Tissue engineering and biomaterials, microvascular growth and remodeling, stem cell engineering
The Botchwey Laboratory takes a multidisciplinary approach for improvement of tissue engineering therapies through study of microvascular remodeling, inflammation resolution and host stem cells. Our goal is development of effective new strategies to repair, replace, preserve or enhance tissue or organ function.
Immunoengineering, biomaterials, drug delivery, gene delivery, cancer, immunotherapy, tissue engineering, stem cells, regenerative medicine
The overall goal of our research endeavor is the development of new biomaterial-based strategies for gene/drug delivery and stem cell engineering. Towards this, my laboratory focuses on three major directions: (a) design and development of novel delivery systems for nucleic-acid based immunotherapy and cancer chemotherapy (b) engineering complex microenvironments to study and manipulate stem cells and understand their behavior in biomimetic, three-dimensional conditions and (c) developing novel engineering tools and high throughput methods to generate functional T cells and Dendritic cells from stem cells.
Physics of soft materials with a focus on the connection between microscopic order and macroscopic properties.
Soft materials are materials whose properties are determined by internal structures with dimensions between atomic sizes and macroscopic scales. They are characterized by energies that are typically comparable to kT. As a result, they have low elastic moduli, often ~1-10 Pascals. Typical soft materials include liquid crystals, polymers, colloidal suspensions and emulsion drops. These materials, unlike conventional simple liquids, are locally heterogeneous and can have broken symmetries that affect their physical properties. Hence, although they often exhibit liquid-like behavior, soft materials also often exhibit properties of solids. Our laboratory studies the physics of soft materials with a focus on the connection between microscopic order and macroscopic properties. The underlying theme is to pursue basic understanding and address fundamental questions. However, we also address applied problems and pursue industrial collaborations since many of the materials we study can be viewed as model systems for those that are often used in applications. Current projects include (i) studying the phase and non-equilibrium behavior and properties of dense microgel suspensions, (ii) understanding the consequences of confinement and curvature over the equilibrium states of ordered materials, which in many cases require the existence of topological defects in their ground states, and (iii) electrohydrodynamics of toroidal droplets and jets.
Nanomedicine, engineering immunity, and biomedical microsystems
Human health has been transformed by our collective capacity to engineer immunity — from the pivotal development of the smallpox vaccine to the curative potential of recent cancer immunotherapies. These examples motivate our research program that is conducted at the interface of Engineering and Immunology, and where we develop biomedical technologies and applications that shape a diverse array of immunological systems.
The questions that are central to our exploration include: How do we begin to study an individual's repertoire of well over one billion immune cells when current technologies only allow us to study a handful of cells at a time? What are the biomarkers of immunological health as the body responds to disease and ageing, and how may these indicators trigger clinical decisions? And how can we genetically rewire immune cells to provide them with entirely new functions to better fight complex diseases such as cancer?
To aid in our studies, we use high-throughput technologies such as next-generation sequencing and quantitative mass spectrometry, and pioneer the development of micro- and nanotechnologies in order to achieve our goals. We focus on clinical problems in cancer, infectious diseases and autoimmunity, and ultimately strive to translate key findings into therapies for patients.
The overall research of the lab focuses on a systems integration approach to musculoskeletal disease and regenerative engineering by applying novel imaging and engineering approaches to mechanistic biology problems. Our current work has three main thrusts: (i) cell and biologic therapies for the healing of large bone and muscle defects, (ii) multi-scale mechanical regulation of bone regeneration, (iii) intra-articular therapeutic delivery for post-traumatic osteoarthritis. Combining backgrounds in mechanical engineering, vascular biology and musculoskeletal tissue regeneration, our research integrates mechanics principles and analytical tools with molecular biology techniques to uniquely address challenges of musculoskeletal disease and regeneration.
James Dahlman is an Associate Professor in the Georgia Tech BME Department. He studied RNA design and gene editing as a post-doc with Feng Zhang at the Broad Institute, and received his Ph.D. from MIT and Harvard Medical School in 2014, where he studied RNA delivery with Robert Langer and Daniel Anderson.
The Lab for Precision Therapies at Georgia Tech, also called the 'Dahlman Lab', works at the interface of drug delivery, nanotechnology, genomics, and gene editing. James has designed nanoparticles that deliver RNAs to the lung and heart; these nanoparticles have been used by over ten labs across the US to date. He has also developed targeted in vivo combination therapies; nanoparticles deliver multiple therapeutic RNAs at once, in order to manipulate several nodes on a single disease pathway. More recently, he developed a method to quantify the targeting, biodistribution, and pharmacokinetics of dozens to hundreds of distinct nanoparticles at once directly in vivo.
Finally, James uses molecular biology to rationally design the genetic drugs he delivers. He recently reported 'dead' guide RNAs; these engineered RNAs can be used to simultaneously up- and down-regulate different genes in a single cell using Cas9.
James has won the NSF, NDSEG, NIH OxCam, Whitaker Graduate, and LSRF Fellowships, the Weintraub Graduate Thesis Award, and was recently named a Bayer Young Investigator and Parkinson's Disease Foundation Young Investigator. He has had significant help along the way. Besides having great scientific advisors, James has been lucky to mentor excellent students, including two that were finalists for the Rhodes Scholarship.
In the Dahlman Lab, we focus on the interface between nanotechology, molecular biology, and genomics. We design drug delivery vehicles that target RNA and other nucleic acids to cells in the body. We have delivered RNAs to endothelial cells, and have treated heart disease, cancer, inflammation, pulmonary hypertension, emphysema, and even vein graft disease. Because we can deliver RNAs to blood vessels at low doses, sometimes we decide to deliver multiple therapeutic RNAs to the same cell at once. These 'multigene therapies' have been used to treat heart disease and cancer. Why is this important? Most diseases are caused by combinations of genes, not a single gene. We also rationally design the nucleic acids we want to deliver. For example, we re-engineered the Cas9 sgRNA to turn on genes, instead of turning them off. This enabled us to easily turn on gene A and turn off gene B in the same cell.
Blair Brettmann received her B.S. in Chemical Engineering at the University of Texas at Austin in 2007. She received her Master's in Chemical Engineering Practice from MIT in 2009 following internships at GlaxoSmithKline (Upper Merion, PA) and Mawana Sugar Works (Mawana, India). Blair received her Ph.D. in Chemical Engineering at MIT in 2012 working with the Novartis-MIT Center for Continuous Manufacturing under Prof. Bernhardt Trout. Her research focused on solid-state characterization and application of pharmaceutical formulations prepared by electrospinning. Following her Ph.D., Blair worked as a research engineer for Saint-Gobain Ceramics and Plastics for two years. While at Saint-Gobain she worked on polymer-based wet coatings and dispersions for various applications, including window films, glass fiber mats and architectural fabrics. Later, Blair served as a postdoctoral researcher in the Institute for Molecular Engineering at the University of Chicago with Prof. Matthew Tirrell.
Continuous pharmaceutical manufacturing, roll-to-roll coatings and films, electrospinning, polymer science, molecular engineering, surface and interfacial science, charged polymers, biomedical coatings
Blair's current research interests focus on rational design of functional advanced materials through understanding of interactions in multicomponent mixtures on the molecular scale, both at equilibrium and during processing. Her research group designs and studies new processing and characterization technologies using both experiments and theory, focusing on linking molecular to micron scale phenomena in complex systems to product performance. Application areas include pharmaceutical product development, renewable bioproducts and polymer composites.