(12l) Engineering the Molecular Interactions for Biomedical Applications

 

 

Handan Acar

The Institute for Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA

hacar@uchicago.edu

Research Interests:

Interest in peptides as potential drug candidates has naturally increased with recent progress in enhancing their structural and chemical stability, along with their ability to cross the cell membrane. Peptide-based therapeutics that target not only specific cells but also specific protein-protein interactions in the cytoplasm will herald a new era of â??personalized medicineâ?. In this approaching new era, chemical tools to engineer peptides into molecular probes will be invaluable. The combination of carefully selected and localized interactions will produce stable assemblies, which can be reversible, highly tunable, dynamic, and modular as required by the specific application. Effective approaches to the design of molecular therapeutics must be safe, sensitive, efficient, and rapidly adapted to new targets with minimal effort and expense. To enable new translational clinical technologies, my research will focus on molecular design that incorporates these aspects into the new materials.

I have extensive research experience in the design and synthesis of self-assembling peptide-based nanostructures, including the modulation of the fundamental driving forces of self-assembly. As a Ph.D student of Prof. Mustafa Ozgur Guler (Bilkent University, Ankara, Turkey), I designed and synthesized self-assembling peptide sequences to generate targeted structures in both organic solvents and water via the specific interactions of rationally placed amino acid sequences. My innovative work produced a novel bottom-up synthesis method for peptide template-directed self-assembled mineralization, generating one-dimensional inorganic nanostructures. I was awarded a patent for this technology.

I sought to broaden the translational focus of my research during my postdoctoral work at Institute for Molecular Engineering at the University of Chicago with Matthew Tirrell, PhD. Taking advantage of the universityâ??s rich mix of clinicians and translational scientists, I work closely with James LaBelle MD, PhD, a pediatric oncologist in the Pritzker School of Medicine whose research involves peptide therapeutic translation to refractory malignancies. This cutting-edge collaboration between myself, Dr. Tirrell and Dr. LaBelle led to the development of a self-assembled nanoparticle platform, comprised of enzymatically cleavable peptide amphiphiles, that carries therapeutic peptides into cells. This platform offers the unique ability to follow intracellular drug trafficking and enzymatic cleavage in real time. The broad-ranging application of this technology to clinical medicine, biochemical research, and peptide-based nanoparticle development led us to file a patent application through the University of Chicago.

Teaching Interests:

I have extensive teaching experience, starting as a Ph.D. student; I was the teaching assistant of three graduate courses in Bilkent University. As an independent teacher at university level, I designed and implemented the â??Fundamentals of Thermodynamics for Mechanical Engineeringâ? at Iowa State University (Spring 2014), which greatly assisted in my development as an instructor. At the end of the semester my students attained grades higher than the departmental average, a clear indication of my abilities as a teacher. Finally, I have mentored graduate and undergraduate students in my group as a postdoctoral researcher.

Future Direction:

My research lab will establish chemical methodologies to tune the supramolecular interactions of self-assembling molecules to surmount the key challenges for peptide-based therapeutics, diagnostics and delivery platforms. In self-assembly processes, the fundamental building blocks organize themselves into functional structures as driven by the energetics in the system. These behaviors typically emerge from supramolecular phenomena such as hydrogen bonding, hydrophobic effects, electrostatics, metal-ligand and Ï?-Ï? interactions, and van der Waals forces. Sufficient combinations of these rationally placed interactions can produce the reversible self-assembly of stable structures, with these structures presenting a highly tunable and modular platform for a variety of applications.

As an independent investigator, I will combine my experiences to build a lab with a strong focus on designing materials from a molecular perspective for translational clinical technologies. A specific emphasis will be placed on using an interdisciplinary approach from physical and synthetic chemistry for biomedical applications.

Selected Publications: (out of 14)

Acar, H.; Srivastava, S.; Chung E.J.; Scnorenberg, M.R.; Barett; LaBelle, J.L.; Tirrell, M.; â??Self-Assembling Peptide-Based Building Blocks in Medical Applicationsâ?, accepted to Advanced Drug Delivery Reviews (2016).

Acar, H.; Cinar, S.; Thunga, M.; Kessler, M.R.; Hashemi, N.; Montazami, R.; 2014 â??Study of physically transient insulating materials for transient and biocompatible electronicsâ?; Advanced Functional Materials; 24(26), 4135â??4143 (2014).

Acar, H.; Genc, R.; Urel, M.; Erkal, T.S.; Dana, A.; Guler, M.O.; Self assembled peptide nanofiber template one-dimensional gold nanostructures exhibiting resistive switching�; Langmuir; 28, 16347-54 (2012).

Acar, H.; Garifullin, R.; Guler, M.O.; Self-assembled template-directed synthesis of one-dimensional silica and titania nanostructures; Langmuir; 27, 1079-84 (2011).

For more information, please visit: http://tirrell.ime.uchicago.edu/People/Handan_Acar.html