Design and Modular Assembly of Synthetic Intramembrane Proteolysis Receptors for Custom Gene Regulation in Therapeutic Cells
Iowis Zhu, Raymond Liu, Axel Hyrenius-Wittsten, Dan I. Piraner, Josef Alavi, Divya V. Israni, Ahmad S. Khalil and Kole T. Roybal
bioRxiv, doi: 10.1101/2021.05.21.445218
Here to Stay: Writing Lasting Epigenetic Memories (Preview)
Hagar F. Moussa*, James F. Angstman* and Ahmad S. Khalil
Cell, 184: 2281-2283 (2021)
Clinically-Driven Design of Synthetic Gene Regulatory Programs in Human Cells
Divya V. Israni*, Hui-Shan Li*, Keith A. Gagnon, Jeffry D. Sander, Kole T. Roybal, J. Keith Joung, Wilson W. Wong and Ahmad S. Khalil
bioRxiv, doi: 10.1101/2021.02.22.432371
Engineering Clinically-Approved Drug Gated CAR Circuits
Hui-Shan Li*, Nicole M. Wong*, Elliot Tague, John T. Ngo, Ahmad S. Khalil and Wilson W. Wong
bioRxiv, doi: 10.1101/2020.12.14.419812
Transcriptional Kinetic Synergy: A Complex Landscape Revealed by Integrating Modelling and Synthetic Biology
Rosa Martinez-Corral, Minhee Park, Kelly Biette, Dhana Friedrich, Clarrissa Scholes, Ahmad S. Khalil, Jeremy Gunawardena and Angela H. DePace
bioRxiv, doi: 10.1101/2020.08.31.276261
Environmental Fluctuations Reshape an Unexpected Diversity-Disturbance Relationship in a Microbial Community
Christopher P. Mancuso, Hyunseok Lee, Clare I. Abreu, Jeff Gore and Ahmad S. Khalil
bioRxiv, doi: 10.1101/2020.07.28.225987
Colonization with Heterologous Bacteria Reprograms a Caenorhabditis elegans Nutritional Phenotype
Qing Sun*, Nicole M. Vega*, Bernardo Cervantes, Christopher P. Mancuso, Ning Mao, Megan Taylor, James J. Collins, Ahmad S. Khalil, Jeff Gore and Timothy K. Lu
bioRxiv, doi: 10.1101/2020.03.01.972349
Computational Model To Quantify the Growth of Antibiotic-Resistant Bacteria in Wastewater
Indorica Sutradhar, Carly Ching, Darash Desai, Mark Suprenant, Emma Briars, Zachary Heins, Ahmad S. Khalil and Muhammad H. Zaman
mSystems, 6: e0036021 (2021)
A Code of Ethics for Gene Drive Research
George J. Annas, Chase L. Beisel, Kendell Clement, Andrea Crisanti, Stacy Francis, Marco Galardini, Roberto Galizi, Julian Grünewald, Greta Immobile, Ahmad S. Khalil, Ruth Müller, Vikram Pattanayak, Karl Petri, Ligi Paul, Luca Pinello, Alekos Simoni, Chrysanthi Taxiarchi and J. Keith Joung
CRISPR J, 4: 19-24 (2021)
Automated Continuous Evolution of Proteins In Vivo
Ziwei Zhong*, Brandon G. Wong*, Arjun Ravikumar, Garri A. Arzumanyan, Ahmad S. Khalil and Chang C. Liu
ACS Synthetic Biology, 9: 1270-1276 (2020)

  Commentary in preLights by Pavithran Ravindran (link)
Barcoded Microbial System for High-Resolution Object Provenance
Jason Qian*, Zhi-xiang Lu*, Christopher P. Mancuso*, Han-Ying Jhuang*, Rocío del Carmen Barajas-Ornelas*, Sarah A. Boswell*, Fernando H. Ramírez-Guadiana, Victoria Jones, Akhila Sonti, Kole Sedlack, Lior Artzi, Giyoung Jung, Mohammad Arammash, Mary E. Pettit, Michael Melfi, Lorena Lyon, Siân V. Owen, Michael Baym, Ahmad S. Khalil, Pamela A. Silver, David Z. Rudner and Michael Springer
Science, 368: 1135-1140 (2020)

  Commentary in Science by Jeff Nivala (PDF)
Protein Assembly Systems in Natural and Synthetic Biology
Giulio Chiesa*, Szilvia Kiriakov and Ahmad S. Khalil
BMC Biology, 28: 35 (2020)
Sphingomonas solaris sp. nov., Isolated From a Solar Panel in Boston, Massachusetts
Kristie Tanner, Christopher P. Mancuso, Juli Peretó, Ahmad S. Khalil, Cristina Vilanova and Javier Pascual
International Journal of Systematic and Evolutionary Microbiology, 70: 1814-1821 (2020)
Designing Automated, High-Throughput Continuous Cell Growth Experiments Using eVOLVER
Zachary J. Heins, Christopher P. Mancuso, Szilvia Kiriakov, Brandon G. Wong, Caleb J. Bashor and Ahmad S. Khalil
Journal of Visualized Experiments, 147: e59652 (2019)
Complex Signal Processing in Synthetic Gene Circuits Using Cooperative Regulatory Assemblies
Caleb J. Bashor*, Nikit Patel*, Sandeep Choubey, Ali Beyzavi, Jane Kondev, James J. Collins and Ahmad S. Khalil
Science, 364: 593-597 (2019)

  Commentary in Science by Andrew H. Ng & Hana El-Samad (PDF); in Nature Biotechnology by Ross Cloney (PDF)
Functional Genomics of the Rapidly Replicating Bacterium Vibrio natriegens by CRISPRi
Henry H. Lee, Nili Ostrov, Brandon G. Wong, Michaela A. Gold, Ahmad S. Khalil and George M. Church
Nature Microbiology, 4: 1105-1113 (2019)

  Commentary in Nature Microbiology by Jonathan D'Gama & Matthew Waldor (PDF)
Engineering Epigenetic Regulation Using Synthetic Read-Write Modules
Minhee Park, Nikit Patel, Albert J. Keung and Ahmad S. Khalil
Cell, 176: 227-238 (2019)

  Recommended for Faculty of 1000 (link)
  Commentary in Nature Reviews Genetics by Michelle Trenkmann (PDF); in Nature Methods by Nicole Rusk (PDF); in Biochemistry by Theresa Loveless & Chang Liu (PDF); in Molecular Cell by Timothy Chang, James Kuo & Pamela Silver (PDF); in Nature Chemical Biology by Yiyun Song (link)
Modeling the Impact of Drug Interactions on Therapeutic Selectivity
Zohar B. Weinstein, Nurdan Kuru, Szilvia Kiriakov, Adam C. Palmer, Ahmad S. Khalil, Paul A. Clemons, Muhammad H. Zaman, Frederick P. Roth and Murat Cokol
Nature Communications, 9: 3452 (2018)
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, 36: 614-623 (2018)

  Commentary in Nature by Mike May (PDF)
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*, Zoe A. Feder, 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. by Andrew Jermy (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)

Living cells use “circuits” of interacting molecules to process signals, remember information, and interact with their environments. My team develops two approaches to study the design principles of these biological systems, and to create synthetic systems that can program biomedically useful cellular behaviors. First, we pioneer synthetic biology approaches, in which we design and build molecular circuits from the bottom-up and test their function in eukaryotic cells. Using this approach, we have discovered key principles governing the circuits that control transcription regulation and epigenetic memory, and in turn developed systems for programming gene expression control in therapeutic human cells. Second, we develop new methods to study and harness the process of evolution in the design of biological systems. A central pillar of this effort is “eVOLVER”, an open-source, flexible, and scalable continuous culture platform we invented that is now being used across academic and industry settings to implement custom and automated microbial culture and evolution experiments. Using eVOLVER, we are developing high-throughput methods for the automated continuous directed evolution (CDE) of proteins with radically altered activities and specificities in order to reveal basic insights into protein evolution and enable a new generation of therapeutics.

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