Control of Organ Size and Cancer by the Hippo Pathway

Grant number: 1078220 | Funding period: 2015 - 2020

Completed

Abstract

The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Hippo pathway controls tissue growth and cancer. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.

Related publications (11)

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Hippo signaling regulates the nuclear behavior and DNA binding times of YAP and TEAD to control transcription

B Kroeger, SA Manning, V Mohan, J Lou, G Sun, S Lamont, AJ McCann, M Francois, JM Polo, E Hinde, KF Harvey

2025-07-25

Over the past two decades, genetic and proteomic screens have identified the Hippo pathway as a complex signaling network that con..

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Identification of resistance mechanisms to small-molecule inhibition of TEAD-regulated transcription

A Kulkarni, V Mohan, TT Tang, L Post, YC Chan, M Manning, N Thio, BL Parker, MA Dawson, J Rosenbluh, JHA Vissers, KF Harvey

2024-09-10

The Hippo tumor suppressor pathway controls transcription by regulating nuclear abundance of YAP and TAZ, which activate transcrip..

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The JNK and Hippo pathways control epithelial integrity and prevent tumor initiation by regulating an overlapping transcriptome

Katrina A Mitchell, Joseph HA Vissers, Jonathan M Pojer, Elliot Brooks, Abdul Jabbar Saiful Hilmi, Anthony T Papenfuss, Jan Schroder, Kieran F Harvey

2024-09-09

Epithelial organs maintain their integrity and prevent tumor initiation by actively removing defective cells, such as those that h..

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The Drosophila Hippo pathway transcription factor Scalloped and its co-factors alter each other's chromatin binding dynamics and transcription in vivo

SA Manning, B Kroeger, Q Deng, E Brooks, Y Fonseka, E Hinde, KF Harvey

2024-07-08

The Hippo pathway is an important regulator of organ growth and cell fate. The major mechanism by which Hippo is known to control ..

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The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer

SJ Vervoort, SA Welsh, JR Devlin, E Barbieri, DA Knight, S Offley, S Bjelosevic, M Costacurta, I Todorovski, CJ Kearney, JJ Sandow, Z Fan, B Blyth, V McLeod, JHA Vissers, K Pavic, BP Martin, G Gregory, E Demosthenous, M Zethoven

2021-06-10

Gene expression by RNA polymerase II (RNAPII) is tightly controlled by cyclin-dependent kinases (CDKs) at discrete checkpoints dur..

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Taz-camta1 and yap-tfe3 alter the taz/yap transcriptome by recruiting the atac histone acetyltransferase complex

N Merritt, K Garcia, D Rajendran, ZY Lin, X Zhang, KM Mitchell, N Borcherding, C Fullenkamp, MS Chimenti, AC Gingras, KF Harvey, MR Tanas

2021-04-01

Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma that metastasizes early in its clinical course and lacks an effective..

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The Hippo Pathway as a Driver of Select Human Cancers

A Kulkarni, MT Chang, JHA Vissers, A Dey, KF Harvey

2020-09-01

The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Althou..

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The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis

X Zhang, L Yang, P Szeto, GK Abali, Y Zhang, A Kulkarni, K Amarasinghe, J Li, IA Vergara, R Molania, AT Papenfuss, C McLean, M Shackleton, KF Harvey

2020-07-23

Melanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younge..

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Pits and CtBP control tissue growth in drosophila melanogaster with the hippo pathway transcription repressor tgi

JHA Vissers, LG Dent, CM House, S Kondo, KF Harvey

2020-05-01

The Hippo pathway is an evolutionarily conserved signaling network that regulates organ size, cell fate, and tumorigenesis. In the..

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Somatic hypermutation of the YAP oncogene in a human cutaneous melanoma

X Zhang, JZ Tang, IA Vergara, Y Zhang, P Szeto, L Yang, C Mintoff, A Colebatch, L McIntosh, KA Mitchell, E Shaw, H Rizos, GV Long, N Hayward, GA McArthur, AT Papenfuss, KF Harvey, M Shackleton

2019-07-01

Melanoma is usually driven by mutations in BRAF or NRAS, which trigger hyperactivation of MAPK signaling. However, MAPK-targeted t..

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The Scalloped and Nerfin-1 Transcription Factors Cooperate to Maintain Neuronal Cell Fate

JHA Vissers, F Froldi, J Schröder, AT Papenfuss, LY Cheng, KF Harvey

2018-11-06

The ability of cells to stably maintain their fate is governed by specific transcription regulators. Here, we show that the Scallo..

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