Haiyong Han

Haiyong Han Ph.D.

Professor
Molecular Medicine Division

Head
Basic Research Unit, Pancreatic Cancer Program

Haiyong Han Ph.D.

Dr. Han’s research at TGen involves the development of early detection makers and novel therapeutics for the diagnosis and treatment of cancer, particularly pancreatic cancer.

Pancreatic cancer is the third leading cause of cancer deaths in the United States and has the worst survival rates of any cancer (The 5-year survival rate of patients with advanced disease is less than 8%). This dismal picture of pancreatic cancer is mainly due to the lack of early diagnosis and effective treatments for advanced disease. In order to make real progress against this devastating disease, we are involved in research to discover basic genetic, molecular, and biochemical abnormalities and help translate the findings into practical and effective therapies for patients with pancreatic cancer. The development of targeted therapies based on distinguishing characteristics of pancreatic cancer cells versus normal cells relies on our ability to identify alterations that are present in pancreatic cancer cells and the supportive microenvironment they reside.

Currently the lab has projects in the following areas:

  1. Development of new tumor microenvironment (TME) targeted therapeutic regimens for pancreatic cancer.

Components of tumor microenvironment have gained major attraction as drug targets in cancer drug discovery in recent years. The unique desmoplastic, hypoxic, and inflammatory environment of pancreatic cancer not only presents challenges for drug development (e.g. dense fibrosis impedes drug development) but also provides opportunities for novel multi-pronged approaches for drug discovery. We have developed projects that aimed at targeting different components of the pancreatic TME including the extracellular matrix, stromal fibroblasts, and immune cells.

  1. Discovery of new biomarkers for pancreatic cancer.

Early detection will play a key role in making a major impact on the prognosis of patients with pancreatic cancer. NCI has made biomarker discovery for pancreatic cancer one of the main priority areas. We have developed and participated in several projects that aimed at identifying and developing biomarkers for pancreatic cancer. Those projects include the development of multimeric ligands for cell surface markers, identification of glycan markers using glycomics, and identification of microRNA biomarker. We are currently seeking to expand the research in this area by initiating new projects and establishing new collaborations with experts in the field. We are working with clinicians to collect and analyze samples from patients with pancreatic cancer or precancerous lesions and high risk individuals.

  1. Development of small molecule agents targeting novel drug targets in pancreatic cancer

The majority of pancreatic tumors harbor genetic alterations in two of the most common oncogenes K-Ras and c-Myc. Targeting K-Ras and c-Myc has proven to be difficult. We are working with scientists at University of Arizona to develop small molecules that selectively target cells harboring alterations in K-Ras and/or c-Myc. Other molecular targets we are developing inhibitors for include NEK2 and ROCK1. The goal for this area of research is to take the advantage of our rich preclinical models for pancreatic cancer and work closely with medicinal chemists to generate candidate molecules that are ready to enter clinical trials.

SELECT PUBLICATIONS

Inhibition of ROCK1 kinase modulates both tumor cells and stromal fibroblasts in pancreatic cancer. C. J. Whatcott, S. Ng, M. T. Barrett, G. Hostetter, D. D. Von Hoff,  H. Han. PLoS One, 2017; In Press

Preparation and metabolic assay of 3-dimensional spheroid co-cultures of pancreatic cancer cells and fibroblasts. P. Noel, R. Muñoz, G. W. Rogers, A. Neilson, D. D. Von Hoff, H. Han. J Vis Exp. 2017; Epub May.2017

Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expressionK. Yoshida, S. Toden, P. Ravindranathan, H. Han, A. Goel. Carcinogenesis. Epub June, 2017.

Clinical study of genomic drivers in pancreatic ductal adenocarcinoma. M. T. Barrett, R. Deiotte, E. Lenkiewicz, S. Malasi, T. Holley, L. Evers, R. G. Posner, T. Jones, H. Han, M. Sausen, V. E. Velculescu, J.  Drebin, P. O’Dwyer, G. Jameson, R. K. Ramanathan, D. D. Von Hoff.  Br J Cancer. 2017; 117:572-582.

Blocking nerve growth factor signaling inhibits perineural invasion in pancreatic cancer. A. Bapat, R. M. M. Munoz, D. D. Von Hoff, and H. Han. PLoS One, 2016;11:e0165586.

Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer.  C. J. Whatcott, C. H. Diep, P. Jiang, A. Watanabe, J. LoBello, C. Sima, G Hostetter, H. M. Shepard, D. D. Von Hoff, H. Han. Clin Cancer Res. 2015; 21:3561-8.

Orchestrating the tumor microenvironment to improve survival for patients with pancreatic cancer: normalization, not destruction.  C. J. Whatcott, H. Han, D. D. Von Hoff. Cancer J. 2015; 21:299-306

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