Our research focuses on the development of vibrational spectroscopy, specifically spontaneous Raman scattering, as a new route to uncovering functional and molecular changes that unfold in the tumor and its microenvironment. Defining cancer in biomolecular, rather than morphological, terms has two major implications: first, it facilitates clinically relevant tumor characterization for precision diagnosis; and second, it represents an outstanding opportunity to refine the therapeutic regimen chosen for a particular cancer. Our approach features label-free Raman spectroscopic mapping, a protocol that focuses simultaneously on multiplexed molecular changes in the tumor and its microenvironment, and data analysis of frequent patterns in molecular expression. This non-perturbative, non-ionizing approach could transform the areas of radiation oncology and immuno-oncology to guide personalized treatment.

Single cell analysis has become particularly important in the mechanistic elucidation of biological functions considering the emerging consensus of cellular heterogeneity even within an isogenic cell population. Cellular heterogeneity, however, is missed by population analysis as classical methods only reports the mean expression levels of a bulk cell population. Furthermore, snapshot analyses confound different dynamic behaviors. Flow cytometry, for instance, can reveal cellular heterogeneities but cannot detect the underlying dynamics. What is warranted is new strategies for continuous, single-cell analysis. Our vision is to create a 3D self-assembling platform for following and predicting a cell’s behavior and function over time.

To perform their myriad functions, cells experience and modulate a broad range of entwined intra- and extracellular events. Many of the interactions are shaped by mechanical forces and fields at the micro and nanoscale, which are transduced into a cascade of biochemical signals ultimately leading to precise biological responses, notably changes in cell membrane activity, alterations in protein synthesis and modified cell morphology. Regulation and coordination of cell shapes, movement and division are central to the ‘native’ physiology during all stages of organismal existence. On the other hand, mis-regulation of intrinsic mechanical attributes can lead to aberrant changes in key cellular functions, including migration, proliferation and differentiation, leading to difficult-to-treat diseases. Over the past three decades, poking, prodding and squishing cells have fundamentally shaped our understanding of the critical role of mechanochemistry in diverse pathophysiological niches. Our lab develops tools to resolve the role of geometry, mechanical forces and, importantly, the interaction of mechanics with biochemical signaling at the nanoscale.

The thought of visualizing dynamic events in live cells may have once seemed like science fiction, but recent advances in optical imaging and contrast agent development have revealed cellular features and processes with previously unimagined detail. New super-resolution imaging techniques have broken the diffraction limit offering glimpses of a new reality where video-rate imaging with molecular resolution is possible. While the bulk of attention has been focused on exploiting fluorescent probes, surface plasmons provide an intriguing complementary route towards nano-imaging of biological samples in unperturbed natural conditions. Although spontaneous Raman spectra offers rich label-free information and unequivocal detection without quenching concerns, the probability of the Raman process is much smaller than that of fluorescence owing to the second-order optical process involved. Field enhancement is, thus, of key significance in Raman scattering and has transformed surface-enhanced Raman scattering (SERS) into a potent analytical tool by virtue of its near single-molecule sensitivity. Our laboratory engineers multi-functional theranostic nanoprobes for in vivo SERS imaging and nanostructured substrates that form the basis of ultrasensitive in vitro assays for disease screening.