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Jonathan Brunger

Assistant Professor of Biomedical Engineering

Biomedical Engineering

Intellectual Neighborhoods

Research Focus

We design and implement synthetic biology tools to forward engineer cells as robust therapeutic engines, with a primary focus on musculoskeletal and autoimmune diseases. We integrate engineering and biology to quantitatively probe the complex dynamics of cell behaviors and to rationally assemble new biological systems with controllable properties. Through our synthetic biology approach to regenerative engineering, we aim to (1) systematically perturb natural cellular signaling pathways to understand the interactions that give rise to pluripotent stem cell differentiation; (2) construct new biological parts to modulate regenerative behaviors of transplanted cells; and (3) create living therapies engineered with defined properties to overcome limitations intrinsic to traditional therapies. To achieve these aims, we use platforms such as CRISPR-based genome and transcriptome editing systems to dissect networks engaged in PSC differentiation, and to reconfigure the behaviors of cells in response to given inputs. We also construct synthetic signaling modules to allow cells to interrogate specific features of their niche and autonomously implement appropriate regenerative programs (e.g., proliferation, differentiation, organization, etc.) with engineered feedback control.

Selected publications:

Toda, S., Brunger, J.M., Lim, W.A., 2019. Synthetic development: learning to program multicellular self-organization. Curr. Opin. Syst. Biol., Synthetic biology 14, 41–49.

Adkar, S.S., Brunger, J.M., Willard, V.P., Wu, C.-L., Gersbach, C.A., Guilak, F., 2017. Genome Engineering for Personalized Arthritis Therapeutics. Trends Mol. Med. 23, 917–931.

Farhang, N., Brunger, J.M., Stover, J.D., Thakore, P.I., Lawrence, B., Guilak, F., Gersbach, C.A., Setton, L.A., Bowles, R.D., 2017. CRISPR-Based Epigenome Editing of Cytokine Receptors for the Promotion of Cell Survival and Tissue Deposition in Inflammatory Environments. Tissue Eng. Part A 23, 738–749.

Brunger, J.M., Zutshi, A., Willard, V.P., Gersbach, C.A., Guilak, F., 2017a. Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs. Stem Cell Rep. 8, 1202–1213.

Brunger, J.M., Zutshi, A., Willard, V.P., Gersbach, C.A., Guilak, F., 2017b. CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation-Resistant Tissues. Arthritis Rheumatol. 69, 1111–1121.

Brunger, J.M., Huynh, N.P.T., Guenther, C.M., Perez-Pinera, P., Moutos, F.T., Sanchez-Adams, J., Gersbach, C.A., Guilak, F., 2014. Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage. Proc. Natl. Acad. Sci. U. S. A. 111, E798-806.

Perez-Pinera, P., Ousterout, D.G., Brunger, J.M., Farin, A.M., Glass, K.A., Guilak, F., Crawford, G.E., Hartemink, A.J., Gersbach, C.A., 2013. Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nat. Methods 10, 239–242.