Jennifer Kavran Lab
Investigating how cells communicate with each other and their environment
About the Kavran Lab
The Kavran Lab investigates the molecular mechanisms of signaling pathways using a combination of structural biology, biochemistry, and cell-based assays. This allows us to understand how a pathway is regulated, how small molecules can influence a pathway, or how mutations to pathway components can alter its activity.
We want to understand how cells receive information from their environment and know how to respond accordingly. We do this by taking a “LEGO” approach to science to determine what to the components look like, how they fit together, and how these molecular machines work.
Research Overview
The Kavran Lab is interested in understanding the regulation of signaling pathways. Our goal is to dissect these biological processes into their essential components and define their activities on a molecular, biochemical, and biophysical level.
How big should an eye grow? When should a cell stop dividing? The wrong answer may have potentially dire consequences. During development, the interrelated decisions of cell fate, size, and number are controlled by a few key pathways including the Hippo pathway. In addition to its role during development, the Hippo pathway also has a role in stem cell maintenance, tissue regeneration, and tumorigenesis, making it an attractive target for therapeutic intervention. Despite its importance in human health, the molecular regulation of this pathway is poorly understood and ripe for investigation. The Kavran Lab seeks to determine the molecular mechanism governing the activity of the Hippo pathway using a combination of biochemistry, structural biology, and cell-based assays.
Hippo Kinase Regulation
Research led by PhD student T.J. Koehler and postdoctoral fellow Thao Tran revealed details about the kinetic regulation of key Hippo kinase MST2. They showed that by far the largest driver of MST2 activity was if it was phosphorylated. They revealed a novel role of the C-terminal SARAH domain: It dramatically increased activity in unphosphorylated proteins, but reduced it in phosphorylated proteins, with evidence suggesting that it disrupted interactions with ATP. They also found that some factors that affect MST 1/2 activity in cells had little impact on in vitro activity, suggesting that these factors influence non-kinetic aspects of the pathway, such as cellular localization.
Kinetic Regulation of the Mammalian Sterile 20-like Kinase 2 (MST2), Koehler TJ, Tran T, Weingartner KA, Kavran JM, Biochemistry, 2022.
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.
Ingavat N, Kavran JM, Sun Z, Rokita SE. Active Site Binding Is Not Sufficient for Reductive Deiodination by Iodotyrosine Deiodinase. Biochemistry, 2017.
How to Join the Kavran Lab
The Kavran Lab recruits members at a range of career stages. Common ways to join the lab are below.
PhD Students
The Kavran Lab is part of several PhD training programs at Johns Hopkins University. Visit the websites below to learn more about the specifics of each program and the admissions process. All programs provide full tuition and stipend support.
Master's Students
The Kavran Lab takes students from the Department of Biochemistry and Molecular Biology Master of Health Science and Master of Science programs.
Undergraduate Students
The Kavran Lab hosts undergraduates from a variety of programs. If you are interested in joining the Kavran Lab as an undergraduate, contact Jennifer Kavran by email.
Postdoctoral Fellows
The Kavran Lab is currently accepting applications for postdoctoral fellow. Interested candidates should send their CV and a statement of interest to Jennifer Kavran by email. In addition to training within our lab, the Biochemistry and Molecular Biology Department has an active postdoctoral training program.