Thomas Chan, PhD - US grants

Acquired immunodeficiency syndrome (AIDS) is a progressively fatal disease that is believed to be the result of infection by the lymphotrophic virus HIV. Hundreds of drugs have been screened for activity against the HIV, and the ones that have been found effective in vitro are all members of the dideoxynucleosides. It has recently come to the attention of researchers that the intracellular anabolism of these nucleosides into active nucleotides (triphosphates) has different efficiencies in different cell types and showed varying degrees of competition with the endogenous metabolites. We have recently demonstrated that dipyridamole, a potent membrane nucleoside transport inhibitor, can augment the anti-tumor activity of a nucleoside analog cytarabine (araC) if administered in a sequential regimen. The mechanism of synergy resides in the ability of dipyridamole to increase cellular exposure to the active metabolite araCTP by preventing araC efflux. We plan to test the applicability of this type of sequential regiment in augmenting the anti-viral activity of a prototype anti-=viral nucleoside 2',3' -dideoxycytidine. Since the HIV has been shown to replicate in lymphocytes, macrophages, and bone marrow cells, we plan to use these cells as our experimental models. Our plan of action includes; a) demonstrating that their is a specific nucleoside transport system in each of the cell types; b) showing that such a nucleoside transport system is responsible for 2'3' -dideoxycytidine uptake into these immune effector cells; c) proving that this membrane nucleoside transport system is inhibitable by dipyridamole; d) confirming that dipyridamole can trap high concentrations of 2'3' -dideoxycytidine and its triphosphate within the immune effector cells for extended periods; and e) showing that prolonged entrapment of 2'3' -dideoxycytidine within cells is associated with improved anti-viral activity. Dipyridamole is a good drug to use because it has already been shown to be well tolerated in cardiac patients requiring anti-platelet therapy. In addition to the important therapeutic implications, this study will also provide valuable information on nucleoside metabolism in immune cells which is important in certain autoimmune diseases.

biomedical equipment purchase;

This grant supports research that generates new knowledge of how humans and virtual reality systems interact to help learn motor skills for physical rehabilitation. When humans put on a virtual reality headset, they are transported into an immersive digital world that can be anything or anywhere. Recent advancements of virtual reality systems make it so that these digital worlds closely mimic the real-world -- opening up many possibilities to train rehabilitative skills. However, in order for this potential to be fully realized, a better understanding of the components of immersive virtual environments that translate to real-world motor skill development is needed. Correspondingly, this award supports the fundamental research of human movements and experiences linked to learning in virtual reality environments that best fit their learning needs. Findings from the current study will benefit the U.S. economy and society as many schools and workplaces are using virtual reality systems to provide people with scalable training of complex motor skills. To properly examine the complexities of motor learning in virtual worlds, this project involves researchers from several disciplines including mechanical engineering, kinesiology, psychology, and vision science. Moreover, the multi-disciplinary approach of this project helps broaden participation of underrepresented groups, along with aids to bridge gaps between engineering and social science research fields. <br/><br/>The multidisciplinary research team in this project will develop two dynamic human-virtual reality interaction systems—one involving walking through a virtual world while avoiding obstacles, and the other controlling a prosthetic arm and hand with a foot controller. Each system includes a virtual reality headset with strategically designed adaptive environments that scale to the skill level of the user, and other subsystems to record vital user data such as gait, eye gaze behaviors, and toe tapping events (while controlling the prosthesis). The developed systems rely on various sensors, such as eye trackers, 3D motion capture systems, foot controller insoles, that can fully capture the biomechanics of the users and their strategies in performing the assigned tasks. Analyzing the collected data will lead to clearer understanding of the bidirectional relationships between humans and the virtual reality systems during motor learning or rehabilitation tasks—humans enhancing their skills, and the VR system adapting to the user needs. This research will fill a knowledge gap in the human-virtual reality interaction research by demonstrating the potential of virtual reality to improve learning and rehabilitation through the designed systems.<br/><br/>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.