Department of Surgery

Virus-Like Particle Translational Oncology Lab


Pancreatic Cancer Pathogenesis and Therapy

Media Component
miR-198 modulation by Scott Holmes, CMI
Modulation of miR-198

Pancreatic cancer has one of the highest mortality rates and ranks as the third leading cause of cancer death in North America. Survival is poor because there are no reliable tests for early diagnosis and no effective therapies to treat metastatic disease. There is a need to better understand the molecular mechanisms of pancreatic cancer tumorigenesis and to develop effective treatments. My lab currently focuses on the study of key molecules in pancreatic cancer, including mesothelin (MSLN), trop2, and semaphorin 3E, and in their mechanisms of regulation. I am also interested in the involvement of microRNAs (miR-198) in pancreatic cancer, and how their dysregulation leads to pathogenesis. We are also currently exploring tumor-associated molecule targeted therapies and RNA interference delivery by liposomes and nanoparticles in vivo.  Our group has shown that vaccinating mice with chimeric virus- like particles containing MSLN significantly inhibited tumor progression, suggesting a new therapeutic vaccine strategy whereby MSLN is targeted to attempt to control pancreatic cancer progression.  We are also employing a K-ras mutation spontaneous pancreatic cancer mouse model, humanized tumor-bearing mouse model, and patient-derived xenograft (PDX) model to study prevention and the potential of our therapeutic regimens in pancreatic cancer.


Funded Studies

  1. A novel miR-198 replacement therapy for pancreatic cancer
    Agency: NIH/NCI R01
  2. Rational Selection of PDAC Samples for Evaluating Immunotherapy Efficacy in PDX-bearing Humanized Mouse Model
    Agency: CPRIT BCM PDX Core
  3. Pancreatic cancer PDX genomic profiling and characterization
    Agency: CPRIT BCM PDX Core
  4. Lymphatic delivery of checkpoint blockade inhibitors for more effective immunotherapy
    Agency: CPRIT 
  5. Stratification of Pancreatic Cancer Subpopulations for Effective Immunotherapy
    Agency: VA CSR&D Merit Award 1 I01 CX001822-01A2
  6. Patient derived classifier for PDAC subtyping to identify responders to therapies
    Agency: Dan L Duncan Comprehensive Cancer Center Seed Fund
  7. Developing a New SCID Swine Pancreatic Ductal Adenocarcinoma Model 
    Agency: St. Luke’s Foundation, Phillip Salem Cancer Research Award
  8. CCSG supplement: PDX Development and Trial Centers Research Network (PDXNet). Development of MTAP targeted combination therapy in pancreatic cancer PDX model
    Agency: NIH U54 supplement
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