Nancy L. Allbritton
Paul Debreczeny Distinguished Professor
Department of Chemistry
M.D., Medicine
Johns Hopkins University, Baltimore, MD
Ph.D., Medical Physics/Medical Engineering
Massachusetts Inst. of Tech., Cambridge, MA
Biosketch [.pdf]
Chemistry Department
Lineberger Comprehensive Cancer Center
Research Interests
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Microanalytical separation techniques to study cell signaling
Development of synthetic chemical reporters of enzyme activity
Microfabricated platforms for cell manipulation and analysis
Microfluidic systems for cell analysis
Research Synopsis
Profiling cellular signal transduction networks
A major focus of research addresses quantitative measurements of the
enzymatic activity of signal transduction proteins in cells. A powerful
chemical cytometry method for biochemical assays has been pioneered by
the laboratory that enables the activity of one or more enzymes to be
measured simultaneously in a single cell. This technology is unique in
both enabling the measurement of multiple enzymes and its applicability
to primary cells obtained directly from organisms and patients. An
important aspect of the system is the development of sampling techniques
that enable single mammalian cells of picoliter volumes to be rapidly
lysed and efficiently loaded into the analysis device. Cell lysis in
millisecond timescales has been achieved by both laser and electrical
means. This feature is required in many assays to immediately terminate
biochemical reactions, thus preventing measurement artifacts resulting
from the sampling process. The assay strategy is applicable to a broad
range of intracellular enzymes, including kinases, phosphatases,
proteases, and lipid metabolic enzymes. A significant ongoing effort in
this regard is the design and validation of enzyme substrates that can
be taken up by cells or expressed, and act as faithful intracellular
indicators of the enzyme activity of interest.
Microfluidics
Microfluidic technologies for biochemical assays require solutions to
fundamental issues in analytic chemistry and micro-systems engineering
to successfully carry out analyses of intracellular biochemical reactions
using this “lab-on-a-chip” technology. Challenges related to sampling
human tumor cells and performing high-throughput chemical separations on
glass-based devices are being met through a long-standing collaboration
with Dr. J. Michael Ramsey here at UNC. This work has been funded by the
NIH since 1998 to develop a device for profiling human tumor cells for
upregulated kinase activity. Applications of these glass microfluidic
devices are expected to be in areas requiring high-throughput, high
quality separations, for example, screening large numbers of cells for
inhibition of enzymatic activity in response to candidate pharmaceutical
compounds. A collaborative effort with investigators at UC Irvine is
targeted towards the development of polymer-based devices and integrated
micro-systems. One aspect of this work is focused on the development of
an inexpensive, disposable device for clinical applications, for example
profiling drug sensitivities of a patient's tumor cells to the new
generation of kinase-inhibiting, chemotherapeutic agents.
Micropallet Arrays for Cell Sorting
Another line of research is the development of integrated platforms for
positive selection and isolation of adherent cells and for
high-throughput biochemical assays of adherent cells. A new technology
for cell sorting has been developed that is comprised of a transparent
array formed from pedestals of micron dimensions, termed micropallets,
on which cells are cultured. A distinctive feature is that the individual
micropallets and their attached cells can be released from the array using
a laser and collected with very high rates of cell viability. By means
of the micropallet array, cells can be selected based on a large number
of attributes including morphology, fluorescence, dynamic traits (e.g.,
growth rate) and the transmission of properties to daughter cells. The
cell arrays have been used for a variety of purposes including single-cell
and colony sorting and rapid cloning of stably transfected cells. A
number of collaborations are ongoing in the further development and
application of this new cell sorting technique.
Recent Publications
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Phillips, K.S., Kottegoda, S., Kang, K.M., Sims, C.E., Allbritton, N.L. (2009) Separations
in poly(dimethylsiloxane) microchips coated with supported bilayer membranes. Anal
Chem 80: 9756–9762 [epub ahead of print]. Abstract
Shadpour, H., Sims, C.E., Thresher, R.J., Allbritton, N.L. (2009) Sorting and expansion of
murine embryonic stem cell colonies using micropallet arrays. Cytometry A 75A:121-129
[epub ahead of print]. Abstract
Lai, H.-H, Quinto-Su, .PA., Sims, C.E., Bachman, M., Li, G.P., Venugopalan, V.,
Allbritton, N.L. (2008) Characterization and use of laser-based lysis for cell analysis
on-chip. J R Soc Interface 5: Suppl 2: S113-21. Abstract
Quinto-Su, P.A., Salazar, G.T., Sims, C.E., Allbritton, N.L., Venugopalan, V. (2008)
Mechanism of Pulsed Laser Microbeam Release of SU-8 Polymer Micropallets for the
Collection and Separation of Adherent Cells. Anal Chem 80: 4675-4679. Abstract
Borland, L.M., Allbritton, N.L. (2008) Use of micellar electrokinetic chromatography to
measure palmitoylation of a peptide. J Chromatogr B Analyt Technol Biomed Life Sci
875: 451-458. Abstract
Wang, Y., Salazar, G., Pai, J.-H., Sims, C.E., Allbritton, N.L. (2008) Micropallet arrays
with poly(ethylene glycol) walls. Lab Chip 8: 734-740. Abstract
Kottegoda, S., Aoto, P.C., Sims, C.E., Allbritton, N.L. (2008) The
Biarsenical-Tetracysteine Motif as a Fluorescent Tag for Detection in Capillary
Electrophoresis. Anal Chem 80: 5358-5366. Abstract
Marc, P.J., Sims, C.E., Bachman, M., Li, G.P., Allbritton, N.L. (2008) Fast-lysis cell traps
for chemical cytometry. Lab Chip 8: 710-716. Abstract
Salazar, G., Wang, Y., Bachman, M., Sims, C.E., Li, G.P., Allbritton, N.L. (2008)
Characterization of the laser-based release of micropallets from arrays. J Biomed Optics
13: 034007. Abstract
Lee, K.J., Mwongela, S.M., Kottegoda, S. Borland, L., Nelson, A.R., Sims, C.E.,
Allbritton, N.L. (2008) Determination of sphingosine kinase activity for cellular signaling
studies. Anal Chem 80: 1620-1627. Abstract
Quinto-Su, P.A., Lai, H.-H., Yoon, H.H., Sims, C.E., Allbritton, N.L., Venugopalan, V.
(2008) Examination of laser microbeam cell lysis in a PDMS microfluidic channel using
time-resolved imaging. Lab Chip 8: 408-414. Abstract
Nelson, A.R., Borland, L., Allbritton, N.L., Sims, C.E. (2007) Myristoyl-based transport
of peptides into living cells. Biochemistry 46: 14771-14781. Abstract
Fernandes, N., Bailey, D.E., Vanvranken, D.L., Allbritton, N.L. (2007) Use of docking
peptides to design modular substrates with high efficiency for mitogen-activated protein
kinase extracellular signal-regulated kinase. ACS Chem Biol 2: 665-73. Abstract
Marc, P.J., Sims, C.E., Allbritton, N.L. (2007) Coaxial flow system for chemical
cytometry. Anal Chem 79: 9054-9059. Abstract
Contact Information
Office Location:
241 Chapman Hall
Mailing Address:
CB # 3216
UNC-CH Dept. of Chemistry
Chapel Hill, NC 27599-3216
Office Phone: 919-966-2291
Lab Phone: 919-962-8682
Fax: 919-962-2388
nlallbri@unc.edu