Dr. Daniel J. Siegwart is an Associate Professor in the Department of Biochemistry (primary) and the Simmons Comprehensive Cancer Center (secondary) at the University of Texas Southwestern Medical Center. 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 ribonucleic acids (RNAs) to improve cancer outcomes. An array of coding and non-coding RNAs can now be used as cancer therapeutics (siRNA, miRNA, mRNA, CRISPR RNAs) because they are able to manipulate and edit expression of the essential genes that drive cancer development and progression. For example, gene silencing via the RNA Interference (RNAi) mechanism is a promising strategy to treat cancer. However, the success of short interfering RNA (siRNA) or microRNA (miRNA)-based therapies has been limited by the difficulty of delivering these highly anionic biomacromolecular drugs into cells. Moreover, the potential of CRISPR/Cas, a revolutionary gene editing technology, is currently hindered by the lack of safe and effective synthetic delivery systems. The Siegwart lab has developed targeted delivery strategies to mediate genomic editing in specific tissues for correction of genetic diseases.
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 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.
- Lehigh University (2003), Biochemistry
- Graduate School
- Carnegie Mellon University (2005), Chemistry
- Graduate School
- Carnegie Mellon University (2008), Chemistry
- Dendrimer-Based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I.
- Cheng Q, Wei T, Jia Y, Farbiak L, Zhou K, Zhang S, Wei Y, Zhu H, Siegwart DJ Adv. Mater. Weinheim 2018 Oct e1805308
- High-Contrast Fluorescence Detection of Metastatic Breast Cancer Including Bone and Liver Micrometastases via Size-Controlled pH-Activatable Water-Soluble Probes.
- Xiong H, Zuo H, Yan Y, Occhialini G, Zhou K, Wan Y, Siegwart DJ Adv. Mater. Weinheim 2017 May
- Non-Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co-Delivery of Cas9 mRNA and sgRNA.
- Miller JB, Zhang S, Kos P, Xiong H, Zhou K, Perelman SS, Zhu H, Siegwart DJ Angew. Chem. Int. Ed. Engl. 2016 Dec
- Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model.
- Zhou K, Nguyen LH, Miller JB, Yan Y, Kos P, Xiong H, Li L, Hao J, Minnig JT, Zhu H, Siegwart DJ Proc. Natl. Acad. Sci. U.S.A. 2016 Jan 113 3 520-5
- Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells
- Yunfeng Yan, Li Liu, Hu Xiong, Jason B. Miller, Kejin Zhou, Petra Kos, Kenneth E. Huffman, Sussana Elkassih, John W. Norman, Ryan Carstens, James Kim, John D. Minna, and Daniel J. Siegwart.* Proceedings of the National Academy of Sciences, U.S.A. 2016 Early view
- Activatable water soluble probes enhance tumor imaging by responding to dysregulated pH and exhibiting high tumor-to-liver fluorescence emission contrast.
- Hu Xiong, Petra Kos, Yunfeng Yan, Kejin Zhou, Jason B. Miller, Sussana Elkassih, and Daniel J. Siegwart* Bioconjugate Chemistry 2016
- Rapid synthesis of a lipocationic polyester library via ring-opening polymerization of functional valerolactones for efficacious siRNA delivery
- Jing Hao, Petra Kos, Kejin Zhou, Jason B. Miller, Lian Xue, Yunfeng Yan, Hu Xiong, Sussana Elkassih, and Daniel J. Siegwart* Journal of the American Chemical Society 2015 137 9206-9209
- Tumor activated water-soluble photosensitizers for near-infrared photodynamic cancer therapy.
- Xiong H, Zhou K, Yan Y, Miller JB, Siegwart DJ ACS Appl Mater Interfaces 2018 Apr
- Aerosol delivery of stabilized polyester-siRNA nanoparticles to silence gene expression in orthotopic lung tumors.
- Yan Y, Zhou K, Xiong H, Miller JB, Motea EA, Boothman DA, Liu L, Siegwart DJ Biomaterials 2017 Feb 118 84-93
- Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis.
- Chen P, Zuo H, Xiong H, Kolar MJ, Chu Q, Saghatelian A, Siegwart DJ, Wan Y Proc. Natl. Acad. Sci. U.S.A. 2017 Jan 114 3 580-585