The central goal of the Siegwart Lab is to use materials chemistry to solve challenges in cancer therapy and diagnosis. In particular, we 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.
Dr. Daniel J. Siegwart obtained his Ph.D. at Carnegie Mellon University (CMU) under the guidance of Prof. Krzysztof Matyjaszewski, who developed Atom Transfer Radical Polymerization (ATRP), one of the most powerful Controlled/living Radical Polymerization (CRP) techniques. One of Dan's main projects involved combining ATRP with radical ring-opening polymerization to produce injectable degradable polymers and hydrogels for bone fracture repair. He also co-developed ATRP in inverse miniemulsion to produce nanogels for drug delivery. Dan received the Joseph A. Solomon Memorial Fellowship in Chemistry at CMU and was also awarded a National Science Foundation (NSF) East Asia and Pacific Summer Institutes (EAPSI) Fellowship to study at the University of Tokyo with Prof. Kazunori Kataoka in 2006.
In order to apply his background in polymer chemistry to translational medical applications, Dan conducted NIH NRSA-sponsored postdoctoral research with Prof. Robert Langer at MIT and focused on combinatorial, high-throughput methods in material discovery. There, he directed a project reporting the first large library of 1,536 structurally defined core-shell nanoparticles that identified key chemical functionalities for designing polymers for siRNA delivery. Dan also worked on the automated synthesis of non-fouling zwitterionic materials for cell encapsulation to treat diabetes, injectable materials to treat spinal cord injuries, and catalyst development for the automated synthesis of thiol-functionalized polymers for siRNA conjugation.
At the University of Texas Southwestern Medical Center, the Siegwart Research Group’s long-term goals are to develop new materials for therapuetic nucleic acid delivery (siRNA, miRNA, mRNA, CRISPR/Cas), develop new polymers to deliver chemotherapeutic drugs to hypovascular tumors, develop theranostic "turn on" probes, and 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 therapies. They 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
- 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
- Intercalation-mediated nucleic acid nanoparticles for siRNA delivery
- Kejin Zhou, Petra Kos, Yunfeng Yan, Hu Xiong, Yi-Li Min, Jonathan T. Minnig, Jason B. Miller, and Daniel J. Siegwart.* Chemical Communications 2016
- 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
- Progress towards the synthesis of amino polyesters via ring-opening polymerization (ROP) of functional lactones
- Jing Hao, Sussana Elkassih, and Daniel J. Siegwart.* Synlett 2016
- Tumor imaging based on photon upconversion of Pt(II) porphyrin rhodamine co-modified NIR excitable cellulose enhanced by aggregation.
- Atsushi Nagai, Jason B. Miller, Petra Kos, Sussana Elkassih, Hu Xiong, and Daniel J. Siegwart* ACS Biomaterials Science & Engineering 2015
- Precise regulation of let-7 levels balance organ regeneration against tumor suppression.
- Linwei Wu, Liem H. Nguyen, Kejin Zhou, Yvanka de Soysa, Lin Li, Jason B. Miller, Jianmin Tian, Joseph Locker, Shuyuan Zhang, Gen Shinoda, Marc T. Seligson, Lauren R. Zeitels, Asha Acharya, Sam C. Wang, Joshua T. Mendell, Jinsuke Nishino, Sean J. Morrison, Daniel J. Siegwart, George Q. Daley, Ng Shyh-Chang, and Hao Zhu.* eLife 2015
- Biocompatible organic charge transfer complex nanoparticles based on a semi-crystalline cellulose template.
- Atsushi Nagai, Jason B. Miller, Jia Du, Petra Kos, Mihaela C. Stefan, and Daniel J. Siegwart.* Chemical Communications 2015
- One-pot synthesis of functional poly(amino ester sulfide)s and utility in delivering pDNA and siRNA.
- Yunfeng Yan, Lian Xue, Jason B. Miller, Kejin Zhou, Petra Kos, Sussana Elkassih, Atsushi Nagai, Hu Xiong, and Daniel J. Siegwart.* Polymer 2015