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Karl Griswold

Professor of Engineering

karl.e.griswold@dartmouth.edu

The Griswold Research Group is developing high-throughput screens for evolutionary protein engineering, new strategies for protein deimmunization, enhanced protein expression systems, and powerful antibacterial agents to treat drug-resistant infections. (Photo by John Sherman)

Research Interests

Protein engineering; directed evolution; biotherapeutics; applied biocatalysis; high throughput screening

Education

BS, Chemistry, Southwest Texas State University 1995
PhD, Chemistry, University of Texas at Austin 2005

Awards

Wallace H. Coulter Foundation Early Career Translational Research Award in Biomedical Engineering (2008)
NIH Biotechnology Training Grant (2000-2003)
Royston M. Roberts - Regents Fellowship, University of Texas (1999)
DOW Chemical Foundation Scholar, Texas State University (1991-1995)
Presidential Upper Division Scholar, Texas State University (1994-1995)
ACS Polymer Education Committee Award for Organic Chemistry (1993)

Professional Activities

Senior Fellow, NAI
Member, AIChE
Member, ACS
Member, SIM
Member, ASEE

Startups

Stealth Biologics
Co-Founder and CEO

Research Projects

Enzyme therapeutics

Enzyme therapeutics

Enzyme therapeutics are a potential means of addressing the emerging health care crisis resulting from drug resistant microbial pathogens. Efforts are focused on the redesign of antimicrobial proteins for enhanced bactericidal activity towards various clinically relevant targets. One facet of this work relates to complications associated with the genetic disease cystic fibrosis, and is being investigated in conjunction with the Cystic Fibrosis Foundation Research Development Program at The Geisel School of Medicine at Dartmouth.
Immunogenicity prediction

Immunogenicity prediction

Immunogenicity prediction is an important means to control the safety of protein drugs, which can be recognized by the patient's immune system as foreign, inducing an adaptive immune response that can cause significant toxicity. We are developing approaches in which the immunogenicity of proteins can be assessed in vitro using protein engineering tools.
Cellular engineering of protein expression hosts

Cellular engineering of protein expression hosts

Cellular engineering of protein expression hosts provides the ability to modify proteins in a site specific and controlled fashion—something increasingly important for the development of therapeutic proteins. We are developing methods by which cells are genetically engineered to incorporate sugars on a recombinant protein in a site-specific sequence dependent manner. Once a sugar is positioned on a given protein, conventional chemical modification such as PEGlylation can be used to further modify the protein and improve its therapeutic properties.
Protein engineering tools in immunology

Protein engineering tools in immunology

Protein engineering tools in immunology can be used as an unbiased and systematic means of identifying new targets, generating diagnostic and therapeutic reagents, and characterizing the basic biology of infectious disease.

Selected Publications

Scanlon, T.C., Dostal, S.M., Griswold, K.E. A High Throughput Screen for Antibiotic Drug Discovery. Biotechnology & Bioengineering (2013), [Epub ahead of print]; PMID: 23955804
Teneback, C.C., Scanlon, T.C., Wargo, M.J., Bement, J., Griswold, K.E., Leclair, L.W. Bioengineered lysozyme reduces bacterial burden and inflammation in a murine model of mucoid Pseudomonas aeruginosa lung infection. Antimicrobial Agents and Chemotherapy (2013), 57(11), pp. 5559–5564
Lamppa, J.W., Tanyos, S.A., Griswold, K.E. Engineering Escherichia coli for Soluble Expression and Single Step Purification of Active Human Lysozyme. Journal of Biotechnology (2013), 164, pp. 1-8
Choi Y., Griswold K.E., Bailey-Kellogg C. Structure-based Redesign of Proteins for Minimal T cell Epitope Content. Journal of Computational Chemistry (2013), 34(10), pp. 879-891
Lamppa, J.W., Griswold, K.E. Alginate Lyase Exhibits Catalysis-Independent Biofilm Dispersion and Antibiotic Synergy. Antimicrobial Agents and Chemotherapy (2013), 57(1), pp. 137-145
Osipovitch, D.C., Parker, A.S., Makokha, C.D., Desrosiers, J., Kett, W.C., Moise, L., Bailey-Kellogg, C., Griswold, K.E. Design and Analysis of Immune-Evading Enzymes for ADEPT Therapy. Protein Engineering, Design & Selection (2012), 25(10), pp. 613-624

Patents

System and apparatus for porously-encapsulated magnetic-nanoparticle biosensors | 10,502,735
Deimmunized lysostaphin and methods of use | 10,358,636
Therapeutic charge engineered variants of lysozyme and methods for using same to treat infection | 9,074,201