While we are currently engaged in projects in a range of fields with collaborators around the world, a few areas of emphasis are highlighted.
Current focus areas
Genomic-based approaches to characterize and monitor cancer progression for more effective and targeted therapeutic strategies, while necessary and important, do not encompass the full complexity of cancer. Growing evidence illustrates that the tumor microenvironment and the complex ecology of interactions between different cell types, extracellular matrix, and the body's natural physiology play a significant role in tumor initiation, progression, and response to treatment. Overlaid upon this complex ecology is the natural and pathologic cellular heterogeneity of normal and cancerous tissue that creates a plastic biological system that can evolve new characteristics to impede or promote progression as well as evade therapy. The MMB Lab develops and applies technologies for deeper insight into these fundamental aspects of tumor ecology - namely, the roles of the microenvironment, the various types of symbiotic ecological interactions, and heterogeneity in cancer. Key to our approach is the ability to create simple but enabling technologies that can be rapidly translated into clinical practice. With this approach, we strive to do "more with less", allowing us to explore enabling, advanced, high-content functional and molecular studies with patient samples from a wide range of cancers.
The implementation of molecular diagnostics has been limited in low- and middle-income countries (LMICs) due to financial and logistical constraints. An important step to overcoming this challenge is the cost of sample preparation required for downstream analysis. We have developed a range of sample preparation improvements across multiple analyte types (e.g. whole cells, proteins, nucleic acids) and multiple diseases (e.g. HIV, malaria, tuberculosis), including multi-disease assays. Our initial focus has been on the development of a low cost HIV viral load (VL) assay. VL assays are critical for proper management of anti-retroviral therapy (ART) for HIV+ patients. The high cost of this assay, however, makes it unaffordable for many of the countries at the epicenter of the HIV epidemic. In a partnership with the Joint Clinical Research Center (JCRC) in Uganda, we have developed, tested and validated a VL assay that will reduce costs five-fold without any loss of performance. Following a successful initial clinical trial, we are in the process of implementing this assay in a remote region of Uganda that currently lacks access to VL assays. Additionally, we are continue to expand the applications of this project through the development of a new suite of assays to assist in achieving a "functional cure" for HIV+ patients, currently an intense focus of the HIV/AIDS field.
Interactions between human cells and microbes are essential in normal human physiology but also drive a number of allergic and infectious diseases. Understanding these complex multikingdom interactions - between human cells and bacteria or fungus - is essential for treating and preventing diseases such as asthma, fungal infections, and sepsis. Small molecule signals provide a rich vocabulary for cellular communication, and microbes have evolved the capacity to mimic or hijack these signals in a defensive or symbiotic maneuver, exponentially increasing the scope and complexity of this chemical language. The study of this molecular crosstalk, i.e. the host-microbe metabolome, is limited by the lack of (1) integrated systems that enable the microscale multikingdom culture of human cells and microbes and (2) bioanalytical tools allowing the capture of the chemical signals exchanged. We develop new integrated microfluidic systems allowing culture of human cells and microbes in organotypic models, extraction and quantification of small molecules signals, and determination of the biological effects of these signals using functional readouts. Importantly, these systems are simple to operate and enable higher throughput for arrayed investigations of the complex microenvironmental factors regulating host-microbe interactions. Our overarching goal is to create broadly applicable microscale methods to unlock the secret language of cell-to-cell communication in intra- and inter-kingdom interactions.
An underlying principle that guides technology development in the MMB Lab is that simple is usually better than complex. Since we are particularly interested in studying cells, we focus our technology development at relevant cellular scales - specifically the micron to millimeter scale relevant to cell behavior and cell signaling. By understanding the basic physics of the scale (e.g. diffusion, surface tension) it is sometimes possible to create novel and elegant solutions to long standing challenges. We strive to create technologies that are simple yet functional and that provide fundamental advantages or capabilities that provide new biological insights and/or improved clinical outcomes. The MMB Lab's location in the heart of the UW medical complex helps us stay focused on important and high impact biological questions and clinical challenges.