Charles Gersbach

Positions:

Rooney Family Associate Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Associate Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Associate Professor of Surgery

Surgery, Surgical Sciences
School of Medicine

Associate Professor of Orthopaedic Surgery

Orthopaedics
School of Medicine

Associate of the Duke Initiative for Science & Society

Duke Science & Society
Institutes and Provost's Academic Units

Core Faculty in Innovation & Entrepreneurship

Duke Innovation & Entrepreneurship
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

B.S. 2001

Georgia Institute of Technology

Ph.D. 2006

Georgia Institute of Technology

Grants:

Regulatory Mechanisms of CD4+ T Cell Differentiation

Administered By
Biostatistics & Bioinformatics
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Regulatory Mechanisms of CD4+ T Cell Differentiation

Administered By
Integrative Genomics
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Investigating Autophagy in GSD-Ia

Administered By
Pediatrics, Medical Genetics
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Mechanotransduction in Meniscus Health and Repair

Administered By
Orthopaedics
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

To support research on the development of CRISPR-based epigenome editing tools to refine genome wide association studies

Administered By
Biomedical Engineering
Role
Principal Investigator
Start Date
End Date

Publications:

Editorial Overview: Synthetic biology and biomedical engineering

Authors
MLA Citation
Gersbach, C. A. “Editorial Overview: Synthetic biology and biomedical engineering.” Current Opinion in Biomedical Engineering, vol. 4, Dec. 2017, pp. vi–vii. Scopus, doi:10.1016/j.cobme.2017.12.005.
URI
https://scholars.duke.edu/individual/pub1418249
Source
scopus
Published In
Current Opinion in Biomedical Engineering
Volume
4
Published Date
Start Page
vi
End Page
vii
DOI
10.1016/j.cobme.2017.12.005

Gene delivery and biomedical engineering

Authors
MLA Citation
Gersbach, C. A. “Gene delivery and biomedical engineering.” Current Opinion in Biomedical Engineering, vol. 7, Sept. 2018, pp. iii–v. Scopus, doi:10.1016/j.cobme.2018.11.003.
URI
https://scholars.duke.edu/individual/pub1418248
Source
scopus
Published In
Current Opinion in Biomedical Engineering
Volume
7
Published Date
Start Page
iii
End Page
v
DOI
10.1016/j.cobme.2018.11.003

Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.

Class 2 CRISPR-Cas systems, such as Cas9 and Cas12, have been widely used to target DNA sequences in eukaryotic genomes. However, class 1 CRISPR-Cas systems, which represent about 90% of all CRISPR systems in nature, remain largely unexplored for genome engineering applications. Here, we show that class 1 CRISPR-Cas systems can be expressed in mammalian cells and used for DNA targeting and transcriptional control. We repurpose type I variants of class 1 CRISPR-Cas systems from Escherichia coli and Listeria monocytogenes, which target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation and nuclear localization in human cells, and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering activation and repression domains to Cascade, we modulate the expression of targeted endogenous genes in human cells. This study demonstrates the use of Cascade as a CRISPR-based technology for targeted eukaryotic gene regulation, highlighting class 1 CRISPR-Cas systems for further exploration.
Authors
Pickar-Oliver, A; Black, JB; Lewis, MM; Mutchnick, KJ; Klann, TS; Gilcrest, KA; Sitton, MJ; Nelson, CE; Barrera, A; Bartelt, LC; Reddy, TE; Beisel, CL; Barrangou, R; Gersbach, CA
MLA Citation
Pickar-Oliver, Adrian, et al. “Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells..” Nat Biotechnol, vol. 37, no. 12, 2019, pp. 1493–501. Pubmed, doi:10.1038/s41587-019-0235-7.
URI
https://scholars.duke.edu/individual/pub1381738
PMID
31548729
Source
pubmed
Published In
Nat Biotechnol
Volume
37
Published Date
Start Page
1493
End Page
1501
DOI
10.1038/s41587-019-0235-7

Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D.

Cooperating gene mutations are typically required to transform normal cells enabling growth in soft agar or in immunodeficient mice. For example, mutations in Kras and transformation-related protein 53 (Trp53) are known to transform a variety of mesenchymal and epithelial cells in vitro and in vivo. Identifying other genes that can cooperate with oncogenic Kras and substitute for Trp53 mutation has the potential to lead to new insights into mechanisms of carcinogenesis. Here, we applied a genome-wide CRISPR/Cas9 knockout screen in KrasG12D immortalized mouse embryonic fibroblasts (MEFs) to search for genes that when mutated cooperate with oncogenic Kras to induce transformation. We also tested if mutation of the identified candidate genes could cooperate with KrasG12D to generate primary sarcomas in mice. In addition to identifying the well-known tumor suppressor cyclin dependent kinase inhibitor 2A (Cdkn2a), whose alternative reading frame product p19 activates Trp53, we also identified other putative tumor suppressors, such as F-box/WD repeat-containing protein 7 (Fbxw7) and solute carrier family 9 member 3 (Slc9a3). Remarkably, the TCGA database indicates that both FBXW7 and SLC9A3 are commonly co-mutated with KRAS in human cancers. However, we found that only mutation of Trp53 or Cdkn2a, but not Fbxw7 or Slc9a3 can cooperate with KrasG12D to generate primary sarcomas in mice. These results show that mutations in oncogenic Kras and either Fbxw7 or Slc9a3 are sufficient for transformation in vitro, but not for in vivo sarcomagenesis.
Authors
Huang, J; Chen, M; Xu, ES; Luo, L; Ma, Y; Huang, W; Floyd, W; Klann, TS; Kim, SY; Gersbach, CA; Cardona, DM; Kirsch, DG
MLA Citation
Huang, Jianguo, et al. “Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D..” Sci Rep, vol. 9, no. 1, Nov. 2019. Pubmed, doi:10.1038/s41598-019-53572-w.
URI
https://scholars.duke.edu/individual/pub1421434
PMID
31748650
Source
pubmed
Published In
Scientific Reports
Volume
9
Published Date
Start Page
17220
DOI
10.1038/s41598-019-53572-w

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles.

Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo.
Authors
Evans, BC; Fletcher, RB; Kilchrist, KV; Dailing, EA; Mukalel, AJ; Colazo, JM; Oliver, M; Cheung-Flynn, J; Brophy, CM; Tierney, JW; Isenberg, JS; Hankenson, KD; Ghimire, K; Lander, C; Gersbach, CA; Duvall, CL
MLA Citation
Evans, Brian C., et al. “An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles..” Nature Communications, vol. 10, no. 1, Nov. 2019. Epmc, doi:10.1038/s41467-019-12906-y.
URI
https://scholars.duke.edu/individual/pub1417845
PMID
31676764
Source
epmc
Published In
Nature Communications
Volume
10
Published Date
Start Page
5012
DOI
10.1038/s41467-019-12906-y