Chun Zhang Yang, Ph.D.

Chun Zhang Yang, Ph.D.
Investigator
Dr. Chun Zhang Yang is a principle investigator in the Neuro-Oncology Branch (NOB), which is a collaboration between the National Cancer Institute (NCI) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Yang is experienced in multi-discipline medical research, with focuses on signaling pathways, functional genetics, and metabolomics in brain tumors. He has been leading and performing research endeavors in the fields of basic, translational, and clinical research projects, aiming for a more efficient translation from laboratory findings to pre-clinical testing. Dr. Yang’s group focuses on exploring the signaling mechanisms that are related to tumor aggressiveness and malignancy and seeking novel therapeutic approaches by targeting these pathways.
Areas of Expertise
1) cancer biology 2) cancer stem cells 3) functional genetics 4) signaling transduction 5) assay development 6) genetic engineering

Contact Info

Chun Zhang Yang, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 1142E
Bethesda
Ph: 240-760-7083
Fax: 240-541-4466
yangc2@mail.nih.gov

Glioma, a devastating disease affecting thousands of lives in the United States, is the most common form of central nervous system cancer, with an estimated 20,000 newly diagnosed cases each year. It causes multiple neurological symptoms ranging from headache, nausea to drowsiness, dysphagia, epilepsy, and mortality. Gliomas are difficult to treat and exhibit unfavorable disease outcomes. For example, patients with WHO Grade IV glioblastoma (GBM), the median survival is < 18 months, with a 5% five-year survival rate. While the prognosis for patients with lower grade gliomas is better, these cancers remain incurable. Although advances in glioma research have revealed the genetic, epigenetic, and metabolic signatures of different glioma molecular subtypes, the standards of care in glioma management remain limited and nonselective. There are many caveats to the translation of knowledge on glioma molecular subtypes into effective therapeutics. Therefore, there is an urgent need to improve the present therapeutic regimen based on molecular signatures to achieve better selectivity and efficacy with prolonged patient survival.

The goal of our research program is to identify the therapeutic vulnerabilities in the major glioma molecular subtypes. In particular, we focused on glioma with isocitrate dehydrogenase (IDH) mutations, which is the most prevalent genetic abnormality in over 80% of patients with WHO II/III glioma. Several findings suggested that mutations in IDH result in distinctive changes in tumor biology, such as overproduction of oncometabolite 2-hydroxyglutarate (2-HG), development of a hypermethylation phenotype, and redox imbalance. Based on the knowledge of IDH1-mutated glioma, we hypothesize that the distinctive pattern of cancer biology, metabolism, and therapeutic resistance in IDH-mutated glioma offer novel therapeutic targets, suggesting that the present therapeutic regimen could be optimized/enhanced by targeted therapy. Based on this hypothesis, we began our investigation by comparing the transcriptomic and metabolomic profiles between IDH1 wild type and mutated cells. In addition, we have been developing patient-derived cells, intracranial xenograft models, and genetically engineered mouse models for IDH1-mutated glioma, which serve as useful tools to validate cancer-susceptible and -resistant genes. Our findings demonstrate that several protective mechanisms, including macropinocytosis-derived nutrient uptake, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-governed detoxification, and DNA repair pathways, play central roles to prevent metabolic stress and apoptotic changes in IDH1-mutated cells. Based on our preliminary findings, we identified novel therapeutic targets and validated them using in vitro assays and preclinical animal models. Our findings suggest novel therapeutic strategies that can result in optimized efficacy and selectivity for IDH1-mutated cancer. Our research on IDH1-mutated glioma cells and mouse models will introduce complementary techniques and impart knowledge that can be extended to future glioma translational research.

We believe that our contribution will be of great significance because our research introduces conceptual advances in glioma biology and therapeutics. In addition, the portfolio of this research platform, including IDH1-mutated cells and genetically engineered mouse models, will serve as foundational resources for the emerging field of cancer metabolism. We expect that our immediate results, as well as subsequent work, will improve the quality of life and medical outcomes for patients with glioma.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Genetics and Genomics, Molecular Biology and Biochemistry, Stem Cell Biology

Selected Key Publications

  1. Liu Y, Lu Y, Celiku O, Li A, Wu Q, Zhou Y, Yang C
    Journal of the National Cancer Institute. Epub ahead of print: 2019. [ Journal Article ]
  2. Pang Y, Lu Y, Caisova V, Liu Y, Bullova P, Huynh TT, Zhou Y, Yu D, Frysak Z, Hartmann I, Taïeb D, Pacak K, Yang C
    Clinical Cancer Research. 24: 3423-3432, 2018. [ Journal Article ]
  3. Lu Y, Kwintkiewicz J, Liu Y, Tech K, Frady LN, Su YT, Bautista W, Moon SI, MacDonald J, Edwend MG, Gilbert MR, *Yang C, Wu J. (*Corresponding author)
    Cancer Research. 77(7): 1709-1718, 2017. [ Journal Article ]
  4. Yang C, Iyer RR, Yu AC, Yong RL, Park DM, Weil RJ, Ikejiri B, Brady RO, Lonser RR, Zhuang Z
    Proc Natl Acad Sci U S A. 109(18): 6963-6968, 2012. [ Journal Article ]
  5. Zhuang Z, *Yang C, Lorenzo F, Merino M, Fojo T, Kebebew E, Popovic V, Stratakis CA, Prchal JT, Pacak K (*Co-first author)
    N Engl J Med. 367(10): 922-930, 2012. [ Journal Article ]
Dr. Chun Zhang Yang received his Philosophy Doctorate (Ph.D.) degree in neurobiology with a focus on glial cell biology and glutamate metabolism from Peking University (PKU) in 2009. In 2010, Dr. Yang joined the Surgical Neurology Branch (SNB) at the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH. He has been active in a diverse set of research fields including tumor genetics, cell biology, and biochemistry. Dr. Yang was the first to identify HIF2A mutations in human cancers, which act as key genetic events in tumor formation. In addition, he has led many breakthroughs in understanding the molecular basis of human cancers in the nervous system. In 2015, Dr. Yang joined the Neuro-Oncology Branch as a tenure track investigator. The goal of Dr. Yang’s research is to understand the distinctive genetic and metabolic aspects of different types of brain tumors, such as glioblastoma, meningioma, and hemangioblastoma, and uncover unique small molecular antagonists as possible chemotherapeutic agents for brain tumors.
Position Keywords Contact Name Contact E-mail Number of Positions
Postdoctoral Fellow - cancer biology, brain tumor

cancer biology, protein chemistry, brain tumor

Chunzhang Yang

chunzhang.yang@nih.gov

1
Name Position
Sue Han Ph.D. Postdoctoral Fellow (Visiting)
Yang Liu Ph.D. Postdoctoral Fellow (Visiting)
Mingyu Qian Special Volunteer
Yiqiang Zhou Ph.D. Postdoctoral Fellow (Visiting)