We aim to understand and engineer the protein machinery of living cells for solving complex problems in biology and medicine
Research
Research in the DeLisa Research Group (DLRG) focuses on understanding and controlling the molecular mechanisms underlying protein biogenesis - folding and assembly, membrane translocation and post-translational modifications - in the complex environment of a living cell. We focus on the molecular machines of protein biosynthesis both as a toolbox for the discovery, design and manufacturing of biopharmaceuticals and as targets for reprogramming cellular physiology. One approach in our laboratory is to exploit untapped mechanistic features of existing cellular machinery such as intrinsic protein quality control mechanisms that ensure correct folding and assembly of native and non-native proteins. This approach is helping to illuminate important structure-function relationships for protein machinery and is providing a basis by which the machines themselves can be harnessed for producing novel biotechnological products. A second related approach is to engineer microbial cells with unnatural protein machinery, thereby expanding the repertoire of useful biological and chemical functions far beyond those bestowed by nature. Such engineered cells represent a robust platform for cost-effective biosynthesis of complex therapeutic proteins and vaccines for a range of human diseases.
We are currently focused on the following research themes:
For more info, see Cornell Research & Innovation feature or Cornell College of Engineering feature
Stark JC, Jaroentomeechai T, Warfel KF, Hershewe JM, DeLisa MP and Jewett MC
"Rapid biosynthesis of glycoprotein therapeutics and vaccines from freeze-dried bacterial cell lysates"
Nature Protocols (in press) (2023) Link
Robinson M-P, Jung J, Lopez-Barbosa N, Chang M, Li M, Jaroentomeechai T, Cox E, Zheng X, Berkmen M and DeLisa MP
"Isolation of full-length IgG antibodies from combinatorial libraries expressed in the cytoplasm of Escherichia coli"
Nature Communications 14: 3514 (2023) Link
Moeller TD, Shah SB, Lai K, Lopez-Barbosa N, Desai P, Wang W, Zhong Z, Redmond D, Singh A and DeLisa MP
"Profiling germinal center-like B cell responses to conjugate vaccines using synthetic immune organoids"
ACS Central Science 9: 787-804 (2023) Link
[*Featured in ACS Press Room "Testing vaccine candidates quickly with lab-grown mini-organs"]
Weyant KB, Oloyede A, Pal S, Liao J, Rivera-De Jesus M [...] Locher C, de la Maza LM, Coleman MA and DeLisa MP
"A modular vaccine platform enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens"
Nature Communications 14: 464 (2023) Link
[*Editor's Highlight - top 50 best papers in “Microbiology and infectious diseases”]
Jaroentomeechai T, Kwon YH, Liu Y, Young O [...] Chapla DG, Moremen KW, Jewett MC, Mizrachi D and DeLisa MP
"A universal glycoenzyme biosynthesis pipeline that enables efficient cell-free remodeling of glycans"
Nature Communications 13: 6325 (2022) Link
[*Editor's Highlight - top 50 best papers in “Biotechnology and methods”]
Li M, Zheng X, Shanker S, Jaroentomeechai T, Moeller TD, Hulbert S [...] Cox EC, Labonte JW, Gray JJ and DeLisa MP
"Shotgun scanning glycomutagenesis: a simple and efficient strategy for constructing and characterizing neoglycoproteins"
Proceedings of the National Academies of Sciences U S A 118: e2107440118 (2021) Link
Stark JC, Jaroentomeechai T, Moeller TD, Hershewe JM, Warfel KF [...] Jones BD, DeLisa MP and Jewett MC
"On-demand biomanufacturing of protective conjugate vaccines"
Science Advances 7: eabe9444 (2021) Link
Natarajan A, Jaroentomeechai T, Cabrera M, Mohammed J, Cox EC [...] Vadhin S, Varner JD, Azadi P and DeLisa MP
"Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria"
Nature Chemical Biology 16: 1062–1070 (2020) Link
Kightlinger W, Duncker KE, Ramesh A, Thames AN, Natarajan A, Lin L, Stark JC, Mrksich M, DeLisa MP and Jewett MC
"A cell-free biosynthesis platform for modular construction of protein glycosylation pathways"
Nature Communications 10: 5404 (2019) Link
Ludwicki MB, Li J, Stephens EA, Roberts RW, Koide S, Hammond PT and DeLisa MP
"Broad-spectrum proteome editing with an engineered bacterial ubiquitin ligase mimic"
ACS Central Science 5: 852-866 (2019) Link
Meksiriporn B, Ludwicki MB, Stephens, EA [...] Waraho-Zhmayev D, Kummer L, Brandl F, Plückthun A and DeLisa MP
"A survival-selection strategy for engineering synthetic binding proteins that specifically recognize post-translationally phosphorylated proteins"
Nature Communications 10: 1830 (2019) Link
Jaroentomeechai T, Stark JC, Natarajan A, Glasscock CJ, Yates LE, Hsu KJ, Mrksich M, Jewett MC and DeLisa MP
"Single-pot glycoprotein biosynthesis using a cell-free transcription-translation system enriched with glycosylation machinery"
Nature Communications 9: 2686 (2018) Link
Kightlinger W, Lin L, Rosztoczy M, Li W, DeLisa MP, Mrksich M and Jewett MC
"Design of glycosylation sites by rapid synthesis and analysis of glycosyltransferases"
Nature Chemical Biology 14: 627-635 (2018) Link
Stevenson T, Cywes-Bentley C, Moeller TD, Weyant KB, Putnam D, Chang Y-F, Jones BD, Pier GB and DeLisa MP
"Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies"
Proceedings of the National Academies of Sciences U S A 115: E3106-E3115 (2018) Link
The complete list of DLRG publications...
Selected Publications
Team Members
Principal Investigator
Matt DeLisa
William L. Lewis Professor of Engineering
Director, Cornell Institute of Biotechnology, 2019-
Gastprofesseur, ETH-Zürich, 2010-2011
Postdoctoral Fellow, UT-Austin, 2000-2003
Ph.D. University of Maryland, 2000
M.S. University of Maryland, 1998
B.S. University of Connecticut, 1996
Email: md255 at cornell dot edu
To read more about Matt, go here
Postdoctoral research associates
Connor Donahue
Chemistry
Ph.D. University of Maryland, 2023
B.S. St. Mary's College of Maryland, 2016
Email: tcd62 at cornell dot edu
Project: Expanding the repertoire of PTMs in cell-free protein synthesis systems
Hyun Gyu Hwang
Bioscience and Bioengineering
Ph.D. POSTECH, 2021
B.S. Handong Global University, 2015
Email: hh745 at cornell dot edu
Project: In vitro prototyping of human O-linked glycosylation pathways
Mehman Bunyatov
Chemical Biology and Drug Discovery
Postdoc University of Georgia
Ph.D. Utrecht University, 2021
B.S. Moscow State University, 2014
Email: mb2758 at cornell dot edu
Project: Chemical biological approaches to glycoconjugate synthesis
Chandra Bandi
Chemical and Biochemical Engineering
Ph.D. Rutgers University, 2021
M.S. Rutgers University, 2016
B.S. IIT-Kharagpur, 2013
Email: cb922 at cornell dot edu
Project: In vitro prototyping of engineered N-llinked glycosylation pathways
Keehun Kim
American Heart Association Postdoc Fellow
Molecular, Cellular, Dev Biology & Genetics
Ph.D. University of Minnesota, 2021
B.S. Kyungpook National University, 2013
Email: kk779 at cornell dot edu
Project: Cell-free expression and engineering of transmembrane proteins
Jinjoo Jung
Chemical Biology
Ph.D. Seoul National University, 2019
B.S. Soongsil University, 2012
Email: jj757 at cornell dot edu
Project: Engineering glycan-binders for high content resolution of glycomes
Graduate research assistants
Weiyao Wang
Chemical and Biomolecular Engineering
B.S. Tulane University, 2018
Email: ww462 at cornell dot edu
Project: Engineering high-affinity antibodies against carbohydrate antigens
Azmain Alamgir
Chemical and Biomolecular Engineering
Cornell Fleming Scholar
NIH Chemistry-Biology Interface T32 Fellow
B.S. Northwestern University, 2019
Email: ma2283 at cornell dot edu
Project: Intracellular protein delivery via bioconjugation (w/ Chris Alabi)
Tina Ye
Chemical and Biomolecular Engineering
B.S. UC-Berkeley, 2019
Email: ty369 at cornell dot edu
Project: Engineering therapeutic properties of ubiquibodies
Connor Monticello
Biomedical Engineering
B.S. University of Colorado, 2019
Email: crm362 at cornell dot edu
Project: Exploring the modularity of ubiquibodies for proteome editing
Daniel Kwon
Chemical and Biomolecular Engineering
B.S. University of Minnesota, 2017
Email: yk782 at cornell dot edu
Project: Engineering the structure and function of glyco-enzymes
Primit Desai
Biochemistry, Molecular and Cell Biology
B.S. Rutgers University, 2019
Email: pd367 at cornell dot edu
Project: Understanding and engineering immune responses to glycan epitopes
Sophia Hulbert
Biochemistry, Molecular and Cell Biology
NIH Immuno-Engineering T32 Fellow
B.S. University of Southern Maine, 2019
B.A. Barnard College, Columbia Univ, 2017
Email: swh87 at cornell dot edu
Project: Glycomutagenesis of therapeutic proteins and vaccines
Erik Bidstrup
Chemical and Biomolecular Engineering
NIH Chemistry-Biology Interface T32 Fellow
NSF Graduate Research Fellow
B.S. Northwestern University, 2020
Email: ejb339 at cornell dot edu
Project: Cell-free glycoprotein synthesis as a route to customized antibodies
Belen Sotomayor
Chemical and Biomolecular Engineering
B.S. Universidad Tecnica Particular de Loja (UTPL), 2017
Email: mbs332 at cornell dot edu
Project: Understanding and engineering single-subunit oligosaccharyltransferases
Allison Chen
Biomedical Engineering
NSF Graduate Research Fellow
B.S. UCSD, 2020
Email: arc272 at cornell dot edu
Project: Targeted delivery of ubiquibodies using mRNA-LNPs (w/ Chris Alabi)
Ruoxin Li
Biomedical Engineering
B.S. UCLA, 2021
Email: rl655 at cornell dot edu
Project: Engineering viral vectors for targeted delivery of ubiquibodies (w/ Shaoyi Jiang)
Ayomide Oloyede
Biomedical Engineering
B.S. University of New Mexico, 2020
Email: aoo35 at cornell dot edu
Project: Immunoengineering bacterial outer membrane vesicles
Darianna Colina
Biochemistry, Molecular and Cell Biology
NIH Chemistry-Biology Interface T32 Fellow
M.S. Johns Hopkins University, 2020
B.S. Florida Gulf Coast University, 2017
Email: dc676 at cornell dot edu
Project: Engineering peptide guide-driven ubiquibodies for cancer immunotherapy
Jiazhen Chen
Chemical and Biomolecular Engineering
B.E. East China University of Science and Technology, 2019
B.S. Technische Hochschule Lübeck, 2019
Email: jc3494 at cornell dot edu
Project: Understanding and engineering single-subunit oligosaccharyltransferases
Richard Huang
Chemical and Biomolecular Engineering
B.Eng. Central South University, 2020
Email: yh936 at cornell dot edu
Project: Engineering glycan-directed affinity reagents for imaging the glycocalyx
Amy Nguyen
Chemical and Biomolecular Engineering
B.S. Drexel University, 2019
Email: pmn35 at cornell dot edu
Project: Engineering multivalent vaccines against enteric pathogens
Yufan Qin
Chemical and Biomolecular Engineering
M.S.E. University of Michigan, 2021
B.S. UC-Irvine, 2020
Email: yq262 at cornell dot edu
Project: Discovery of biocatalysts for efficient conjugate vaccine biosynthesis
Helene Walker
Chemical and Biomolecular Engineering
B.S. University of New Mexico, 2022
Email: hcw45 at cornell dot edu
Project: Discovery of carbohydrate-specific antibodies from non-immune libraries
Deana Moffat
Biomedical Engineering
M.S. Binghamton University, 2022
B.S. Binghamton University, 2021
Email: dmm375 at cornell dot edu
Project: Engineering glycan-directed cell therapies against solid tumors
Jaymee Palma
Biochemistry, Molecular and Cell Biology
B.S. KAIST, 2022
Email: jp2325 at cornell dot edu
Project: TBD
Undergraduate research assistants
Marisa Brown-Johnson
Biological Engineering, Global and Public Health Sciences (2023-Present)
Email: bas372 at cornell dot edu
Project: Conjugate vaccine engineering via glycomutagenesis
Sofia Patterson-Malendrez
Chemical and Biomolecular Engineering
(2023-Present)
Email: sp2229 at cornell dot edu
Project: Engineering anti-glycan antibodies
Spoorthi Patil
Biomedical Engineering
(2023-Present)
Email: ssp224 at cornell dot edu
Project: Understanding and engineering bacterial glycoenzymes
Atid Techanitisawad
Biology
(2023-Present)
Email: at668 at cornell dot edu
Project: Cancer immunotherapy via glycosylated outer membrane vesicles
Alina Chisti
Chemical and Biomolecular Engineering
(2022-Present)
Email: azc7 at cornell dot edu
Project: Cell-free glycoprotein synthesis
Jane Lee
Chemical and Biomolecular Engineering
(2022-Present)
Email: jyl99 at cornell dot edu
Project: Glycoenzyme engineering
Michael Constant
Chemical and Biomolecular Engineering
(2022-Present)
Email: mjc456 at cornell dot edu
Project: Ubiquibody engineering
Jahi Noel
Biological Sciences
(2022-Present)
Email: jjn58 at cornell dot edu
Project: Design and engineering of glycoconjugate vaccines