Biomedical Engineering Reference
In-Depth Information
number of atoms of the tag introduced. Accordingly, using elemental standards, it
might become routine to measure the absolute number of atoms per cell, regardless of
the number of metal isotopes used. Again, such attributes should greatly enhance
cytometry-based clinical assays, drug screening panels, and overall assessment of
regulatory phosphorylation at the single-cell level.
15.7.4 Future of Mass Cytometry
The traditional three to five color fluorescence flow cytometer helped define the
major cell subsets of the immune system that we understand today (T cells, B cells,
macrophages, among others). Eight-color machines brought characterization of
even more rare immune subsets and stem cells, leading to advances in stem cell
biology and cancer stem cell characterization. Merging this capability with in-
tracellular staining, 11-15 color analysis provided by state-of-the-art instruments
allowed analysis of regulatory signaling networks, drug design/screening, and
patient stratification of clinical and drug response outcomes. Given this, the new
generation of mass cytometry instrumentation will likely drive an unparalleled
revolution in the understanding of hematologic processes—both in mapping
biological mechanisms in normal human development and disease processes that
impacttheimmunesystem.
15.8 SUMMARY
What has become evident during our work is that drug discovery and patient treatment
should best be viewed as a cyclic process. Analyzing diseased patient samples tells us
much about the complexity of disease, how it affects particular groups of signaling
pathways, sets of cell types, and the time dependence of certain features. Analyzing
the effects of many compounds on signaling pathways in primary cell samples shows
patterns of druggability. When both these aspects are coupled, a more thorough
understanding of signaling networks emerges and more effective therapies can be
developed. For instance, a target may be identified from patient samples, but this
target may be known to be undruggable based on prior screening efforts. By under-
standing the repertoire of druggable targets and matching those to potential disease-
specific targets, drug discovery will become more effective and rapid and treatments
will be individualized.
REFERENCES
1. Krutzik PO, Irish JM, Nolan GP, Perez OD. Analysis of protein phosphorylation and
cellular signaling events by flow cytometry: techniques and clinical applications. Clin.
Immunol. 2004;110:206-221.
2. Clutter MR, Krutzik PO, Nolan GP. Phospho-specific flow cytometry in drug discovery.
Drug Discov. Today 2005;2:295-302.
Search WWH ::
Custom Search