Cancer Biology, Metabolism,Mechanisms, and Therapeutics Discovery
Summary: The laboratory of Dr. Hua Lu is interested inunderstanding the molecular and biochemical basis that underlies physiologicaland pathological signaling pathways, which lead to gene expression andsubsequent cell growth arrest, differentiation, senescence, autophagy, orapoptosis. Specifically, his lab has been focusing on the tumor suppressor p53and the oncoprotein c-Myc pathways that are highly associated with all types ofhuman cancers. Different approaches including quantitative and analyticalprotein biochemistry, chemical biology, proteomics, metabolomics, immunologicaltools, gene microarray, RNA seq, single cell RNA seq, molecular and cellularbiological methods as well as genetic methods (such as murine model, organoid,orthotopic and PDX tumor model systems) will be employed in these studies. Wewill also pursue translational research by screening anti-cancer drugstargeting the above pathways and aiming at identification of anti-cancer drugcandidates for clinical trials eventually. The effort will be complemented bycollaborating with various group. Specific projects include:
1). To understand the role ofthe ribosomal stress-MDM2-p53 and AMPK-MDMX-p53 pathway in liver progenitorcell proliferation and liver cancer development by regulating one carbonmetabolism, as we have created a MDM2 and MDMX double knock-in mouse line (DKI)and identified a specific target gene that is involved in one carbonmetabolism.
2) To understand the role ofPHLDB3 in metabolism and fatty liver development via p53-dependent andindependent mechanisms. This project stemmed from our previous publication inNature Communication (2016).
3) To understand the role ofCCDC3 in breast cancer development. Our recent findings surprisingly revealedthat CCDC3, previously reported by others and us to play a role in lipidmetabolism as a secreted protein by targeting hepatocytes (2017), can alsofunction in the nucleus to activate p53 and consequently suppress the growth ofbreast cancer cells.
4) To understand the role ofVCP in pancreatic cancer development by boosting the GOF of mutant p53.
5) To developnanoparticles-encapsulated INZ-C into an effective anti-cancer agent formetastatic colorectal and lung cancer.
6) To understand the role ofNGFR in melanoma development by suppressing p53 activity and boosting BRAFsignaling.
7) To understand the role ofserine crotonylation of p53 in colorectal cancer development in response to gutmicrobiota-produced crotonic acids.
8) To understand the role of p53-R249S(mouse R246S) in liver cancer development under unhealthy diet conditionsincluding western diet and/or alcohol or with HBV infection.
9) To understand the role ofCCDC3 in liver lipid metabolism. We have generated CCDC3-knock out mice andfound that the animals show less liver lesion with reduced fatty liverphenotype under the high fat diet.
10) To understand the role of a small gutmicrobiota-produced molecule in suppressing cancer metastasis.
