Fellow of the Cockrell Chair in Engineering Excellence
Department of Biomedical Engineering
The University of Texas at Austin
1 University Station, C0800
Austin, Texas 78712-1062
Phone: (512) 232-3477
Laboratory for Cellular and Macromolecular Engineering
The behavior of cells and tissues and that of the whole organism is a unique combination of their genetic makeup and their environment. The ability to effectively transfer genes into humans provides unique possibilities for the treatment of various diseases. Efficient expression of antigenic proteins in-vivo following gene delivery, can "train" our immune system to fight against incurable cancers and deadly infectious diseases. On the other hand rational manipulation of cellular gene expression by engineering their microenvironment provides us with the opportunity to control the structural and functional properties of bio-engineered tissues. The quest for novel biomaterials and unique engineering techniques to manipulate the genetic and micro-environmental milieu of cells and tissues and understand the fundamental processes of immune response and tissue development is the driving force behind my research.In the Laboratory of Cell and Macromolecular Engineering, we have developed a comprehensive research and educational program in biopolymer-based gene therapy and stem cell-based tissue engineering The overall goal is to achieve a basic understanding of how the immune system responds to genetic manipulations and how cellular fate is decided based on microenvironmental cues. Not only is this going to help us find novel treatments for diseases but will also help us understand the fundamentals of genetic manipulations, cell differentiation and cell-cell interactions i.e. the complex interplay between cells and their environment.
Research in our lab is designed to address three areas of complexities both in applied therapeutics and in basic biomedical sciences.
- Development of novel hybrid biomaterials for combinatorial delivery of drugs and genes
- Development of micro-fabricated polymer structures with pre-designed spatio-temporal patterning to study stem cell differentiation into complex tissue structures
- Design and development of BioMEMS-based, injectable devices for sensor-controlled drug delivery and simultaneous therapeutic imaging
My co-appointments at the Texas Materials Institute, The Center for Nano and Macromolecular Sciences and the Institute of Cellular and Molecular Biology at UT, provide me with an excellent infrastructure to explore multidisciplinary research across the various realms of science.
Development of novel hybrid biomaterials for combinatorial delivery of drugs and genes
We are developing novel, hybrid macromolecule by grafting synthetic polyamines onto the backbone of the natural polysaccharides or on the surface of micro and nanoparticles synthesized from biodegradable and biocompatible polymers. These unique biomaterials provide us with an opportunity to combine the attributes of synthetic and natural polymers as well as highly specialized polymers thereby creating novel entities for drug and gene delivery applications. One major motivation behind this research is the development of combinatorial delivery systems, where a single injectable or needle-free formulation can delivery multiple therapeutic agents (vaccines, adjuvants, chemokines etc.) to a specific cell population. Another aspect of this research is the development of transcutaneous delivery systems for biodegradable polymer nanoparticles carrying vaccines. With the help of a grant from the National Institutes of Health (National Institute of Allergy and Infectious Diseases) we have developed a novel patch-type system for effective delivery of such particles into the immune cell-rich epidermal region of the skin. We are currently collaborating with clinicians and researchers at The M.D. Anderson Cancer Center at Houston and the University of Texas Medical Branch at Galveston to develop improved DNA-based vaccines against cancer and tropical diseases.
Development of micro-fabricated polymer structures with pre-designed spatio-temporal patterning to study stem cell differentiation into complex tissue structures
The second major effort in the lab is in the area of microfabricated scaffold structures for stem cell engineering. This is a unique combination of developing manufacturing techniques to create spatially and temporally patterned microenvironments and studying the fundamental mechanisms of cell-environment interaction in the context of stem cell differentiation into multiple tissue lineages. With funding from the Whitaker Foundation we are developing a layer-by-layer micro-manufacturing process using laser photo-crosslinkable polymers that would allow us to spatially embed various growth factors (either as soluble entities or encapsulated within controlled release polymer particles) at pre-designed spatial location within a porous tissue-engineering scaffold. This concept would allow us to create three dimensional structures containing different microenvironments in different regions and enable us to differentiate pluripotent stem cells into multiple lineages. Ultimately our goal is to create hybrid tissue structures with pre-designed pattern of cells and extracellular matrices, similar to the process of organ regeneration. This could one day allow us to fabricate functional complex tissues having multiple cell types for on demand transplantation or in-vitro cell function studies (e.g. drug or vaccine screening, liver functions etc.). Two specific directions that this project is pursuing are (a) creating bone and cartilage within the same structure starting from a single stem cell population and (b) fabrication of a lymph-node like structure containing T, B and dendritic cells that is capable of antigen processing and presentation with an ultimately goal of generating a high-throughput vaccine/drug screening system.
Understanding stem cell interactions with complex microenvironments:
A related focus in the lab is understanding hematopoiesis, specifically lineage commitment of mouse embryonic and adult stem cells into dendritic cells, T cells sand B cells in 3D environment and in the presence of functional biomaterials that can trigger specific cell signaling pathways. We are investigating how notch-signaling through engineering biomaterials would allow differentiation of stem cells into lymphoid lineages. We are also investigating the effects of 3D culture conditions and bioreactors on the growth and differentiation of stem cells.
Design and development of BioMEMS-based, injectable devices for sensor-controlled drug delivery and simultaneous therapeutic imaging
The fourth area of focus is in micro/nano electro-mechanical systems specifically targeted for drug/gene delivery and therapeutic imaging. As a member of the NSF-IGERT program in diagnostic and therapeutic imaging at The University of Texas, my major interest is to combine biosensors, on-demand drug delivery and imaging for therapeutic monitoring within the same platform. The field of drug and gene delivery, till now, has primarily focused on bottom-up design approaches (self-assembly, polymer particles, hydrogels etc.). In recent years few researchers have started focusing on top-down manufacturing approaches to create MEMS-type delivery platforms (drug microchips, microfabricated oral delivery particles etc.). However, these top-down efforts are yet to achieve true nano-scale structures, an achievement that could truly revolutionize drug delivery and therapeutic imaging by creating "injectable" BioMEMS structures capable of sensor-controlled delivery of drugs and genes and simultaneously allowing for high-resolution, real-time imaging of the target organ. Our goal is to combine the bottom-up and top-down approach in a single platform to microfabricate 100nm-5m size injectable drug reservoirs that could release drugs inside a target cell when, and only when, triggered by a specific physiological stimulus. Simultaneously, the design would allow for monitoring the drug release profile and tissue distribution of the MEMS particles using non-invasive imaging techniques. On-demand, sensor-triggered drug release in-vivo could allow for novel therapeutic strategies for cancer and other diseases with significantly lower systemic toxicity along with continual monitoring of therapy.
- L. Nguyen, A. Kudva, N. Saxena and K. Roy, Engineering articular cartilage with spatially varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel, Biomaterials. 2011 Oct; 32(29):6946-52. Epub 2011 Jul 1, Impact Factor 7.882.
- A. Singh, H. Qin, I. Fernandez, J. Wei, J. Lin, L. W. Kwak and K. Roy, An injectable synthetic immune-priming center mediates efficient T-cell class switching and T-helper 1 response against B cell lymphoma, Journal of Controlled Release, J Control Release. 2011 Oct 30;155 (2):184-92. Epub 2011 Jun 21. Impact Factor 7.164.
- M. Caldorera-Moore, M. Kyoo Kang, Z. Moore, V. Singh, S.V. Sreenivasan, L. Shi, R. Huang and K. Roy, Swelling behavior of nanoscale, shape- and size-specific, hydrogel particles fabricated using imprint lithography, Soft Matter, January 2011, DOI:10.1039/C0SM01185A, Impact Factor: 4.457.
- J. Lin, I. Fernandez, K. Roy, Development of feeder free culture systems for efficient generation of ckit+sca1+ progenitors from mouse iPS cells, Stem Cell Reviews and Reports, 2011 Sep;7(3):736-47, Impact Factor: 6.774.
- L. Nguyen, A. Kudva, N. Guckert, K. Linse, K. Roy, Unique biomaterial compositions direct bone marrow stem cells into specific chondrocytic phenotypes corresponding to the various zones of articular cartilage, Biomaterials. 2011 Feb;32(5):1327-38. Epub, November 10, 2010. Impact Factor: 7.882.
- K. Fridley, I. Fernandez, A. Li, B. Kettelewell, K. Roy, ,nique Differentiation Profile of Mouse Embryonic Stem Cells in Rotary and Stirred Tank Bioreactors, Tissue Eng Part A. 2010 Nov; 16(11):3285-98. Epub, July 12, 2010. Impact Factor: 4.636.
- S. Taqvi and K. Roy, Influence of scaffold physical properties and stromal cell co-culture on hematopoietic differentiation of mouse embryonic stem cells, Biomaterials. 2006 Dec;27(36):6024-31. Epub 2006 Sep 7
- H. Liu, J. Lin and K. Roy, Effect of 3D scaffold and dynamic culture condition on the global gene expression profile of mouse embryonic stem cells, Biomaterials. 2006 Jul 7; Biomaterials. 2006 Dec;27(36):5978-89. Epub 2006 Jul 7
- S. Taqvi, L. Dixit and K. Roy, Biomaterial-based notch signaling for the differentiation of hematopoietic stem cells into T cells, Biomed Mater Res A. 2006 Dec 1;79(3):689-97
- S. P. Kasturi, H. Qin, K. S. Thomson, S. El-Bereir, S.-C. Cha, S. Neelapu, L. W. Kwak and K. Roy, Prophylactic anti-tumor effects in a B cell lymphoma model with DNA vaccines delivered on polyethylenimine (PEI) functionalized PLGA microparticles, J Control Release. 2006 Jul 20;113(3):261-70
- Y. Lu, G. Mapili, G Suhali, S. Chen and K. Roy, A digital micro-mirror based device for the fabrication of spatially patterned tissue engineering scaffolds, J Biomed Mater Res A. May;77(2):396-405. (2006)
- S. Kasturi, K. Sachaphibulkij and K. Roy, Covalent-conjugation of polyethyeleneimine on biodegradable polymer microparticles for delivery of plasmid DNA vaccines, Biomaterials. Nov; 26(32):6375-85. (2005)
- G. Mapili, Y. Lu, S. Chen and K. Roy, Laser-layered microfabrication of spatially patterned functionalized tissue-engineering scaffolds, J Biomed Mater Res B Appl Biomater. Nov;75(2):414-24 (2005)
- H. Liu and K. Roy, Biomimetic 3D Cultures Significantly Increases Hematopoietic Differentiation Efficacy of Embryonic Stem Cells. Tissue Engineering, 11 (1-2), 319-330, Jan-Feb (2005)
- H. Gu and K. Roy, Topical permeation enhancers significantly increase delivery of polymer micro and nanoparticles to epidermal Langerhans' cells. Journal of Drug Delivery Science & Technology, 14 (4) 265-273 (2004)
- Roy K, Wang D, Hedley ML, Barman SP, Gene delivery with in-situ crosslinking polymer networks generates long-term systemic protein expression. Molecular Therapy 7 (3):401-8 (2003)