(6am) Interfacing Cell/Tissue Engineering with Gene Editing Tools and Sequencing Technologies for Regenerative Medicine

Understanding genetic mechanisms of brain diseases and developing regenerative therapeutics need genetically tractable in vitro models. Such models should recapitulate physiological properties, cellular and architectural complexity, and genetic makeup of the human brain as well as be compatible with genome editing, transcriptome profiling technologies, and gene delivery tools. My research interfaces biomaterials, stem cell biology, gene editing and delivery, single cell sequencing technologies, and computational biology to develop engineered biomaterials templated stem-cell based biomimetic in vitro tissues to model brain diseases/injuries and discover translational therapeutic targets and strategies.

In my PhD research, I focused on developing microscale technologies for spatial and geometrical control of multicellular organizations. I developed dynamic microstructures by utilizing a thermoresponsive polymer. These microscale templates enabled to spatially arrange same or different cell types in different compartments of microgels or directly in microwells without an encapsulating material. This controlled cell organization can lead to complex cell-cell and cell-matrix interactions for better recapitulating native tissues.

For my postdoctoral studies, I developed engineered neural tissues composed of brain-related cells derived from human stem cells and adapted encapsulating hydrogel materials to replicate complex brain-related associations in culture. I conceived a method of differentiating human glial cells, an abundant cell-type in the brain, directly from stem cells in a rapid manner and then engineered material properties enveloping the neurons and glia in a 3D structure. Based on the transcriptome profile of these neural tissues, I investigated how tailoring hydrogel material properties changed the RNA-signature and maturity of neural tissues through comparisons to human brain transcriptome data. Using single-cell sequencing, I demonstrated 3D tissues I developed reflect transcriptional patterns of cell types in the human brain. I also exploited CRISPR-Cas gene editing technologies via viral gene delivery tools to interrogate neurological disease-associated genes in neurons within a 3D matrix.

As I establish my own research program combining biomaterials science, stem cell biology, high-throughput sequencing technologies, CRISPR genome editing and gene delivery tools, and computational biology, I will build on the full spectrum of my training experience to develop leading technologies to replicate brain diseases in vitro and search for therapeutic targets and methodologies that restore the health of the brain.

Education and Training:

• Postdoc, 2013-2018, Broad Institute of Massachusetts Institute of Technology and Harvard, Biomedical Sciences and Genomics
• PhD, 2013, Massachusetts Institute of Technology, Electrical Engineering and Computer Science, (minor in Medical Engineering)
• MS, 2007, Istanbul Technical University, Faculty of Electrical and Electronics Engineering, Control Engineering
• BS, 2005, Istanbul Technical University, Faculty of Electrical and Electronics Engineering, Control Engineering

Research Experience:

• Broad Institute of Massachusetts Institute of Technology and Harvard, October-2013 to July-2018, Postdoctoral Associate, Advisor: Feng Zhang, PhD
• Massachusetts Institute of Technology, January-2013 to July 2013, Postdoctoral Associate, Advisor: Robert S. Langer, ScD
• Massachusetts Institute of Technology, July 2007 to December 2012, Graduate Research Assistant, Advisors: Robert S. Langer, ScD and Ali Khademhosseini, PhD

Selected Publications:

* Denotes corresponding author(s).

H. Tekin*, S. Simmons, B. Cummings, L. Gao, X. Adiconis, C. C. Hession, A. Ghoshal, D. Dionne, S. R. Choudhury, V. Yesilyurt, N. E. Sanjana, X. Shi, C. Lu, M. Heidenreich, J. Q. Pan, J. Z. Levin, F. Zhang. “Effects of 3D culturing conditions on the transcriptomic profile of stem-cell derived neurons”. Nature Biomedical Engineering. 2018.

S.R. Shin, H. Bae, J.M. Cha, J.Y. Mun, Y.C. Chen, H. Tekin, H. Shin, S. Farshchi, M. Dokmeci, S. Tang, A. Khademhosseini*. “Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation”. ACS Nano, 2012, 6 (1): 362-372.

H. Tekin, J.G. Sanchez, C. Landeros, K. Dubbin, R. Langer*, A. Khademhosseini*. “Controlling spatial organization of multiple cell types in defined 3D geometries”. Advanced Materials, 2012, 24 (41): 5543-5547. (Frontispiece Cover).

H. Tekin, T. Tsinman, J.G. Sanchez, B.J. Jones, G. Camci-Unal, J.W. Nichol, R. Langer*, A. Khademhosseini*. “Responsive micromolds for sequential patterning of hydrogel microstructures”. Journal of the American Chemical Society, 2011. 133 (33): 12944–12947.

H. Tekin, J.G. Sanchez, T. Tsinman, R. Langer, A. Khademhosseini. “Thermoresponsive platforms for tissue engineering and regenerative medicine”. AIChE Journal, 2011, 57 (12): 3249–3258. (Cover Article).

H. Tekin, G.O. Ince, T. Tsinman, K.K. Gleason, R. Langer*, A. Khademhosseini*, M.C. Demirel*. “Responsive microgrooves for the formation of harvestable tissue constructs”. Langmuir, 2011, 27 (9): 5671–5679.

H. Tekin, M. Anaya, M. Brigham, C. Nauman, R. Langer*, A. Khademhosseini*. “Stimuli-responsive microwells for formation and retrieval of cell aggregates” Lab on a Chip, 2010, 10 (18): 2411-2418.

Selected Awards/Honors:

2013, JALA Ten Award (The Top 10 Technological Breakthroughs Selected by The Journal of Laboratory Automation)

2012, MIT’s Outstanding Undergraduate Research Mentor Award (Graduate Mentor of the Year)

2011, Materials Research Society Best Student Oral Presentation Award

2011, Bioanalysis Highly Commended Young Investigator Award

2005, Werner von Siemens Excellence Award

Teaching Interests:

I am always excited about teaching and mentoring next-generations for building future by teaching them scientific foundations and creating an environment to motivate them. My interest and commitment in mentoring students were recognized by MIT’s prestigious Outstanding Undergraduate Research Mentor Award. I will leverage all mentoring and teaching skills I built up to educate next-generation of scientists and engineers in my faculty career. I am excited about teaching both basic and applied courses at the undergraduate and graduate level in the scope of engineering cells and biomaterials, quantitative biology, and interdisciplinary biosciences.