Charles Alan Gersbach, Ph.D.

Researchers at Duke University have adapted CRISPR technologies to enable high-throughput screening of gene function in human immune cells, and discovered that a single master regulator of the genome can be used to reprogram a network of thousands of genes in T cells and greatly enhance cancer cell killing.

The master regulator transcription factor (TF) gene is called BATF3 and is one of several genes that the researchers identified and tested for improving T cell therapies. These targets, and the methods developed to identify, test, and manipulate them, could make any of the T-cell cancer therapies currently in use and under development more potent. Combined with other advances, the platform could also enable generalized, off-the-shelf versions of the therapy and expansion into other disease areas such as autoimmune disorders… Continue reading.

Genetic reprogramming can help stem cells mature into desired cell types, but it is often kludgy, which is to say, clumsy and inefficient—or worse, inexact. It may produce cells that don’t mature quite as much as they should, or that fail to represent the exact right subtype. These shortcomings may be avoided if more elegant genetic programming methods become available, methods of the sort being developed by scientists in the Duke University laboratory led by Charles Gersbach, PhD, an associate professor of biomedical engineering.

According to a new study from the Gersbach laboratory, genetic reprogramming may be improved with a CRISPR-based method called CRISPR activation (CRISPRa). The Gersbach team used CRISPRa to identify factors that could improve the efficiency with which stem cells are turned into neurons. CRISPRa, the scientists pointed out, could have a more general application. That is, CRISPRa could be extended to other cell reprogramming applications and facilitate the production of cell types other than neurons. Ultimately, CRISPRa could help researchers generate cell sources that would be useful for disease modeling, drug screening, and regenerative medicine… Continue reading.

Sleek CRISPR systems get almost all the attention. They rely on single-protein nucleases instead of multiunit effectors, which are, presumably, too unwieldy for gene engineering applications. Yet CRISPR jumbles have been given a tumble by scientists at Duke University. Led by Charles Gersbach, PhD, the Rooney Family associate professor of biomedical engineering and Adrian Oliver, PhD, a postdoctoral fellow, these scientists used a multiunit effector system to turn target genes on and off in human cells.

Specifically, the scientists used a class 1 CRISPR-Cas system called Cascade (CRISPR-associated complex for antiviral defense). And as if it wasn’t clunky enough already, the scientists tacked on a couple of extras—activation and repression domains. The system, however, omitted the Cas enzyme that would have ordinarily been present… Continue reading.

To advance the engineering of biology at the molecular and cellular levels, the National Science Foundation (NSF) has awarded $16 million for research to characterize the regulation of gene activity and expression, and to create strategies to modify those processes without altering the DNA sequence.

Chromatin — a combination of DNA, RNA and proteins within a cell’s nucleus — can be modified by attaching additional molecules. This can cause altered gene expression without actually changing the cell’s DNA. These so-called epigenetic changes can alter an organism’s traits, or phenotype, and may even be passed to offspring.

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The NSF EFRI Chromatin and Epigenetic Engineering (CEE) investment will support potentially transformative research by eight interdisciplinary teams:

• Ascribing function to chromatin with coordinated live-cell epigenomic sensors and scalpels, Albert Keung, North Carolina State University, with Caroline Laplante and Balaji Rao
• Engineering technologies to determine causal relationships between chromatin structure and gene regulation, Charles Gersbach, Duke University, with Brenton Hoffman, Michael Rubinstein and Xiling Shen
• Epigenetic cell reprogramming in situ: A novel tool for regenerative engineering, Guillermo Ameer, Northwestern University, with Panagiotis Ntziachristos and Hariharan Subramanian
• Epigenomic regulation over multiple length scales: Understanding chromatin modifications through label free imaging and multi-scale modeling, Juan De Pablo, University of Chicago, with Ali Shilatifard and Hao Zhang
• Human cardiac opto-epigenetics with HDAC inhibitors, Emilia Entcheva, George Washington University, with Shu Jia, Zhenyu Li, Ralph Mazitschek and Alejandro Villagra
• Macrogenomic engineering via modulation of chromatin nanoenvironment, Vadim Backman, Northwestern University, with Michael Kennedy, Hemant Roy and Igal Szleifer
• Optically controlled localized epigenetic chromatin remodeling with photoactivatable CRISPR-dCas9, Lev Perelman, Beth Israel Deaconess Medical Center, with Irving Itzkan, J. Thomas Lamont, Le Qiu and Darren Roblyer
• Sculpting the genome by design: Epigenetic and chromatin looping inputs to measure and manipulate chromatin organization and dynamics, Megan King, Yale University, with Simon G. Mochrie and Corey O’Hern

Continue reading…

WASHINGTON, D.C.— The American Institute for Medical and Biological Engineering (AIMBE) has announced the pending induction of Charles Alan Gersbach, Ph.D., Rooney Family Associate Professor of Biomedical Engineering, Department of Biomedical Engineering, Duke University, to its College of Fellows. Dr. Gersbach was nominated, reviewed, and elected by peers and members of the College of Fellows For outstanding contributions to the fields of biomolecular and genome engineering, synthetic biology, gene therapy, and genomics and epigenomics..