Deirdre Meldrum develops technologies that enable the study of live organisms in harsh environments from the human body to the oceans. She develops tools, sensors and automated systems to detect and analyze differences between healthy and diseased cells. In addition to her responsibilities at the Biodesign Institute, Dr. Meldrum is Dean of ASU's Ira A. Fulton School of Engineering.
The Center for Ecogenomics is the headquarters for the Microscale Life Sciences Center (MLSC), which Meldrum directs, as well as the facility for Meldrum's part in an oceanography project called NEPTUNE. The MLSC is a National Institutes of Health Center of Excellence in Genomic Science. In that role, Professor Meldrum leads research to study the fundamental mechanisms governing the birth, growth and decline of human cells with the aim of better understanding and finding ways to combat the most widespread diseases and other threats to human health. As the result of achievements in its first five years, the MLSC has been awarded a second five-year $18 million federal grant to continue its work. MLSC research partners include the University of Washington, the Fred Hutchinson Cancer Research Center, and Brandeis University.
In addition to her appointment in Microbiology, Dr. Mary Lidstrom holds the Frank Jungers Chair of Chemical Engineering. She received a B.S. in microbiology from Oregon State University, and a M.Sc. and Ph.D. in bacteriology from the University of Wisconsin. Dr. Lidstrom conducted postdoctoral work as a Leverhulme Fellow in Microbiology at the University of Sheffield, and has held academic appointments in microbiology at the University of Washington, in the Center for Great Lakes Studies in Milwaukee, Wisconsin and in Environmental Engineering Science at the California Institute of Technology. She serves on the advisory boards of the DOE Energy Biosciences Council and the Environmental Sciences Division of the Oak Ridge National Laboratory. She is also the Vice Provost for Research at the University of Washington.
Research in Dr. Lidstrom's laboratory is focused on molecular and metabolic manipulations of methylotrophic bacteria, which are capable of growth on methane, methanol, and methylated amines. The long-term goal of this research is to develop environmentally sound and economically viable alternatives to current chemical production and cleanup strategies. Genetic, physiological and metabolic modeling approaches are used to understand key metabolic pathways in these bacteria, with the goal of directed manipulation of key metabolic pathways and enzymes. The laboratory's recent discovery that methylotrophic bacteria contain a metabolic pathway previously thought to be found only in methanogenic archaea has generated a new research thrust focused on evolution of C1 metabolic pathways across the bacterial/archaeal boundaries. These studies are now being augmented by genomic approaches, including proteomics and expression microarrays. In addition, the laboratory is involved with an interdisciplinary center, the Microscale Life Sciences Center, with a focus on studying metabolism in single cells.
Babak received his graduate degrees from the University of Michigan in Ann Arbor. During his graduate studies he worked on developing microfabrication technologies for distributed micro-propulsion and micro-flight, high frequency distributed electrostatic micro-actuators, fluid flow in nano and micro scales, and a range of problems regarding physics, scaling, and modeling of nano and micro systems. From 2000 to 2001 he was with Nanovation Technologies Inc. as a device designer and a product manager working on MEMS-based integrated photonics systems. He joined the Department of Chemistry and Chemical Biology at Harvard University as a postdoctoral research fellow in 2001. At Harvard, he was involved in research on developing novel nanofabrication technologies, self-assembled systems, cell patterning, low-cost biosensing, and using organics for electronics and MEMS. He joined the Electrical Engineering Department at the University of Washington as an assistant professor in October 2003. Babak is a founding member of the American Academy of Nanomedicine; a senior member of the IEEE, and a member of the American Association for Advancement of Science, Sigma Xi, and the American Chemical Society.
Mark Holl received his B.S. degree in mechanical engineering from Washington State University, Pullman, WA in 1986. He received his M.S. degree in mechanical engineering from the University of Washington, Seattle, WA, in 1990, and his Ph.D. degree in mechanical engineering from the University of Washington in 1995.
Together with Professor Paul Yager (University of Washington), Mark was a principal inventor of a laminate-based microfluidic technology and a founding member of the startup company born in part of this work, Micronics, Inc.
Dr. Holl's research interests include microfabrication technologies, systems integration for total analysis systems, integration for micro and nanotechnology components in robust and simple to use formats, microscale systems for biological applications, bioprocess automation, process sensors, and process characterization and control with emphasis on biomedical, genomic, and, proteomic science applications.
Mark is a member of IEEE, AAAS, ASME, SPIE, in addition to being an investigator in the NIH Center of Excellence in Genomic Sciences, the Microscale Life Sciences Center (MLSC) at Arizona State University.
Professor Alex Jen joined the faculty of the Department of Materials Science and Engineering as the Boeing-Johnson Professor in December 1999. He has amassed a considerable amount of expertise from both industrial and academic research in the areas of organic/polymer synthesis and several new types of physical phenomena in organic functional polymers. The focus of his interdisciplinary research group is on the synthesis and characterization of organic functional materials/polymers that possess novel optical, electrical, and biological properties. For the past few years, his group has concentrated on the development of new synthetic methodologies of making highly efficient, processible, and thermally stable chromophores and polymers for nonlinear optical and light-emitting applications. In addition, he is collaborating with physicists and biologists to evaluate the suitability of using these materials for two-photon absorbing studies, such as two-photon microscopy for deep tissue imaging, 3-D microfabrication for photonic crystals and optical memory, and photodynamic therapy for the treatments of cancer tumors.
He is currently funded by several government agencies, such as the National Science Foundation (NSF), Office of Naval Research (ONR), Air Force of Scientific Research (AFOSR), Defense Advanced Research Projects Agency (DARPA), and National Institute of Science and Technology (NIST), and Washington Technology Center (WTC). In addition, he is also funded by several industrial partners, such as the Lockheed-Martin, Lightwave Microsystems, Lumera, Telephotonics, and Gemfire.
The major thrust of the Burgess group is the investigation of new concepts in the development of integrated multi-component analysis systems for real-time industrial, biomedical and environmental monitoring applications. Major components of this effort involve integrated and guided wave optics and micro fluidics. The work is highly multidisciplinary and problem oriented.
A burgeoning effort is in the area of developing cutting edge technology for multi-parameter analysis of single cells, and to facilitate the application of this technology to the understanding of biological questions characterized by cellular heterogeneity. To this end we have developed technology for respiration measurements at the level of a single cell and have begun to develop approaches for additional metabolic markers. This is part of a larger collaborative program to design and build fully integrated and automated micro systems for the interrogation of individual cells. These systems will be able to simultaneously measure many variables in cells in real-time and provide data to analyze complex molecular outcomes such as cell proliferation, differentiation, apoptosis, and pathogenesis.
Examples of other work includes the development of novel sampling interfaces for Raman spectroscopy, including the development of a micro-liter volume liquid core waveguide cell that can be directly interfaced to chromatographic systems, and developments in Grating Light Reflection Spectroscopy (GLRS) and optical low coherence reflectometry (OLCR). Both of these techniques are well suited for the direct monitoring of changes in heterogeneous and highly scattering matrices during manufacturing, and have been demonstrated at high concentrations, and over a wide range of particle size, in applications such as pharmaceutical nano-milling.
Dr. Brad Cookson received a B.S. degree from the University of Utah, where he worked on genetic regulation of NAD metabolism in Salmonella typhimurium with Dr. John Roth. He purified and defined the molecular structure of the Bordetella pertussis tracheal cytotoxin to earn his Ph.D. at Washington University in the lab of Dr. William Goldman. He also received a M.D. from Washington University, was awarded an Olin Medical Fellow, and received the Alexander Berg Award in Microbiology and Immunology. After completing residency training in Clinical Pathology at the University of Washington, his post-doctoral studies on cellular immune responses to microbial pathogens were conducted in the laboratory of Dr. Michael Bevan, also at the University of Washington. In addition to an appointment in the Department of Microbiology, Dr. Cookson is an Associate Professor in the Department of Laboratory Medicine. He received a Pfizer New Faculty Scholar award.
Research in Dr. Cookson's lab revolves around the idea that a greater understanding of immune responses will provide novel insights into host-pathogen interactions. This information will help us develop effective tools for diagnosing infectious diseases and help us design therapeutic strategies that favor quality outcomes for infected hosts. Salmonella and Yersinia infections cause both systemic and localized diseases, and studying these systems provides an excellent opportunity to understand: 1) the mechanisms of protective immunity conferred by novel immunization strategies; 2) how virulent bacteria escape primary immune responses and cause sepsis; 3) the contributions of innate immune functions to the development of immunity; and 4) the role of T cell-macrophage interactions in combating infections caused by pathogens like Salmonella, the Mycobacteria, and Leishmania. In the course of these studies, the Cookson lab uses techniques in cellular immunology, bacterial genetics, biochemistry, and molecular biology.
We also partner with engineers and private industry to utilize and develop biotechnology in two areas. First, to define the mechanism of proinflammatory programmed eukaryotic cell death called pyroptosis (to distinguish it from noninflammatory apoptosis) induced by certain bacterial infections. The pyroptosis pathway has broad implications for a variety of biological systems, including the immune, cardiovascular, and central nervous systems. The goal is to better understand organ damage resulting from infections, heart attacks, and strokes. Second, to utilize powerful amplification and detection systems to diagnose bacterial and fungal infections. The goal is to improve the medical management of hospitalized patients suffering from infectious diseases.
The Human Genome Project was the most ambitious research project in the history of analytical chemistry. The goal of that project was the determination of the primary structure of the human genome, which is a group of molecules with a combined molecular weight of 3 billion kilograms. Capillary array electrophoresis with laser induced fluorescence detection in a sheath flow cuvette was the primary analytical instrument used in sequencing the genome; that instrumentation was developed, in part, by Dovichi's research group.
Now that the genome is sequenced, interest is focused on the study of the proteome, which is the protein content of an organism, tissue, or cell. Dovichi's group is developing tools to study the proteome with two-dimensional capillary electrophoresis and laser-induced fluorescence. This group's long-term goal is to study protein expression in single cells and to determine how protein expression changes across a cellular population during cancer progression and during the development of an embryo.
Dovichi's group is collaborating with Brian Reid at the Fred Hutchinson Cancer Research Center to employ this technology to characterize compositional changes that accompany Barrett's esophagus, a precancerous condition. Gastroesophageal cancer is the second leading cause of cancer death world-wide. If current rates of increase hold, deaths from esophageal adenocarcinoma will exceed those of prostate and breast cancer in a decade and colorectal cancer in two decades. There is a vital need to develop tools to help guide therapy for those individuals with Barrett's esophagus, the only known precursor to esophageal adenocarcinoma.
Proteomics provides a parts list for a cell; it does not necessarily describe how those parts function. Ultimately, the characterization of a cells metabolism, which describes the production and consumption of small molecules, is necessary to understand health and disease. Dovichi's group also is studying metabolic pathways in single cells. In general, a fluorescent substrate is synthesized. Any enzymatic transformation of the substrate can be monitored with exquisite sensitivity as long as the fluorescent label is preserved. We are collaborating with Ole Hindsgaul and Monica Palcic of the Carlsberg Institute to characterize sphingolipid metabolism in single cells. These glycolipids make up a very large fraction of neuronal membrane, and defects in their metabolism leads to devastating genetic diseases.
Dr. Hockenbery's laboratory study the genetic and biochemical mechanisms of programmed cell death, or apoptosis, in a variety of experimental systems. Normal cell death occurring during development and following terminal differentiation has typical morphologic and biochemical features collectively termed apoptosis. The precise control of these events is obviously of great importance to the organism and many model systems have demonstrated the requirement for active RNA and protein synthesis for cell death to proceed, suggesting an internally programmed process. One regulator of this process is the bcl-2 oncogene, which blocks apoptosis in vitro and in vivo and appears to normally control the timing of cell death in many cell lineages. The following projects are currently active in the lab:
- Investigation of the mitochondrial functions of the Bcl-2 family of apoptotic regulatory proteins. Recent efforts have led to the discovery of novel small molecules that inhibit Bcl-2 and related proteins.
- Structure-function analysis of Bcl-xL homodimers, with recent demonstration of x-ray crystal structure of 3D domain swapped dimers.
- Analysis of mitochondrial proteomics and mitochondrial assembly in apoptosis, with a focus on the effects of Hsp90 inhibitors on mitochondrial protein turnover.
- Investigation of the role of the c-myc transcription factor in bioenergetic regulation in different cell contexts, including cell growth and division, neoplastic transformation and apoptosis.
- Analysis of cell signaling and transcriptional responses to nutrient excess, in particular glucose sensing mechanisms employed in cells susceptible to neoplastic transformation.
Dr. Reid is the Head of the Seattle Barrett's Esophagus Program. As an undergraduate and graduate student in Genetics, he discovered yeast cell cycle mutations and participated in developing the first genetic model of eukaryotic cell division. After graduate school, he entered medical school to study neoplastic evolution with the goal of improving care for patients who are at risk for or have cancer. He became a gastroenterologist and he has been investigating Barrett's esophagus since 1983. The goal of Dr. Reid's work on Barrett's esophagus is to understand the mechanisms by which environmental exposures (i.e. chronic reflux ; aspirin or other nonsteroidal antiinflammatory agents) affect the evolution of clones that leading to the development of esophageal adenocarcinoma in patients with Barrett's esophagus. This understanding can then be used to develop interventions to prevent progression to cancer or to detect the cancers and premalignant abnormalities when they are early and curable.