(6an) Engineering Microsystems for Regulating Cellular Behavior: From Implantable Drug Factories to Novel Platforms for Single-Cell Genomics

We are built from trillions of cells, but there is a gap in our understanding of how these cells work together. The ability to precisely probe individual cells in the context of their complex environments and control their behavior could open new opportunities for developing next-generation targeted therapies. My lab will harness microfluidics to create novel platform technologies which can accurately measure biomolecules (DNA, RNA, and proteins) within single cells. We are particularly interested in applying these technologies for studying cellular diversity and cell-cell interactions in the context of cancer and immune diseases. Finding from these will help us develop new therapies and guide the development of smart biomaterials. My interdisciplinary research training in microsystem engineering, biomaterials development, and single-cell analysis uniquely positions me to integrate approaches in the proposed areas of research

Teaching Interests:

My teaching philosophy has been shaped by my learning experience during my undergrad at IIT and later as a graduate student at MIT. My fundamental philosophy of education is to foster my students’ ability to gain a clear grasp over the fundamentals, think critically and gain problem-solving skills. During my graduate school, I have been teaching assistant for two core undergraduate curriculum - Thermal and Fluid Engineering I & II (class size of more than 120 students) for three semesters. These courses teach fluid mechanics, heat transfer and thermodynamics, and adopt an integrated approach to designing thermal systems. I had a transformative experience while teaching these courses which helped me develop into a better educator. More recently, I have been involved in designing and teaching Undergraduate Chemical Design (Course 10.494) along with my postdoc adviser Prof. Daniel Anderson. I was responsible for coming up with a suitable design project for the students, and give lectures to on the fundamental concepts required for the design project. My lecture was very well received (rated 6.9/7) which gave me immense satisfaction, and confidence for developing new courses in the future. My strong background in core engineering courses along I took during my undergraduate and graduate work has prepared me well for teaching several core classes in Transport and Fluid Mechanics within the Chemical Engineering program. I am also interested in developing a new course on - ‘Convergent approaches to solving biological problem’ where the students will be exposed to current interdisciplinary approaches to solving pressing current problems in biology and medicine.

Research experience:

My graduate and postdoctoral training has allowed me to gain expertise in a broad range of fields ranging from microfluidics, numerical modeling, surface chemistry, biomaterials, pre-clinical animal studies, and next-generation genomics. The breadth of my experience has allowed me to draw original ideas and novel techniques from across disciplines and work effortlessly with chemists, biologist, and clinicians as a team. This ability makes me a unique candidate to execute research at the interface of science and engineering.

I was trained in quantitative mathematical modeling during my undergraduate and master’s research, where I used numerical approaches to study thermodynamic system (IJHMT 2008, IJR 2007) and biological transport processes (Biophy. J 2010). In my graduate research, I developed novel bio-inspired microfluidic cell-sorting technologies. These devices exploited the physiological processes of cell homing to isolate specific immune cells (Sci rep. 2014), and harnessed DNA nanotechnology to effectively capture rare tumor cells from blood (PNAS 2013). While working on these technologies, I developed expertise in microfabrication, bio-conjugation chemistry, surface chemistry, and nanotechnology, and learned how to incorporate these approaches to build integrated devices that can process biological samples.

The first couple of years of my postdoctoral training focused on gaining expertise in biomaterials, drug delivery systems, and translational research. Funded by a JDRF Postdoctoral Fellowship, I have developed a biocompatible cell-encapsulation macrodevice that can effectively transplant immunogenic therapeutic cells in animals (in final revision). I discovered that membrane porosity could modulate infiltration of immune cells in vivo, and developed an effective surface coating that can mitigate device fibrosis. This work required innovation in device engineering and material chemistry, along with extensive in vivo studies in several animal models. Currently, enabled by a K99/R00 Award and in collaboration with Prof. Phillip Sharp, I have developed a microfluidic platform to enable high throughput sequencing of microRNA from single cells. The droplet-based microfluidic device performs co-immunoprecipitation to isolate miRNA from individual cells and process them for sequencing using DNA barcoding technology. I am using the platform to study miRNA regulation during differentiation of ES cells, and study heterogeneity of leukemia cells

Selected Awards and Honors:

• Koch Image Award (2019)
• NIH/NIBIB K99 Pathway to Independence Award, MIT (2018-23)
• Future of Science Award, Keystone Single-cell omics, Sweden (2017)
• Top 40 under 40 Healthcare Innovators, MedTech Boston (2016)
• JDRF Postdoctoral Fellowship, MIT (2015-18)

Selected Publications (full list at google scholar):

• Bose, N. Xue, A. Navia, E. Yoon, V. Chauhan, A. Shalek, P. Sharp, S. Garg, D. Anderson, Highly parallel single cell profiling of microRNAs for cellular identification in leukemia. (in preparation).
• Bose, L. Volpatti, D. Thiono, V. Yesilyurt, C. McGladian, O. Veish, A. Wang, G. Weir, R. Langer, DG Anderson, A biocompatible macrodevice enables long-term survival of therapeutic xenogeneic cells in vivo. (In final revision)
• Bose, R. Singh, M-H Hollatz, C. Shen, C-H Lee, D. M. Dorfman, J. M. Karp, R. Karnik: Affinity flow fractionation of cells via transient interactions with asymmetric molecular patterns. Scientific Reports 3, 2013
• Zhao*, C. Cui*, S. Bose*, D. Guo, C. Shen, W. P. Wong, K. Halvorsen, O. Farokhzad, G. Teo, J. Phillips, D. Dorfman, R. Karnik, J. M. Karp: A bioinspired multivalent DNA network for capture and release of cells. Proceedings of National Academy of Sciences USA, 2012. *equal contributions
• C-H Lee*, S. Bose*, K. Van Villet, J. M. Karp, R. Karnik: Examining the lateral displacement of HL60 cells rolling on asymmetric P-Selectin patterns, Langmuir, 27(1), 2011.
• Bose, S. Das, J. M. Karp, R. Karnik: A semianalytical model to study the effect of cortical tension on cell rolling, Biophysical Journal, 99(12), 2010.