Andreas Herrlich, M.D., Ph.D.

Associate Professor
Internal Medicine
Nephrology

Molecular Cell Biology Program

  • 314 747-0565

  • aherrlich@wustl.edu

  • www.herrlichlab.org

  • We aim to identify cellular and molecular mechanisms in the novel and rapidly expanding field of interorgan crosstalk in health and disease.

Research Abstract:

To date diseases have mostly been modeled and studied from a single organ focused approach. Today novel technologies such as single-cell RNAseq and "omics"-technologies enable us to take a broader view and study relationships between organs in health and disease. These relationships are frequently very critical for clinical outcomes and are poorly understood.

Acute or chronic kidney injury causes morbidity and mortality primarily due to its secondary complications: acute lung injury and cardiovascular disease (remote injury). However, kidney disease effects almost any organ, including for example bone, brain, liver, gut and the microbiome. These effects are in part related to a systemic inflammatory response syndrome (SIRS), similar to what is induced by COVID-19, and involves activation of immune cells in organs remote to the primary injury. Therapeutic strategies to prevent secondary organ damage are severely lacking.

Currently we are particularly interested in the KIDNEY-LUNG and KIDNEY-HEART axis and in kidney-released factors that drive deleterious interorgan crosstalk. We established mouse models of acute kidney injury-induced acute lung injury and of acute kidney injury or chronic kidney disease complicating heart failure, three common clinical scenarios with high morbidity and mortality. We recently identified novel kidney released mediators of acute lung injury that we are studying mechanistically.

Our approaches include a combination of in vivo and in vitro studies, using novel genetically-engineered mouse models, shRNA, siRNA, CRISPR-Cas9, functional genomics, single-cell or single-nucleus RNAseq and their computational analysis, as well as clinical specimens and targeted therapeutics.

Selected Publications:

Kefaloyianni E., Raja Keerthi Raja M., Schumacher J., Muthu ML., Krishnadoss V., Waikar SS, Herrlich A (2019) Proximal tubule-derived amphiregulin amplifies and integrates profibrotic EGFR signals in kidney fibrosis. Journal of the American Society of Nephrology, 2019 Dec;30(12):2370-2383. doi: 10.1681/ASN.2019030321.

Chang-Panesso M., Kadyrov F.F., Lalli M., Wu H., Ikeda S., Kefaloyianni E., Abdelmageed M.M., Herrlich A., Kobayashi A. and Humphreys B.D. (2019) FOXM1 drives proximal tubule proliferation during repair from acute ischemic kidney injury. Journal of Clinical Investigation 2019;129(12):5501-5517. https://doi.org/10.1172/JCI125519.

Kefaloyianni E, Muthu LM, Kaeppler J, Sun X, Sabbisetti V, Chalaris A, Rose-John S, Wong E, Sagi I, Waikar SS, Rennke H, Humphreys BD, Bonventre JV., Herrlich A. (2016) ADAM17 substrate release in proximal tubule drives kidney fibrosis. Journal of Clinical Investigation Insight, 18;1(13). pii: e87023; PMID: 27642633.

Parra L., Hartmann M., Schubach S., Yong L., Herrlich P*. and Herrlich A*. (2016) Growth factor and co-receptor release by structural regulation of substrate metalloprotease accessibility. Scientific Reports, accepted November 2016, DOI: 10.1038/srep37464. *co-senior authors.

Parra L., Hartmann M., Schubach S., Yong L., Herrlich P. and Herrlich A. (2015) Distinct ICD substrate modifications selectively regulate ectodomain cleavage of NRG1 or CD44. Molecular and Cellular Biology; PMID: 26217011.

Hartmann, M., Parra, L. M., Ruschel, A, Behme, S., Li, Y., Morrison, H., Herrlich, A.*, and Herrlich, P.* (2015) Tumor Suppressor NF2 Blocks Cellular Migration by Inhibiting Ectodomain Cleavage of CD44. Molecular Cancer Research : MGR, PMID: 25652588. *co-senior authors. Featured on the AACR "Must Read List" 2015.

Hartmann, M., Parra, L. M., Ruschel, A, Lindner, C., Morrison, H., Herrlich, A.*, and Herrlich, P*. (2015) Inside-out Regulation of Ectodomain Cleavage of Cluster-of-Differentiation-44 [CD44] and of Neuregulin-1 requires Substrate Dimerization. The Journal of Biological Chemistry, PMID: 25925953. *co-senior authors.
"JBC Paper of the week" and "JBC Paper of the Year 2015" in the Signal Transduction Category

Last Updated: 3/18/2021 11:06:14 AM

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