Han-Fei Ding, PhDHan-Fei Ding, PhD

Professor, Pathology

Member, Tumor Signaling and Angiogenesis Program

Research Summary

Our group studies the molecular mechanisms that control the metabolic processes critical for sustaining cancer cell growth and proliferation, with a focus on the childhood cancer neuroblastoma. We investigate how cancer cells increase the production of building blocks for the synthesis of macromolecules for cell growth and proliferation, which may direct the development of new cancer therapeutics designed to target vulnerabilities of cancer cells.

Contact Us

The Han-Fei Ding Lab

Health Sciences Campus

Georgia Cancer Center - M. Bert Storey Research Building

1410 Laney Walker Blvd., CN2132, Augusta, GA 30912

(706) 721-4286


Research Interests

Transcriptional and epigenetic control of cancer metabolism

It is well established that cancer cells reprogram their metabolism to meet the biosynthetic challenge of growth and proliferation. How cancer metabolism is initiated and maintained in cancer cells is a central question of cancer research. We have pioneered the novel concept that histone lysine methyltransferases (KMTs) and demethylases (KDMs) are key players in reprogramming cell metabolism for cancer cell growth and proliferation. Therefore, they represent a new class of metabolic oncogenes or tumor suppressors and new drug targets for cancer therapy. We were the first to provide experimental evidence in support of this model by showing that the histone H3 lysine 9 methyltransferase G9A and demethylase KDM4C epigenetically activate amino acid biosynthesis and transport to sustain cancer cell survival and proliferation. We are currently investigating how oncogenic transcription factors, such as MYCN and ATF4, cooperate with KMTs and KDMs in transcriptional reprogramming of cancer metabolism, with a focus on the serine-glycine-one-carbon metabolic network that generate building blocks for the synthesis of proteins, lipids, and nucleotides. We are also testing small molecule inhibitors and drugs that block key metabolic pathways as cancer therapeutics in cell lines and animal models of human cancer.

Molecular and cellular bases of neuroblastoma development

Neuroblastoma is a common pediatric cancer of the sympathetic nervous system. High-risk neuroblastoma, accounting for about half of neuroblastoma cases, is one of the deadliest childhood cancers. The overall survival rate for children with high-risk neuroblastoma is less than 50% even after intensive, multimodal therapy. A long-term goal of our research is to identify genes and metabolic pathways that drive or sustain high-risk neuroblastoma, which may suggest new therapeutic targets and strategies. We have been working on several oncogenes and tumor suppressor genes for their roles in neuroblastoma pathogenesis, including MYCN, ATF4, BMI1, and HOX family genes. We have defined an essential role of BMI1 in neuroblastoma pathogenesis by maintaining neuroblastoma stem cells through upregulating cyclin E1 and promoting p53 protein degradation. We have also defined a key role of the HOX family of genes (HOXC9, HOXD and MEIS2) in the control of neuroblastoma cell proliferation and differentiation. More recently, we have isolated and characterized neuroblastoma stem cells from a mouse model of human neuroblastoma. Studies with mouse neuroblastoma stem cells have uncovered a common metabolic program shared by high-risk human neuroblastoma, one of the deadliest childhood cancers. This metabolic program is characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways. We are currently investigating how oncogenic signals are linked to the activation of this metabolic program in high-risk neuroblastoma, with a focus on MYCN, an oncogene with a major role in driving high-risk neuroblastoma development. We are also testing several drugs that inhibit this metabolic program for neuroblastoma therapy.

Selected Publications

Ding, J., Li, T., Wang, X., Zhao, E., Choi, J., Yang, L., Zha, Y., Dong, Z., Huang, S., Asara, J.M., Cui, H., Ding, H.-F. The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation. Cell Metab. 18:896-907. 2013. PMID: 24315373

Zhao, E., Ding, J., Xia, Y., Liu, M., Choi, J., Yan, C., Dong, Z., Huang, S., Zha, Y., Yang, L., Cui, H., and Ding, H.-F. KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism. Cell Rep. 14:506-519, 2016

Liu, M., Xia, Y., Ding, J., Ye, B., Zhao, E., Choi, J.-H., Alptekin, A., Yan, C., Dong, Z., Huang, S., Yang, L., Cui, H., Zha, Y., and Ding, H.-F. Transcriptional profiling reveals a common metabolic program in high-risk human neuroblastoma and mouse neuroblastoma sphere-forming cells. Cell Rep. 17:609-623, 2016

Alptekin A., Ye B., Yu Y., Poole C.J., van Riggelen J., Zha Y., Ding H.-F. Glycine decarboxylase is a transcriptional target of MYCN required for neuroblastoma cell proliferation and tumorigenicity. Oncogene 38:7504-7520, 2019

Xia Y., Ye B., Ding J., Yu Y., Alptekin A., Thangaraju, M., Prasad, D. P., Ding Z.-C., Park E., Choi J., Gao B., Fiehn O., Yan C., Dong Z., Zha Y., Ding H.-F. Metabolic reprogramming by MYCN confers dependence on the serine-glycine-one-carbon biosynthetic pathway. Cancer Res. 79:3837–50, 2019

Research Team

Jane Ding, BM (MD Equivalent)

  • Senior Research Associate

(706) 721-4285

Rui Mao, PhD

  • Postdoctoral Fellow

(706) 721-3403

Gia-Buu Tran

  • Postdoctoral Fellow