Programmable Peptide-DNA Hybrid Nanomaterials

Research Interests: Natural biomaterials systems evolved over billions of years to solve some of the most challenging engineering problems. These optimized properties result from hierarchical designs exhibiting structure and function on multiple scales. The structure and function of natural materials have inspired scientists in attempts to mimic their designs and construction principles with the goal of mimicking the native qualities using synthetic materials. Moreover, by employing novel chemistries, processing and fabrication tools now available, we might be able to improve on Nature’s designs and functions. Although tremendous advance was achieved in mimicking the structural and functional properties of native biomaterials, some key features are still very challenging to reproduce. These include (i) development of matter that is programmable on both temporal and spatial scales (ii) Controlling the Hierarchical Structure (iii) Integrating Sense and Response to the structural design, and more. Specifically, creation of regenerative material and tissue engineering systems with this intricate functionality necessitates new composites that are highly dynamic and can coordinate multiple interacting components. Merging different types of molecules such as peptides and nucleic acids into hybrid materials will generate a new class of materials that are amenable to structural and functional programming. Postdoctoral Project:  “Instructing Cells With Programmable Peptide-DNA Hybrid Nanomaterials.”Under supervision of Samuel I. Stupp, Simpson Querrey Institute for BioNanotechnology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States   PhD Dissertation:  “Functionalized Semiconductor Quantum Dots for Optical Sensing” Under supervision of Itamar Willner, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.   Research Experience: I have had highly multidiciplinary training. I obtained my undergraduate degree in chemistry and computer science at Bar-Ilan University in Israel, followed by a Master’s degree in chemistry at The Hebrew University of Jerusalem. I then began doctoral studies in chemistry and nanobiotechnology at The Hebrew University of Jerusalem, Israel, in the lab of Prof. Itamar Willner. My PhD focused on the synthesis of functionalized semiconductor and metallic nanoparticles as well as DNA nanostructures for the multiplexed analysis of biomarkers and probing intracellular processes. During my postdoctoral training at Northwestern University I studied self-assembling nanomaterials for regenerative medicine in the lab of Prof. Samuel Stupp and introduced a new area into the lab, focusing on DNA-peptide hybrids for constructing cell scaffolds with programmable control over structure and function. I also collaborated extensively with medical doctors and biologists to create nanomaterials of biomedical interest in areas like neural stem cell differentiation, regeneration of neurons, and siRNA delivery. As a result of my versatile training and extensive collaborations I have gained experience in many fields such as synthetic chemistry, material science, biology, medicine, optical imaging, and biomedical engineering.  Teaching Interests: Aside from my research career, I also have extensive teaching experience. At the Hebrew University of Jerusalem I was a teaching assistant of a variety of courses including Organic Chemistry, Biological Chemistry of Materials, Computational Quantum Chemistry and several introductory labs in chemistry and nanotechonolgy. At Northwestern, I served as a co-instructor with my postdoctoral advisor teaching a course on Materials and Nanochemistry intended for undergraduate (senior year) and graduate students.            Lastly, I also have had the privilege of mentoring several graduate and undergraduate students. Fellowships: 1. European Molecular Biology Organization Long-term Postdoctoral Fellowship. (2013-2015) 2. The Shlomiuk award for outstanding P.hD. research study. (2013) 3. The Charles Clore fellowship for outstanding graduate students in natural sciences. (2010-2012) 4. Converging Technologies fellowship for excellent graduate students. (2008-2009)   Future Direction:  As faculty I would like to continue developing hybrid materials based on nucleic acids and peptides for different applications in nanomedicine. In particular I would like to integrate my PhD experience in developing nanoparticles-based sensing devices, DNA switches and machines with my postdoctoral experience in peptide self-assembly to create biomaterials, or systems of materials, that simultaneously provide structure, sensing, and response - all integrated into function. The oligonucleotide-peptide hybrids will merge the programmability and nanoscale control afforded by DNA nanotechnology with the biological function of peptides and proteins. Applications that will drive and inspire the research include systems that can regulate cell behavior (stem cell; immune cells), injectable materials that "know" to travel to an injury site and trigger tissue regeneration by harnessing the body's own power to heal, and new generations of wearable materials (electronic and others) as “Sense and Treat” systems that could be used as scaffolds to follow certain biomarkers and promote wound healing. Selected Publications: H-Index: 33; Citations – 4016   1. Freeman R., Stephanopoulos N., Sur S., Boekhoven J., Lee S.S., Stupp S.I., Instructing cells with programmable DNA peptide hybrids, Nature, 2016 (in revisions). 2. Freeman R., Boekhoven J., Dickerson M.B., Naik R.R., Stupp S.I., Biopolymers and supramolecular polymers as biomaterials for biomedical applications, MRS Bulletin, 2015, 40, 1089-1101. 3. N. Stephanopoulos, R. Freeman, H.N. Scheler, S. Sur, S. Jeong, F. Tantakitti, J.A. Kessler, S.I. Stupp, Bioactive DNA-Peptide Nanotubes Enhance the Differentiation of Neural Stem Cells Into Neurons, Nano Letters, 2015, 15, 603-609. 4. Freeman R., Girsh J., Fang-ju Jou A., Annie Ho J., Hug T., Dernedde J, Willner I. Optical Aptasensors for the Analysis of the Vascular Endothelial Growth Factor (VEGF), Anal. Chem., 2012, 84, 6192-6198. 5. Freeman R., Liu X.Q., Willner I. Chemiluminescent and Chemiluminescence Resonance Energy Transfer (CRET) Detection of DNA, Metal Ions and Aptamer-Substrate Complexes Using Hemin / G-Quadruplexes and CdSe/ZnS Quantum Dots, J. Am. Chem. Soc., 2011, 133, 11597-11604. (cited 287 times) 6. Freeman R., Finder T., Gill R. Willner I. Probing Protein Kinase (CK2) and Alkaline Phosphatase with CdSe/ZnS Quantum Dots. Nano Lett.,2010, 10, 2192-2196. 7. Freeman R., Finder T., Willner I., Multiplexed analysis of Hg2+ and Ag+ ions by nucleic acids-functionalized CdSe/ZnS quantum dots and their use for logic gate operations, Angew. Chem. Int. Ed., 2009, 121, 7958 - 7961. (cited 344 times)