Research

We are interested in understanding the molecular mechanisms that regulate tumor cell metastasis. Tumor progression depends on a multitude of signaling pathways, and we hope that our understanding of these will result in the discovery of novel markers and therapies for metastatic disease. Our lab is specifically interested in elucidating what roles reactive oxygen species, antioxidant enzymes and mitochondrial function play in metastatic progression of ovarian cancer. Some of our current projects include:

mitochondria copy
1. Role of antioxidant enzymes in ovarian cancer metastasis: 
Many tumor cells adapt their antioxidant expression profile to cope with exogenous and intrinsic changes in reactive oxygen species during tumor progression. We focus on the mechanisms of regulation and function of different antioxidant enzymes, and try to understand how oxidant scavenging and manipulation of the cellular redox environment by antioxidants aids in ovarian cancer metastasis and alters mitochondrial function.

GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment.

Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma.

Figure2_Hemachandra

2. Mitochondrial Function and Metabolism Differences of Ovarian Cancer Histological Subtypes: Ovarian cancer is comprised of a number of different diseases that vary greatly in their tissue of origin, genetic and epigenetic backgrounds. This projects aims to elucid
ate the molecular mechanisms behind our observed histological variances in mitochondrial (dys)function and metabolism. We are currently investigating the role of altered mitochondrial fission/fusion dynamics and mitophagy in this context, and are assessing how different histological subtypes may benefit from metabolism-based therapeutics to target their divergent metabolic requirements.

Bioenergetic analysis of ovarian cancer cell lines: profiling of histological subtypes and identification of a mitochondria-defective cell line.

JC1

3. Redox signaling in the regulation of bladder and ovarian cancer cell migration and invasion: Many metastatic tumor cells are able to survive and thrive with higher steady-state levels of intracellular reactive oxygen species. This project focuses on how intrinsic shifts in oxidants regulate protein oxidation and influence cellular signaling cascades to alter the metastatic behavior of cancer cells.

Crosstalk between calcium and reactive oxygen species signaling in cancer.

Regulation of MMP-1 expression in response to hypoxia is dependent on the intracellular redox status of metastatic bladder cancer cells.

Intracellular redox status controls membrane localization of pro- and anti-migratory signaling molecules.

Acquisition of the metastatic phenotype is accompanied by H2O2-dependent activation of the p130Cas signaling complex.

Figure1_ROS_Metastasis

CURRENT AND PAST FUNDING SOURCES: National Cancer Institute (NCI)/NIH: 1R01CA230628-01A1, R00CA143229; Department of Defense (DoD) Ovarian Cancer Research Program (OCRP): W81XWH-16-1-0117; Rivkin Center for Ovarian Cancer; Penn State Cancer Institute.  

 

 

 

  • TRiMAD - Penn State - Nov 2015

Skip to toolbar