Principal Investigator

Guido Erwin Michael
Awardee Organization

University Of California Los Angeles
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Chemoprevention and mechanisms of obesity-promoted pancreatic adenocarcinoma

The Program Project Grant “Chemoprevention and mechanisms of obesity-promoted pancreatic adenocarcinoma” constitutes a highly collaborative, multidisciplinary research program designed to make a significant impact on the investigation of obesity in the development of pancreatic cancer. A detailed understanding of the biological mechanisms of action of obesity on pancreatic cancer development can form the rationale for biologically-based practices, scientifically-founded recommendations and interventional strategies in the prevention of this disease. The Program Project includes expertise from the UCLA campus and Cedars Sinai Medical Center. The Program is led by experienced pancreatic cancer researchers, who have organized investigative teams to develop highly interactive and synergistic research programs. The goal is to study the mechanisms, by which obesity promotes pancreatic cancer development and to explore interventional, cancerpreventing strategies. Innovative animal and cell culture models and novel concepts strongly supported by a wealth of preliminary data are proposed. The Projects will focus on: Adipose tissue inflammation in obesitypromoted pancreatic cancer (Project 1); Chemoprevention of pancreatic cancer with lipid-lowering and antidiabetic agents (Project 2); Role of the pancreatic fibro-inflammatory microenvironment in obesitypromoted pancreatic cancer (Project 3). The projects will utilize an Administrative Core (with Biostatistics SubCore) and a Shared Resource Core, the Animal and Cell Models Core (with Pathology Sub-Core). An External Advisory Board comprised of nationally and internationally recognized translational pancreatic cancer investigators and advocates has been assembled. The Program Project is designed for maximum integration and synergy of research and key investigators, who have been collaborating for more than 12 years so that the proposed Program can be focused on the most promising investigations with the greatest translational potential and impact.


  • Wang H, Li X, Lai LA, Brentnall TA, Dawson DW, Kelly KA, Chen R, Pan S. X-aptamers targeting Thy-1 membrane glycoprotein in pancreatic ductal adenocarcinoma. Biochimie. 2021 Feb;181:25-33. Epub 2020 Nov 23. PMID: 33242496
  • Pandol SJ, Forsmark CE, Consortium for the Study of Chronic Pancreatitis Diabetes and Pancreatic Cancer (CPDPC). Consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer: achievements and future directions. Current opinion in gastroenterology. 2021 Sep 1;37(5):486-490. PMID: 34156036
  • Pan S, Brand RE, Lai LA, Dawson DW, Donahue TR, Kim S, Khalaf NI, Othman MO, Fisher WE, Bronner MP, Simeone DM, Brentnall TA, Chen R. Proteome heterogeneity and malignancy detection in pancreatic cyst fluids. Clinical and translational medicine. 2021 Aug;11(8):e506. PMID: 34459141
  • Lew D, Kamal F, Phan K, Randhawa K, Cornwell S, Bangolo AI, Weissman S, Pandol SJ. Epidemiologic risk factors for patients admitted with chronic pancreatitis and pancreatic ductal adenocarcinoma in the United States. World journal of clinical oncology. 2022 Nov 24;13(11):907-917. PMID: 36483975
  • Barreto SG, Habtezion A, Gukovskaya A, Lugea A, Jeon C, Yadav D, Hegyi P, Venglovecz V, Sutton R, Pandol SJ. Critical thresholds: key to unlocking the door to the prevention and specific treatments for acute pancreatitis. Gut. 2021 Jan;70(1):194-203. Epub 2020 Sep 24. PMID: 32973069
  • Arjani S, Saint-Maurice PF, Julián-Serrano S, Eibl G, Stolzenberg-Solomon R. Body Mass Index Trajectories Across the Adult Life Course and Pancreatic Cancer Risk. JNCI cancer spectrum. 2022 Nov 1;6. (6). PMID: 36255251
  • Jeon CY, Kim S, Lin YC, Risch HA, Goodarzi MO, Nuckols TK, Freedland SJ, Pandol SJ, Pisegna JR. Prediction of Pancreatic Cancer in Diabetes Patients with Worsening Glycemic Control. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022 Jan;31(1):242-253. Epub 2021 Nov 2. PMID: 34728468
  • Eibl G, Rozengurt E. Obesity and Pancreatic Cancer: Insight into Mechanisms. Cancers. 2021 Oct 10;13. (20). PMID: 34680216
  • Ketavarapu V, Ravikanth V, Sasikala M, Rao GV, Devi CV, Sripadi P, Bethu MS, Amanchy R, Murthy HVV, Pandol SJ, Reddy DN. Integration of metabolites from meta-analysis with transcriptome reveals enhanced SPHK1 in PDAC with a background of pancreatitis. BMC cancer. 2022 Jul 19;22(1):792. PMID: 35854233
  • Eibl G. Endocrine-exocrine signals in obesity-associated pancreatic cancer. Nature reviews. Gastroenterology & hepatology. 2020 Aug;17(8):455-456. PMID: 32483354
  • Aguilera KY, Dawson DW. WNT Ligand Dependencies in Pancreatic Cancer. Frontiers in cell and developmental biology. 2021 Apr 28;9:671022. doi: 10.3389/fcell.2021.671022. eCollection 2021. PMID: 33996827
  • Anwar T, Sinnett-Smith J, Jin YP, Reed EF, Rozengurt E. Ligation of HLA Class I Molecules Induces YAP Activation through Src in Human Endothelial Cells. Journal of immunology (Baltimore, Md. : 1950). 2020 Oct 1;205(7):1953-1961. Epub 2020 Aug 26. PMID: 32848033
  • Bogumil D, Conti DV, Sheng X, Xia L, Shu XO, Pandol SJ, Blot WJ, Zheng W, Le Marchand L, Haiman CA, Setiawan VW. Replication and Genetic Risk Score Analysis for Pancreatic Cancer in a Diverse Multiethnic Population. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020 Dec;29(12):2686-2692. Epub 2020 Sep 21. PMID: 32958499
  • Sinnett-Smith J, Anwar T, Reed EF, Teper Y, Eibl G, Rozengurt E. Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer Cells: Implications for Targeted Therapy. Molecular cancer therapeutics. 2022 Nov 3;21(11):1652-1662. PMID: 35999654
  • Teper Y, Eibl G. Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer. Cancers. 2020 Jul 17;12. (7). PMID: 32709161
  • Park JY, King J, Reber H, Joe Hines O, Mederos MA, Wang HL, Dawson D, Wainberg Z, Donahue T, Girgis M. Poorly differentiated histologic grade correlates with worse survival in SMAD4 negative pancreatic adenocarcinoma patients. Journal of surgical oncology. 2021 Feb;123(2):389-398. Epub 2020 Nov 4. PMID: 33146409
  • Hu C, Yin L, Chen Z, Waldron RT, Lugea A, Lin Y, Zhai X, Wen L, Han YP, Pandol SJ, Deng L, Xia Q. The unique pancreatic stellate cell gene expression signatures are associated with the progression from acute to chronic pancreatitis. Computational and structural biotechnology journal. 2021 Nov 26;19:6375-6385. doi: 10.1016/j.csbj.2021.11.031. eCollection 2021. PMID: 34938413
  • Huang BZ, Liu L, Zhang J, USC Pancreas Research Team, Pandol SJ, Grossman SR, Setiawan VW, Okwo C, Han B, Lenz HJ, Hill R. Rising Incidence and Racial Disparities of Early-Onset Pancreatic Cancer in the United States, 1995-2018. Gastroenterology. 2022 Jul;163(1):310-312.e1. Epub 2022 Mar 11. PMID: 35288111
  • Aguilera KY, Le T, Riahi R, Lay AR, Hinz S, Saadat EA, Vashisht AA, Wohlschlegel J, Donahue TR, Radu CG, Dawson DW. Porcupine Inhibition Disrupts Mitochondrial Function and Homeostasis in WNT Ligand-Addicted Pancreatic Cancer. Molecular cancer therapeutics. 2022 Jun 1;21(6):936-947. PMID: 35313331
  • Kenner B, Chari ST, Kelsen D, Klimstra DS, Pandol SJ, Rosenthal M, Rustgi AK, Taylor JA, Yala A, Abul-Husn N, Andersen DK, Bernstein D, Brunak S, Canto MI, Eldar YC, Fishman EK, Fleshman J, Go VLW, Holt JM, Field B, Goldberg A, Hoos W, Iacobuzio-Donahue C, Li D, Lidgard G, Maitra A, Matrisian LM, Poblete S, Rothschild L, Sander C, Schwartz LH, Shalit U, Srivastava S, Wolpin B. Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review. Pancreas. 2021 Mar 1;50(3):251-279. PMID: 33835956
  • Ako S, Teper Y, Ye L, Sinnett-Smith J, Hines OJ, Rozengurt E, Eibl G. Statins Inhibit Inflammatory Cytokine Production by Macrophages and Acinar-to-Ductal Metaplasia of Pancreatic Cells. Gastro hep advances. 2022;1(4):640-651. Epub 2022 Apr 25. PMID: 36313271
  • Wang R, Nissen NN, Zhang Y, Shao C, Chu CY, Huynh C, Posadas EM, Tomlinson JS, Lewis MS, Pandol SJ. Circulating Fatty Objects and Their Preferential Presence in Pancreatic Cancer Patient Blood Samples. Frontiers in physiology. 2022 Feb 14;13:827531. doi: 10.3389/fphys.2022.827531. eCollection 2022. PMID: 35237181
  • Farias AJ, Streicher SA, Stram DO, Wang S, Pandol SJ, Le Marchand L, Setiawan VW. Racial/ethnic disparities in weight or BMI change in adulthood and pancreatic cancer incidence: The multiethnic cohort. Cancer medicine. 2021 Jun;10(12):4097-4106. Epub 2021 May 16. PMID: 33998145
  • Li C, Peng Z, Wang Y, Lam G, Nissen N, Tang J, Yuan X, Lewis M, Greene MI, Pandol SJ, Wang Q. Epithelial cell transforming 2 is regulated by Yes-associated protein 1 and mediates pancreatic cancer progression and metastasis. American journal of physiology. Gastrointestinal and liver physiology. 2021 Mar 1;320(3):G380-G395. Epub 2021 Jan 27. PMID: 33501895
  • Eibl G, Rozengurt E. Metformin: review of epidemiology and mechanisms of action in pancreatic cancer. Cancer metastasis reviews. 2021 Sep;40(3):865-878. Epub 2021 Jun 17. PMID: 34142285
  • Truong E, Pandol S, Jeon C. Uniting epidemiology and experimental models: pancreatic steatosis and pancreatic cancer. EBioMedicine. 2022 May;79:103996. Epub 2022 Apr 8. PMID: 35405390
  • Che M, Kweon SM, Teo JL, Yuan YC, Melstrom LG, Waldron RT, Lugea A, Urrutia RA, Pandol SJ, Lai KKY. Targeting the CBP/β-Catenin Interaction to Suppress Activation of Cancer-Promoting Pancreatic Stellate Cells. Cancers. 2020 Jun 5;12. (6). PMID: 32516943
  • Massoumi RL, Teper Y, Ako S, Ye L, Wang E, Hines OJ, Eibl G. Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells. Pancreas. 2021 Apr 1;50(4):524-528. PMID: 33939664
  • Anwar T, Sinnett-Smith J, Jin YP, Reed EF, Rozengurt E. Lipophilic Statins Inhibit YAP Nuclear Localization, Coactivator Activity, and Migration in Response to Ligation of HLA Class I Molecules in Endothelial Cells: Role of YAP Multisite Phosphorylation. Journal of immunology (Baltimore, Md. : 1950). 2023 Apr 15;210(8):1134-1145. PMID: 36881871
  • Jin YP, Nevarez-Mejia J, Terry AQ, Sosa RA, Heidt S, Valenzuela NM, Rozengurt E, Reed EF. Cross-Talk between HLA Class I and TLR4 Mediates P-Selectin Surface Expression and Monocyte Capture to Human Endothelial Cells. Journal of immunology (Baltimore, Md. : 1950). 2022 Oct 1;209(7):1359-1369. Epub 2022 Sep 2. PMID: 36165200
  • Rozengurt E, Eibl G. Crosstalk between KRAS, SRC and YAP Signaling in Pancreatic Cancer: Interactions Leading to Aggressive Disease and Drug Resistance. Cancers. 2021 Oct 13;13. (20). PMID: 34680275
  • Wei Q, Qi L, Lin H, Liu D, Zhu X, Dai Y, Waldron RT, Lugea A, Goodarzi MO, Pandol SJ, Li L. Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What's Known and What's to Know. Frontiers in physiology. 2020 Oct 28;11:570276. doi: 10.3389/fphys.2020.570276. eCollection 2020. PMID: 33250773
  • Mehta RM, Pandol SJ, Joshi PR. Idiopathic chronic pancreatitis: Beyond antioxidants. World journal of gastroenterology. 2021 Nov 21;27(43):7423-7432. PMID: 34887640
  • Liu Y, Yang Y, Xu C, Liu J, Chen J, Li G, Huang B, Pan Y, Zhang Y, Wei Q, Pandol SJ, Zhang F, Li L, Jin L. Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity. Nature communications. 2023 Jan 21;14(1):351. PMID: 36681689
  • Farias AJ, Wu AH, Porcel J, Marchand LL, Wilkens LR, Monroe KR, Maskarinec G, Pandol SJ, Setiawan VW. Diabetes-Related Complications and Pancreatic Cancer Incidence in the Multiethnic Cohort. JNCI cancer spectrum. 2020 May 4;4(5):pkaa035. doi: 10.1093/jncics/pkaa035. eCollection 2020 Oct. PMID: 33134820
  • Huang BZ, Wang S, Bogumil D, Wilkens LR, Wu L, Blot WJ, Zheng W, Shu XO, Pandol SJ, Le Marchand L, Setiawan VW. Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts. International journal of cancer. 2021 Apr 12. Epub 2021 Apr 12. PMID: 33844845
  • Moore AM, Zhou L, Cui J, Li L, Wu N, Yu A, Poddar S, Liang K, Abt ER, Kim S, Ghukasyan R, Khachatourian N, Pagano K, Elliott I, Dann AM, Riahi R, Le T, Dawson DW, Radu CG, Donahue TR. NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition. Proceedings of the National Academy of Sciences of the United States of America. 2021 Feb 23;118. (8). PMID: 33597293
  • Mancinelli G, Torres C, Krett N, Bauer J, Castellanos K, McKinney R, Dawson D, Guzman G, Hwang R, Grimaldo S, Grippo P, Jung B. Role of stromal activin A in human pancreatic cancer and metastasis in mice. Scientific reports. 2021 Apr 12;11(1):7986. PMID: 33846512