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Alexander, R.A. Anderson, the co-director of Integrated Mathematical Oncology and senior member of the Moffitt Cancer Center, will present on April 4, 2017, as part of the Institute for Computational Medicine’s Distinguished Seminar Series. The title of his presentation is “Steering Cancer Evolution: Harnessing Phenotypic Heterogeneity to Design Better Therapies.”
The seminar begins at 11 a.m. in Clark Hall 110 on the Homewood campus, and it will be video-teleconferenced to Traylor 709 on the Johns Hopkins School of Medicine campus. Click here to view webcast. Lunch will provided to those in attendance on the Homewood campus.
Abstract: Heterogeneity in cancer is an observed fact, both genetically and phenotypically. Cell-to-cell variation is seen in all aspects of cancer, from early development to invasion and subsequent metastasis. This heterogeneity is also at the heart of why many cancer treatments fail, as it facilitates the emergence of drug resistance. The complex spatial and temporal process by which tumors initiate, grow and evolve is a major focus of the oncology community and one that requires the integration of multiple disciplines. Tumor heterogeneity at the tissue scale is largely due to ecological variations in terms of the tumor habitat driven by spatially heterogeneous vascularity, which is readily observed on cross sectional imaging. Molecular techniques have historically averaged genomic signals from large numbers of cells obtained in a single biopsy site, thus smoothing and potentially hiding underlying spatial variations. The complex dialogue between tumor cells and environment that produces intra- and inter-tumoral heterogeneity is fundamentally governed by Darwinian dynamics. That is, local micro- environmental conditions select phenotypic clones that are best adapted to survive and proliferate and, conversely, the phenotypic properties of the cells affect the environmental properties. While these complex interactions have enormous clinical implications because they promote resistance to therapy, the dynamics are impossible to fully capture via experimentation alone.
Here we present an integrated theoretical/experimental approach to develop dynamical models of the complex multiscale interactions that manifest as temporal and spatial heterogeneity in cancers and ultimately govern tumor response and resistance to therapy. Specifically, we examine the impact of micro-environmental modulation on cancer evolution both in silico, using a hybrid multiscale mathematical model, and in vivo, using three different spontaneous murine cancers. These models allow the tumor to be steered into a less invasive pathway through the application of small but selective biological force. Our long term goal is explicitly translational as we focus our integrated approach on an emerging cancer treatment paradigm that actively harnesses evolutionary dynamics to improve patient outcomes.
Desmond Lawler, PhD
Nassir I. Al-Rashid Chair in Civil Engineering
Department of Civil, Architectural and Environmental Engineering
The University of Texas at Austin
Abstract: The philosophy of municipal wastewater treatment has changed only slowly in the past 100 years. From approximately 1920 to 1970, a wastewater discharge was considered acceptable if the dissolved oxygen level in the receiving stream did not dip below 5 mg/L downstream of the discharge. Protecting aquatic life, particularly fish, from immediate death due to low oxygen levels was the primary motivation and the goal. The passage of the Clean Water Act in 1970 reflected a broader view to include concerns about eutrophication by nutrients and ecological and human health concerns with the naming of “priority pollutants.” Nevertheless, the central concept was that discharge concentrations would be acceptable if they took advantage of the assimilative capacity of receiving waters; that is, if they limited the harm to acceptable values. Now we are embarking on a new philosophy, captured by the phrase “One Water” by the Water Environment Federation, in which we think of wastewater not as a problem for disposal but as a resource.
Why is this shift in philosophy happening? At least two major changes have occurred since the old philosophies were developed. First, a dramatically increased population has led to a substantial increase in “indirect potable reuse” of wastewater, whereby the effluent discharge from one city is a part of the drinking water source for a downstream city. In many areas of the arid Southwest, that “part” can often be nearly 100%. An extension of this trend, due to water shortages, is the drive toward direct potable reuse of wastewater. Second, not only do the chemical and pharmaceutical industries now produce tens of thousands of synthetic chemicals that were not dreamed of when the “priority pollutant” list associated with the Clean Water Act was developed, we now understand that some of these products are endocrine disruptors and others lead to microbial antibiotic resistance.
In this talk, I will try to make the case that wastewater treatment needs to be changed, perhaps radically, to reflect the new philosophy and to meet the needs of the 21st century. The thrust of the presentation will be to explore some possibilities for these radical changes and try to back them up with preliminary engineering calculations.