Possible Rotation Projects:
- How do signals from lung epithelial cells shape macrophage inflammatory behavior? Lung macrophages live in close contact with the epithelial cells lining the air space, and the interactions between these cell types help keep macrophages in a restrained, non-inflammatory state. Potential projects may involve analysis of spatial transcriptomics data to map these interactions within intact lung tissue or setting up epithelial-macrophage co-culture systems to test how cell-cell interactions shape macrophage behavior.
- How do inflammatory signals reprogram macrophage signaling networks? In inflammatory diseases, macrophages are exposed to many signals simultaneously. The complexity of signal integration makes it challenging to identify targetable biochemical pathways driving dysregulated transcriptional programs. Potential projects include stimulating human monocyte-derived macrophages with disease-relevant ligands and measuring signaling and gene expression readouts, contributing to proteomic datasets that support computational modeling of signaling-to-transcription networks.
Training Technologies Used:
- High content imaging, quantitative analysis of macrophage function, and analysis of proteomic and transcriptomic datasets
- 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
Kruszelnicki S.M., Chakraborty S., Wang X., Rehman J., Singh H., Gottschalk R.A. Regulatory network architecture constrains inflammatory responses in tissue-resident alveolar macrophages. bioRxiv. doi: https://doi.org/10.64898/2026.02.16.706134, 2026
Jackson-Strong M.*, Ganguly S.*, Francis F.*, Rago F., Kanshana J., Michalides B.A., Teng L., Betsur O.S., Kruszelnicki S., Shoger K.E., Kim A., Bajpai K., Suleyman A., Sekyere A., Hara M., Sriram V., Kumar A., Delgoffe G.M., Natarajan N., Alcorn J.F., Kohan A.B., Gottschalk R.A. GATA2 controls alveolar macrophage inflammatory gene expression and metabolic function. JCI Insight, In Press. 10.1172/jci.insight.196246, 2026 *co-first authors
Cheemalavagu N, Shoger KE, Cao YM, Michalides BA, Botta SA, Faeder JR, Gottschalk RA. Predicting gene level sensitivity to JAK-STAT signaling perturbation using a mechanistic-to-machine learning framework. Cell Syst. Jan 17;15(1):37-48, 2024
Gottschalk R.A. Signaling is the pathway to macrophage function. Trends Immunol. May 29;S1471-4906(23)00080-7, 2023
Myers S.A., Gottschalk R.A. Mechanisms encoding STAT functional diversity for context-specific inflammatory responses. Curr. Opin. Immunol. Feb;74:150-155, 2022
Shoger K.E., Cheemalavagu N., Cao Y.M., Michalides B.A., Chaudhri V.K., Cohen J.A., Singh H., Gottschalk R.A. CISH attenuates homeostatic cytokine signaling to promote lung-specific macrophage programming and function. Sci Signal. 14(698):eabe5137, 2021
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
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
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
Understanding how extracellular cues are linked to gene expression is a fundamental challenge in biology, and more specifically, innate immune signal integration is central to understanding healthy versus aberrant regulation of inflammation. My laboratory uses quantitative approaches to address these problems, with major projects including (1) computational modeling of signaling-to-transcription in macrophages, (2) interrogating tissue-specific macrophage signaling, and (3) dissecting molecular determinants of monocyte and macrophage inflammatory function. We use experimental approaches, together with both data-driven and mechanistic modeling to integrate transcription factor activity, phosphorylation, and transcriptomic data to explore signaling mechanisms that shape stimulus-specific macrophage function. These efforts will yield insights into dysregulation of signaling and inflammation, while informing therapeutic strategies.
