresti, M. E. Bianchi, Samuel Zambrano*, E. Vénéreau. “Exploiting Live Imaging to Track Nuclei During Myoblast Differentiation and Fusion”. J. Vis. Exp. (146), e58888, (2019).
F. Colombo, Samuel Zambrano*, A. Agresti. “NF-kB, the importance of being dynamic: role and insights in cancer”. Biomedicines, 6 (2), 45 (2018).
E. Ramos-Marquès, Samuel Zambrano, A. Tiérrez, M. E. Bianchi, A. Agresti and F. García-del Portillo. “Single-cell analyses reveal an attenuated NF-kB response in the Salmonella-infected fibroblast”. Virulence 8:6, 719-740 (2017).
Samuel Zambrano, I. De Toma, A. Piffer, M. E. Bianchi and A. Agresti. “NF-kB oscillations translate into functionally related patterns of gene expression”. eLife 5:e09100 (2016).
Samuel Zambrano, Marco E. Bianchi, Alessandra Agresti and Nacho Molina. “Interplay between stochasticity and negative feedback leads to pulsed dynamics and distinct gene activity patterns”. Phys. Rev. E 92, 02271 (2015).
Samuel Zambrano, M. E. Bianchi, A. Agresti. “A simple model of NF-kB dynamics reproduces experimental observations” Journal of Theoretical Biology, 347(21) 44-53 (2014).
Samuel Zambrano, M. E. Bianchi, A. Agresti. “High-Throughput Analysis of NF-kB Dynamics in Single Cells Reveals Basal Nuclear Localization of NF-kB and Spontaneous Activation of Oscillations”. PLoS ONE 9(3): e90104(2014).