Construction of a Synthetic, Chromatin-Based Epigenetic System in Human Cells
Minhee Park, Nikit Patel, Albert J. Keung and Ahmad S. Khalil
in revision
Precise, Automated Control of Conditions for High-Throughput Growth of Yeast and Bacteria with eVOLVER
Brandon G. Wong*, Christopher P. Mancuso*, Szilvia Kiriakov, Caleb J. Bashor and Ahmad S. Khalil
Nature Biotechnology, in press
Hsf1 Phosphorylation Generates Cell-to-Cell Variation in Hsp90 Levels and Promotes Phenotypic Plasticity
Xu Zheng*, Ali Beyzavi*, Joanna Krakowiak, Nikit Patel, Ahmad S. Khalil and David Pincus
Cell Reports, 22: 3099-3106 (2018)
Hsf1 and Hsp70 Constitute a Two-Component Feedback Loop that Regulates the Yeast Heat Shock Response
Joanna Krakowiak*, Xu Zheng*, Nikit Patel*, Jayamani Anandhakumar, Kendra Valerius, David S. Gross, Ahmad S. Khalil and David Pincus
eLife, 7: e31668 (2018)
Uncovering and Engineering the Protein Aggregome
Gregory A. Newby*, Erinc Hallacli*, Szilvia Kiriakov* and Ahmad S. Khalil
In: Principles of Systems Biology, No. 23
Cell Systems, 5: 428-430 (2017)
A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance
Gregory A. Newby*, Szilvia Kiriakov*, Erinc Hallacli*, Can Kayatekin, Peter Tsvetkov, Christopher P. Mancuso, J. Maeve Bonner, William R. Hesse, Sohini Chakrabortee, Anita L. Manogaran, Susan W. Liebman, Susan Lindquist and Ahmad S. Khalil
Cell, 171: 966-979 (2017)

  Recommended for Faculty of 1000 (link); highlighted in The Scientist by Ruth Williams (link)
Prospective Isolation of NKX2-1–Expressing Human Lung Progenitors Derived From Pluripotent Stem Cells
Finn Hawkins, Philipp Kramer, Anjali Jacob, Ian Driver, Dylan C. Thomas, Katherine B. McCauley, Nicholas Skvir, Ana M. Crane, Anita A. Kurmann, Anthony N. Hollenberg, Sinead Nguyen, Brandon G. Wong, Ahmad S. Khalil, Sarah X.L. Huang, Susan Guttentag, Jason R. Rock, John M. Shannon, Brian R. Davis and Darrell N. Kotton
The Journal of Clinical Investigation, 127: 2277-2294 (2016)
Heat Shock Signaling, Fast and Slow
David Pincus and Ahmad S. Khalil
In: Principles of Systems Biology, No. 12
Cell Systems, 3: 504-506 (2016)
Dynamic Control of Hsf1 During Heat Shock By a Chaperone Switch and Phosphorylation
Xu Zheng, Joanna Krakowiak, Nikit Patel, Ali Beyzavi, Jideofor Ezike, Ahmad S. Khalil and David Pincus
eLife, 5: e18638 (2016)

  Commentary in eLife by Laura Le Breton & Matthias P. Mayer (PDF)
The Epigenome: The Next Substrate for Engineering
Minhee Park, Albert J. Keung and Ahmad S. Khalil
Genome Biology, 17: 183 (2016)
Cellular Advantages to Signaling in a Digital World (Preview)
Christopher P. Mancuso, Szilvia Kiriakov and Ahmad S. Khalil
Cell Systems, 3: 114-115 (2016)
Biological Insights From Synthetic Biology (Editorial)
Jordi Garcia-Ojalvo, Ahmad S. Khalil and John McCarthy
Integrative Biology, 8: 380-382 (2016)
A Unifying Model of Epigenetic Regulation (Perspective)
Albert J. Keung and Ahmad S. Khalil
Science, 351: 661-662 (2016)
Antibiotic Efficacy is Linked to Bacterial Cellular Respiration
Michael A. Lobritz, Peter Belenky, Caroline B.M. Porter, Arnaud Gutierrez, Jason H. Yang, Eric G. Schwarz, Daniel J. Dwyer, Ahmad S. Khalil and James J. Collins<
Proc. Natl. Acad. Sci. USA, 112: 8173-8180 (2015)
Chromatin Regulation at the Frontier of Synthetic Biology
Albert J. Keung, J. Keith Joung, Ahmad S. Khalil and James J. Collins
Nature Reviews Genetics, 16: 159-171 (2015)
Using Targeted Chromatin Regulators to Engineer Combinatorial and Spatial Transcriptional Regulation
Albert J. Keung, Caleb J. Bashor, Szilvia Kiriakov, James J. Collins and Ahmad S. Khalil
Cell, 158: 110-120 (2014)

  Commentary in Nature Reviews Genetics by Darren J. Burgess (PDF)
Antibiotics Induce Redox-Related Physiological Alterations as Part of Their Lethality
Daniel J. Dwyer, Peter A. Belenky, Jason H. Yang, I. Cody MacDonald, Jeffrey D. Martell, Noriko Takahashi, Clement T. Y. Chan, Michael A. Lobritz, Dana Braff, Eric G. Schwarz, Jonathan D. Ye, Mekhala Pati, Maarten Vercruysse, Paul S. Ralifo, Kyle R. Allison, Ahmad S. Khalil, Alice Y. Ting, Graham C. Walker and James J. Collins
Proc. Natl. Acad. Sci. USA, 111: E2100-E2109 (2014)
Engineering Life
Ahmad S. Khalil, Caleb J. Bashor, and Timothy K. Lu
The Scientist, August 1, 2013

Iterative Plug-and-Play Methodology for Constructing and Modifying Synthetic Gene Networks
Kevin D. Litcofsky, Raffi B. Afeyan, Russell J. Krom, Ahmad S. Khalil and James J. Collins
Nature Methods, 9: 1077-80 (2012)

  Commentary in Nature Methods by Jeffrey J. Tabor (PDF)
A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions
Ahmad S. Khalil*, Timothy K. Lu*, Caleb J. Bashor*, Cherie L. Ramirez, Nora C. Pyenson, J. Keith Joung and James J. Collins
Cell, 150: 647-658 (2012)

  Commentary in Nature Biotechnology by Susan Jones (PDF); in Nature Methods (PDF)
Signaling-Mediated Bacterial Persister Formation
Nicole M. Vega, Kyle R. Allison, Ahmad S. Khalil and James J. Collins
Nature Chemical Biology, 8: 431-433 (2012)

  Commentary in Nature (PDF); in Science (PDF); in Nature Medicine (PDF); in Nat. Rev. Microbiol. (PDF)
Synthetic Biology: Applications Come of Age
Ahmad S. Khalil and James J. Collins
Nature Reviews Genetics, 11: 367-370 (2010)

  Highlighted in The New York Times by Olivia Judson (link); in Folha de S. Paulo (PDF)
Functionalized Endothelialized Microvascular Networks with Circular Cross Sections in a Tissue Culture Substrate
Jeffrey T. Borenstein, Malinda M. Tupper, Peter J. Mack, Eli J. Weinberg, Ahmad S. Khalil, James Hsiao and Guillermo Garcia-Cardena
Biomedical Microdevices, 12: 71-79 (2010).
Next-Generation Synthetic Gene Networks
Timothy K. Lu, Ahmad S. Khalil and James J. Collins
Nature Biotechnology, 27: 1139-1150 (2009).
Kinesin's Cover-Neck Bundle Folds Forward to Generate Force
Ahmad S Khalil, David C Appleyard, Anna K. Labno, Adrien Georges, Martin Karplus, Angela M. Belcher, Wonmuk Hwang and Matthew J. Lang
Proc. Natl. Acad. Sci. USA, 105: 19247-19252 (2008).

Single M13 Bacteriophage Tethering and Stretching
Ahmad S. Khalil, Jorge M. Ferrer, Ricardo R. Brau, Stephen T. Kottmann, Christopher J. Noren, Matthew J. Lang and Angela M. Belcher
Proc. Natl. Acad. Sci. USA, 104: 4892-4897 (2007).

A Combined FEM/Genetic Algorithm for Vascular Soft Tissue Elasticity Estimation
Ahmad S. Khalil, Brett E. Bouma and Mohammad R. Kaazempur-Mofrad
Cardiovascular Engineering, 6: 93-102 (2006)
Tissue Elasticity Estimation with Optical Coherence Elastography: Toward Complete Mechanical Characterization of In Vivo Soft Tissue
Ahmad S. Khalil, Raymond C. Chan, Alexandra H. Chau, Brett E. Bouma and Mohammad R. Kaazempur-Mofrad
Annals of Biomedical Engineering, 33: 1631-1639 (2005)
OCT-Based Arterial Elastography: Robust Estimation Exploiting Tissue Biomechanics
Raymond C. Chan, Alexandra H. Chau, W. Clem Karl, Seemantini Nadkarni, Ahmad S. Khalil, Nicusor Iftimia, Milen Shishkov, Guillermo J. Tearney, Mohammad R. Kaazempur-Mofrad and Brett E. Bouma
Optics Express, 12: 4532-4572 (2004)

Cells use networks of interacting molecules to process information, make memories, and execute computations. We are broadly interested in the design and function of these cellular regulatory systems. To examine them, we primarily develop synthetic biology approaches, which allow us to construct artificial versions of these regulatory systems from components “parts” and systematically explore their functional properties. This engineering approach offers a unique way to explore how cellular systems can balance (seemingly paradoxical) functional properties – e.g. specific computation, functional robustness, and adaptability – in order to learn about their evolutionary design, understand their role in development and disease, and guide the engineering of cells with sophisticated functions for practical application. On a translational level, we are applying our synthetic biology technologies to address unmet biomedical needs. This includes creating gene expression control schemes for next-generation gene and cell therapy, and new cell-based models and screening platforms for neurodegenerative disease. In parallel to our synthetic biology efforts, we invent high-throughput technologies / devices and use quantitative systems approaches to help us experimentally interrogate both short-term adaptation and long-term adaptive evolution in microbial systems.

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