2006 Fall Research Awardees

Fellow: Betty Doan, Ph.D.
Mentor: Giovanni Parmigiani, Ph.D.
Johns Hopkins University

This project focuses on lung cancer. To make screenings such as CT scans and chest x-rays more accurate for early detection of lung cancer, Drs. Doan and Parmigiani aim to create a risk prediction model for lung cancer. The risk prediction model will be able to identify those at greatest risk for developing lung cancer. The model will use family and smoking history to estimate risk scores, the chance of having disease or a disease mutation. The risk score will be used in a screening decision tool to identify optimal ages to start a screening regimen and the optimal test frequency that corresponds to the highest chance of detecting disease. The risk score will also be used to identify families that may be more genetically caused (i.e., higher scores) to enhance the ability to find disease gene locations. Knowing these locations will help identify the disease gene, and genetic testing can then be offered. This risk prediction model and screening tools that identifies individuals at greatest risk will increase the early detection rate and ultimately disease curability.

Fellow: Gabriela Ion, Ph.D.
Mentor: W. Hardman, Ph.D.
Marshall University

Dr. Ion and Dr. Hardman’s study will investigate one possible protective mechanism of two food components, n-3 and n-6 Fatty Acids (FA), on breast cancer development. It hypothesizes that n-3 FAs (present in canola oil) versus n-6 FAs (present in corn oil) will disrupt the signaling events between breast tumoral cells and adjacent cells, in this casepreadipocytes, by decreasing the level of pro-inflammatory cytokines to aid cancer prevention. This study may help to understand the effect of dietary changes at a cellular level. A better understanding of n-3 FAs mechanisms for suppression of tumorigeneses may lead to dietary recommendations that could reduce the incidence of cancer for future generations.

PI: Jung Eun Lee, Sc.D
Mentor: Edward Giovannucci, MD, Sc.D

Brigham and Women’s Hospital – Channing Laboratory

The underlying hypothesis is that folate deficiency and low intake of vitamin D are associated with increased risk of colorectal cancer and polyps early in carcinogenesis. The protective role of vitamin D against colorectal cancer risk has been strongly debated since a clinical trial study of vitamin D and calcium showed no benefit on colorectal cancer. This study aims to examine if dose and timing of folate and vitamin D intake are associated with colorectal cancer risk. The proposed research has the potential to help explain some of the disparate results that have been reported in this area. Adding to the conflicting data on risk factors for colorectal cancer would be an important contribution.

Fellow: Mark Rubinstein, Ph.D.
Mentor: Ananda Goldrath, Ph.D.
University of California, San Diego

Dr. Rubinstein and Dr. Goldrath’s research project has the potential to make an impact in the development of preventive cancer vaccines. This project proposes to augment primary immune responses using a novel vaccine component that we have previously developed. Specifically, researchers will take a natural substance found in the body, which can stimulate the immune system, and increase its biological activity over 50 fold. It is believed that incorporation of this novel stimulatory agent into vaccine design will lead to dramatically improved immune protection and aid in the development of preventative cancer vaccines.

Fellow: David Stachura, Ph.D.
Mentor: David Traver, Ph.D.

University of California, San Diego

The goals of this study are to explore the molecular signature of hematopoietic stem cells inzebrafish and determine pathways leading to their oncogenic transformation. The experiments proposed in this fellowship will aid in understanding an important stage ofhematopoietic development especially sensitive to leukemic transformation. Knowledge gained from this research will help us to understand leukemic initiation and progression, lead to improved diagnostic tools and treatment strategies for patients, and aid in preventing leukemia. The zebrafish model provides a practical approach to dissecting specific genes and applying them to the human condition.

Fellow: Jean Tang, Ph.D.
Mentor: Ervin Epstein, M.D.
Children’s Hospital & Research Center, Oakland

The proposal will determine if vitamin D and/or statins can prevent basal cell carcinoma (BCC) of the skin in mice. The researchers propose to perform the first in vivo experiments where they will feed vitamin D and statins to mice to assess whether these drugs may prevent BCC tumors from forming on their skin. The proposed studies will clarify the role of sunlight, vitamin D, and diet for prevention of the most common cancer in the U.S. This work could have large impact on cancer prevention through easily obtainable means – oral or topical vitamin D and statins.

Researcher: Wenli Cai, Ph.D.
Massachusetts General Hospital

Dr. Cai’s research proposes a non-cathartic approach to Computedtomographic colonography (CTC), aka virtual colonoscopy. The approach of CTC is based on the combination of fecal tagging with orally administered contrast agents and post-acquisition electronic cleansing (EC) of tagged fecal materials. A non-cathartic approach to CTC has the potential to revolutionize colon screening. The main technical barrier is the lack of an effective EC scheme for electronic cleansing the tagged fecal materials. In this project we will develop and evaluate an advanced EC scheme for interpretation of CTC images of patients examined with non-cathartic bowel preparation. This EC-aided non-cathartic CTC examination may permit colon screening to be performed without the use of pre-examination cathartic bowel cleansing, thus providing a highly-acceptable alternative to patients and highly accurate tool for diagnoses.

Researcher: Chun Liu, M.D.
Tufts University

Large epidemiologic studies across regions and populations have consistently shown that beta-cryptoxanthin is associated with a reduced risk of developing lung cancer, particularly among current smokers. However, the molecular mechanisms by which beta-cryptoxanthinaffects lung carcinogenesis are poorly understood. This study proposes to examine thechemopreventive effect of beta-cryptoxanthin supplementation in both low- and high-dose on cigarette smoke-induced lung carcinogenesis in ferrets by measuring molecular markers, including p53 tumor suppressor gene (which plays a critical role in suppressing lung carcinogenesis), p53 target genes, cell growth, programmed cell deaths in the lungs of ferrets, and by examining lung oxidative stress and oxidative DNA damage and lung pathological changes. Data from this study will provide important information for the evaluation of the potential usefulness of beta-cryptoxanthin as a chemopreventive agent against the development of lung cancer.

Researcher: Jong Park, Ph.D.
H. Lee Moffitt Cancer Center & Research Institute

Dr. Park’s research represents a novel approach to develop a highly sensitive probe to detect DNA methylation. In this proposal, the researchers will prepare templates for aptamer(molecular probes which are man-made, flexible, and are single-stranded DNA) selection and counter-selection, and capture these templates by synthesizing other man-made molecules called peptide nucleic acids (PNAs). Aptamers will be useful to recognize the complexes assembled by the cell for epigenetic silencing. Templates made by this research will later lead to identification of small molecule aptamers that detect the complexes responsible for tumor suppressor gene silencing in cancer. In the future, high-throughput panels of aptamersagainst silenced tumor suppressor and repair genes in biopsy and non-invasive samples (e.g. blood, sputum, and urine) could create the potential for highly effective cancer screening, early detection, therapeutic monitoring and prevention.

Researcher: Robert Strange, Ph.D.
University of Colorado

Moderate exercise has recently been linked to a decreased risk of cancer; however, the mechanism responsible for the decreased risk is not understood. Dr. Strange’s research proposes that, with exercise, angiogenesis will preferentially be increased in muscle, and blood flow will be directed and redistributed to muscle. Conversely, it is hypothesized that exercise will result in decreased angiogenesis and reduced blood supply in the tumor. This will in turn lead to an increase in tumor cell death, slowed tumor growth, and tumor regression. This study represents a first attempt to evaluate the effect of exercise on breast cancer progression by examining the mechanism responsible for exercise-mediated tumor growth inhibition.

Researcher: Marilyn Tseng, A.M., Ph.D.
Fox Chase Cancer Center

Dr. Tseng will examine associations among central adiposity, adiposity-related “thrifty genes,” and breast density among foreign-born US Chinese women. Because of its strong association with breast cancer, higher breast density, measured from a mammogram, is thought to be a useful marker for breast cancer risk. The work will be conducted using data collected from a separately funded study on breast density in recently immigrated US Chinese women. The ~300 participants in that study are pre-menopausal, age 40 years and up, with US residence of 12 years or more. Data collection includes interviews; body measurements; DNA samples; and a screening mammogram assessed for breast density. The proposed work will add on genotyping and statistical analyses to investigate associations among genes of interest, central adiposity, and breast density. Findings from the proposed work will be relevant to breast cancer prevention in all women regardless of ethnicity. Findings could clarify whether reducing fat accumulation during adulthood can prevent breast cancer; improve our ability to predict risk based on genetic characteristics; and identify women who may be genetically susceptible to both central adiposity and breast cancer.

Researcher: Xiangsheng Zuo, Ph.D., M.D.
University of Texas, M.D. Anderson Cancer Center

Dr. Zuo’s proposal seeks to examine the role of a specific protein (PPAR-delta) in tumor formation in the colon. Evidence has been found supporting the idea that PPAR-d promotes the formation of colon tumors, but data from some other research groups have shown that PPAR-d might have the opposite or no effects. The work proposed in this research project aims to test the effects of genetically stopping the production of PPAR-d in the mouse intestine on tumor formation. The results of this proposal will provide needed information not only to determine whether PPAR-d has a role in developing chemopreventive agents against cancer but also to ensure that drugs used to treat other diseases by stimulating the function of PPAR-d are safe for use.

Researcher: Jin-Rong Zhou, Ph.D.
Beth Israel Deaconess Medical Center

Scientific evidence suggests that dietary intake of soy or black tea individually may have a potent anti-prostate cancer effect. Dr. Zhou will investigate this evidence further by looking at the combination of soy and black tea as a potential dietary target for prostate cancer prevention. Dr. Zhou will examine if the dietary combination will significantly inhibit development and progression of prostate cancer in a synergistic manner. The results of this research, along with evidence from previous studies, could lead to further studies of men at high risk for prostate cancer and eventually to a realistic prostate cancer prevention strategy.

Researcher: Eduard Chekmenev, Ph.D.
Huntington Medical Research Institutes

Dr. Chekmenev’s research proposes a non-invasive approach to early detection and diagnosis of breast cancer that capitalizes on the metabolic differences between tumors tissue and normal tissue. Dr. Chekmenev and his team will use a technique they have developed called PASADENA, which has brought magnetic resonance molecular imaging to within striking range of the sensitivity of other molecular imaging techniques. This work could lay the foundation for early diagnosis of breast tumors, which would significantly improve breast cancer prevention and early treatment.