(7iy) Leveraging Physiological Microenvironment to Transport across Biological Barriers

Research Interests: Each tissue in our body is composed of specific biological components that constitute a defined niche, and these characteristic compositions can be exploited to rationally design drug delivery systems to improve drug efficacy and reduce systemic toxicity. Tissue compositions alter significantly under pathological conditions compared with normal tissue at the genetic, molecular and cellular levels. Approaches that employ key biochemical or biophysical cues at the site of disease may effectively respond to endogenous stimuli in the biological milieu to cross biological barriers for targeted drug delivery and on-demand release. I am highly interested in understanding the biological changes associated with disease types and states, and how to apply these pathophysiological features as cues in systems for drug delivery and tissue regeneration.

I work at the interface of chemical engineering, biomedical engineering, material science, and immunological research, seeking innovative solutions for safer and more effective treatment of skeletal and gastrointestinal disorders. My research experience covers drug delivery systems for treatment of inflammation-associated diseases, including inflammation-targeting hydrogel microfibers for local drug delivery in inflammatory bowel disease (1), and bone-seeking bisphosphonate-modified nanoparticles targeting the bone microenvironment for treatment of multiple myeloma (2). I have also studied disulfide-linked bisphosphonate-conjugated proteins for triggered release (3), and protein-encapsulated polymeric nanoparticles for controlled release at the implantation site for de novo bone formation (4, 5).

Future Research: As a faculty member, I will focus on employing engineering strategies to tackle biological and immunological problems for medical innovations and applications. The gastrointestinal tract contains the most complex human immune system, which closely interacts with the gut microbiota. The healthy or diseased state of the gut is also connected with skeletal fitness. I will direct my research in the following areas to translate biological findings into therapies, and to provide clinically relevant solutions for medical applications:

(1) Targeting inflammation for autoimmune gastrointestinal disorders
(2) Promoting mucosal healing for intestinal homeostasis
(3) Modulating microbiome for integrative skeletal regeneration

Teaching Interests: My teaching philosophy focuses on inspiring students to understand fundamental concepts and apply knowledge to solve practical problems. I promote interactive teaching and learning activities, and appreciate the diversity of students’ background and academic goals. I focus on teaching and evaluating the class in a manner that centers on effective communication, conceptual understanding, and creativity. At different stages of my academic training, I sharpened my pedagogical skills and cultivated my passion for teaching and mentoring through being Assignment Grader, Teaching Assistant, and Lecturer. As a graduate student, I was a teaching assistant for Mass Transfer and Heat Transfer. I was a lecturer in the Department of Chemical and Materials Engineering at the University of Alberta after I completed my Ph.D. studies. I developed and delivered lectures, designed midterms and finals, and held office hours for students. I am well prepared to teach core chemical engineering courses and special topic courses that I plan to develop, including Transport Phenomena in Living Systems, Biomaterial Science and Nanomedicine, and Drug Delivery Fundamentals and Design Principles. My mentoring experience also included working with seven undergraduates, five visiting students, and three technicians in a laboratory environment. I am open to fresh and effective teaching ideas that facilitate the teaching and learning processes, and dedicated to the training and development of young students.

Grant Writing:

1. Crohn’s and Colitis Foundation – I was awarded a Research Fellowship Award from the Crohn’s and Colitis Foundation (2015 – 2017).

2. NIH K99/R00 – I composed a K99/R00 to the National Institute of Diabetes and Digestive and Kidney Diseases – an impact score of 27 in 2013.

3. NIH R21 – I assisted in writing an R21 to the National Institute of Dental and Craniofacial Research – funded in 2013 (2013 – 2015).

4. NSERC – I was awarded the Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowship (2010 – 2012).

References (Selected Publications):

1. S. Zhang*, J. Ermann*, M.D. Succi, A. Zhou, M.J. Hamilton, B. Cao, J.R. Korzenik, J.N. Glickman, P.K. Vemula, L.H. Glimcher, G. Traverso, R. Langer, J.M. Karp. An Inflammationtargeting Hydrogel for Local Drug Delivery in Inflammatory Bowel Disease. Science Translational Medicine. 2015, 7, 300ra128. (* denotes equal contribution) Highlighted in: Science, 2015, 349, 702; Nature Reviews Drug Discovery, 2015, 14, 678; Nature Reviews Gastroenterology & Hepatology, 2015, 12, 551.

2. A.Swami, M.R. Reagan, P. Basto, Y. Mishima, N. Kamaly, S. Glavey, S. Zhang, M. Moschetta, D. Seevaratnam, Y. Zhang, J. Liu, T. Memarzadeh, J. Wu, S, Manier, J, Shi, N. Bertrand, Z. N. Lu, K. Nagano, R. Baron, A. Sacco, A. M. Roccaro, O. C. Farokhzad, I. M. Ghobrial. Engineered Nanomedicine for Myeloma and Bone Microenvironment Targeting. Proceedings of the National Academy of Sciences of the United States of America. 2014, 111(28): 10287-10292.

3. S. Zhang, J. E.I. Wright, G. Bansal, P. Cho, H. Uludağ. Cleavage of disulfide-linked fetuinbisphosphonate conjugates with Three Physiological Thiols. Biomacromolecules, 2005, 6: 2800-2808.

4. S. Zhang, C. Kucharski, M. R. Doschak, W. Sebald, H. Uludağ. Polyethylenimine-PEG Coated Albumin Nanoparticles for BMP-2 Delivery. Biomaterials. 2010, 31(5): 952-963.

5. S. Zhang, M. R. Doschak, H. Uludağ. Pharmacokinetics and Bone Formation by BMP-2 Entrapped in Polyethylenimine-Coated Albumin Nanoparticles. Biomaterials. 2009, 30(28): 5143-5155.