2001 — 2003 |
Kam, Lance C |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Cell Adhesion On Protein-Micropatterned Lipid Bilayers
The goal of this proposed research is to develop micropatterned lipid bilayers into a mature system with great potential in cellular bioengineering. In preliminary feasibility studies, I discovered a technique for creating multi functionalized surfaces containing microscale patterns of cell-adhesive proteins, surround by region of lipid bilayers. These barriers facilitated the spreading of anchorage-dependent cells across lipid bilayers, overcoming a fundamental obstacle in the use of these supported membranes to study and modulate cell response. The propose research will use contemporary surface analysis and molecular biophysical approaches to characterize these newly developed surfaces ,providing the understanding needed to effectively manipulate this system. The ability of adherent endothelial cells to interact with bilayer-associated biomolecular targets, including lipid-tethered peptides and membrane spanning proteins involved in cell-cell communication, will also be examined. These surfaces will be used to identify specific membrane properties that regulate cellular function, leading to new techniques in biomaterials engineering. Successful completion of the goals set forth in this study will also provide tools needed to develop interfaces between cells and biosensors in vitro, and will culminate in the design of a proposed interface based on membrane proteins and supported lipid bilayers.
|
0.911 |
2017 — 2020 |
Kam, Lance |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Predictive Optimization of T Cell Expansion
PI: Kam, Lance C. Proposal: 1743420
Adaptive immunity provides our bodies with a powerful and robust means to neutralize a wide range of ever-changing challenges, such as viruses and bacteria in the environment. This system has been re-engineered to treatment of human diseases, as seen in the field of immunotherapy. In particular, training T cells, key agents of the immune system, to target cancer is on the cusp of being developed into practical therapies. Current research focuses largely on designing and even personalizing the ways in which cells recognize their targets. This project focuses on growth and production of T cells, which is essential to future therapies and complementary to that of improving targeting. This project focuses on the systems used to grow cells, developing and optimizing a new biomaterial platform. Recent studies show that in addition to molecular factors presented on materials, cell growth is dependent on the mechanical rigidity of these materials. Moreover, additional results suggest that the precise conditions used to optimally grow cells, including molecular factors and rigidity, may change as a function of individual and disease progression. This project seeks to develop a systematic way to identifying parameters that promote optimal expansion of cells based on properties of an individual's cells. Successful completion of this project has the potential to improve the reliability and efficacy of cellular immunotherapy, which will reduce the burden of cancer on society. While the direct impact of this work will be on T cell expansion, the methods and concepts to be developed will be widely applicable to other cell expansion systems and to other aspects of biomaterial design. Given the remarkable opportunities for custom manufacturing that are becoming available, the concept that a biomaterial can be optimized for an individual's therapy is compelling. In addition, this project will provide training in the process of converting academic discoveries into practical solutions, developing a workforce capable of commercializing new ways of improving human health. Additional education and outreach opportunities will accelerate interdisciplinary studies between immunology and biomedical engineering, greatly enhancing both underlying fields.
The expansion of a starting population of T cells into a therapeutically relevant product is a vital step in emerging forms of adoptive cellular immunotherapy. This project focuses on development and optimization of a new platform for cell expansion, consisting of electrospun fibers of elastomer coated with antibodies to CD3 and CD28, receptors on the T cell surface that when engaged provide function activation of cells, initiating expansion. Previous studies from the PI's group showed that reducing the mechanical rigidity of activating substrates corresponds with improved T cell expansion, even rescuing cells from patients undergoing care for CLL which typically show signs of unresponsiveness and exhaustion. Furthermore, preliminary results suggest that the specific set of conditions that best expand a population of T cells depends on the individual and disease progression. The concept inspiring this project is that having a systematic means for identifying optimal conditions for expansion, based on readily obtainable biomarkers or clinical history of a patient, will improve the reliability of cell production for cellular immunotherapy, making these treatments effective for an increasing number of patients. The first stage will be carried out with cells from healthy donors, investigating the effect of fiber coating, culture conditions, and, in particular, mechanical rigidity of the fibers that make up our system on cell expansion. Two commercially available platforms will be included in these experiments for comparison. Markers associated with clinical efficacy, including cell proliferative potential and the phenotypic makeup of the resultant population, will be analyzed as a function of the design parameters. In the second stage, this knowledge will be used to understand expansion of cells from patients undergoing care for Chronic Lymphocytic Leukemia (CLL), including data of clinical history and both protein and genomic markers that are currently collected as part of treatment. If successful, the data generated by this study will provide a way to personalize and optimize T cell expansion for immunotherapy by bringing together two underlying fields of research: 1) the emerging field of immune mechanobiology, specifically that T cells can respond to the rigidity of their environment and 2) the personalization of biomaterials to an individual's cell response. This strategic union of fields represents a new approach to making T cell manufacturing more reliable and available to a wider range of patients.
|
1 |
2019 — 2020 |
Guo, X. Edward Kam, Lance Myers, Kristin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Planning Grant: Engineering Research Center For Integrated Mechanobiology For Women's Health (Imwel)
Planning Grant: Engineering Research Center for Integrated Mechanobiology for Women's Health (IMWEL)
Mechanical forces have profound effects on human physiology. The impacts of zero gravity in space travel and of bone remodeling for world-class athletes serve as powerful examples of how forces modify the body under extreme performance conditions. Equally striking examples affecting the broader population are seen in childbirth and post-menopausal osteoporosis. However, despite new understanding of how mechanical forces affect molecules, cells, tissues, and organisms, transformation into advanced strategies for health remains elusive. Women's health topics in particular have been underserved, despite having clear importance in areas such as pregnancy, maternal health, and cancer. To bridge this gap, we envision a Center that brings together engineers, scientists, educators, entrepreneurs, and medical professionals at this intersection of mechanobiology and women's health, developing new knowledge and tools. A multidisciplinary Center is needed for this endeavor, as the underlying fields of mechanobiology and women's health are dramatically underserved, and real progress will require convergent thinking and creative solutions. By bringing together these often-disparate groups, investment in this Center through NSF aims to dramatically advance the science and practice of women's health through mechanobiology, leading to knowledge that will be transformed into new tools for modern healthcare.
The goal of this Planning Grant is to expand a core group of investigators at Columbia University into a larger, more diverse team that will be strategically suited to lead the envisioned Engineering Research Center for Integrated Mechanobiology for Women?s Health (IMWEL). Columbia University has a rich history in biomechanics, which continues to adapt to contemporary challenges. Today, topics in biomechanics at Columbia University include how forces affect molecules involved in cellular function, how tissues actively change during pregnancy, and in developing the computational frameworks needed to turn basic science into realistic models and solutions. These investigators have, in small teams, developed connections with researchers around the United States of America that focus on different aspects of biomechanics. Through this Planning Grant, they intend to further develop these and additional connections across the country to ensure that the resultant IMWEL leadership team brings convergent expertise representing a diverse range of capabilities, insights, and societal groups. This will be accomplished through a series of workshops around mechanobiology and women's health, which will be complemented by later visits to the participating teams outside of Columbia University. Furthermore, this Planning Grant will include discussions and visits with complementary NSF-supported Centers to identify ways that the larger program can effectively interact.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
|
1 |