Education & Training
- B.S., Biology, Emory University-2005
- Ph.D.,Immunology, Weill Cornell Graduate School of Medical Sciences-2012
- Post-doctoral Fellowship, Laboratory of Systems Biology, NIAID, NIH
Research Interest Summary
Our lab uses quantitative approaches to understand how cells process stimuli to determine the appropriate functional response. Identifying the receptors, kinases, and transcription factors that make up signaling pathways is necessary but not sufficient to predict how a cell will respond. Context-dependent factors, such as tissue-specific stimuli, age, or genetic traits, can cause small variations in signaling components. These changes may tune the sensitivity of cells to stimuli, setting the threshold for a functional response and influencing susceptibility to disease.
The major focus of our lab is understanding context-specific macrophage signaling and function. One such context is the tissue-specific tuning of macrophage signaling at barrier sites, where macrophages face ongoing exposure to the microbiota. These efforts involve modeling how lung-specific homeostatic cytokines impact regulation of macrophage signaling and gene expression, and investigation of novel signaling regulators that are highly expressed in the lung, but not other tissues. Current projects also include interrogating the influence of aging on monocyte and macrophage signaling sensitivity and response dynamics. Specifically, we are investigating whether monocytes from young and old humans or mice have distinct potential for functional polarization, in vitro and in mouse models of inflammation and resolution. We hope our efforts will bring us closer to predicting inflammatory response regulation based on context-specific gene expression, informing tissue-specific and age-specific therapeutic strategies.
Gottschalk R.A.*#, Dorrington M.G.*, Dutta B., Krauss K.S., Martins A.J., Uderhardt S., Chan W., Tsang J.S., Torabi-Parizi P., Fraser I.D., Germain R.N.#. IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses. eLIFE. 2019;8:e46836, 2019 *co-first authors, #co-corresponding authors.
Oh K.S.*, Gottschalk R.A.*#, Lounsbury N.W.*, Sun J., Dorrington M.G., Baek S., Sun G., Wang Z., Krauss K.S., Milner J.D., Dutta B., Hager G.L., Sung M.H., Fraser I.D.# Dual roles for Ikaros in regulation of macrophage chromatin state and inflammatory gene expression. J. Immunol. 201(2):757-771, 2018 *co-first authors, #co-corresponding authors.
Oh K.S., Patel H., Gottschalk R.A., Lee W.S., Baek S., Fraser I.D., Hager G.L., Sung M.H. Anti-inflammatory chromatinscape suggests alternative mechanisms of glucocorticoid receptor action. Immunity. 47(2):298-309, 2017.
Martins A.J., Narayanan M., Prüstel T., Fixsen B., Park K., Gottschalk R.A., Lu Y., Pfannkoch C., Lau W.W., Wendelsdorf K.V., Tsang J.S. Environment tunes propagation of cell-to-cell variation in the human macrophage gene network. Cell Syst. 4(4):379-392, 2017.
Gottschalk R.A.#, Martins A.J., Angermann B.R., Dutta B., Ng C.E., Uderhardt S., Tsang J.S., Fraser I.D., Meier-Schellersheim M., Germain R.N.# Distinct NF-kB and MAPK activation thresholds uncouple steady-state microbe sensing from anti-pathogen inflammatory responses. Cell Syst. 2(6): 378-90, 2016 #co-corresponding authors.
Sung M.H., Li N., Lao Q., Gottschalk R.A., Hager G.L., Fraser I.D. Switching of the relative dominance between feedback mechanisms in lipopolysaccharide-induced NF-kB signaling. Sci Signal. 7(308): ra6, 2014.
Gottschalk R.A.*, Martins A.J.*, Sjoelund V.H., Angermann B.R., Lin B., Germain R.N. Recent progress using systems biology approaches to better understand molecular mechanisms of immunity. Semin Immunol. Pii: S1044-5323(12), 2012 *co-first authors.
Gottschalk R.A., Corse E., Allison J.P. Expression of Helios in peripherally induced Foxp3+ regulatory T cells. J Immunol. 188(3): 976-980, 2012.
Gottschalk R.A., Hathorn M.M., Beuneu H., Corse E., Dustin M.L., Altan-Bonnet G., Allison J.P. Distinct influences of peptide-MHC quality and quantity on in vivo T cell responses. Proc Natl Acad Sci. 109(3): 881-886, 2012.
Gottschalk R.A., Corse E., Allison J.P. TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo. J Exp Med. 207(8): 1701-11, 2010.