(3hs) Holistic Design of Polymeric Biomaterials through Statistical Learning and Interfacial Engineering

Polymeric biomaterials are poised to fulfill the curative potential of gene editing and regenerative medicine by bridging technological and regulatory barriers to clinical translation. Synthetic polymers have created complex multivariate design spaces in nanomedicine, necessitating systematic examination of numerous physical and chemical design parameters. Rapid and fruitful exploration of these design parameters is impeded by incomplete mechanistic understanding of how polymer properties and microenvironmental cues together govern gene editing outcomes. Consequently, time-consuming and expensive experimental campaigns that focus on iteratively optimizing a single material design parameter at a time have emerged as the default mode of polymer discovery. I propose to integrate high-throughput experimentation, data mining and particle engineering into a holistic polymer discovery platform that will aid biologists to rapidly overcome operational barriers to the clinical deployment of gene editing and stem cell technologies.

The Kumar Group will focus on:

1) Developing data-driven vector discovery pipelines to rapidly identify polymers that achieve efficient genome editing. We will expand and diversify the pool of candidate polymers through combinatorial design and develop statistical frameworks that systematically examine correlations between structure, properties and biological performance. I propose to accelerate the discovery of well-defined polymeric vectors for diverse nucleic acid payloads by applying high-throughput experimental platforms such as parallel polymer synthesis and image cytometry, in tandem with statistical learning.

2) Deploying surface engineered cell culture substrates in tandem with polymeric gene delivery to effect efficient genome editing of pluripotent stem cells. Current approaches to stem cell genome editing have overlooked the critical roles played by the stem cell niche, especially the interfacial properties of the substrates used during cell culture. I hypothesize that the modulation of substrate properties can be a useful lever of control in enhancing gene editing outcomes for these challenging cell types. We will combine bio-instructive coatings for stem cell engineering, with polymeric transfection methods to develop robust, fully defined, and scalable gene editing platforms for these therapeutically valuable cell types.

3) Implementing physical approaches to gene delivery by tailoring particle shapes, biomechanics and sizes. The design space of polyplexes for gene delivery can be rapidly expanded by moving beyond the chemical domain into physical domains by creating nanoparticle libraries of desired mechanical properties, particle shapes and size distributions. Particle engineering will be used to access diverse morphologies and mechanical behaviors, subsequent to which surface-initiated polymerization will be performed to graft cationic polymer chains from particle surfaces. These “hairy nanoparticles” will facilitate modular polyplex design and the ability to tune surface chemistry and particle properties precisely and independently.

About the candidate:

After completing my chemical engineering undergraduate degree at BITS Pilani, India, I spent three years in pharmaceutical product development, developing platforms for continuous active pharmaceutical ingredient manufacturing and implementing quality-by-design workflows. My industrial stint allowed me to gain proficiency in statistical discovery and motivated me to approach biomaterial design with a data-driven mindset. In 2012, I was accepted into the chemical engineering PhD program of the University of Michigan where I was advised by Prof. Joerg Lahann. As a part of an interdisciplinary group, the Biointerfaces Institute, I worked in collaboration with clinicians from the medical school and the school of dentistry. During my doctoral training, I worked at the intersection of macromolecular engineering, biointerfacial science and statistical modeling. I examined the interactions of cells, pathogens and biomolecules with multifunctional polymer coatings and applied this knowledge to tailor biomedical coatings that possessed the desired functionality, be it rapid self-renewal of pluripotent stem cells or the inhibition of viral binding, or the phenotypically selective capture of macrophages. After graduating from Michigan in July 2018, I began my post-doctoral training with Prof. Theresa Reineke at the University of Minnesota in order to deepen my expertise in macromolecular engineering and to gain experience in biological evaluation of synthetic polymers. At Minnesota, I’ve established high-throughput experimental platforms and statistical learning methodologies for discovering polymers that can deliver CRISPR/Cas9 constructs efficiently. My doctoral training in engineering polymer interfaces for modulating cellular responses, along with my post-doctoral work in polymeric gene delivery will aid me in pursuing clinically relevant problems in biomaterial design.

Teaching & mentoring:

I have a strong interest in undergraduate teaching, especially at the sophomore and junior levels, because I believe that this is the crucial period which determines how passionate students become about the chemical engineering profession. Through my teaching, I want my students to become aware of all the potentialities, excitement and possibilities the profession offers, not just the heavy workload and exam stress typical of their undergraduate years. I am very lucky to have experienced life as a chemical engineer in both industry and in academia and to have acquired expertise in two domains (pharmaceuticals and polymers). My experiences as a non-traditional graduate student allowed me to motivate my students in multiple ways using field visits, lab visits, games, case studies and role plays. I was awarded the Towner prize for the best graduate student instructor, a recognition of my inclusive teaching methods.

Having taught Chemical and Engineering Thermodynamics in the past, I believe I’m well-suited to teach the course again. I’m excited about the challenge of teaching the introductory course, Introduction to material and energy balances. I would also be thrilled to teach CHE 344 Chemical Reaction Engineering since I have applied this course extensively both in industry and in my dissertation. I would like to develop a graduate-level class, "Polymeric materials and bioconjugation in biomedical engineering". In this course, I plan to introduce graduate students with research interests in polymers and interfaces to the ways in which macromolecular chemistry is driving the evolution of biomaterials.

I have mentored eight undergraduate students, most of whom had their first taste of academic research in my lab. Two of my mentees went on to win NSF GRFs and are making exciting beginnings to their academic careers. Three of my mentees have co-authored manuscripts published during my PhD and postdoc. I will continue working with undergraduate students at all levels of prior research experience.

Proposal writing:

1. Rackham predoctoral fellowship awarded for research proposal that was among 30 successful applications in a university-wide competition.
2. Co-authored proposal that was awarded €170,000 by the Virtual Materials Design Initiative at the Karlsruhe Institute of Technology, Germany..
3. Co-authored successful proposal to obtain DARPA funding through the PReemptive Expression of Protective Alleles and Response Elements (PREPARE) program

Awards & Honors:

1. Procter & Gamble Team Innovation Award, 2016, 40th Annual Macro Symposium, University of Michigan. Recognized for innovative and collaborative research.
2. Richard & Eleanor Towner Prize for outstanding Graduate Student Instructor (GSI), 2016, University of Michigan. For exceptional \& innovative teaching.
3. Rackham Predoctoral Fellowship, 2017-18, University of Michigan.
4. PMSE Future Faculty Scholar, 2019, Polymeric Material Science and Engineering Division, American Chemical Society.
5. Career Development Award, Spring 2019, Post-doctoral Association, University of Minnesota, Twin Cities.
6. Finalist, AIChE Graduate Student Awards, Biomaterials, 2018, Minneapolis.
7. Departmental nominee, Richard & Eleanor Towner Prize for Outstanding PhD research, College of Engineering, University of Michigan.
8. Poster award, Second Place, Material Science & Engineering session, Engineering Graduate Symposium, 2016, University of Michigan.
9. Poster award, First Place, Material & Chemical Technology session,Engineering Graduate Symposium, 2014, University of Michigan.
10. Fall semester fellowship, Department of Chemical Engineering, University of Michigan, September-December 2012.
11. Monali Dey Memorial Award, BITS Pilani, December 2008, for the most outstanding chemical engineering undergraduate in a graduating class.

Publications:

1. Z. Tan, Y. Jiang, M. S. Ganewatta, R. Kumar, A. Keith, K. Twaroski, T. Pengo, J. Tolar, T. P. Lodge, T. M. Reineke "Block Polymer Micelles Enable CRISPR/Cas9 Ribonucleoprotein Delivery: Physico-Chemical Properties Affect Packaging Mechanisms and Gene Editing Efficiency", Macromolecules 2019, 52, 8197–8206.
2. R. Kumar, D. Kratzer, K. Cheng, J. Prisby, J. Sugai, W. V. Giannobile, & J. Lahann. "Carbohydrate-Based Polymer Brushes Prevent Viral Adsorption on Electrostatically Heterogeneous Interfaces", Macromolecular Rapid Communications, 2018, 40, 1800530.
3. R. Kumar, A. Welle, F. Becker, I. Kopyeva, & J. Lahann. "Substrate-Independent Micropatterning of Polymer Brushes Based on Photolytic Deactivation of Chemical Vapor Deposition Based Surface-Initiated Atom-Transfer Radical Polymerization Initiator Films", ACS Applied Materials & Interfaces, 2018, 10 (38), 31965-31976.
4. F. Bally-Le Gal, C. Hussal, J. J. P. Kramer, K. C. Cheng, R. Kumar, T. Eyster, V. Trouillet, M. Nieger, S. Brase, S., & J. Lahann. "Polylutidines: Multifunctional surfaces via vapor-based polymerization of functional pyridinophanes" Chemistry: A European Journal, 2017, 23, 13342-13350.
5. R. Kumar, I. Kopyeva, K. C. Cheng, K. Liu, & J. Lahann. "Examining Interfacial Kinetics on Electrostatically Heterogeneous Surfaces using Zeta-potential Measurements" Langmuir, 2017, 33 (25), pp 6322-6332.
6. M. Konig, R. Kumar, C.Hussal, J. Biscarat, L. Barner, A. Schafer, A. & J. Lahann. "pH-Responsive Aminomethyl Functionalized Poly(p-xylylene) Coatings by Chemical Vapor Deposition Polymerization" Macromolecular Chemistry & Physics, 2017, 218, 1600521.
7. R. Kumar, R. & J. Lahann. "Predictive Model for the Design of Zwitterionic Polymer Brushes: A Statistical Design of Experiments Approach" ACS Applied Materials & Interfaces, 2016, 8 (26), 16595-16603.
8. X. Qian, L. G.Villa-Diaz, R. Kumar, J. Lahann, & P. H. Krebsbach. "Enhancement of the propagation of human embryonic stem cells by modifications in the gel architecture of PMEDSAH polymer coatings" Biomaterials, 2014, 35(36), 958190.