Welcome to

the Gilbert-Ross Lab.

Limiting the progression of human cancer by studying how cancer cells work

Located in the Department of Hematology & Medical Oncology in the Emory School of Medicine, the Gilbert-Ross Lab investigates the mechanistic role played by endocytic tumor suppressors in limiting the progression of human cancer.

To solve complex problems in cancer biology, the lab uses a variety of techniques—including genetics (mouse and fruit fly), cell biology, advanced microscopy, genomics and bioinformatics, 3D cell culture, and pre-clinical trials.

The lab is a part of the Winship Cancer Institute of Emory University—an NCI-designated Comprehensive Cancer Center.

Currently, our lab is focused on three main areas of cancer biology.

Endocytic control of tissue growth and tumor progression

A defining characteristic of cancer is a loss of cell polarity and cell adhesion. Whether loss of cell polarity is causative—or a consequence of deregulated cell growth and proliferation—has been a salient question in cancer biology.
To investigate this issue, we designed a mosaic screen in the Drosophila eye that mimics a multi-hit model of mammalian tumorigenesis—and identified and characterized myopic (mop), the Drosophila ortholog of mammalian His-domain protein tyrosine phosphatase (HD-PTP). Our work identified the in vivo oncogenic target of Mop/HD-PTP as Yorkie (mammalian Yap1), which is the co-transcriptional activator of the Hippo/Mst2 tumor suppressor pathway.
Our more recent work extends to human HD-PTP; our findings support HD-PTP as a bone fide lung tumor suppressor.

Pre-clinical therapeutics for treatment-resistant lung adenocarcinoma

The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. More specifically, molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that contribute to unique growth properties and therapeutic susceptibilities.
To better understand these invasive properties, we screened for targetable signaling pathways linked to early invasion phenotypes in the two most prominent molecular subtypes, TP53 and LKB1, of KRAS-driven lung adenocarcinoma (LUAD). By combining live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix with RNA transcriptome profiling, we identified the LKB1-specific upregulation of bone morphogenetic protein 6 (BMP6).
Examination of early-stage lung cancer patients confirmed upregulation of BMP6 in LKB1-mutant lung tumors. At the molecular level, we found that the canonical iron regulatory hormone Hepcidin is induced via BMP6 signaling upon LKB1 loss, where intact LKB1 kinase activity is necessary to maintain signaling homeostasis. Furthermore, pre-clinical studies in a novel Kras/Lkb1-mutant syngeneic mouse model show that potent growth suppression was achieved by inhibiting the ALK2/BMP6 signaling axis with single agents that are currently in clinical trials.