Jennifer Kavran
Hippo signaling & protein kinases
Associate Professor
Program Advisor for Student Matters
Department of Biochemistry and Molecular Biology
Bloomberg School of Public Health
Research Overview
The Kavran lab studies the molecular mechanisms that control signaling pathways with a focus on protein kinases. We are a multi-disciplinary lab, using a combination of structural biology, structural bioinformatics, biophysics, enzymology, biochemistry, and cell biology to answer these questions. Our recent work has focused on using the Hippo pathway as a model system to dissect protein kinase regulation. Hippo signaling controls organ size during development, helps maintain the stem cell niche, and can function as a tumor-suppressor. The core activity of this pathway is controlled by a kinase cassette (comprised of the kinases MST1/2 and LATS1/2) that repress the activity of the transcriptional cofactors YAP/TAZ. Our work has helped resolve how different upstream signals can activate the Hippo pathway kinase MST1/2, how its activity is regulated by different protein:protein interactions, and explored the contribution of phase separation to signal transduction. We are currently exploring other aspects of Hippo pathway regulation including its dysregulation in specific cancer contexts and developing tools to modulate Hippo pathway activity. Additionally our interests have expanded to include other members of the human kinome and we are always open to exploring the next exciting new research direction.
Simply, we want to understand how cells communicate with each other, their environment, and how they respond to that information so to understand how mutations or drugs can change these events in both healthy and diseased cells.
Selected Publications
- Weingartner KA, Tran T, Tripp KW, Kavran JM. Dimerization and autophosphorylation of the MST family of kinases are controlled by the same set of residues. The Biochemistry Journal, 2023.
- Koehler TJ, Tran T, Weingartner KA, Kavran JM. Kinetic Regulation of the Mammalian Sterile 20-like Kinase 2 (MST2). Biochemistry, 2022.
- Tran T, Mitra J, Ha T, Kavran JM. Increasing kinase domain proximity promotes MST2 autophosphorylation during Hippo signaling. Journal of Biological Chemistry, 2020. Selected as an Editor’s Pick.
- Cairns L, Patterson A, Weingartner KA, Koehler TJ, DeAngelis DR, Tripp KW, Bothner B, Kavran JM. Biophysical characterization of SARAH domain-mediated multimerization of Hippo pathway complexes in Drosophila. Journal of Biological Chemistry, 2020.
- Cairns L, Tran T, Fowl BH, Patterson A, Kim YJ, Bothner B, Kavran JM. Salvador has an extended SARAH domain that mediates binding to Hippo kinase. Journal of Biological Chemistry, 2018.
- Kavran JM, McCabe JM, Byrne PO, Connacher MK, Wang Z, Ramek A, Sarabipour S, Shan Y, Shaw DE, Hristova K, Cole PA, Leahy DJ. How IGF-1 activates its receptor. eLife, 2014.