Integrated Calendar

Novel treatments that are under development for heart failure, metabolic disorders, kidney disease, and other debilitating illnesses generally target specific molecular and cellular mechanisms of action. However, assessment of such treatments is often complicated by the lack of easily measurable blood biomarkers, and a reliance upon repeated tissue biopsy. Subsequently, many exploratory studies utilize non-invasive imaging methods to characterize changes in whole organ structure and function as surrogate markers for underlying cellular and molecular changes. Although such measurements can be performed serially, such macro-level imaging measurements are often insensitive to physiologically meaningful treatment responses. In addition, the lack of target specificity represents a fundamental barrier both in pre-clinical development and clinical trials where the information potentially gleaned from a more physiologically rich data set would be of high value to further therapeutic development. My primary research interest is in using magnetic resonance imaging (MRI) as a platform technology for non-invasive and multiplexed molecular imaging in heart and kidney failure. Using a first principles approach, my group seeks to unify changes in myocardial and kidney MRI physics properties with advanced pulse sequence design and analysis in order to enable integrative physiological imaging that both identifies mechanisms of failure earlier than existing diagnostics, and directly measures the impacts of new therapies on their intended therapeutic targets. Using a process of chemical exchange saturation transfer (CEST) we have designed pre-clinical methods to quantify viral carriers of somatic cell gene editing machinery, gene transfer following adeno associated viral gene therapy, and to longitudinally quantify cell survival/proliferation following intra-myocardial implantation in mouse models of regenerative cell therapy. In addition, cardiac CEST approaches for imaging of myocardial creatine and fibrosis using endogenous contrast mechanisms have been translated from mouse models to clinical application in obese adults and renal failure patients on routine hemodialysis. Most recently we have developed methods to probe renal physiology and failure based on endogenous CEST contrast generated by urea. When integrated, these approaches can enable serially non-invasive and multi-scale analysis from the level of gene expression up to whole organ function in disease settings that currently have limited non-invasive molecular tools.

Subsurface systems, such as alluvial aquifers and soils, store and govern the quality of groundwater by sustaining a unique balance of biogeochemical and hydrological processes. The complex characteristics of subsurface systems are demonstrated in both spatial and compositional sediment heterogeneities that ultimately control the rate and extent of elemental cycling. Different redox environments commonly form within the subsurface and may largely influence these cycles. Heavy metals, occurring naturally (geogenic) or as anthropogenic contaminants, are particularly sensitive to varying redox conditions, even if they are not directly redox active.
In this seminar, I will show how sediment hotspots and interfaces influence elemental cycling, contaminant attenuation, and groundwater quality. I will present examples of how an alluvial aquifer system exhibiting redox heterogeneities may influence heavy metal mobility by preferential retention in fine-grained sediment lenses embedded within the coarse aquifer. Several mechanisms contribute to the retention in fine-grained sediments, and we also observe a significant impact of nitrate-rich conditions on the extent and phases of metal retention.
Further, I will share our findings on the dynamic and unique composition of iron-rich colloids, detected in reducing zones of a floodplain subsurface. Our results demonstrate the presence of partially oxidized iron rich colloids in otherwise reducing conditions, thanks to a protective organic-silicon coating. The lifecycle and composition of these colloids may have direct effects on element cycling as they may serve as vectors for the transport of nutrients and organic matter into groundwater and surface water recipients.
Lastly, I will present my future research visions, in a lab devoted to the study of biogeochemical heterogeneity and coupled elemental cycling under dynamic conditions.

Biological systems sense and respond to mechanical forces. The hallmark of a mechano-sensing molecule is a functional switch when subjected to a mechanical force. I will present results on how we have identified, using Molecular Dynamics simulations in conjunction with biophysical experiments, protein molecules and protein-based materials as new candidates for such mechanical switches. These include kinases such as Focal Adhesion Kinase and Src kinase. I will also show how we discovered collagen upon tension to generate mechanoradicals and oxidative stress molecules through scission of chemical bonds. As a source and buffer of oxidative signaling molecules, collagen is not a mere force-carrying material but instead can forward mechanical stimuli to biochemical circuits.