Biography

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.

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

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