NIH Funded Projects

The Hirshberg Foundation for Pancreatic Cancer Research is proud to announce the following NIH awards, granted to UCLA Investigators who have been Seed Grant recipients from the Foundation.

The National Institutes of Health recognition represents a milestone for the Foundation’s mission of funding discoveries of the cause, cure and prevention of pancreatic cancer.

We extend our Congratulations to the following recipients:

Chymotrypsin in pancreatitis

Principle Investigator: Miklos Sahin-Toth
Dates: 04/01/2021 – 12/31/2024
Total Amount: $495,855

Description:

The current grant proposal will investigate how genetic changes in the digestive enzyme chymotrypsin increase susceptibility for pancreatitis, a progressive inflammatory disease of the pancreas. The underlying hypothesis is that chymotrypsin deficiency results in pancreatitis in the context of additional genetic or environmental risk factors. Results from this study can advance the development of novel therapeutic and preventive interventions for acute and chronic pancreatitis in humans.

Targeting KRAS and adenosine mediated immunosuppression in pancreatic cancer

Principle Investigator: Caius Gabriel Radu, Timothy R Donahue, Zev A Wainberg
Dates: 03/01/2021 – 02/28/2026
Total Amount: $634,454

Description:

Immunotherapy has revolutionized the way we treat a number of malignancies, but to date its impact in pancreatic cancer has been marginal. We know, for example, that conventional immune checkpoint inhibitors approved for use in melanoma, lung cancer, and other solid tumors show little or no benefit for the vast majority of pancreatic cancer patients, and that additional “priming” of the immune system will be absolutely necessary to overcome the intrinsic resistance of pancreatic tumors to immunotherapy. To achieve this goal, we will study in preclinical models of pancreatic cancer and in a clinical trial a new immunotherapeutic strategy that combines drugs across several therapeutic classes shown by our data to be highly interdependent.

Leveraging Vulnerabilities Induced by STING Activation in Pancreatic Cancer

Principle Investigator: Caius Gabriel Radu, Timothy R Donahue
Dates: 02/15/2021 – 01/31/2026
Total Amount: $630,802

Description:

STING agonists are a promising anticancer treatment currently being explored in pancreatic ductal adenocarcinoma (PDAC), a disease which is notoriously resistant to current therapies. A systematic metabolomic and proteomic profiling identified previously unappreciated consequences of STING activation in PDAC malignant cells, specifically the depletion of nucleotide pools and activation of the replication stress response pathway. This proposal will examine mechanistic underpinnings of these observations and will test rationally designed therapies with the goal of defining new therapeutic options for PDAC for future clinical translation.

Chemoprevention and mechanisms of obesity-promoted pancreatic adenocarcinoma

Principle Investigator: Miklos Sahin-Toth
Dates: 07/01/2018–03/31/2023
Total Amount: $487,848

Description:

The current grant proposal will investigate how mutations in the gene for the pancreatic digestive enzyme trypsinogen induce or increase susceptibility for pancreatitis, a progressive inflammatory disease of the pancreas. Results from this study can advance the development of novel therapeutic and preventive interventions for acute and chronic pancreatitis in humans.

Molecular pathomechanism of hereditary pancreatitis

Principle Investigator: Miklos Sahin-Toth
Dates: 09/30/2015–06/30/2021
Total Amount: $351,000

Description:

The current grant proposal investigates how mutations in the gene for the pancreatic digestive enzyme carboxypeptidase A1 (CPA1) increase the risk for chronic pancreatitis, a progressive inflammatory disease of the pancreas. Results from this study can advance the development of novel diagnostic and therapeutic interventions for all forms of human pancreatitis.

Authentic mouse model of PRSS1-related hereditary pancreatitis

Principle Investigator: Zsanett Jancso, Miklos Sahin-Toth
Dates: 03/01/2020-02/28/2022
Total Amount: $312,000
DOD, Congressionally Directed Medical Research Programs: Discovery Award

Description:

Chronic pancreatitis is a relapsing-recurring inflammatory disorder of the pancreas characterized by destruction of pancreatic acinar and islet cells, inflammatory cell infiltration, fibrosis, and calcifications within the pancreatic ducts. These morphological changes typically result in the clinical symptoms/diseases of malabsorption, abdominal pain, and diabetes mellitus. Chronic pancreatitis increases the risk for pancreatic cancer. Owing to the unavailability of specific therapy and the persistent and often severe symptoms, the cost of lifelong supporting care for Veterans and active military personnel presents a significant financial and logistical challenge for the military healthcare system. Animal models that mimic features of human chronic pancreatitis are essential for understanding the disease mechanism and for the development of new therapeutic and preventive approaches. The aim of the present proposal is to generate and characterize a preclinical mouse model of hereditary pancreatitis. This new model will carry a mutation that is frequently found in patients with hereditary pancreatitis. These mice are expected to develop pancreatitis spontaneously or show increased sensitivity to experimentally elicited pancreatitis. The proposed experiments will generate much-needed insight into the pathological mechanisms of chronic pancreatitis and open up new avenues for therapy and prevention.

PET Imaging-guided Personalized Therapy in Pancreatic Cancer

Principle Investigator: Caius Gabriel Radu, Timothy R Donahue, Johannes Czernin
Dates: 08/18/2014 – 07/31/2020
Total Amount: $585,018

Description:

Oncologists now face the challenging decision of how to best treat pancreatic cancer given the recent FDA approval of the gemcitabine/Abraxane combination and the emergence of new chemotherapeutic regimens. To address this unmet clinical need and enable a more personalized approach to pancreatic cancer treatment, we will develop a new non-invasive companion biomarker to gemcitabine/Abraxane which will allow the identification of patients who are likely responders to this combination at the beginning of their therapy.

NCI/NIH

Principle Investigator: U01 Nel, Meng, Zink, Donahue (Multi-PIs)
Dates: 11/01/15 – 10/31/20
Total Amount: $2,391,050

Description: UCLA Multifunctional Nanotherapeutics Platform for Treatment of Pancreas Cancer

Hirshberg Foundation

Principle Investigator: Meng
Dates: 11/15/15 – 11/14/16
Total Amount: $30,000

Description: Targeted delivery of irinotecan by the combined use of a transcytosis-inducing iRGD peptide and mesoporous silica nanoparticle for pancreatic cancer treatment

NSF grant

Principle Investigator: Li
Dates: 11/01/14 – 10/31/18
Total Amount: $100,000

Description: Thermal Drawing of Fibers with Individually Addressable Nanoelectrode Array for Cellular Electrophysiology

P&F grant

Principle Investigator: Meng
Dates: 08/01/16 – 07/31/17
Total Amount: $30,000

Description: Custom Design of Polyrotaxane Nanocarrier for CRISPR/Cas9 Delivery in DMD

NIH NIDDK P30 DK41301

Principle Investigator: Dr. Enrique Rozengurt
Dates: 11/30/2014 – 11/30/2019
Total Amount: $701,247/year

Description: CURE: Digestive Diseases Research Center

The major goals of this P30 Core Grant are to support multidisciplinary research, transfer of information and the award of seed grants. The CURE: Digestive Diseases Research Core Center Grant supports multiple Scientific Cores, a Pilot and Feasibility Program, the recruitment of a Named New Investigator and an array of Enrichment Activities regarding the function and diseases of the digestive system, including the pancreatic inflammation and cancer.

NIH NIDDK 5 R01 DK100405

Principle Investigator: Dr. Enrique Rozengurt
Dates: 06/01/2014-07/31/2018
Total Amount: $217,500/year

Description: PKD1 Signaling and Crosstalk Mechanisms in Intestinal Epithelial Cell Regulation

The major goals of this project are to: 1) Characterize the role of PKD1 signaling in intestinal epithelial cell proliferation in vivo and in stem cell-derived intestinal organoids. 2) Characterize crosstalk mechanisms between PKD1 and β-catenin signaling systems in intestinal epithelial cells. 3) Identify a novel mechanism of PKD1 regulation through PAK-mediated PKD1 phosphorylation at the N-terminal residue Ser203.

NIH NCI P01CA163200

Principle Investigator: Project 2: Dr. Enrique Rozengurt
Dates: 08/01/2012-07/31/2017
Total Amount: $132,279/year

Description: Chemoprevention of pancreatic cancer with anti-diabetic agents

The long term aim of this project is to characterize the chemo-preventive effects of metformin on the progression of PanINs using the conditional KrasG12D model subjected to standard or a high fat, high calorie diet (HFCD).

Department of Veteran Affairs IBX001473A

Principle Investigator: Dr. Enrique Rozengurt
Dates: 04/01/2012-03/31/2016
Total Amount: $150,000/year

Description: Calcium-Sensing Receptor Signaling In The Regulation Of Colonic Epithelial Cells

The major goals of this project are to: 1). Characterize the role of the CaSR in colon epithelial cell proliferation, differentiation, and cancer using a novel CaSR GI tract-specific knock-out mouse model. 2).Identify the signal transduction pathways that mediate the decrease in β-catenin phosphorylation at Ser-552 and Ser-675 in response to CaSR stimulation in colon-derived epithelial cells. 3) Characterize β-catenin sub-cellular distribution and transcriptional activity in response to CaSR stimulation in colon-derived epithelial cells.

NIH/NCI P01 CA163200-01A1 (Guido Eibl, MD)

Dates: 07/2012 – 07/2017
Total Costs: $7,500,000

Description: Targeting Diet-Induced Promotion of Kras-initiated Pancreatic Adenocarcinoma

The purpose of this study is to unravel the mechanisms by which obesity enhances pancreatic cancer development. In addition, strategies to prevent obesity-induced pancreatic cancer will be investigated.

Hirshberg Foundation for Pancreatic Research Sponsored Biobank

Principal Investigator: Dawson
Dates: 07/01/05 – present
Total Amount: $25,000 per annum

Description: UCLA Pancreatic Tissue Bank

This grant supports efforts to bank fresh pancreatic tumor tissues from surgical resection specimens and the creation of pancreatic tissue microarrays from archival FFPE material.

American Cancer Society RSG-12-083-01-TBG

Principal Investigator: Dawson
Dates: 01/2012 – 12/2015
Total Costs: $720,000

Description: Regulation and therapeutic targeting of Wnt signaling in pancreatic cancer

This award investigates mechanisms responsible for deregulated Wnt signaling in pancreatic cancer and their potential therapeutic implications.

David Geffen School of Medicine, UCLA Spitzer Grant

Principal Investigator: Dawson
Dates: 04/2015 – 3/2016
Total Costs: $30,000

Description: Global proteomic changes linked to the therapeutic efficacy of Wnt inhibitors in pancreatic cancer

This seed grant utilizes global proteomics approaches to more broadly define the biochemical changes associated with inhibitors of Wnt ligand secretion.

UCLA Department of Pathology Translational Research Grant

Principal Investigator: Dawson
Dates: 07/01/09 – 06/30/11
Total Amount: $8,000

Description: Evaluation of prognostic and predictive biomarkers in periampullary cancer by tissue microarray

This seed grant will create a periampullary neoplasm tissue microarray of 250 archival specimens with linked clinical information to be used for biomarker discovery and validation.

NIH/NCI P01 CA163200-01A1

Principal Investigator: Eibl
Dates: 07/2012 – 07/2017
Total Costs: $7,500,000

Description: Targeting Diet-Induced Promotion of Kras-initiated Pancreatic Adenocarcinoma

The purpose of this study is to unravel the mechanisms by which obesity enhances pancreatic cancer development. In addition, strategies to prevent obesity-induced pancreatic cancer will be investigated.

NIH/NIDDK P01 DK098108

Principal Investigator: Gukovskaya
Dates: 07/2014 – 06/2019
Total Costs: $7,500,000

Description: Organelle Disorders in Pancreatitis

This Program Project investigates pathogenic mechanisms of pancreatitis resulting from dysfunction of key acinar cell organelles.

NIH Reference #1 P01 AT003960-01A1

Principal Investigator: Dr. Vay Liang W. Go
Date of Grant: 09/30/2007 – 09/29/2012
Funding Institution: National Institutes of Health / National Center for Complementary and Alternative Medicine
Total Amount: $5,675,865

Description: UCLA Center for Excellence in Pancreatic Diseases

The goal of this Center for Excellence is to study phytonutrient mechanism of action in both inflammatory and proliferative diseases of the pancreas using molecular biology and metabolomics technology to investigate altered cellular functions.

NIH Reference #1 R01 CA123273-01A1

Principal Investigator: Dr. Anthony Heaney
Date of Grant: 10/01/2007 – 09/30/2012
Funding Institution: National Institutes of Health/National Cancer Institute
Total Amount: $1,250,000

Description: Refined Fructose Promotes Pancreatic Cell Growth

The goal of this application is to study the effects of diet rich in fructose on pancreatic cancer cells growth in vitro and in a tumor model.

NIH Reference #1 R01 CA122042-01A1

Principal Investigator: Dr. Guido Eibl
Date of Grant: 08/01/2007 – 05/31/2012
Funding Institution: National Institutes of Health / National Cancer Institute
Total Amount: $1,463,000

Description: The Role of n-3 Polyunsaturated Fatty Acids in Pancreatic Cancer

This project is designed to explore the efficacy of n-3 polyunsaturated fatty acids in therapy and prevention of pancreatic cancer using xenograft and transgenic animal models of the disease.

NIH Reference #1 R01 CA104627

Principal Investigator: Dr. Guido Eibl
Date of Grant: 02/01/2004 – 02/29/2009
Funding Institution: National Institutes of Health / National Cancer Institute
Total Amount: $1,100,000

Description: The Role of COX-2 and PPARY in Pancreatic Cancer

NIH Reference #R01 DK55003

Principal Investigator: Dr. Enrique Rozengurt
Date of Grant: 02/28/2008 – 05/30/12
Funding Institution: National Institutes of Health/ National Institute of Diabetes and Digestive And Kidney Diseases
Total Amount: $1,637,250

Description: Gastrointestinal Peptide Signaling through PKC/PKD

The major goals of this project are to characterize the activation of the PKC/PKD pathway and define the role of PKD in proliferative signal transduction in gastrointestinal (GI) cells.

NIH Reference #R01 DK56930

Principal Investigator: Dr. Enrique Rozengurt
Date of Grant: 05/30/2006 – 06/01/2011
Funding Institution: National Institutes of Health/ National Institute of Diabetes and Digestive And Kidney Diseases
Total Amount: $1,356,255

Description: GI Peptide signaling through tyrosine phosphorylation

The major goals of this project are to identify the role of GI peptide-induced tyrosine phosphorylation in signal transduction pathways implicated in cell migration and proliferation.

NIH Reference #P30 DK41301

Principal Investigator: Dr. Enrique Rozengurt
Date of Grant: 11/30/2009-11/30/2014
Funding Institution: National Institutes of Health/ National Institute of Diabetes and Digestive And Kidney Diseases
Total Amount: $4,725,000

Description: CURE: Digestive Diseases Research Center

The major goals of the P30 Core Grant are to support multidisciplinary research, transfer of information and the award of seed grants. The CURE: Digestive Diseases Research Core Center Grant supports multiple Scientific Cores, a Pilot and Feasibility Program, the recruitment of a Named New Investigator and an array of Enrichment Activities regarding the function and diseases of the digestive system, including the exocrine pancreas.

NIH Reference #M01 RR00425-33

Principal Investigator: Dr. Paul Lee
Date of Grant: 12/01/2006 – 11/30/2011
Funding Institution: National Institutes of Health/National Center for Research Resources
Total Amount: $732,095

Description: Biomedical Mass Spectrometry Core

NIH Reference #5 P60 AA11999

Principal Investigator: Dr. Hidekazu Tsukamoto
Date of Grant: 01/01/2009 – 12/31/2014
Funding Institution: National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism
Total Amount: $756,165

Description: USC-UCLA Southern California Research Center for ALPD and Cirrhosis: Alcohol Abuse and Pancreatic Necrosis

The long-term objective of this project is to determine the role of PKC isotypes in ethanol- induced sensitization of the inflammatory response using in vitro and in vivo models of the pancreas.

VA Merit Award

Recipient: Dr. Anna Gukovskaya
Date of Grant: 10/01/2006 – 09/30/2010
Funding Institution: Department of Veterans Affairs
Total Amount: $980,000

Description: NOX4, Protein Tyrosine Phosphatases, and Pancreatic Cancer Cell Survival

This project is designed to determine the effects of pancreatic cancer Nox4 in regulating protein tyrosine phosphatases; and the role of phosphatases in mediating pancreatic cancer cell survival.

VA Merit Award

Recipient: Dr. Steve Pandol
Date of Grant: 10/01/2007 – 09/30/2011
Funding Institution: Department of Veterans Affairs
Total Amount: $500,000

Description: Inflammation Medicates Necrosis in Pancreatitis

This project is to determine the effects of infiltrating neutrophils; NADPH oxidase; pharmacologic and genetic inhibition of PI 3kinase; and genetic inhibition of PTEN on pancreatic apoptosis, necrosis, PTEN/Akt system and its downstream pro-apoptic targets during experimental pancreatitis.

AACR Foundation

Recipient: Dr. David Dawson
Date of Grant: 07/01/2008 – 06/30/2010
Funding Institution: American Association of Cancer Research
Total Amount: $200,000

Description: Wnt signaling in pancreatic cancer

NIH Reference #R21 CA137292

Principal Investigator: Dr. Enrique Rozengurt
Date of Grant: 05/01/2009 – 04/30/2011
Funding Institution: National Institutes of Health/National Cancer Institute
Total Amount: $338,000

Description: Targeting crosstalk between insulin and Gq signaling systems in pancreatic cancer

The major goals of this project are to characterize a novel crosstalk between insulin receptor and Gq signaling in human pancreatic cancer cell lines. Furthermore, we will test whether metformin inhibits this crosstalk and offers a novel approach for the treatment of human pancreatic cancer, using tumor xenogafts in nude mice.

NIH Reference #1 R21 CA124609-01A1

Principal Investigator: Dr. Oscar Joe Hines
Date of Grant: 07/01/2007 – 06/30/2009
Funding Institution: National Institutes of Health/National Cancer Institute
Total Amount: $308,000

Description: The Role of CXCR2 in Pancreatic Cancer

The study investigates the role of CXCR2 in pancreatic cancer biology and angiogenesis as well as determine chemokine and receptor expression in human specimen.

NIH Reference #1 R01 CA119025-01

Principal Investigator: Dr. Anna Gukovskaya
Date of Grant: 07/01/2006 – 05/31/2010
Funding Institution: National Institutes of Health/National Cancer Institute
Total Amount: $300,000

Description: NADPH Oxidase and Pancreatic Cancer Cell Survival

This project is designed to determine the mechanisms of growth factors-induced NADPH oxidase activation in pancreatic cancer cells, as well as the role of this activation in promoting pancreatic cancer cell survival.

NIH Reference #1 R01 CA104627

Principal Investigator: Dr. Guido Eibl
Date of Grant: 02/01/2004 – 02/29/2009
Funding Institution: National Institutes of Health/National Cancer Institute
Total Amount: $1,100,000

Description: The Role of COX-2 and PPARY in Pancreatic Cancer

NIH Reference #R21 AA016840

Principal Investigator: Dr. Ilya Gukovsky
Date of Grant: 07/01/2008 – 06/30/2010
Funding Institution: National Institutes of Health/ National Institute of Diabetes and Digestive And Kidney Diseases
Total Amount: $275,000

Description: Alcoholic Chronic Pancreatitis Results from Dysregulated Immune Response

This project is designed to determine the mechanism and role of immune regulation by ethanol in mediating chronic alcoholic pancreatitis.

NIH Reference #1 R21 AA015781-01

Principle Investigator: Dr. Aurelia Lugea
Date of Grant: 07/10/2006 – 06/30/2008
Funding Institution: National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism
Total Amount: $275,000

Description: Plasminogen System and Alcoholic Pancreatitis

This project is designed to determine the effects and role of changes in the plasminogen system in alcohol-induced pancreatic disease. There is no scientific or budgetary overlap with any other active or pending project.

VA Merit Award

Recipient: Dr. Anna Gukovskaya
Date of Grant: 10/01/2006 – 09/30/2010
Funding Institution: Department of Veterans Affairs
Total Amount: $980,000

Description: NOX4, Protein Tyrosine Phosphatases, and Pancreatic Cancer Cell Survival

This project is designed to determine the effects of pancreatic cancer Nox4 in regulating protein tyrosine phosphatases; and the role of phosphatases in mediating pancreatic cancer cell survival.

AGA Foundation

Recipient: Dr. Olga Mareninova
Date of Grant: 07/01/2007 – 06/30/2010
Funding Institution: Designated Research Scholar Award in Pancreatitis
Total Amount: $250,000

Description: Bcl-2 Proteins Regulate Death Responses of Acute Pancreatitis

This project is designed to determine the mechanism and role of immune regulation by ethanol in mediating chronic alcoholic pancreatitis.