Project 1:

Fibronectin and Adhesion Signaling in Epithelial-Mesenchymal Plasticity

Focus: We have identified a role for posttranslational hypusination and cytoplasmic localization of eIF5A1/2 in controlling the translation of the PEAK1 pseudokinase. Given the established role for PEAK1 in mediating cellular adhesion to extracellular matrix proteins like fibronectin, we are currently investigating how fibronectin matrix signaling regulates eIF5A1/2 signaling and function.

Relevant publication: Güth et al. 2019 BBRC, Geller et al. 2023 bioRxiv

Collaborators: Joseph Taube (Baylor), Touradj Solouki (Baylor) and Dwayne Simmons (Baylor)

Project 2:

Epithelial Intrinsic and Extrinsic Functions of Lipocalin-2

Focus: Given the pleiotropic functions of Lcn2 in the context of disease progression, we are investigating the roles of Lcn2 in solid tumors using spheroid/organoid systems. Simultaneously, we aim to understand how circulating Lcn2 can modify tissues to to prime them for disease.

Relevant publication: Meade et al. 2019 Oncotarget

Collaborators: Isaac Harris (U. Rochester), Jack Bui (UCSD) and Aaron Wright (Baylor)

Project 3:

Mechanistic Determinants of a Multicellular PEAK1-Dependent Signaling Cascade

Focus: We have identified a previously unrecognized PEAK1 pseudokinase dependent intercellular signaling program initiated within HER2-positive breast cancer associated fibroblasts (CAFs), that promotes metastasis and therapy resistance via activin-A responses in both stromal and tumor cell compartments. We aim to determine the spatiotemporal mechanisms by which PEAK1 governs fibroblast heterogeneity and intercellular activin-A signaling to potentiate disease progression.

Relevant publication: Hamalian et al. 2021 Oncogene

Collaborators: Thea Tlsty (UCSF), Michael Lewis (BCM), Julia Tchou (UPenn), Anupma Nayak (UPenn), and Touradj Solouki (Baylor)

Project 4:

Modeling Disease in 3D to Screen New Therapeutics

Focus: While patient-derived 3D cultures hold promise for personalizing disease treatment, the time required to generate these models is not time-efficient for drug screening. We aim to develop and leverage unique bioengineering platforms to efficiently produce multicellular patient-derived 3D models that can be used to interrogate therapy responsiveness and dormancy.

Relevant publication: Gharibi et al. 2017 Scientific Reports, Aquino et al. 2024 BBRC

Collaborators: Marcin Iwanicki (Stevens Institute), Todd Aguilera (UTSW) and Cathy Yao (BCM)

Project 5:

Extracellular Remodeling of TGFβ-2 Stores by Fibrillin and RAI14

Focus: We have identified that mutations of fibrillin-1, a repository for latent TGFβ, are associated with characteristics of human primary open angle glaucoma (POAG). Our ongoing work aims to decifer the mechanisms by which fibrillin-1 cooperates with retinoic acid 14 to increase access of recipient cell to active pools of TGFβ-2 in disease contexts.

Relevant publication: Ko et al. 2022 Scientific Reports, Tan et al. 2024 Scientific Reports

Collaborators: James C. Tan