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 College of Engineering feature
The complete list of DLRG publications is here
Αlamgir A, Ghosal S, DeLisa MP and Alabi CA
Bioreversible anionic cloaking enables intracellular protein delivery with ionizable lipid nanoparticles
ACS Central Science (in press) (2024) Link
*Featured on supplementary cover
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 18: 2374-98 (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
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
Lan Na
Chemistry
Postdoc Rosalind Franklin Institute
Ph.D. UC-Davis, 2020
M.S. Sogang University, 2015
B.S. Sogang University, 2013
Email: TBD at cornell dot edu
Project: TBD
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
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
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
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
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
Biomedical Engineering
B.S. University of New Mexico, 2020
Email: aoo35 at cornell dot edu
Project: Immunoengineering bacterial outer membrane vesicles
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
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
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
Deana Moffat
Biomedical Engineering
NIH IMSD T32 Fellow
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: Glycoengineering vaccines and therapeutics for combatting antimicrobial resistance
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
Deepali Venkatesh Prasanna
Chemical and Biomolecular Engineering
M.S. Northwestern University, 2023
B.E. RV College of Engineering, 2020
Email: dv287 at cornell dot edu
Project: Engineering PTM biosynthesis in cell-free protein synthesis systems
Ching-Chih Feng
Chemical and Biomolecular Engineering
B.S. National Taiwan University, 2022
Email: cf534 at cornell dot edu
Project: Engineering multivalent bacterial vesicle vaccines against enteric pathogens
Harry Zou
Biomedical Engineering
B.S. University of Maryland, 2023
Email: hxz2 at cornell dot edu
Project: TBD
Aarya Darak
Chemical and Biomolecular Engineering
B.S. Institute of Chemical Technology, 2023
Email: ad2252 at cornell dot edu
Project: TBD
Undergraduate research assistants
Gaurvi Awasthi
Biology and Society
(2023-Present)
Email: ga322 at cornell dot edu
Project: Bacterial glycoengineering
Isabella Censullo
Biomedical Engineering
(2023-Present)
Email: ilc8 at cornell dot edu
Project: Bacterial glycoengineering
Neha Chopade
Biomedical Engineering
(2023-Present)
Email: nc457 @ cornell dot edu
Project: Peptide-guided ubiquibodies for targeted protein degradation
Carla Hu
Human Biology, Health and Society
(2023-Present)
Email: ch652 at cornell dot edu
Project: Targeted protein degradation
Julia Vizza
Chemical Engineering
(2023-Present)
Email: jev74 at cornell dot edu
Project: Targeted protein degradation
Emily Hansen
Global and Public Health Sciences
(2023-Present)
Email: erh68 at cornell dot edu
Project: Bacterial glycoengineering
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
Atid Techanitisawad
Biology
(2023-Present)
Email: at668 at cornell dot edu
Project: Cancer immunotherapy via glycosylated outer membrane vesicles
Spoorthi Patil
Biomedical Engineering
(2023-Present)
Email: ssp224 at cornell dot edu
Project: Understanding and engineering bacterial glycoenzymes
Alina Chisti
Chemical and Biomolecular Engineering
(2022-Present)
Email: azc7 at cornell dot edu
Project: Cell-free glycoprotein synthesis
Chris Cizmeciyan
Biology/Biological Sciences
(2022-Present)
Email: cac487 at cornell dot edu
Project: Cell-free protein synthesis of functional GPCRs
