2016 Internship Directory: Summer Research Experience Program in Cancer Science (17 pages)

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1 2016 Directory: Summer Experience Program in Science (17 pages) Andrei Bakin, PhD Dept. of Genetics rei-bakin genetics Novel Mediators of progression Metastasis in Tumor Microenvironment Tumor microenvironment facilitates cancer recurrence metastasis, can reduce the efficacy of anti-cancer therapy. Tumor-infiltrating immune cells tumor-associated fibroblasts (TAFs) play important roles in disease progression treatment. We identified novel factors that can control tumor interaction with immune cells TAFs. This project will assess their functional significance in preclinical animal models using novel CRISPR/Cas technology the levels in human cancers. Page 1 of 17

2 2016 Directory: Summer Experience Program in Science (17 pages) Dhyan Chra, PhD Dept. of Pharmacology Therapeutics dhyan-chra genetics Radiation Oncology Role of Mitochondria in Prevention Therapy The main focus of our research is to underst the molecular basis of therapy resistance in multiple cancer types including in prostate, breast, colon cancers. To accomplish our goals, we are investigating two different, but complementary projects. The first project delineates how mitochondria-mediated cell death signaling is defective in cancer cells cancer stem cells. The second project defines the role of heat-shock proteins in cancer cell survival death. We are also characterizing the role of mitochondria in health disparities among prostate breast cancer patients. Our research suggests that protein complexes are important regulators of cancer cell death survival. We use multiple biochemical, genetic, cellular, molecular approaches to identify characterize protein complexes in subcellular compartments including in the mitochondrion. Detailed understing of protein complexes will lay a foundation for targeting cell death survival machinery for cancer therapy. Our model system includes both laboratory cell culture mouse model of cancer to examine cellular signaling in response to anticancer agents as well as phytochemicals. Our ultimate goal is to target mitochondria cell death for prevention therapy of multiple types of cancer. Page 2 of 17

3 2016 Directory: Summer Experience Program in Science (17 pages) Gokul Das, PhD Dept. of Pharmacology Therapeutics gokul-das bioinformatics genetics Clinical Mechanisms by which Hormone Receptors Tumor Suppressors Impact The research in Das lab focuses on understing the cellular molecular mechanisms of cancer, especially breast,lung, ovarian cancers. For example, we are analyzing the role of hormone receptors (such as the estrogen receptor) tumor suppressors (such as the p53 protein) in cancer onset progression using cell culture mouse genetic models. Summer projects will involve modern cellular molecular biological techniques. Analyzing Hormone Receptor Tumor Suppressor Signaling in Patient Tissues The research Das lab focuses on understing the cellular molecular mechanisms of breast, lung, ovarian cancers. Based on a discovery made in our laboratory, a prospective clinical trial in breast cancer patients is ongoing at present. Summer projects will involve cellular molecular biological investigation of hormone receptor tumor suppressor signaling in patient tissues analyzing the clinical data in a vibrant friendly laboratory environment. Page 3 of 17

4 2016 Directory: Summer Experience Program in Science (17 pages) John Ebos, PhD Dept. of Medicine john-ebos bioinformatics biostatistics Resistance metastasis following tumor microenvironment inhibition Use of clinically relevant models of spontaneous metastatic disease resistant to antiangiogenic (VEGF pathway) immunecheckpoint (PD-1 pathway) inhibitors. Tumor immunology & immunotherapy Medical Oncology Irwin Gelman, PhD Dept. of Genetics irwin-gelman The role of nuclear SSeCKS/AKAP12 in PKC Src signaling control The intern will help analyze the cells growth conditions that foster the nuclear location signaling of the SSeCKS/AKAP12 kinase scaffolding protein. This will involve cell culture, transfection, protein staining, fluorescence microscopy signaling analysis (e.g.- immunoblots). Maciej Goniewicz, PharmD, PhD Dept. of Prevention Population Sciences maciej-goniewicz prevention epidemiology Safety of electronic cigarettes projects are focused on new nicotinecontaining products alternative forms of tobacco. We examine safety efficacy of electronic nicotine delivery devices, commonly called e-cigarettes. These studies include the laboratory evaluation of the products, pharmacological toxicological assessment, surveys among their users, their potential application in harm reduction, cancer prevention smoking cessation. Page 4 of 17

5 2016 Directory: Summer Experience Program in Science (17 pages) Katerina Gurova, MD, PhD Dept. of Cell Stress Biology katerina-gurova Targeting of chromatin remodeling factors for the treatment of cancer Our current scientific interest is exploring difference in chromatin structure as a source of potential targets for cancer treatment. Difference in chromatin structure between normal tumor cells is one of the first noticed by pathologists long time ago; however absence of knowledge of mechanisms responsible for this difference tools to investigate this did not allow utilizing this phenomenon for anything else except diagnostic marker. With accumulation of knowledge about chromatin structure in general in cancer cells specifically, differences in DNA histone posttranslational modifications were noticed what eventually led to the development of drugs, inhibiting enzymes responsible for these modifications (DNMT HDAC inhibitors). But this is just the very first layer of chromatin organization many other layers factors responsible for their support are still unexplored. Our lab pioneered in the research assessing the role of one of histone chaperones, FACT, in cancer. Current data accumulated in the lab suggest that this complex may be ideal target for the treatment of some types of cancer. Thus we are evaluating perspective, mechanisms consequences of FACT inhibition in several types of cancer. We also explore the role of other histone chaperones in cancer their requirement viability of cancer normal cells. Page 5 of 17

6 2016 Directory: Summer Experience Program in Science (17 pages) Rodney Haring, PhD, MSW Dept. of Prevention Population Sciences rodney-haring prevention epidemiology Intervention Dissemination in the Native American Lscape Beyond Native American males experience greater health disparities compared to all other U.S. racial ethnic groups. For example, Native men have the highest age-adjusted prevalence of type 2 diabetes among U.S. men, while non-hispanic White men have the lowest. In recent decades, Natives have seen a disproportionate increase in diabetesrelated complications mortality compared to all other groups, such that age-adjusted diabetes death rates in Native men are now almost twice those in White men. Several large studies in non- Natives confirm that type 2 diabetes can be prevented by interventions that promote healthy lifestyles, but little data exist on interventions to prevent diabetes in Native men. Many explanations have been suggested for the low participation rates among men of all races in lifestyle interventions. Recruiting Native men in clinic-based programs is difficult because they tend to seek clinical care less often than women. Therefore, an urgent need exists for risk reduction programs tailored to the unique values habits of Native men. The project s specific aims are to refine an intervention program called Strong Men, Strong Communities with feedback from focus groups in a tribal community; compare change in diabetes risk score modifiable diabetes health risk factors in the intervention; to evaluate the ability of the intervention to retain Native American male participants in health disparities research conducted in collaboration with a comprehensive cancer center. Page 6 of 17

7 2016 Directory: Summer Experience Program in Science (17 pages) Eugene Kel, PhD Dept. of Cell Stress Biology eugene-kel biophysics genetics Cell stress response pathways as new therapeutic targets. We study cell stress responses in order to improve protection of normal cells uncover vulnerabilities in cancers. We use culture, genetic engineering, pharmacological biophysical treatment of mammalian cells, as well as biochemical analysis of cell functions individual gene expression. Page 7 of 17

8 2016 Directory: Summer Experience Program in Science (17 pages) Anm Nazmul Khan, MBBS, PhD Dept. of Medicine anm-nazmul-khan Tumor immunology & immunotherapy Role of neutrophil extracellular traps (NETs) in ovarian tumor progression Cellular necrosis is associated with release of damage-associated molecular patterns (DAMPs) that activate innate immune responses. It has been shown that circulating DAMPs, specifically mitochondrial DNA (mtdna), released following traumatic injury activate innate immune cells such as neutrophils, elicit neutrophil-mediated inflammation. Our lab found that advanced epithelial ovarian cancer (EOC) is associated with accumulation of neutrophils immature myeloid cells in the local tumor environment. We also observed that mtdna accumulate in the cell-free ascites of patients with advanced EOC; however, their role in shaping innate immune responses ovarian tumor growth is unknown. Furthermore, we have also shown that purified mtdna cellfree ascites from EOC stimulate ex vivo generation of neutrophil extracellular traps (NETs). NETs promote metastasis in tumor-bearing mice presence of NETs was observed in resected human EOC, however the role of NETs in tumor progression in human cancer is unknown. The goal of this project is to evaluate that mtdna in cell-free ascites of EOC induce NET generation NETs can augment tumor growth metastasis. To achieve this aim in vitro cellular assay flowcytometry will be used involving human ovarian tumor cell lines. Xiang Ling, PhD Dept. of Pharmacology Therapeutics xiang-ling Anticancer drug evaluation mechanism study Our current research focuses on: the molecular mechanisms of action of FL118, the DMPK profile potential side effects induced by FL118 treatment. In addition, survivin isoforms perform different functions in distinct subcellular compartments. Type of work involved: cell culture, cell viability assay, western blot, qpcr animal experiment. Page 8 of 17

9 2016 Directory: Summer Experience Program in Science (17 pages) Asoke K. Mal, PhD Dept. of Cell Stress Biology asoke-mal Pediatrics Identification of therapeutic targets in the molecular signaling of childhood muscle cancer alveolar rhabdomyosarcoma The research in our laboratory focuses on rhabdomyosarcoma (RMS), a highly aggressive soft-tissue sarcoma which primarily affects children adolescents. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, the prognosis of patients with metastatic or refractory has not been substantially improved, with a 5-year overall survival rate being 20-30%. Furthermore, current aggressive treatments involve traditional chemotherapy cocktails which are associated with significant lifelong side effects in young patients, including organ toxicity secondary cancers. Thus, there is a clear need to develop new RMSspecific therapeutic strategies to both improve long term survival minimize treatment-related morbidity. The goal of our laboratory is to better underst the molecular pathways that are relevant to the pathogenesis of RMS in order to identify novel targeted therapeutic strategies. We take approaches, spanning both basic translational research, which include molecular biology, biochemistry, genetics, cell biology, other disciplines to address clinically relevant questions to RMS biology. Our efforts also include drug discovery approaches, wherein we leverage our current understing of RMS to screen for identify novel compounds which may have activity against this tumor. Collectively, we hope that the efforts in our laboratory contribute tangible substantial benefit to pediatric patients suffering from RMS in the future. Susan McCann, PhD Dept. of Prevention Population Sciences prevention epidemiology Diet nutritional epidemiology cancer prevention; mostly computer work, some data entry, data analysis susan-mccann Page 9 of 17

10 2016 Directory: Summer Experience Program in Science (17 pages) June Mikkelson, MS Dept. of Clinical Genetics s/treatmentservices/specializedservices/clinical-geneticsservice Clinical genetics Clinical Exploring issues related to genetic counseling/testing for hereditary cancer risk This internship is directed toward students pursuing a graduate degree in genetic counseling. Students will complete clinical observations (a requirement when applying to graduate programs in genetic counseling) as well as gain valuable clinical research experience. Past projects have included data review of past Clinical Genetics Service patients to demonstrate the importance of periodic follow up patient decision making when pursuing testing through a multi-gene panel. Additional opportunities include construction of genetic pedigrees through the Progeny program, composing patient literature, possibly limited direct patient interactions. Hans Minderman, PhD Dept. of Flow Image Cytometry hans-minderman experimental diagnostics Tumor immunology & immunotherapy Effects of a somatostatin analog on the immune system Background: Somatuline is a somatostatin analog that is being clinically evaluated in the treatment of neuroendocrine tumors. Little is know about the effects of somatuline on the immune system. This project will involve characterization of the expression profile of somatostatin receptors on immune cells determining the consequences of their expression on the immune response. Methods: cell culture, immunophenotyping, flow cytometry imagestream cytometry. Highly translational study close to the relatively new clinical application of this drug. Medical Oncology Page 10 of 17

11 2016 Directory: Summer Experience Program in Science (17 pages) Daryl Nazareth, PhD Dept. of Radiation Medicine daryl-nazareth bioinformatics biophysics Radiation Oncology Applying computational methods to medical physics The internship will involve developing new computational techniques for improving radiation dose calculation treatment delivery parameters. This will include algorithm design, computer programming, data analysis, loving every minute of it. You will join a team of excited motivated students one very hip medical physicist. The party won't stop until you've applied a technique called monte carlo modeling to a problem called VMAT plan optimization. If you have mad love for physics, mathematics, or computer science, along with an insatiable desire to learn about a fascinating field, there is no cooler way to spend your summer. Michael Nemeth, PhD Dept. of Immunology michael-nemeth Tumor immunology & immunotherapy Hematology Determining mechanisms of chemotherapy resistance The overall goal of this project is to elucidate aspects of the mechanisms that underlay the development of resistance to chemotherapy agents in myeloid leukemia. This project will involve the use of mouse leukemia models to test hypotheses on how leukemia stem cells evade develop resistance to the chemotherapy agent decitabine. Richard O'Connor, PhD Dept. of Prevention Population Sciences richard-oconnor prevention epidemiology Consumer responses to alternative tobacco products Students will have the opportunity to assist with data processing from two studies examining consumer response to smokeless tobacco electronic cigarettes. In the first, participants completed a five week trial of their choice of products, we will be examining extent of substitution of alternatives to cigarettes. In the second, participants complete a battery of consumer perception metrics, including sensory measures. Summer interns would assist in the analysis of these data. Page 11 of 17

12 2016 Directory: Summer Experience Program in Science (17 pages) Toru Ouchi, PhD Dept. of Genetics toru-ouchi genetics Study Mechanism of Human Carcinogenesis Goal: (1) Detail the molecular pathways involved in cancer development (2) Investigate the mechanism of cancer metastasis Types of Work: (1) Biochemistry cell culture-based studies, including DNA/RNA/Protein analysis, q-pcr/rt- PCR, immunoblot, immunocytochemistry. (2) Computer based studies for systems biology. (3) Animal model of human carcinogenesis. We will provide one (or, two) projects during the period on internship, which could be achieved in the fixed term. Progress should be discussed on the daily basis. Page 12 of 17

13 2016 Directory: Summer Experience Program in Science (17 pages) Santosh Patnaik, MD, PhD Dept. of Surgical Oncology santosh-patnaik bioinformatics biostatistics experimental diagnostics genetics molecular cellular biology molecular epidemiology prevention epidemiology Clinical genetics Tumor immunology & immunotherapy Medical Oncology Experimental computational examination of genes in cancer immunology We are interested in genetics (gene mutations, gene expression, etc.) epigenetics (micrornas, RNA editing, etc.) as it pertains to cancer the human body's immunological response to it. This is a very broad area, allows for a visiting student to contribute their ideas to develop an exciting yet feasible project to carry out during their stay. The work will involve one or more of the following: (1) Cell biology: cell culture, genetic engineering of cells, etc. (2) Molecular biology: various DNA, RNA protein assays, including their development, etc. (3) Animal biology: growing foreign tissue/cells in the mouse, analysis of DNA/RNA/proteins of mouse, etc. (4) Computation: large-scale data analysis, data visualization, bioinformatics, software programming, etc. As a mentor, my goal will be to help the visiting student attain the following: (1) Experience these aspects of scientific research -- the collation of facts from published knowledge knowledgeable individuals; hypothesization; design, preparation for, execution of experiments; data collection, analysis, presentation; the setting forth of future directions. (2) Learn some common biomedical research techniques. (3) Bring to completion during the student's stay an independent short project that the student helps with the design, execution analysis of. Radiation Oncology Surgical Oncology Page 13 of 17

14 2016 Directory: Summer Experience Program in Science (17 pages) Beth Pflug, PhD Dept. of Urology beth-pflug Targeting Dysregulated Energy Sensing Pathways in Prostate Changes in energy sensing pathways cellular metabolism are associated with the ability of prostate tumor cells to escape growth regulation reliance on the prostate microenvironment. Folic acid also known as folate (the form naturally occurring in the body), is an essential vitamin that is important for cell division growth through DNA RNA synthesis, maintaining the integrity of the DNA. In addition, folate is needed for single carbon transfer reactions for methylation that helps silence or activate DNA, RNA, proteins lipids. The folate pathway is considered a major energy sensing pathway as cell growth DNA synthesis is regulated by availability of the vitamin. Folate during development in normal cells promotes energy pathway stability, however, folate induces dysregulated growth in tumor cells. We have found that folate is also a major regulator of the lipid synthesizing enzyme, fatty acid synthase (FASN). Our hypothesis is that increased folate availability promotes prostate tumor progression via modulation of fatty acid synthase. The FASN lipid synthesis pathway in normal cells is not an active pathway due to dietary fat intake. However in prostate cancer, it is highly upregulated the mechanisms of normal pathway control are lost. In this study, we have two research aims for the summer program. Our first aim will be to identify the mechanism(s) by which folate regulates FASN expression pathway activity. We hypothesize that the major energy sensing pathway of AMPK is the direct link that connects he expression lipid synthesizing activity of FASN with control by dietary folate. The FASN protein has regions that are similar to methyltrasferase enzymes (transfer methyl groups to DNA, RNA proteins or lipids) therefore may have an additional function of methyl group transfer. Aim 2 will test the hypothesis that nuclear FASN has a role in methylation reactions. We will determine the role of nuclear FASN identify the target(s) of its potential methyltransferase activity. Laboratory methods will include cell culture, gene knockdown, growth assays, real-time PCR, western blot, enzyme bioassays. Page 14 of 17

15 2016 Directory: Summer Experience Program in Science (17 pages) Matthew Podgorsak, PhD Dept. of Radiation Medicine matthew-podgorsak Radiation Oncology Medical Physics Clinical Medical Physics applications A student intern will study clinical aspects of medical physics. Medical physics is the branch of physics that combines physics with medical applications. Our group is primarily involved in the treatment of cancer patients with radiation, so a student intern would learn basic clinical approaches to the application of radiation in the treatment of cancer. Steven Pruitt, PhD Dept. of Molecular Cellular Biology steven-pruitt bioinformatics genetics Stem/progenitor cell replication in cancer aging Work under this internship will be directed at understing how normal abnormal DNA replication cell proliferation of stem progenitor cells contribute to tissue maintenance genome stability in cancers during aging. Depending on the specific project, the work may include molecular cloning, molecular biological techniques (e.g. gel electrophoresis, western blot analyses, PCR), cell culture (including transduction/transfection FACS), generation of /or histological/molecular characterization of transgenic mice, whole genome bioinformatic analyses. Brahm Segal, MD Dept. of Medicine brahm-segal Tumor immunology & immunotherapy Innate Immune Responses in Ovarian The intern will work under the supervision of a senior scientist or PhD student to evaluate immune responses in patients with ovarian cancer. Work may also involve mouse models of ovarian cancer. Page 15 of 17

16 2016 Directory: Summer Experience Program in Science (17 pages) Mark Travers, PhD Dept. of Prevention Population Sciences mark-travers Tobacco products exposure science Examining exposure to tobacco smoke pollution new emerging tobacco products Air pollution is a leading cause of cancer, whether from the tip of a burning cigarette, the exhaust of a truck on the road, a coal-fired power plant, or biomass burned for cooking in developing countries. Reducing exposure to airborne carcinogens can be achieved through public policies changing health behaviors. Accurate, easy to communicate, empirical data on exposures is necessary to justify the interventions to evaluate their effectiveness. This internship will provide provide participants the opportunity to conduct original research into exposures to harmful pollutants in the environment around us, in particular exposure to tobacco smoke emissions from new emerging products such as waterpipe (hookah) electronic cigarettes. This research is used to inform public policies to protect public health. Work can involve any combination of laboratory research, field data collection, secondary data analysis. Xinjiang Wang, PhD Dept. of Pharmacology Therapeutics xinjiang-wang Development of Novel Targeted Therapies for Leukemia Treatment The goal of this study is to evaluate the antitumor effect of newly identified small molecule inhibitors for Mdm2-MdmX E3 in leukemia cells. Single or combination treatment will be tested. Cell proliferation cell death will be analyzed. Cell culture, cell growth assay, Western blotting analysis of target proteins biochemical events of apoptosis will be performed. Page 16 of 17

17 2016 Directory: Summer Experience Program in Science (17 pages) Anna Woloszynska- Read, PhD Dept. of Pharmacology Therapeutics anna-woloszynska-read genetics Urology epigenetics Epigenetics of bladder cancer The goal of the internship in my laboratory is to learn about cancer epigenetics specifically DNA methylation histone modifications in cancer biology. We have utilized RNA sequencing DNA methylation arrays to determine the role of low concentrations of DNA de-methylating agents on the transcriptome methylome, respectively, in muscle-invasive bladder cancer. We have identified several targets that require laboratory validation by quantitative RT-PCR DNA methylation pyrosequencing. The summer intern will learn molecular biology techniques will also be exposed to bioinformatics approaches used in analysis of data from high-throughput genomic assays. Yuesheng Zhang, MD, PhD Dept. of Prevention Population Sciences yuesheng-zhang Targeting ErbB receptor tyrosine kinases in cancer Cell membrane-bound ErbB receptor tyrosine kinases, particularly ErbB1 ErbB2, are major oncogenic drivers cancer therapeutic targets. We have recently found that recombinant human prolidase targets both ErbB1 ErbB2 are doing research to better underst the antitumor activity of prolidase. Jianmin Zhang, PhD Dept. of Genetics jianmin-zhang genetics Dysregulation of Hippo pathway signaling in breast cancer Using molecular, cellular biochemical approaches as well as the 3-D cell culture system mouse models, we are intensively investigating the roles of EMT the Hippo signaling pathway in the initiation progression of solid carcinomas, e.g., breast cancer. Page 17 of 17