Pilot Projects 2017-04-13T12:00:19+00:00

Pilot Projects

The Center supports meritorious but unfunded studies as Pilot Projects to promote their growth into competitive projects that can attract support federal grants. The Pilot Project Program aims to stimulate the exploration of new, innovative research in pursuit of the Center’s themes and goals and to recruit new and qualified investigators into the field of alcoholic liver and pancreatic diseases and cirrhosis.

If you are interested in applying for pilot project funding, please click on how to apply.

2016

Selma Masri, Ph.D. (UCI)
“Investigating the role of alcohol as a zeitgeber on the gut and liver circadian”

Shabnam Shalapour, Ph.D. (UCSD)
“Role of IgA-producing plasmocytes in development of ASH, NASH and HCC”

Jun Xu, Ph.D. (UCSD)
“IL-17 SIGNALING REGULATES ALCOHOL-RELATED CHANGES OF LIVER-BRAIN AXIS”

2015

Paolo Sassone-Corsi, Ph.D. (UCI)
“Transcriptional and Epigenetic Reprogramming of the Circadian Clock by Alcohol”

Gen-Sheng Feng, Ph.D. (UCSD)
“Dissecting Shp2-regulated signals in alcoholic liver disorders”
The long term goal of this project is to dissect and decipher the putative role in alcoholic liver diseases (ALD) of signaling molecules that are known to be involved in the molecular pathogenesis of non-alcoholic liver diseases (NALD) and liver cancer development.

Keane Lai, M.D. (USC)
“The role of stearoyl-CoA desaturase in tumor-initiating stem-like cells”
Emerging evidence identifies stearoyl-CoA desaturase (SCD) as a mediator of stemness in tumor-initiating stem-like cells (TICs). This research is directed to understanding the mechanism by which SCD induces stemness in hepatic TICs.

Karsten Zengler, Ph.D. (UCSD)
“The role of the microbiome in alcoholic liver disease”
To determine the cause of dysbiosis and bacterial overgrowth and to identify gene products and metabolites from the gut microbiome that lead to alcoholic liver disease, we propose to study the effect of acetate on intestinal microorganisms. We will furthermore determine the transcriptional response of the microbiome to perturbation.

2014

Akiko Eguchi, Ph.D. (UCSD)
“Novel biomarkers and therapeutic targets focusing on extracellular vesicles in alcoholic liver disease”
We recently revealed that damaged hepatocytes release extracellular vesicles (EVs) in vitro and in a Non-alcoholic steatohepatitis (NASH) murine model. We will research whether EVs are released from damaged hepatocytes during alcohol exposure. Furthermore, we will investigate whether EVs activate HSCs and Kupffer cells, resulting in the progression of ALD.

Keane Lai, M.D. (USC)
“The role of stearoyl-CoA desaturase (SCD) in tumor-initiating stem-like cells (TICs) from alcohol-HCV induced HCC”
Emerging evidence identifies stearoyl-CoA desaturase (SCD) as a mediator of stemness in tumor-initiating stem-like cells (TICs). We propose that SCD is induced by β-catenin and SCD activity is required for sustained activation of β-catenin in TICs.

Ramachandran Murali, Ph.D. (Cedars-Sinai Medical Center)
“Decoy receptors in alcohol and tobacco mediated pancreas pathology”
This proposal seeks to understand the role of decoy receptors in pancreatic cancer due to smoking and
chronic alcohol abuse. We hyothesize that the decoy receptors are tumor survival factors. In this proposal, the expression of death receptors and decoy receptors will be documented by immunohistochemisty (IHC) and western blot analysis; pancreatic tissue of K-Ras mutant mouse model treated with and without smoking compound and alcohol, and human pancreatic tissues will be utilized.

Karsten Zengler, Ph.D. (UCSD)
“The role of the microbiome in alcoholic liver disease”
Alcoholic liver disease is dependent on gut-derived bacterial products. It has been demonstrated that alcoholic liver disease is associated with changes in the intestinal microflora with both qualitative (dysbiosis) and quantitative (intestinal bacterial overgrowth) differences. We propose to reveal these key microorganisms and to determine factors that are responsible to initiate dysbiosis in an animal model.

2013

Akiko Eguchi, Ph.D. (UCSD)
“Bid-dependent mitochondrial dysfunction and cell death in alcoholic liver disease”
We will research whether Bid activation in hepatocyte essential for mitochondrial dysfunction, whether suppression of Bid protects against hepatic steatosis and liver damage in ALD and whether Bid inhibition will be an effective approach for treatment of steatohepatitis and fibrosis in ALD. Furthermore, we investigate the communication of cell death between parenchymal and non-parenchymal cells in ALD. These results will reveal the contribution of mitochondrial dysfuction in cell death and propose the new thepapuetic approach.

Douglas E. Feldman, Ph.D. (USC)
“Genetic dissection of the mitochondrial UPR in liver tumor-initiating stem cells”
Emerging evidence indicates that impaired mitochondrial function plays a key role in alcoholic liver disease, liver steatosis and onset of hepatocellular carcinoma. The experimental aims set forth in this proposal address the mechanisms underlying oncogenesis by alcohol-induced mitochondrial dysfunction. These aims are well aligned with the funding program’s long term goals of mechanisms of alcohol-induced liver injury.

EekJoong Park, Ph.D. (UCSD)
“NOD2 inhibits alcohol-induced liver damage through activation of autophagy”
Alcoholic liver disease (ALD) is characterized by severe liver inflammation, steatosis and fibrosis, triggered by the endotoxin, lipopolysacchride (LPS), systemically entering into the liver. This project will demonstrate how NOD2, a pattern recognition receptor, prevents ALD development and will present a new therapeutic target for the treatment of ALD.

Jun Xu, Ph.D., M.D. (USC)
“Metabolomics Core of the Southern Calif. Research Center for ALPD and Cirrhosis”
Alcoholic liver disease (ALD) affects over 2 million people in the U.S. After decade effort in research of therapeutic targets, we still don’t have effective treatment when ALD progresses to the late stage of cirrhosis except liver transplantation. Therefore, new research approaches such as Metabolomics should be sought by the Center because many manifestations of ALD spectra reflect metabolic disturbance in the liver.

2012

EekJoong Park, Ph.D. (UCSD)
“NOD2 inhibits alcohol-induced liver damage through activation of autophagy”
This project will present a new mechanism by which NOD2 prevents TLR4-mediated ALD through activation of autophagy. Targeting these signaling events through TLR4-NOD2-mTOR-autophagy may lead to new therapies for the prevention of ALD.

Takeshi Saito, M.D., Ph.D. (USC)
“ETOH mediated deregulation of hepatic innate immunity that support HCV”
This proposed study is designed to investigate our central hypothesis “Alcohol metabolism in the hepatocytes establishes a platform for efficient HCV replication and deregulate antiviral innate immunity, resulting in the acceleration of liver fibrosis and refractory to antiviral therapy”

Jun Xu, Ph.D., M.D. (USC)
“Metabolomic Core for Southern California Research Center for ALPD and Cirrhosis”
Alcoholic liver disease and alcoholic pancreatitis are major life-style diseases in the United States. The proposed metabolomic studies will advance our understanding of pathogenesis and disease progress of the diseases, which would lead to development of early diagnostic markers and therapeutic targets.

2011

Jun Xu, M.D., Ph.D. (USC)
“Notch signaling in Nos2 activation and steatohepatitis by obesity and alcohol”
This proposal is aimed to study the role of notch signaling in proinflammatory (M1) activation of hepatic macrophage and its effect on steatohepatitis caused by obesity and alcohol feeding in mice. The causal link between glucose metabolism and M1 activation (Nos2 expression) will also be sought both in vitro and in vivo.

Michael Karin, Ph.D. (UCSD)
“IKK in alcoholic pancreatitis”
This project aims to investigate the role of IKK* and IKK*, the two catalytic subunits of IKK complex, in the pathogenesis of alcoholic pancreatitis development. We will determine whether loss of IKK* sensitizes mice to alcoholic pancreatitis. We will investigate the role of defective autophagy in this pathology and will examine how ethanol feeding affects IKK signaling in vivo, using mutant mice with pancreatic-specific deletions of IKK* or IKK*.

EekJoong Park, Ph.D. (UCSD)
“NOD2 inhibits alcohol-induced liver damage through suppression of mTOR signaling”
Alcoholic liver disease (ALD) is well-characterized to be associated with steatosis, inflammation (steatohepatitis), fibrosis, cirrhosis and in some case hepatocellular carcinoma. Toll-like receptor-4 (TLR4) is a major molecule to regulate this alcohol-induced inflammation and liver diseases. Interestingly, a recent study shows that TLR4 activation is inhibited by nucleotide-binding oligomerization domain containing 2 (NOD2), another pattern recognition receptor, in intestinal epithelial cells. Therefore, my project will investigate whether NOD2 activation can prevent TLR4-induced ALD including hepatosteatosis and fibrogenesis.

Takeshi Saito, M.D., Ph.D. (USC)
“ETOH mediated deregulation of hepatic innate immunity that support HCV”
This study is designed to investigate the pathogenesis of immune deregulation caused by the combination of HCV and alcoholic liver diseases (ALDs). This proposal also aims to investigate the link between innate immune deregulation and the progression of liver fibrosis through the understanding of inflammasomes formation by viral hepatitis and ALDs.

2010

Kinji Asahina, Ph.D. (USC)
“Hepatic stellate cell precursors in developing and fibrotic livers”
The study proposes to determine cell lineages of mesenchymal progenitor cells in developing livers and to isolate different liver mesenchymal cell types from adult livers.

Jingzhen (Jenny) Yuan, Ph.D. (UCLA)
“The role of protein kinase D in cell death in alcoholic pancreatitis”
This project is designed to investigate the potential role for a novel PKD1 signaling pathway in mediating alcohol abuse-induced necrosis in pancreatitis and to define the mitochondria-dependent and independent mechanisms by which PKD1 regulates alcohol-caused pancreatitis.

Michael Karin, Ph.D. (UCSD)
“IKK in alcoholic pancreatitis”
This study is to investigate the role of IKKa and IKKβ, the two catalytic subunits of IKK complex, in alcoholic pancreatitis development. Mutant mice with pancreatic-specific deletion of IKKα or IKKβ will be used to determine whether and how the loss of IKKα could sensitize alcoholic pancreatitis by enhanced defective autophagy and how ethanol feeding affects IKKβ/NFkB signaling in vivo.

Fawzia Bardag-Gorce, Ph.D. (UCLA)
“Non toxic low dose of proteasome inhibitor reduces oxidative stress”
This pilot study investigates the attenuation of ethanol-induced oxidative stress by using proteasome inhibitor treatment. It also investigates the beneficial effects of proteasome inhibitor treatment in reducing the ethanol-induced steatosis.

Bernd Schnabl, M.D. (UCSD)
“Early bacterial translocation as mechanism for alcohol-induced liver fibrosis progression”
The major goal is to investigate bacterial translocation and it’s relevance to liver injury in an animal model of intragastric alcohol feeding. In addition, quantitative and qualitative changes in the enteric microbiome are assessed.

2009

Kinji Asahina, Ph.D. (USC)
“Hepatic stellate cell precursors in developing and regenerating livers”
This project pursues to isolate and characterize different mesenchymal cell types in developing livers, to test differentiation potential of submesothelial cells, and to determine whether capsular fibroblasts express the markers of submesothelial cells in adult liver.

Ekihiro Seki, M.D., Ph.D. (UCSD)
“TLR4 regulates the activation of hepatic stellate cells and Kupffer cells in alcoholic liver fibrosis”
This study is receiving the second year of pilot project support from the Center and examines the role of TLR4, the receptor for endotoxin, on hepatic stellate cells and Kupffer cells in the pathogenesis of alcoholic liver disease by using genetic chimeric mice in which TLR4 expression on these two cell types is manipulated by transplantation of bone marrow cells. The study further examines TLR4-inducible gene expression in hepatic stellate cells in alcoholic liver disease.

Jingzhen (Jenny) Yuan, Ph.D. (UCLA)
“The role of protein kinase D1 in alcohol-induced pancreatitis”
This study is to investigate whether the novel protein kinase PKD1 is a key downstream participant in the PKC signal transduction pathways mediating regulatory effects of ethanol on the activation of proinflammatory transcription factors and cell death pathways.

Bernd Schnabl, M.D. (UCSD)
“Early bacterial translocation as mechanism for alcohol-induced liver fibrosis progression”
This project aims to assess the enteric microbiota and bacterial translocation to the systemic circulation in the early course of alcohol-induced liver injury and fibrosis, and to define a mechanism by which alcohol causes intestinal bacterial overgrowth.

Hyeongnam (Joe) Jeong (USC)
“Identification of novel transforming genes in hepatocellular carcinoma (HCC)”
The main purpose of this study is to identify specific transforming genes relating to HCC development through the use of a lentiviral cDNA expression library screen. A novelty of this approach is the use of immortalized liver progenitor (oval) cells as our targets for liver screening, as compelling evidence has identified oval cells as the cell-of-origin for HCC.

2008

Ekihiro Seki, M.D., Ph.D. (UCSD)
“The role of TLR4 in the activation of the hepatic stellate cells and Kupffer cells in alcoholic-induced fibrosis”
This study examines the role of TLR4, the receptor for endotoxin, on hepatic stellate cells and Kupffer cells in the pathogenesis of alcoholic liver disease by using genetic chimeric mice in which TLR4 expression on these two cell types is manipulated by transplantation of bone marrow cells.

Shuping Zhong, Ph.D. (USC)
“How does alcohol affect machinery and activity of RNA pol III transcription?”
This study is receiving the second year of pilot project support from the Center and is defining the role of RNA polymerase III transcription as a priming mechanism of alcohol-induced liver tumor formation.

Tatiana Kisseleva, Ph.D. (UCSD)
“Characterization of the role of fibrocytes in alcoholic liver disease”
This study investigates the origin, fate, and role of bone marrow-derived “fibrocytes” in the pathogenesis of alcoholic liver disease by utilizing innovative genetic mouse models and bone marrow transplantation technique.

2007

David Adelson, Ph.D. (VA/UCLA)
“Neural mechanisms potentiating CCK-induced pancreatitis in ethanol-fed rats”
The proposed study will use an in vivo urethane-anesthetized rat preparation to record impulse activity from splanchnic primary afferent neurons (SPANs) innervating the pancreas, in order to test the hypothesis that pancreatic SPANs in ethanol-fed rats are hyperresponsive, relative to pancreatic SPANs in normally-fed rats, to stimuli that induce acute pancreatitis. The mechanisms responsible for this SPAN hyperresponsiveness will also be investigated.

Vijay Kalra, Ph.D. (USC)
“Dynamics of gene expression and inflammation in liver sinusoidal endothelial cell”
The study proposes to study the effect of ethanol on the expression of cytochemokines (MCP-1, IL-8, MIP-1b, TNF-a, and IL-1b) , chemokine receptors (CCR2 and CCR5) and adhesion molecules (ICAM-1,VCAM-1 and E-selectin) in liver sinusoidal endothelial cells by RNase protection assay (RPA) using custom made RPA panel of probes

Keigo Machida, Ph.D. (USC)
“The role of TLR4 for oncogenic potential by HCV, alcohol, and diabetes”
This project investigates the mechanisms underlying synergistically increased risk of developing liver cancer in HCV core or NS5A transgenic mice exposed to alcohol or high cholesterol/fat diet.

Shuping Zhong, Ph.D. (USC)
“Mechanism of alcohol-induced liver cancer”
The study investigates whether alcohol affects RNA pol III transcription to uncover the mechanism of alcohol-associated human cancers

2006

Mamoru Ishii, Ph.D. (USC)
“Transcriptional regialtion of Msx2 gene by alcohol and its importance in alscohol liver diseases”
This study is aimed at determining whether FGF10 is involved in the proliferation and differentiation of liver progenitor cells from the budding foregut endoderm and whether FGF10 is involved in the regenerative process of the liver in response to injury and that this process is impaired during chronic exposure to alcohol.

Daryl Davies, Ph.D. (USC)
“The action of ehtanol on human peptide transporter activity”
This study examined alcohol-induced inhibition of human di- and tri-peptide transporter (hPepT1) activity as a possible pathophysiological mechanism of known reduction of micronutrient uptake by intestine of alcoholics.

Vijay Kalra, Ph.D. (USC)
“Dynamics of gene expression and inflammation in liver sinusoidal endothelial cell”
The study proposes to study the effect of ethanol on the expression of cytochemokines (MCP-1, IL-8, MIP-1b, TNF-a, and IL-1b) , chemokine receptors (CCR2 and CCR5) and adhesion molecules (ICAM-1,VCAM-1 and E-selectin) in liver sinusoidal endothelial cells by RNase protection assay (RPA) using custom made RPA panel of probes

Keigo Machida, Ph.D. (USC)
“The role of TLR4 for oncogenic potential by HCV, alcohol, and diabetes”
This project investigates the mechanisms underlying synergistically increased risk of developing liver cancer in HCV core or NS5A transgenic mice exposed to alcohol or high cholesterol/fat diet.

Xiao-Ming Ou, Ph.D. (USC)
“Alcohol liver injury mediated by monoamine oxidase B”
This pilot study investigates the effects of alcohol on transcription of monoamine oxidaseB gene as a potential mechanism of alcohol-induced toxicity

2005

Woojin An, Ph.D. (USC)
“Role of Ethanol-induced histone mark for p53 function”
This study aims to investigate whether p53-dependent induction of apoptosis of ethanol-damaged hepatocytes functionally correlate with histone acetylation and methylation to manipulate and utilize the chromatin structure

Mamoru Ishii, Ph.D. (USC)
“Transactional regialtion of Msx2 gene by alcohol and its importance in alcoholic liver diseases”.
This study aims to test whether Msx gene expression in HSC are crucial to molecular regulation of liver regeneration, and whether alcohol impairs liver regeneration via its inhibitory effects on Msx genes

Henry Lin, M.D. (USC)
“Endotoxemia and Liver Injury in Alcohol Liver Disease ”
This study aims to determine whether small intestinal bacterial overgrowth has a cause and effect relationship with endotoxemia and liver injury

Kasper Wang, M.D. (USC/CHLA)
“Role of FGF 10 in liver organogenesis and regeneration”
This study will determine whether FGF10 is involved in the proliferation and differentiation of biliary epithelium from the budding foregut endoderm., and whether FGF10 is involved in the regenerative process of the liver in response to injury and that this process is impaired during chronic exposure to alcohol

2004

Yuan-Ping Han, Ph.D. (USC)
“MMP-9 in the myofibroblastic activation of HSC”
This study seeks to further understand the molecular pathways whereby IL-1a regulates matrix melloproteinase expression and activation, and the specific function of the MMPs in liver fibrosis.

Ite Laird-Offringa, Ph.D. (USC)
“HuR-regulation of TNF alpha in alcoholic liver disease”
This study will examine whether methylation of HuR by CARM1 is increased in Kupffer cells from alcohol-treated liver, and whether that contributes to the increased TNFa levels observed in these cells following inflammatory stimuli.

Jian -Min Yuan, M.D. (USC)
“Pilot study of risk factors for alcoholic liver disease in Los Angeles”
This study seeks to assess the association between self-reported alcohol consumption and the risk of ALD; to determine the modifying roles of obesity, cigarette smoking, and dietary intake of antioxidants, fat and iron in the alcohol-ALD association; and to determine the modifying role of acetaminophen on the alcohol-ALD association.

Aurelia Lugea , Ph.D. (UCLA)
“Plasminogen system and alcohol-induced pancreatic fibrosis”
This project seeks to clarify the underlying mechanisms mediating alcohol-induced alterations in the PIg system and how these changes lead to fibrosis in the pancreas.

2003

Yuan-Ping Han, Ph.D. (USC)
Examined the mechanistic pathway for the induction and activation of matrix metallo-proteinases in liver damage induced by alcohol over dosage.

Joseph Reeve, Ph.D. (UCLA)
Determined the specific phosphorylation sites of PKC isoforms.

Bruce Runyon, M.D. ( Rancho Los Amigos Medical
Compared the use of corticosteroids versus pentoxifylline in the treatment of patients with severe alcoholic hepatitis.

Aurelia, Lugea Ph.D. (UCLA)
Examined the effect of ethanol and its metabolites, acetaldehyde and FAEEs, on components of the plasminogen activating system in rat pancreas.

2002

Gunther Dennert,, Ph.D. (USC)
Examined the effects of alcohol in a small animal model on lymphocyte immunity in the liver.

Chih -Lin Hsieh, Ph.D. (USC)
Dissected how ethanol causes chromosome breaks and to examine the sites of methylation change in rats treated with ethanol for short-term and long-term periods.

Bruce Runyon, M.D. ( Rancho Los Amigos Medical Center)
Compared the use of corticosteroids versus pentoxifylline in the treatment of patients with severe alcoholic hepatitis.

Zhiquin Tan, M.D., Ph.D. (USC)
Examined the effect of alcohol on viral infection in T-lymphocytes and to develop a therapeutic target to block HIV-1 infection.

Yvonne Wan, Ph.D. (Harbor-UCLA)
Determined the impact of interfering retinoid signaling at the receptor level on alcoholic liver disease.

2001

Laurie DeLeve, M.D., Ph.D. (USC)
Examined the changes in the specialized features of liver endothelial cells which are thought to be an initiating factor in alcoholic cirrhosis.

Gunther Dennert, Ph.D. (USC)
Examined the effects of alcohol in a small animal model on lymphocyte immunity in the liver.

Ilya Gukovsky, Ph.D. (VA/UCLA)
Developed an animal model for investigating chronic pancreatitis resulting from ethanol intake.

Xuan Liu, D.D.S., Ph.D. (Charles R. Drew University)
Examined the effect of alcohol on viral infection in T-lymphocytes and to develop a therapeutic target to block HIV-1 infection.

Vincent Wu, Ph.D. (VA/UCLA)
Examined the molecular mechanisms underlying alcohol-mediated sensitization of CCK actions on pancreatic acinar cells.

2000

Laurie DeLeve, M.D., Ph.D. (USC)
Examined the changes in the specialized features of liver endothelial cells which are thought to be an initiating factor in alcoholic cirrhosis.

Anna Gukovskaya, Ph.D. (VA/UCLA)
Examined the mechanisms of ethanol toxicity to pancreas that mediate alcoholic pancreatitis.

Ilya Gukovsky, Ph.D. (VA/UCLA)
The goal of the project was to develop a model of chronic alcohol-induced pancreatitis that can be used for further investigations into the mechanisms underlying the disorder.

Shelly Lu, M.D. (USC)
Examined how changes in methionine metabolism contribute to the pathogenesis of liver injury.

Steven Y. Sussman, Ph.D. & Clyde W. Dent, Ph.D. (USC)
Researched hospital discharge data in Los Angeles County to determine what groups have high prevalence of alcoholic liver and pancreatic disease.

Hal Yee, M.D., Ph.D. (UCLA)
Examined how alcoholic hepatitis, a consequence of acute and massive alcohol ingestion, results in internal bleeding and severe fluid retention.

1999

Anna Gukovskaya, Ph.D. (VA/UCLA)
Examined the mechanisms of ethanol toxicity to pancreas that mediate alcoholic pancreatitis.

Michael Lai, M.D. (USC) Examined the molecular mechanism of enhanced hepatotoxicity which occurs when alcoholic liver disease and hepatitis C virus infection are simultaneously present.