Haiyong Han, Ph.D.
Professor
Clinical Genomics and Therapeutics Division

Head
Basic Research Unit, Pancreatic Cancer Program

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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 5%). 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.

  2. 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 extracellular vesicle associated biomarkers. 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.

  3. 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 to develop small molecules that selectively target cells harboring alterations in K-Ras and/or c-Myc. 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

Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer. Rossi GR, Jensen A, Ng S, Yin Z, Li A, Misra A, Von Hoff DD, Gruber L, Gruber M, Han H. Sci Rep. 2023;13(1):16953.

Single-cell mapping identifies MSI+ cells as a common origin for diverse subtypes of pancreatic cancer. Rajbhandari N, Hamilton M, Quintero CM, Ferguson LP, Fox R, Schürch CM, Wang J, Nakamura M, Lytle NK, McDermott M, Diaz E, Pettit H, Kritzik M, Han H, Cridebring D, Wen KW, Tsai S, Goggins MG, Lowy AM, Wechsler-Reya RJ, Von Hoff DD, Newman AM, Reya T. Cancer Cell. 2023;41(11):1989-2005.e9.

A super-enhancer-regulated RNA-binding protein cascade drives pancreatic cancer. Antal CE, Oh TG, Aigner S, Luo EC, Yee BA, Campos T, Tiriac H, Rothamel KL, Cheng Z, Jiao H, Wang A, Hah N, Lenkiewicz E, Lumibao JC, Truitt ML, Estepa G, Banayo E, Bashi S, Esparza E, Munoz RM, Diedrich JK, Sodir NM, Mueller JR, Fraser CR, Borazanci E, Propper D, Von Hoff DD, Liddle C, Yu RT, Atkins AR, Han H, Lowy AM, Barrett MT, Engle DD, Evan GI, Yeo GW, Downes M, Evans RM. Nat Commun. 2023;14(1):5195.

Effect of acoustic cluster therapy (ACT®) combined with chemotherapy in a patient-derived xenograft mouse model of pancreatic cancer. Ng S, Healey AJ, Sontum PC, Kvåle S, Torp SH, Sulheim E, Von Hoff D, Han H. J Control Release. 2022;352:1134-1143.

An Exosome-based Transcriptomic Signature for Noninvasive, Early Detection of Patients With Pancreatic Ductal Adenocarcinoma: A Multicenter Cohort Study. Nakamura K, Zhu Z, Roy S, Jun E, Han H, Munoz RM, Nishiwada S, Sharma G, Cridebring D, Zenhausern F, Kim S, Roe DJ, Darabi S, Han IW, Evans DB, Yamada S, Demeure MJ, Becerra C, Celinski SA, Borazanci E, Tsai S, Kodera Y, Park JO, Bolton JS, Wang X, Kim SC, Von Hoff D, Goel A. Gastroenterology. 2022;163(5):1252-1266.e2.

Pharmacologic Targeting of TFIIH Suppresses KRAS-Mutant Pancreatic Ductal Adenocarcinoma and Synergizes with TRAIL. Moser R, Annis J, Nikolova O, Whatcott C, Gurley K, Mendez E, Moran-Jones K, Dorrell C, Sears RC, Kuo C, Han H, Biankin A, Grandori C, Von Hoff DD, Kemp CJ. Cancer Res. 2022;82(18):3375-3393.

Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth. Yang L, TeSlaa T, Ng S, Nofal M, Wang L, Lan T, Zeng X, Cowan A, McBride M, Lu W, Davidson S, Liang G, Oh TG, Downes M, Evans R, Von Hoff D, Guo JY, Han H, Rabinowitz JD. Med (N Y). 2022;3(2):119-136.

Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions. Lin W, Noel P, Borazanci EH, Lee J, Amini A, Han IW, Heo JS, Jameson GS, Fraser C, Steinbach M, Woo Y, Fong Y, Cridebring D, Von Hoff DD, Park JO, Han H. Genome Med. 2020;12:80.

Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts. Noel P, Hussein S, Ng S, Antal CE, Lin W, Rodela E, Delgado P, Naveed S, Downes M, Lin Y, Evans RM, Von Hoff DD, Han H. Oncogenesis. 2020;9:100.

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