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Richard B. Jones, Ph.D.
Focused Systems-Level Analyses of Cellular Signal
Transduction
Research Summary
In
order for living creatures to progress from single cells to
multi-cellular tissues, organs, and ultimately to whole organisms, they
must utilize complex autocrine, paracrine, and endocrine communication
mechanisms that we are only beginning to understand at the molecular
level. While large scale analyses of cellular, tissue-level, and
whole
organism gene expression patterns have been performed in a scalable,
systematic, and high-throughput manner with the DNA microarray and
other platforms, the analysis of dynamic protein signaling networks has
proven a much greater technological challenge. At one extreme,
cell
biologists have examined total protein abundance and post-translational
modification state from whole cells and tissues while at the other
extreme biochemists and biophysicists have studied how a single
post-translational modification can give rise to a change in protein
structure and function. The focus of our laboratory lies at the
interface between these extremes and is the result of the belief that
the use of technological approaches at the interface of scientific
disciplines and scales will result in paradigm-shifting systems-level
insights into fundamental biological processes and will simultaneously
result in the development of tools with wide ranging applicability to
cancer and other clinically relevant biology.
Toward
this end, we are utilizing protein micro-array, mass spectrometric, and
cell biological tools to query both the theoretical biophysical nature
of protein-protein interaction connectivity as well as the dynamics of
cellular protein abundance, post-translational modification, and
interaction connectivity. We are focusing our efforts primarily
on
those interactions and modifications that would not be easily addressed
using traditional yeast two hybrid methodologies. Our goal is to
gain
a better understanding of the modular signaling molecules whose
location, abundance, and modification state underlie cell growth,
migration, differentiation, and cell death: These processes lie at the
heart of cancer biology and an understanding of these processes at the
molecular level should enable the identification of many new
therapeutic targets.
We are very interested in
receiving applications from motivated students and postdoctoral
researchers who wish to work at the interface of Biology, Chemistry,
Physics, and Mathematics to better understand the signal transduction
mechanisms that result in cancer, diabetes, and other human disease.
Selected Papers
Yu C, Wang F, Kan M, Jin C, Jones RB, Weinstein M,
Deng CX, McKeehan WL. (2000). Elevated Cholesterol Metabolism and
Bile Acid Synthesis in Mice Lacking Membrane Tyrosine Kinase Receptor
FGFR4. Journal of Biological Chemistry. 275:15482-15489.
Jones RB, Wang F, Luo Y, Yu C, Jin C, Suzuki T, Kan
M, McKeehan WL. (2001). The Nonsense-Mediated Decay Pathway and
Mutually Exclusive Expression of Alternatively Spliced FGFR2IIIb and
IIIc
mRNAs. Journal of Biological Chemistry. 276:4158-4167.
Jones RB, Carstens RP, Luo Y, McKeehan WL. (2001). 5'- and
3'-terminal Nucleotides in the FGFR2 ISAR Splicing Element Core Have
Overlapping Roles in Exon IIIb Activation and Exon IIIc Repression.
Nucleic Acids Research. 29:3557-3565.
Ye S, Luo Y, Lu W, Jones RB, Linhardt RJ, Capila I,
Toida T, Kan M, Pelletier H, McKeehan WL. (2001). Structural Basis
for Interaction of FGF-1, FGF-2, and FGF-7 with Different Heparan
Sulfate
Motifs. Biochemistry 40:14429-14439.
Jones RB, Gordus AG, Krall J, MacBeath G. (2006). A
Quantitative Protein Interaction Network for the ErbB Receptors Using
Protein Microarrays. Nature. 439(7073):168-74.
Newman EA, Muh SJ, Hovhannisyan RH, Warzecha CC, Jones RB, McKeehan WL
and Carstens RP. (2006). Identification of
RNA-binding proteins that regulate FGFR2 splicing through the use of
sensitive and specific dual color fluorescence minigene assays. RNA.
12:
1129-1141.
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