Haifeng Yang, PhD
Philadelphia, PA 19107
Most Recent Peer-reviewed Publications
- The contributions of HIF-target genes to tumor growth in RCC
- The roles of VHL-dependent ubiquitination in signaling and cancer
- The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C
- The von hippel-lindau tumor suppressor protein promotes c-Cbl-independent poly-ubiquitylation and degradation of the activated EGFR
- pVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2
PhD, Syracuse University
Dana-Farber Cancer Institute, Harvard Medical School
Research and Clinical Interests
Cancer is a genetic disease. It develops after spelling errors appear in the blueprint of the book of life: our DNA. Activation mutations in oncogenes and/or inactivation mutations in tumor suppressor drive tumor formation. In human kidney cancer, the highly frequent mutations in a critical tumor suppressor gene VHL are the leading cause of tumor development.
It is now known that VHL loss would trick cells into the state of pseudo hypoxia (oxygen deprivation): the cancer cells think that they are extremely low on oxygen supply, and they activate a transcriptional response (reading from the DNA). Long-term, uncontrolled activation of this hypoxia response program drives the development of kidney cancer. Anti-angiogenesis therapies, which partially block this program, produce positive albeit often transient outcomes in kidney cancer patients. Thus, better understanding of the hypoxia response program might enable us to better exploit the weakness of VHL-defective cancer cells.
Our group discovered that this abnormally activated transcriptional program significantly altered a critical mark on histone, proteins that package DNA and regulate its reading. This was achieved through activating an enzyme called JARID1C. In VHL-defective cancer cells, JARID1C reduced the mark on histone. Furthermore, JARID1C contributed to drug resistance.
Thus in project 1, we will address mechanistically how JARID1C is activated, and whether disrupting JARID1C would defeat the drug resistance.
We have identified that VHL protein regulates the protein stability of the oncogene EGFR. In project 2 we will elucidate the biochemical mechanism.
Recently 40% of kidney cancer was found to harbor mutations in PBRM1. PBRM1 is a critical targeting subunit of a protein complex that remodels the structure of human chromosome. In project 3, we are studying how the tumor-derived mutations of PBRM1 disrupt its biochemical functions, and how PBRM1 collaborates with JARID1C to regulate gene transcription.
In project 4, we are collaborating with the clinicians and scientists at Fox Chase Cancer Center and Cleveland Clinic to investigate whether the unique genetic makeup of the tumors lead to drastically different drug response to current anti-angiogenic therapies.