Designing biomaterials for immune modulation in tissue engineering and regenerative medicine

Research Interests :

Advances in cellular and tissue engineering have made it possible to create transplantable tissues and organoids, which can replace the function of failing organs in patients. Most engineered tissues are non-autologous and are rapidly rejected by the host immune system post-transplantation. This is a significant challenge for long term functioning of engineered grafts in clinical settings. The overarching goal of my lab will be to perform fundamental studies to understand and engineer the host-graft interface. We are interested in developing designer biomaterials, which can modulate the immune interaction with grafted tissue, and ultimately induce graft tolerance. One approach will employ biomaterial development, additive manufacturing, and microfabrication techniques to create implants that can allow long term survival and functioning of engineered tissues. Our technology will develop therapies for type 1 diabetes, auto-immune diseases, and neurodegenerative diseases.

Teaching Interests:

I have been very active in research mentorship and have advised 15 diverse students to-date, including supervising 4 undergraduate theses. I have teaching experience in Chemical engineering and Mechanical Engineering, including lab and course development, teaching assistance, and lecturing. As faculty, I am interested in teaching introductory and advanced courses on topics of transport, biomaterials, and tissue engineering. I am especially interested in developing coursework that explores convergent approaches to solve current biological and clinical problems.

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.

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. 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

Independent Funding

• NIH/NIBIB K99 Pathway to Independence Award, MIT (2018-24)

$950,000 in total cost

• Mission Possible Grand Award, Koch Institute at MIT (2016-2018)

$300,000 in direct cost

• JDRF Postdoctoral Fellowship, MIT (2015-18)

$168,000 in total cost.

Selected Publications (full list at google scholar):

• Bose, L. Volpatti, D. Thiono, V. Yesilyurt, C. McGladian, Y. Tang, A. Facklam, A. Wang, S. Jhunjhunwala, O. Veiseh, C. Bhattacharya, G. Weir, J. Oberholzer, R. Langer, DG Anderson: A biocompatible macrodevice enables long-term survival of therapeutic xenogeneic cells in vivo. Nature Biomedical Engineering 2020.

• Patel, J. Kaczmarek, S. Bose, K. Kauffman, F. Mir, M. Heartlein, F. DeRosa, R. Langer, DG Anderson: Inhaled nanoformulated mRNA polyplexes for protein production in lung epithelium, Advanced Materials 31(8), 2019.

• Xie, W. Zhang, A. Abbaspourrad, J. Ahn, A. Bader, S. Bose, A. Vegas, J. Lin, J. Tao, T. Hang, H. Lee, N. Iverson, G. Bisker, L. Li, M. Strano, D. Weitz, DG. Anderson: Microfluidic Fabrication of Colloidal Nanomaterials-Encapsulated Microcapsules for Biomolecular Sensing, Nano Letters 17(3), 2017.

• 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. PNAS, 2012. *equal contributions