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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:

Recent News

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 (in press) Link

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

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

Mizrachi D, Robinson M-P, Ke N, Ren G, Berkmen M and DeLisa MP

"A water-soluble DsbB variant that catalyzes disulfide bond formation in vivo"

Nature Chemical Biology 13: 1022-1028 (2017)  Link 

Chen L, Valentine JL, Huang C-J, Endicott CE, Moeller TD [...] Azadi P, Putnam D, Trent MS, Jones BD and DeLisa MP

"Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies"

Proceedings of the National Academies of Sciences U S A 113: E3609-18 (2016) Link

Selected Publications

Team Members

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Principal Investigator

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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

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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

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Asher Williams

Cornell Presidential Postdoc Scholar

Chemical and Biomolecular Engineering

Ph.D. RPI, 2020

B.S. NYU Polytechnic, 2015

Email: ajw336 at cornell dot edu

Project: Cell-free biosynthesis of conjugate vaccines against bacterial pathogens

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Jinjoo Jung

Chemical Biology

Ph.D. Seoul National University, 2019

B.S. Soongsil University, 2012

 

 

Email: jj757 at cornell dot edu

Project: Building a molecular toolkit for high content resolution of glycomes 

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Chandra Bandi

Chemical and Biochemical Engineering

Ph.D. Rutgers University, 2021

M.S. Rutgers University, 2016

B.S. IIT-Kharagpur, 2013

Email: TBD

Project: TBD

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Mehman Bunyatov

Chemical Biology and Drug Discovery

Postdoc University of Georgia

Ph.D. Utrecht University, 2021

B.S.  Moscow State University, 2014

Email: TBD

Project: TBD

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Hyun Gyu Hwang

Bioscience and Bioengineering

Ph.D. POSTECH, 2021

B.S. Handing Global University, 2015

 

 

Email: TBD

Project: TBD 

Graduate research assistants

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Alicia Aquino

Chemical and Biomolecular Engineering

NSF Graduate Research Fellow

NIH Chemistry-Biology Interface T32 Fellow

B.S. Worcester Polytechnic Institute, 2017

 

Email: aka77 at cornell dot edu

Project: Glycosylation-on-a-chip for  therapeutic glycoprotein biosynthesis

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Sean Chung

Biochemistry, Molecular and Cell Biology 

M.S. University of Southern California, 2016 

B.S. Pomona College, 2012 

Email: ssc273 at cornell dot edu

Project: Understanding and engineering glycoprotein structure-activity relationships

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Natalia Lopez-Barbosa

Chemical and Biomolecular Engineering

Cornell CBE Fleming Scholar

B.S. Universidad de Los Andes, 2017

Email: nl474 at cornell dot edu

Project: Exploring the occurrence and role of anti-glycan antibodies in immunity

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Weiyao Wang

Chemical and Biomolecular Engineering

B.S. Tulane University, 2018

Email: ww462 at cornell dot edu

Project: Engineering high-affinity antibodies against carbohydrate epitopes

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Azmain Alamgir

Chemical and Biomolecular Engineering

NIH Chemistry-Biology Interface T32 Fellow

B.S. Northwestern University, 2019

Email: ma2283 at cornell dot edu

Project: Novel modes of proteome editing via bioconjugation (w/ Chris Alabi)

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Tina Ye

Chemical and Biomolecular Engineering

B.S. UC-Berkeley, 2019

Email: ty369 at cornell dot edu

Project: Engineering PK/PD properties of ubiquibodies 

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Connor Monticello

Biomedical Engineering

B.S. University of Colorado, 2019

Email: crm362 at cornell dot edu

Project: Proteome editing via intracellular delivery of ubiquibodies

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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 glycosyltransferases

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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

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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: High-resolution mapping of glycosylation permissiveness of IgGs

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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

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Belen Sotomayor

Chemical and Biomolecular Engineering

B.S. Universidad Tecnica Particular de Loja (UTPL), 2017

Email: mbs332 at cornell dot edu

Project: Experimental and computational optimization of protein glycosylation

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Allison Chen

Biomedical Engineering

NSF Graduate Research Fellow

B.S. UCSD, 2020

Email: arc272 at cornell dot edu

Project: Targeted delivery of ubiquibody mRNA-loaded LNPs (w/ Chris Alabi)

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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)

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Ayomide Oloyede

Biomedical Engineering

B.S. University of New Mexico, 2020 

Email: aoo35 at cornell dot edu

Project: Immunoengineering anti-cancer bacterial membrane vesicles

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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 protein degraders for cancer immunotherapy

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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

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Richard Huang

Chemical and Biomolecular Engineering

B.Eng. Central South University, 2020 

Email: yh936 at cornell dot edu

Project: Engineering glycan-directed binding proteins

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Amy Nguyen

Chemical and Biomolecular Engineering

B.S. Drexel University, 2019

Email: pmn35 at cornell dot edu

Project: TBD

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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: TBD

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Helene Walker

Chemical and Biomolecular Engineering

B.S. University of New Mexico, 2022

 

Email: hcw45 at cornell dot edu

Project: TBD

Undergraduate research assistants

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Pedro Da Silveira

Biomedical Engineering

(2022-Present)

 

Email: phd42 at cornell dot edu

Project: Engineering PK/PD properties of targeted protein degraders

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Alina Chisti

Chemical and Biomolecular Engineering

(2022-Present)

 

Email: azc7 at cornell dot edu

Project: Cell-free glycoprotein synthesis

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Mackenzie Rosin

Biological Engineering

(2022-Present)

 

Email: mmr93 at cornell dot edu

Project: Understanding the immunological role of anti-glycan antibodies

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Jorge Rodriguez

Global Public Health Science

(2022-Present)

 

Email: jhr249 at cornell dot edu

Project: Glycoenzyme engineering

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Jahi Noel

Biological Sciences

(2022-Present)

 

Email: jjn58 at cornell dot edu

Project: Design and engineering of glycoconjugate vaccines

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Chris Cizmeciyan

Biological Sciences

(2022-Present)

 

Email: cac487 at cornell dot edu

Project: Design and engineering of glycoconjugate vaccines 

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Jane Lee

Chemical and Biomolecular Engineering

(2022-Present)

 

Email: jyl99 at cornell dot edu

Project: Glycoenzyme engineering

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Michael Constant

Chemical and Biomolecular Engineering

(2022-Present)

 

Email: mjc456 at cornell dot edu

Project: Ubiquibody engineering

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Amy Hidalgo

Biological Engineering (2022-Present)

 

Email: akh228 at cornell dot edu

Project: Immune responses to glycans

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Alex Pang

Economics/Bioengineering (2019-Present)

Email: ayp26 at cornell dot edu

Project: Glycosylation-on-a-chip

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