Project 1:

ECM and Adhesion Signaling in Epithelial-Mesenchymal Plasticity

Focus: We have identified a role for posttranslational hypusination and cytoplasmic localization of eIF5A1/2 in controlling PEAK1-mediated epithelial-mesenchymal transition (EMT) downstreatm of transforming growth factor beta (TGFβ). We have also previously reported that ITGA1 is necessary for TGFβ/collagen crosstalk during EMT. We are currently working to establish a more broad spatiotemporal framework for mechanisms by which cell-matrix adhesion signaling crosstalks with canonical and non-canonical TGFβ pathways to control EMT, MET and hybrid EMT cell states and invasion.

Relevant publication: Güth et al. 2019 BBRC, Geller et al. 2023 bioRxiv, Gharibi et al. 2017 Sci Rep

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