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Grégoire Altan-Bonnet, Ph.D.

Grégoire Altan-Bonnet, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

I have been trained in Statistical Physics and nonlinear dynamics (PhD) and in Immunology (post-doctoral studies). My field of expertise is Systems Immunology: the ImmunoDynamics group I am heading has been developing experimentally validated quantitative models of different aspects of the immune system. In particular, we have addressed the interplay between the robustness and variability of self/non-self discrimination in the immune system. We are also focused on developing quantitative models of lymphocyte-lymphocyte communications via cytokine. Our current projects focus on the multicellular coordination of immune responses against tumors and pathogenic infections. We are particularly interested in developing quantitative models of the integration of signal transduction, gene regulation, cytokine communications, cell differentiation, and proliferation/death across multiple spatio-temporal scales. Our long-term goal is to help in the development of tailored immunotherapies (e.g. against tumors).

Areas of Expertise

1) immunology 2) systems biology 3) computational modeling 4) biological physics 5) machine learning 6) automation/robotics

Publications

Selected Key Publications

A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System.

Oyler-Yaniv A, Oyler-Yaniv J, Whitlock BM, Liu Z, Germain RN, Huse M, Altan-Bonnet G*, Krichevsky O*.
Immunity. 48(4): 609-620, 2017. [ Journal Article ]

Cytokine-mediated communication: a quantitative appraisal of immune complexity

Altan-Bonnet G, Mukherjee R.
Nat Rev Immunol. 19(4): 205-217, 2019. [ Journal Article ]

β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

S Ghosh, TA Dellibovi-Ragheb, A Kerviel, E Pak, Q Qiu, M Fisherq, PM Takvorian, C Bleck, VW Hsu, AR Fehr, S Perlman, SR Achar , MR Straus, GR Whittaker, CAM de Haan, J Kehrl, G Altan-Bonnet* & N Altan-Bonnet*
Cell. 183(6): 1520-1535, 2020. [ Journal Article ]

Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

S Krishna, FJ Lowery, AR Copeland, E Bahadiroglu, R Mukherjee, L Jia, JT Anibal, A Sachs, SO Adebola, D Gurusamy, Z Yu, V Hill, JJ Gartner, YF Li, M Parkhurst, B Paria, P Kvistborg, MC Kelly, SL Goff, G Altan-Bonnet, PF Robbins & SA Rosenberg
Science. 370(6522): 1328-1334, 2020. [ Journal Article ]

Universal antigen encoding of T cell activation fromhigh-dimensional cytokine dynamics

Sooraj R. Achar†, François X. P. Bourassa†, Thomas J. Rademaker†, Angela Lee, Taisuke Kondo, Emanuel Salazar-Cavazos, John S. Davies, Naomi Taylor, Paul François*, Grégoire Altan-Bonnet*
Science. 376: 880-884, 2022.
Full-Text Article
[ Journal Article ]

Job Vacancies

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Team

Graduate Student (NIH-Oxford)
Anagha Krishna, B.Sc
Postdoctoral fellow
Dongya Jia, PhD
Postdoctoral Fellow
Emanuel Salazar Cavazos, Ph.D.
Graduate Student (NIH-Oxford)
Hannah Dada, B.Sc
Postbaccalaureate (CRTA)
Madison Wahlsten, B.Sc
Graduate Student (University of Maryland) - mentor: Don DeVoe
Michael Chen Yeh, B.S.
Graduate Student - Johns Hopkins University (co-mentored with Naomi Taylor
Justin Mirazee, BSc
Graduate Student (NIH-Oxford)
Sooraj Achar, B.Sc.

Covers

Tunable cell-to-cell communications in the immune system

A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System

Published Date

Immune cells communicate by exchanging cytokines to achieve a context-appropriate response, but the distances over which such communication happens are not known. Here, we used theoretical considerations and experimental models of immune responses in vitro and in vivo to quantify the spatial extent of cytokine communications in dense tissues. We established that competition between cytokine diffusion and consumption generated spatial niches of high cytokine concentrations with sharp boundaries. The size of these self-assembled niches scaled with the density of cytokine-consuming cells, a parameter that gets tuned during immune responses. In vivo, we measured interactions on length scales of 80–120 mm, which resulted in a high degree of cell-to-cell variance in cytokine exposure. Such heterogeneous distributions of cytokines were a source of non-genetic cell-to-cell variability that is often overlooked in single-cell studies. Our findings thus provide a basis for understanding variability in the patterning of immune responses by diffusible factors.

Clustering of BCR maps dysfunctional signaling in Chronic Lymphocytic Leukemia

Constitutive Activation of the B Cell Receptor Underlies Dysfunctional Signaling in Chronic Lymphocytic Leukemia

Published Date

In cancer biology, functional interpretation of genomic alterations is critical to achieve the promise of genomic profiling in the clinic. For Chronic Lymphocytic Leukemia (CLL), a heterogeneous disease of B-lymphocytes maturing under constitutive B-cell receptor (BCR) stimulation, the functional role of diverse clonal mutations remains largely unknown. Here, we demonstrate that alterations in BCR signaling dynamics underlie the progression of B cells toward malignancy. We reveal emergent dynamic features, namely bimodality, hypersensitivity, and hysteresis, in the BCR signaling pathway of primary CLL B cells. These signaling abnormalities in CLL quantitatively derive from BCR clustering and constitutive signaling with positive feedback reinforcement, as demonstrated through single-cell analysis of phosphor-responses, computational modeling, and super-resolution imaging. Such dysregulated signaling segregates CLL patients by disease severity and clinical presentation. These findings provide a quantitative framework and methodology to assess complex and heterogeneous leukemia pathology and to inform therapeutic strategies in parallel to genomic profiling.

Citation

 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3346981

Cell-to-Cell Variability Analysis Dissects the Plasticity of Signaling of Common γ Chain Cytokines in T Cells

Cell-to-Cell Variability Analysis Dissects the Plasticity of Signaling of Common γ Chain Cytokines in T Cells

Published Date

This Research Article presents flow cytometric and mathematical analyses of the effect of increasing the abundance of the α subunit of the interleukin-2 (IL-2) receptor (IL-2Rα) on the responsiveness of mouse T cells to cytokines of the γc family, which includes IL-2 and IL-7. The data suggest that the increased IL-2Rα abundance decreases the sensitivity of T cells to IL-7 by sequestering the γc subunit away from the IL-7R, rendering it nonfunctional. The image shows an artist's depiction, looking down onto the cell surface, of the differential abundance of functional IL-7Rs (dimers) and IL-2Rs (trimers), both of which contain the γcsubunit (red), as a consequence of increased IL-2Rα abundance. [Image: Chris Bickel/AAAS]

Citation

https://www.ncbi.nlm.nih.gov/pubmed/23482665