Biography

Dr. Daniel J. Siegwart is an Associate Professor in the Department of Biochemistry and the Simmons Comprehensive Cancer Center (SCCC) at UT Southwestern Medical Center (Dallas, Texas, U.S.A.). He is also the co-director for the Chemistry and Cancer Program within the National Cancer Institute-designated SCCC. He received a B.S. in Biochemistry from Lehigh University in 2003, and a Ph.D. in Chemistry from Carnegie Mellon University (CMU) in 2008 under the supervision of University Professor Krzysztof Matyjaszewski. During his graduate studies, he received the Joseph A. Solomon Memorial Fellowship in Chemistry at CMU and was a National Science Foundation East Asia and Pacific Summer Institutes Fellow at The University of Tokyo in 2006 with Prof. Kazunori Kataoka. He then completed a National Institutes of Health NRSA-sponsored Postdoctoral Fellowship at Massachusetts Institute of Technology with Institute Professor Robert Langer (2008-2012).

The central goal of the Siegwart Research Group is to use materials chemistry to solve challenges in disease therapy and diagnosis. In particular, they are focused on the development of new materials that can deliver genetic medicines to treat cancer and genetic diseases.  An array of coding and non-coding nucleic acids can now be used as therapeutics (siRNA, miRNA, tRNA, mRNA, DNA, CRISPR RNAs, gene editors) because they are able to manipulate and edit expression of the essential genes that drive disease development and progression. However, the success of genetic therapies has been limited by the difficulty of delivering these highly anionic biomacromolecular drugs into cells. 

The Siegwart Lab aims to discover and define the critical physical and chemical properties of synthetic carriers required for therapeutic delivery of small (e.g. ~22 base pair miRNA) to large (e.g. ~5,000 nucleotide mRNA) RNAs. They were the first to report in vivo CRISPR/Cas gene editing using non-viral carriers. They have designed synthetic carriers for various genome editors and applied these technologies for correction of genetic diseases. They have focused on hepatic and extrahepatic delivery for organ and cell specific protein delivery, gene delivery, and gene editing. They developed Selective Organ Targeting (SORT) lipid nanoparticles (LNPs), which was named in Nature's "Seven technologies to watch in 2022."

They aim to globally understand how the physical and chemical properties of materials affect interactions with biological systems in vitro and in vivo in the context of improving cancer and genetic disease therapies.  Their research is grounded in chemical design and takes advantage of the unique opportunities for collaborative research at UTSW Medical Center.  They ultimately aspire to utilize chemistry and engineering to make a beneficial impact on human health.

Education

Undergraduate
Lehigh University (2003), Biochemistry
Graduate School
Carnegie Mellon University (2005), Chemistry
Graduate School
Carnegie Mellon University (2008), Chemistry

Publications

Featured Publications LegendFeatured Publications

In vivo CRISPR screening identifies BAZ2 chromatin remodelers as druggable regulators of mammalian liver regeneration.
Jia Y, Li L, Lin YH, Gopal P, Shen S, Zhou K, Yu X, Sharma T, Zhang Y, Siegwart DJ, Ready JM, Zhu H, Cell Stem Cell 2022 Jan
Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes.
Liu S, Wang X, Yu X, Cheng Q, Johnson LT, Chatterjee S, Zhang D, Lee SM, Sun Y, Lin TC, Liu JL, Siegwart DJ, J Am Chem Soc 2021 Dec 143 50 21321-21330
All-In-One Dendrimer-Based Lipid Nanoparticles Enable Precise HDR-Mediated Gene Editing In Vivo.
Farbiak L, Cheng Q, Wei T, Álvarez-Benedicto E, Johnson LT, Lee S, Siegwart DJ, Adv Mater 2021 Jun e2006619