Interdisciplinary PhD in Structural and Computational Biology and Quantitative Biosciences

Melissa Skala

Associate Professor, Department of Biomedical Engineering Lab Website mcskala@wisc.edu(608) 316-4108

3262 Discovery Building
330 N Orchard St
Madison, WI 53715-1119

Education

B.S., Washington State University
M.S., University of Wisconsin – Madison
Ph.D., Duke University

Combating cancer using photonics-based technologies and developing personal cancer treatment strategies

We develop label-free optical imaging technologies and quantitative analysis tools to study metabolic heterogeneity in cancer, stem cell function, and immune cell behavior. Optical metabolic imaging (OMI) uses two-photon fluorescence lifetime microscopy of metabolic co-enzymes (NADH and FAD, Fig. 1) to quantify cell redox state and enzyme-binding activity. This approach is advantageous because fluorophores that are already present in the cells can be used to monitor metabolism with single cell resolution. We have developed OMI alongside image analysis tools and population density models to quantify cellular heterogeneity within intact 3D samples. In parallel, we have developed photothermal optical coherence tomography (PT-OCT) to monitor changes in absorber concentrations in the eye and in tumors. Ongoing projects require active collaborations and mentorship of trainees from diverse backgrounds in medicine, engineering, biochemistry, and biology. Please see publications for a comprehensive view of projects and applications of these technologies.

Figure 1

Fig. 1: NADH and FAD are metabolic co-enzymes involved in numerous reactions in cells. The fluorescence of NADH and NADPH overlap and are collectively denoted as NAD(P)H. The fluorescence intensity and lifetime of NAD(P)H and FAD provide insight into the redox ratio of the cell and enzyme binding activity across hundreds of reactions per cell. The fluorescence intensity and lifetime of NAD(P)H and FAD reflect functional changes in cancer (e.g., EGFR expression), immune cell behavior, and stem cell function.

Areas of Expertise

  • Personalized Medicine
  • Spectroscopy Microscopy Imaging