Biography

Dr. Daniel J. Siegwart is currently an Assistant Professor in the Simmons Comprehensive Cancer Center and Department of Biochemistry 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 cancer 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 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.  Their long-term goals include development of new materials for therapuetic nucleic acid delivery, new polymers to deliver chemotherapeutic drugs to hypovascular tumors, and theranostic "turn on" probes that respond to the tumor microenvironment. 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 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

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
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
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