The Baird research laboratory integrates a broad range of experimental approaches to investigate molecular mechanisms of receptor-mediated cell signaling that enables cells to sense and respond to environmental cues. Much of our work has focused on the high affinity receptor (FcεRI) for immunoglobulin E (IgE), which sensitizes mast cells to antigen and thereby plays a pivotal role in initiating inflammatory and allergic immune responses. We employ quantitative microscopy and other biophysical methods to monitor changes in the distributions and dynamics of receptors and signaling components that accompany cellular response activities, which we measure in parallel. A particular area of interest is the role of cellular membranes in regulating and targeting signaling pathways. We have long worked to characterize IgE-FcεRI- mediated signaling in RBL mast cells as a model system for addressing fundamental questions of cellular response mechanisms initiated by other receptors and environmental factors. Similarly, we are translating the experimental techniques and cell response concepts developed in our work to elucidate mechanisms in other cell types, including those involved in cancer and neurodegenerative diseases.
Bag, Nirmalya, D. Holowka, B. Baird. 2019. Imaging FCS Delineates Subtle Heterogeneity in Plasma Membranes of Resting Mast Cells. bioRcivRamezani, M., M.M. Wilkes, T. Das, D. Holowka, D. Eliezer and B. Baird. 2019. Regulation of exocytosis and mitochondrial relocalization by Alpha-synuclein in a mammalian cell model. npj Parkinson’s Disease 5(1): 1-17Mitra, E.D., S.C. Whitehead, D. Holowka, B. Baird and J.P. Sethna. 2018. Computation of a Theoretical Membrane Phase Diagram and the Role of Phase in Lipid-Raft-Mediated Protein Organization. J. Phys. Chem. B 122(13): 3500-3513Wakefield, D.L., D. Holowka and B. Baird. 2017. The FceRI signaling cascade and integrin trafficking converge at patterned ligand surfaces. Mol. Biol. Cell 28(23): 3383-3396Korzeniowski, M.K., E. Wisniewski, B. Baird, D.A. Holowka and T. Balla. 2017. Molecular anatomy of the early events in STIM1 activation - oligomerization or conformational change? J. Cell Sci. 130(17): 2821-2832Holowka, D. and B. Baird. 2017. Mechanisms of epidermal growth factor receptor signaling as characterized by patterned ligand activation and mutational analysis. Biochimica et Biophysica Acta – Biomembranes 1859: 1430-1435Shelby, S.A., S.L. Veatch, D.A. Holowka and B.A. Baird. 2016. Functional nanoscale coupling of Lyn kinase with IgE-FcεRI is restricted by the actin cytoskeleton in early antigen-stimulated signaling. Mol. Biol. Cell 27(22): 3645-3658Sun, C., D.L. Wakefield, Y. Han, D.A. Muller, D.A. Holowka, B.A. Baird and W.R. Dichtel. 2016. Graphene Oxide Nanosheets Stimulate Ruffling and Shedding of Mammalian Cell Plasma Membranes. Chem 1(2): 273-286Wilson, J.D., S.A. Shelby, D. Holowka and B. Baird. 2016. Rab11 Regulates the Mast Cell Exocytic Response. Traffic 17(9): 1027-1041Holowka, D. and B. Baird. 2016 Roles for lipid heterogeneity in immunoreceptor signaling Biochimica et Biophysica Acta 1861(8): 830-836Singhai, A., D.L. Wakefield, K.L. Bryant, S.R. Hammes, D. Holowka and B. Baird. 2015. Spatially Defined EGF Receptor Activation Reveals an F-Actin-Dependent Phospho-Erk Signaling Complex. Biophys. J. 107(11): 2639-2651.Holowka, D. and B. Baird. 2015. Nanodomains in Early and Later Phases of FcεRI Signaling. Essays in Biochemistry: Membrane Nanodomains; Vol. 57, pp. 147-163.Kelly, C.V., D.L. Wakefield, D.A. Holowka, H.G. Craighead and B.A. Baird. 2014. Near-Field Fluorescence Cross-Correlation Spectroscopy on Planar Membrane. ACS Nano 8(7): 7392-7404.Wilkes, M.M., J.D. Wilson, B. Baird and D. Holowka. 2014. Activation of Cdc42 is Necessary for Sustained Oscillations of Ca2+ and PIP2 Stimulated by Antigen in RBL Mast Cells. Biology Open 3(8): 700-710.Chylek, L.A., D.A. Holowka, B.A. Baird and W.S. Hlavacek. 2014. An interaction library for the FcεRI signaling network. Front. Immunol. 5: 172.Welch, M. Elizabeth, N.L. Ritzert, H. Chen, N.L. Smith, M.E. Tague, Y. Xu, B.A. Baird, H.D. Abruña and C.K. Ober. 2014. Generalized Platform for Antibody Detection using the Antibody Catalyzed Water Oxidation Pathway. J. Am. Chem. Soc. 136(5): 1879-1883.Shelby, S.A., D. Holowka, B. Baird and S.L. Veatch. 2013. Distinct Stages of Stimulated FcεRI Receptor Clustering and Immobilization Are Identified through Superresolution Imaging. Biophys. J. 105(10): 2343-2354.Bryant, K.L., M.A. Antonyak, R.A. Cerione, B. Baird and D. Holowka. 2013. Mutations in the Polybasic Juxtamembrane Sequence of Both Plasma Membrane- and Endoplasmic Reticulum-localized Epidermal Growth Factor Receptors Confer Ligand-independent Cell Transformation. J. Biol. Chem. 288(48): 34930-34942.Veatch, S.L., B.B. Machta, S.A. Shelby, E.N. Chiang, D.A. Holowka and B.A. Baird. 2012. Correlation Functions Quantify Super-resolution Images and Estimate Apparent Clustering Due to Over-counting. PLoS One 7(2): e31457.Veatch, S., E. Chiang, P. Sengupta, D. Holowka and B. Baird. 2012. Quantitative Nano-Scale Analysis of IgE-FcεRI Clustering and Coupling to Early Signaling Proteins. J. Phys. Chem. B. 116(23): 6923-6935.
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