Our students benefit from the opportunity to perform research projects with faculty who investigate a range of challenging biomedical, environmental, and computational questions. Our faculty’s teaching is enriched by their research interests.
"Equipped with his five senses, man explores the universe around him and calls the adventure Science."
~Edwin Powell Hubble, The Nature of Science, 1954
The laboratory of Dr. Helen Turner focuses on investigating signal information flow in the immune system. (Laboratory of Immunology and Signal Transduction www.istlab.org) We specifically focus on the signal transduction pathways that control inflammatory responses in response to immunological inputs, physical stimuli, exogenous toxins and metabolic disruption.
We have two main focus areas. First , we study calcium signalling in mast cells. Mast cells are key drivers of inflammatory responses. We are studying calcium-dependent pathways of mast cell activation in response to both immunological activation and novel toxins derived from the venoms of the cnidarian Carybdea alata. Our work encompasses both the study of calcium entry mechanisms (such as TRP family cation channels) and the intracellular targets of their activity such as the calcium dependent transcription factors family of NFATs. In these projects we are gaining new understanding of the decision making involved in initiating inflammation, and insights into potential therapeutic targets for the promotion and inhibition of inflammatory responses.
Second, we study pro-inflammatory pathways in adipocytes. A spectrum of metabolic disorders such as anorexia/cachexia and obesity, are characterized by low-level systemic inflammation. Elevated circulating levels of TNF alpha, IL-6 and IL-4, are associated with these strikingly different physiological states. We are interested in elucidating the extent to which this inflammation is governed by classical pro-inflammatory cells, such as mast cells, and the extent to which adipocytes should be considered as a pro-inflammatory component of the immune system. We are studying activation mechanisms that drive pro-inflammatory responses in adipocytes. In these projects we are uncovering the role played by the immune system in metabolic disorders.
Dr Michael Dohmís Laboratory of Toxicology and Genomics (website) studies problems related to the effects of pollutants on both human health and sentinel species that can be used to gauge the effects of pollutants upon the environment. Ozone is a prominent urban air pollutant that is implicated as having significant adverse effects on human heath by both toxicological and epidemiological studies. Ozone is a highly reactive oxidant gas; at ambient pollutant levels as low as 0.2 ppm, O3 induces decrements in spirometric pulmonary function measures in humans. In laboratory animals, O3 induces respiratory tract epithelial tissue injury and inflammation. Because O3 is relatively insoluble, it penetrates to the deep lung and targets particularly the terminal bronchioles and proximal alveoli. we are studying immune defense responses to ozone in vitro exposures to toad (Bufo marinus) phagocytes and to reptile (Gekko gecko) lung epithelial cells. We are also studying the effects of ozone and other gaseous pollutants in transgenic mouse models of cardiovascular disease and airway health, in collaboration with researchers at the University of Hawaii.
Dr. M. Lee Goff is a Forensic Entomologist who studies the application of entomological methods to the investigation of death. Studies include decompositional processes in specialized habitats, including hangings, containers and underwater disposals. Dr. Goff also investigates entomotoxicology, the study of Insects as toxicological evidence. He is about to begin new investigations on the effects of drugs on larval Dipteral development. In both these efforts, students will play a major role as co-investigators.
Dr. Paulo Martins is a computer scientist with an active research program in the development of wireless sesor networks (website). This technology has biomedical, defense and scientific applications. Dr. Martins' research interests cover a number of aspects of real-time systems including scheduling and timing analysis, mode changes and Fieldbus, and real-time communication networks. More recently he began working with wireless sensor networks (WNS). This work is highly motivated by real-world applications. The objective of current work is to introduce flexibility and adaptability to these types of systems by incorporating mode-change protocols. Mode-change protocols are responsible for the coordination of agents in the network (i.e. dissemination, injection, cloning, elimination of network agents and other basic operations) across different phases of operation. The end result is a wireless sensor network system that can serve multiple applications at the same time; that is capable of performing self-configuration; and that is able to self adapt to its environment, i.e. without human intervention (or at least with minimal intervention).
Dr Joel Kawakami seeks to design new anti-tumor drugs. The proposed research endeavor is to investigate new molecular descriptors and assess its computational predictive power in the design of next generation small molecules VEGFR-2/KDR kinase inhibitors as potential treatment for cancer. The inhibition of the receptor, VEGFR-2/KDR, has been shown in various laboratories and human clinical trials to suppress the growth and spread of cancer. Current marketed drugs for cancer, antibody Bevacizumab and small molecule Nexavar (Sorafenib) are prime examples of KDR inhibitors used for the treatment of cancer. In spite of current KDR inhibitor drugs on the market, extensive research continues for a more efficacious oncology drug for this class of target. Several different small molecule compounds are being evaluated as KDR inhibitors for the treatment of cancer. A common reoccurring problem for the discovery of these compounds were the time involved for the optimization of any chemical series to afford the one compound suitable for clinical development. The lead optimization of a chemical series remains a major bottle neck for the discovery of a clinical candidate.
The use of computational chemistry has great potential for accelerating the lead optimization of a chemical series. To date, our group has developed a computational method using a novel molecular descriptor and applied it to a known KDR inhibitor chemical series called Pyrazolo[1,5-a]Pyrimidines. Several compounds within this series have been synthesized based on the computational method. We seek to synthesize additional compounds designed by the method and test them in a KDR kinase in vitro biological assay. We will analyze the predictive power of this computational method based on the result and assess its potential application in the lead optimization of Pyrazolo[1,5-a]Pyrimidines as KDR inhibitors.