Dr. Kenneth Irvine is a Distiguished Professor in the department of Molecular Biology and Biochemistry at Rutgers University. The Irvine lab is located within the Waksman Institute on the Busch campus. 

The lab is engaged in projects whose long-term goal is to define relationships between patterning and growth in developing and regenerating organs. Much of their research takes advantage of the powerful genetic, molecular, and cellular techniques available in Drosophila melanogaster, which facilitate both gene discovery and the analysis of gene function.

Recent Publications

Ibar, C, Kirichenko E, Keepers B, Enners E, Fleisch K, Irvine KD.  2018.  Tension-dependent regulation of mammalian Hippo signaling through LIMD1.. J Cell Sci. 131:jcs214700. AbstractWebsite
Hippo signaling is regulated by biochemical and biomechanical cues that influence the cytoskeleton, but the mechanisms that mediate this have remained unclear. We show that all three mammalian Ajuba family proteins - AJUBA, LIMD1 and WTIP - exhibit tension-dependent localization to adherens junctions, and that both LATS family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization. This localization of Ajuba and LATS family proteins is also influenced by cell density, and by Rho activation. We establish that junctional localization of LATS kinases requires LIMD1, and that LIMD1 is also specifically required for the regulation of LATS kinases and YAP1 by Rho. Our results identify a biomechanical pathway that contributes to regulation of mammalian Hippo signaling, establish that this occurs through tension-dependent LIMD1-mediated recruitment and inhibition of LATS kinases in junctional complexes, and identify roles for this pathway in both Rho-mediated and density-dependent regulation of Hippo signaling.
Irvine, KD, Sun S, Mao Y.  2017.  Role and regulation of Yap in KrasG12D-induced lung cancer.. Oncotarget. 8:110877-110889.
Irvine, KD, Shraiman BI.  2017.  Mechanical control of growth: ideas, facts and challenges.. Development. 144:4238-4248. AbstractWebsite
In his classic book On Growth and Form, D'Arcy Thompson discussed the necessity of a physical and mathematical approach to understanding the relationship between growth and form. The past century has seen extraordinary advances in our understanding of biological components and processes contributing to organismal morphogenesis, but the mathematical and physical principles involved have not received comparable attention. The most obvious entry of physics into morphogenesis is via tissue mechanics. In this Review, we discuss the fundamental role of mechanical interactions between cells induced by growth in shaping a tissue. Non-uniform growth can lead to accumulation of mechanical stress, which in the context of two-dimensional sheets of tissue can specify the shape it assumes in three dimensions. A special class of growth patterns - conformal growth - does not lead to the accumulation of stress and can generate a rich variety of planar tissue shapes. Conversely, mechanical stress can provide a regulatory feedback signal into the growth control circuit. Both theory and experiment support a key role for mechanical interactions in shaping tissues and, via mechanical feedback, controlling epithelial growth.
Mao, Y, Sun S, Irvine KD.  2017.  Role and regulation of Yap in KrasG12D-induced lung cancer.. Oncotarget. 8:110877-110889. AbstractWebsite
The Hippo pathway and its downstream transcriptional co-activator Yap influence lung cancer, but the nature of the Yap contribution has been unclear. Using a genetically engineered mouse lung cancer model, we show that Yap deletion completely blocks KrasG12D and p53 loss-driven adenocarcinoma initiation and progression, whereas heterozygosity for Yap partially suppresses lung cancer growth and progression. We also characterize Yap expression during tumor progression and find that nuclear Yap can be detected from the earliest stages of lung carcinogenesis, but at levels comparable to that in aveolar type II cells, which are a cell of origin for lung adenocarcinoma. At later stages of tumorigenesis, variations in Yap levels are detected, which correlate with differences in cell proliferation within tumors. Our observations imply that Yap is not directly activated by oncogenic Kras during lung tumorigenesis, but is nonetheless absolutely required for this tumorigenesis, and support Yap as a therapeutic target in lung adenocarcinoma.