Research

Our lab aims to dissect the progression of cancer from mechanobiology perspective: the interplay between tumor cells and their physical environment can provide us biological insights on novel drug targets.


What is the impact of cancer metastasis on cellular phenotypes?

During metastasis, cancer cells need to migrate and squeeze through many constrictions, imposed by extracellular matrix, crowded cell environment, endothelial cells layer and capillaries. Recently, we showed that constricted migration damages the nucleus and DNA, leading to genomic aberrations (Irianto et al. 2017). However, mechanisms behind this genomic changes are still unknown. Does it play a role in cancer genomic heterogeneity?

Nuclear blebbing post-constricted migration.A549 expressing GFP-lamin A, migrating through 3 um Transwell membrane. (Red = pre-migration, Green = post-migration)
Nuclear protein segregation within constriction.Micropipette aspiration of U2OS with GFP-53BP1.


Desmoplasia causes significant tissue stiffening in cancer progression.

Microenvironment stiffness dictates cell adhesions and contractility, which is upstream of many mechanotransduction pathways. What is the role of microenvironment stiffening in cancer progression? Here we will use both 2D and 3D cultures of both patient derived cancer cells and multiple lines to answer the question.

Organoid culture of patient derived pancreatic cancer cells.
3D culture of other pancreatic cancer cell lines.


Genomic heterogeneity

Genome instability and mutation is an enabling characteristics of cancer, and such genomic aberrations can either inactivate tumor suppressor genes or activate oncogenes. Genomic heterogeneity in most cancer has been reported by multiple studies, but again mechanisms is unknown. Can we tease out potential mechanisms from the mutation signatures? Here, we will utilize the genomic algorithms to analyze our whole genome sequencing data together with the publicly available genomic data of various cancers.

Funding:

Florida State UniversityCollege of Medicine
Department of Biomedical Sciences
© Irianto Lab, 2018
by Jerome Irianto