School of Medicine
Area of interest
The oxygen-sensing pathway contributes largely to the development of tumors. One of the central players in this pathway is prolyl hydroxylase (EglN1, 2 and 3). Our lab currently studies hypoxia signaling, prolyl hydroxylase and cancer, specifically breast and renal cell carcinoma.
One project focuses on using proteomic and genomic approaches to screen for novel prolyl hydroxylase substrates that play important roles in cancer. We have generated an IVT-compatible breast cancer gene library, which is comprised of 1200-1300 genes that were either reported or predicted to be important for breast tumorigenesis. Then, we developed a 96-well format high-throughput format to screen for whether any of the genes in the library can be hydroxylated in vitro by recombinant EglN2. Preliminary data from this screen identifies FOXO3a as one of potential EglN2 substrate. We are currently investigating the role of EglN2 target FOXO3a in breast cancer. In addition, we also developed an EglN2-substrate trapping strategy followed by TAP-TAG purification and mass spectrometry. Several potential EglN2 substrates have been identified from mass spectrometry and we are investigating their role in breast cancer.
The other project involves integrating CHIP-seq strategy with gene expression profiling in order to identify EglN2 prolyl hydroxylase and hypoxia inducible factor (HIF) targets in the malignant diseases. The ultimate goal is to understand mechanistically how oxygen-sensing pathways contribute to cancer progression, which will facilitate our design of efficient treatment strategies to specifically target cancer.
Awards and Honors
2003 First Prize, Poster Presentations, Annual Retreat, Department of Pharmacology, University of Pittsburgh
2004 The director’s award for research excellence and potential, 16th Annual University of Pittsburgh Cancer Institute Scientific Retreat
2004 First Prize, Poster Presentations, Annual Retreat, Department of Pharmacology, University of Pittsburgh
2005 Travel Award, The Edward A. Smuckler Memorial Workshop: Pathobiology of Cancer, American Association for Cancer Research
2009 Dana Farber Cancer Institute Friends Award, Boston, MA
2009 Terri Brodeur Breast Cancer Foundation Postdoctoral Fellowship
2010 Ruth L. Kirschstein National Research Service Award (NRSA)
2011 NIH Pathway to Independence (K99/R00) Award
2014 Kimmel Scholar Award, Sidney Kimmel Foundation