Our research aims to link physical properties, structure, and physiological function of cells and the cell nucleus.

Here is a sampling of some of our current research projects:

High-throughput screening of cells based on mechanical phenotype

We are developing technologies to screen populations of cells and cell nuclei based on their mechanical phenotype. These techniques have broad potential for screening applications in cancer and to reveal the molecular determinants of cell and nuclear mechanical properties.

Physical phenotypes of cancer cells

Cancer cells show striking alterations in their physical properties: for example, the irregular morphology of their cell nuclei is widely used for diagnosis, and some types of cancer cells show altered mechanical properties. We aim to understand the physical and molecular origins of cancer cell physical phenotypes; this will help to improve our fundamental understanding of functional behaviors, such as invasion. Using our high-throughput mechanical screening platform, we aim to exploit these altered physical characteristics to provide innovative diagnostic and therapeutic approaches.

Physical properties of cancer cells regulated by neurological signaling

Cancer metastasis accounts for 90% of human cancer death. Despite its clinical importance, our knowledge of the genetic, biochemical, and physical determinants of metastasis is very limited. The beta-adrenergic receptor signaling pathway, which is activated by hormones like epinephrine or norepinephrine, has been recently implicated in metastasis and cancer patient survival. Based on our preliminary data, we hypothesize that beta-adrenergic receptor signaling modulates the mechanical properties of cancer cells and thereby affects their metastasis. In collaboration with Dr. Erica Sloan, we are currently investigating the underlying mechanisms by which breast cancer cells modulate their mechanical properties via activation of beta-adrenergic receptor signaling. Our research will provide fundamental insight into the mechanisms and possible therapeutic options to control metastasis in breast cancer patients.

Shape transitions of the cell nucleus

The shape stability of the cell nucleus is essential for genome organization and integrity. However, the molecular and physical origins of nuclear shape are not fully understood. To understand the physical origins of nuclear shape changes, we are using a combination of experiment and theory to measure and predict cell nucleus shape. As a model system, we use human promyelocytic leukemia (HL-60) cells, which can be stimulated to differentiate into neutrophil-type cells; during this differentiation process, the cell nucleus transitions from an ovoid to an irregular, lobulated shape. During this process, there are marked changes in levels of nuclear envelope proteins: expression of the nuclear envelope scaffolding protein, lamin A, decreases, while there is strong upregulation of the nuclear membrane protein, lamin B receptor (LBR). By measuring and manipulating levels of these proteins - which also tune nuclear stiffness and surface area, we are gaining a deeper knowledge of nuclear shape stability.

COLLABORATORS

Our collaborators include Beth Karlan, Kate Lawrenson, and Sandra Orsulic (Cedars-Sinai), Erica Sloan (Monash/UCLA), Robert Damoiseaux (Molecular Shared Screening Resource/UCLA), Jianyu Rao (UCLA), as well as The Cancer Genome Atlas Project including Gordon Robertson (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency).

UCLA MAIN |  BSCRC |  JCCC |  ACCESS