(4ei) Characterization of Human Diseases At Single Cell Level for Therapeutic and Diagnostic Applications

Authors: 
Wu, P. H., Johns Hopkins University



My research interests focus on the application of engineering and physics principles to decipher mechanisms of disease and normal cell functions at the molecular and cellular levels. I received my Ph.D. in Chemical Engineering from the University of Florida. My doctoral research focused on the quantitative characterization of cellular and subcellular dynamics. I improved resolution in particle tracking nanorheology, which allowed me to investigate the association between cell mechanics and cancer progression. During my postdoctoral work with Prof. Denis Wirtz at the Johns Hopkins University I extended this research direction to develop a systematical approach to identifying biophysical signatures cell subpopulations, specifically of metastatic cancer cells. In 2012, I received a postdoctoral fellowship award from the American Heart Association.

As an independent investigator, I plan to apply this new approach to continue the development of novel single cell analysis tools that can be effectively applied toward deciphering complex human diseases in a high-throughput context. I will integrate the extracted single-cell information into the flow of information in biological systems: genetics, epigenetics, environmental inputs, and, finally, appearance and behavior. Together, this data will complete the roadmap to understand disease mechanism. My ultimate research goals are to translate in-depth understanding of disease mechanisms into an effective and novel platform for drug discovery and a predictive model to improve diagnosis and prognosis. 

The proposed research described below combines my previous expertise in cell biology and cell mechanics/motility with state-of-the-art analytical techniques, such as high throughput cell phenotyping, to identify and characterize disease mechanisms. I plan to pursue projects in the following three areas: 1) Dynamic process of cell functions and cell phenotypes. 2) Analysis of cancer metastasis using quantitative cell mechano-phenotyping. 3) Molecular mechanisms of cancer cell mechanics in vivo. These three topics integrate biology, machine vision, and multivariate system analysis algorithms. Cumulatively, these researches will provide innovative approaches for understanding health and disease problems.

Selected Publications (14 total, first/co-first author in 6 papers)

  1. W.C. Chen, P.H. Wu, J.M. Phillip, S.B. Khatau, J.M. Choi, M.R. Dallas, K. Konstantopoulos, S.X. Sun, J.S.H. Lee, D. Hodzic, D. Wirtz, “Functional interplay between cell cycle and cell phenotypes”, Integrative biology (2013) DOI: 10.1039/C2IB20246H.
  2. P.H. Wu, C.M. Hale, W.C. Chen, J.S.H. Lee, Y. Tseng, and D. Wirtz, “High-throughput ballistic injection nanorheology (htBIN) to measure cell mechanics”, Nature Protocols 7 (2012) 155-170.
  3. P.H. Wu, S.H. Hung, T. Ren, I. M. Shih, Y. Tseng, “Cell cycle dependent alteration in nucleus accumbens associated protein-1 (NAC-1) nuclear body dynamics and morphology” Physical Biology 8 (2011) 015005.
  4. P.H. Wu, A. Agarwal, H. Hess, P.P. Khargonekar, Y. Tseng, “Analysis of video-based microscopic particle trajectories using Kalman filtering”, Biophysical Journal 98 (2010) 2822-2830.
  5. P.H. Wu, N. Nelson, Y. Tseng, “A general method for improving spatial resolution by optimization of electron multiplication in CCD imaging”, Optics express 18 (2010) 5199-5212.