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.

Ekihiro Seki, M.D., Ph.D. (UC, San Diego)
“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. (UC San Diego)
“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, 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.

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.

"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

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 Center)
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.