2017 Internship Directory: Summer Research Experience Program in Cancer Science (19 pages)

Transcription

1 2017 Internship Directory: Summer Experience Mentor area(s) Internship Andrei Bakin, PhD Cancer Genetics /Andrei-Bakin Tumor-Fibroblast crosstalk In Breast Cancer progression Tumor microenvironment has been implicated in cancer recurrence and metastasis. In the tumor microenvironment (TME), tumor-associated fibroblasts (TAFs) and infiltrating immune cells play important roles in disease progression and treatment. Two projects are available to investigate novel pathways that control tumor-fibroblast interactions and influence tumor infiltration by immune cells. Joseph Barbi, PhD Immunology /Joseph-Barbi Exploring the mechanisms and therapeutic potential of novel factors capable of modulating immune responses. The immune system s destructive potential is regulated by numerous regulatory mechanisms. By understanding these we can devise novel therapies to unleash optimal anti-tumor responses in cancer patients. These studies will utilize in vitro assays of immune cell function, in vivo (mouse) tumor models, and fluorescence-based techniques for visualizing immune cells. Page 1 of 21

2 2017 Internship Directory: Summer Experience Mentor area(s) Internship David Bellnier, PhD Cell Stress Biology /David-Bellnier Cancer biophysics Photodynamic Therapy of Locally Advanced Tumors Several published studies and our experience suggest that interstitial photodynamic therapy (IPDT) is a promising treatment for patients with locally advanced head and neck cancer (LAHNC) who have failed other treatments. In photodynamic therapy (PDT), systemic administration of a light-sensitive drug (photosensitizer, PS) is followed by illumination and photoactivation of the PS within the target tumor. The preferential retention of the PS in the tumor, and the ability to direct the activating light to malignant tissue while limiting exposure to normal tissues, provide the necessary elements for therapeutic selectivity. Most often, PDT uses a surface illumination (called external-beam PDT, or EBPDT). For IPDT, we insert small-diameter optical fiber(s) into the tumor tissue to deliver PS-activating light. Finite element modeling of light distribution in locally advanced mouse tumors suggests that IPDT in combination with a second antitumor agent or modality might be the optimal treatment approach for patients with LAHNC. The development of combination therapies for malignancies has a long and distinguished history. The use of multiple cytotoxic agents each with therapeutic activity as a single agent in a specific disease, which possess different presumed mechanisms of action and non-overlapping toxicities, proved vitally important for the long-term control of cancer. We will investigate the use of IPDT in a combination setting in small animal models of locally advanced cancer. Page 2 of 21

3 2017 Internship Directory: Summer Experience Mentor area(s) Internship Dhyan Chandra, PhD Pharmacology and Therapeutics /Dhyan-Chandra Role of Mitochondria in Cancer Prevention and Therapy The main focus of our research is to understand the molecular basis of therapy resistance in multiple cancer types including in prostate, breast, and 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 and cancer stem cells. The second project defines the role of heat-shock proteins in cancer cell survival and death. We are also characterizing the role of mitochondria in health disparities among prostate and breast cancer patients. Our research suggests that protein complexes are important regulators of cancer cell death and survival. We use multiple biochemical, genetic, cellular, and molecular approaches to identify and characterize protein complexes in subcellular compartments including in the mitochondrion. Detailed understanding of protein complexes will lay a foundation for targeting cell death and survival machinery for cancer therapy. Our model system includes both laboratory cell culture and mouse model of cancer to examine cellular signaling in response to anticancer agents as well as phytochemicals. Our ultimate goal is to target mitochondria and cell death for prevention and therapy of multiple types of cancer. Gokul Das, PhD Pharmacology and Therapeutics /Gokul-Das Mechanisms by which Hormone Receptors and Tumor Suppressors Impact Cancer The research in Das lab focuses on understanding the cellular and molecular mechanisms of cancer, especially breast,lung, and ovarian cancers. For example, we are analyzing the role of hormone receptors (such as the estrogen receptor) and tumor suppressors (such as the p53 protein) in cancer onset and progression using cell culture and mouse genetic models. Summer projects will involve modern cellular and molecular biological techniques. John Ebos, PhD Medicine /John-Ebos Resistance and metastasis following tumor microenvironment inhibition Use of clinically relevant models of spontaneous metastatic disease resistant to antiangiogenic (VEGF pathway) and immunecheckpoint (PD-1 pathway) inhibitors. Surgical Oncology Page 3 of 21

4 2017 Internship Directory: Summer Experience Mentor area(s) Internship Irwin Gelman, PhD Cancer Genetics /Irwin-Gelman THe role of nuclear SSeCKS/AKAP12 in PKC and Src signaling control The intern will help analyze the cells and growth conditions that foster the nuclear location and signaling of the SSeCKS/AKAP12 kinase scaffolding protein. This will involve cell culture, transfection, protein staining, fluorescence microscopy and signaling analysis (e.g.- immunoblots). Maciej Goniewicz, PhD, PharmD Cancer Prevention and Population Sciences /Maciej-Goniewicz Cancer prevention and epidemiology Safety of electronic cigarettes projects are focused on new nicotine-containing products and alternative forms of tobacco. We examine safety and efficacy of electronic nicotine delivery devices, commonly called e-cigarettes. These studies include the laboratory evaluation of the products, pharmacological and toxicological assessment, surveys among their users, and their potential application in harm reduction, cancer prevention and smoking cessation. Page 4 of 21

5 2017 Internship Directory: Summer Experience Mentor area(s) Internship Rodney Haring, PhD Cancer Prevention and Population Sciences /Rodney -Haring Cancer prevention and epidemiology Cancer Health Literacy Project: Native American Populations Summer interns will be involved in various activities through Roswell Park Cancer Institute s, Office of Cancer Health Disparities. The department is engaged in a number of community-based and community-driven research projects. Interns will have an opportunity to be part of outreach efforts, prevention activities, and cancer screenings. Related to research, interns will be involved in a multi-piece project. First, interns will learn the foundation of health disparities research as well as quality improvement processes through trainings, readings, department events, and the attendance of medical grand rounds. Interns will also be taught in-depth literature review methods through experiential learning with ancillary team specialists and be assigned to a specific cancer health disparity that is of a concern to Native American or First Nation populations. Interns will use these newly acquired skills to develop a short paper on the specified cancer health disparity as well as the field of cancer health literacy. Interns will ultimately collaborate within a Native American community context (Indian Reservation or Native Urban Center) to apply their literature review to a quality improvement project by adapting information sheets, pamphlets, and brochures into a Native language. This will be completed with the assistance of tribal language experts and elders. Final goals include the joint creation of a manuscript for peer-reviewed journal consideration, discussion of next-phase pilot research, and dissemination of translated materials back into their respective collaborating community for immediate use. Page 5 of 21

6 2017 Internship Directory: Summer Experience Mentor area(s) Internship Francisco Hernandez- Ilizaliturri, MD Medicine /Francisco- Hernandez-Ilizaliturri Medical Oncology Clinical Understanding the mechanisms of resistance to rituximab and chemotherapy agents in aggressive lymphomas Our laboratory work focuses in defining cellular pathways associated with rituximab-chemotherapy resistance in B-cell lymphoma and to develop therapeutic strategies to overcome it. To this end, in the last year we had accomplished the following: a) Based on pre-clinical findings demonstrating the ubiquitin-proteasome system (UPS) influences the apoptotic threshold to chemotherapy drugs in refractory B-cell lymphoma, we are successfully conducting a phase I/II study evaluating the safety and efficacy of carfilzomib in combination with standard second line chemotherapy in transplant eligible diffuse large B-cell lymphoma. A total of six patients had been enrolled and significant anti-tumor activity has been observed. Moreover, no dose-limiting toxicities had been observed. b) Demonstrated that entinostat, a selective deacetylase (HDAC) inhibitors increase CD20 gene/protein expression and enhanced the anti-tumor activity of rituximab in vivo, supporting the clinical development of this agent in combination with anti-cd20 antibodies in B-cell malignancies. c) Identified Hexokinase II (HKII) as a biomarker of chemotherapy resistance in B-cell lymphoma. Using pre-clinical models, we demonstrated that HKII was up regulated in rituximab-chemotherapy cell lines and that pharmacological inhibition or transient gene silencing of HII reversed chemotherapy resistance. To further assess the contribution of HKII to rituximab/chemotherapy resistance in a more clinically relevant setting, we analyzed gene expression profiling data from 401 patients with diffuse large B-cell lymphoma (DLBCL) treated with standard systemic chemotherapy (CHOP) or Rituximab and chemotherapy (R+CHOP) as front-line therapy. High levels of HKII correlated with a poor prognosis in DLBCL patients. Our data suggest that over-expression of HKII contribute to the acquirement of resistance to rituximab and chemotherapy agents in DLBCL B-cell lymphoma. Management of B-cell lymphoma In the past, we have our summer students spent one day a week in the clinic in between their laboratory projects. This is with then intention to introduce our students to the challenging field of lymphoma management and for them to understand how we take what we learn in the laboratory and apply it into the clinics. Page 6 of 21

7 2017 Internship Directory: Summer Experience Mentor area(s) Internship Pamela Hershberger, PhD Pharmacology and Therapeutics /Pamela-Hershberger Cross talk between vitamin D and tyrosine kinase inhibitors Tyrosine kinase inhibitors are an important class of drugs used to treat lung cancer. We have uncovered dynamic crosstalk between vitamin D and tyrosine kinase inhibitors. Ongoing molecular and cell based assays are being used to dissect the basis for crosstalk and its implications for lung cancer treatment. Mollie Hutton, Masters in Genetic Counseling Clinical Genetics /Mollie-Hutton 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 and 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, and possibly limited direct patient interactions. Eugene Kandel, PhD Cell Stress Biology /Eugene-Kandel Cell stress response pathways as new therapeutic targets. We study cell stress responses in order to improve protection of normal cells and uncover vulnerabilities in cancers. We use culture, genetic engineering, pharmacological and biophysical treatment of mammalian cells, as well as biochemical analysis of cell functions and individual gene expression. Page 7 of 21

8 2017 Internship Directory: Summer Experience Mentor area(s) Internship Eric Kauffman, MD Urology /Eric-Kauffman Urology Medical Oncology Surgical Oncology Clinical Molecular and cellular research in kidney cancer and prostate cancer The work in my lab is focused on discovering key molecular alterations responsible for kidney and prostate cancer formation and progression. There are two main projects undergoing. The first project investigates the role of heavy metal metabolism (iron, in particular) and the resulting effects on oxygen metabolism ( oxidative stress ) in the development and progression of kidney tumors. Iron metal is among the greatest sources of oxidative stress in cells of the human body, but also provides the sole ingredient needed to transform precursor tissue into kidney tissue during embryo organogenesis. We hypothesize that iron is therefore similarly important in the development of kidney tumors and their progression. Our initial work has confirmed much higher levels of iron in kidney tumors than in benign kidney tissue; and also indicates that kidney cancer cells are highly dependent on iron, and that iron deprivation kills these cancer cells without killing the noncancerous kidney cells. In mice, administration of high levels of iron leads to mouse kidney tumors which morphologically mimic human kidney cancer. Important future studies will test whether these iron-induced mouse kidney tumors have the same molecular alterations that occur in human kidney cancers. Furthermore, drug treatments targeting iron metabolism and oxidative stress metabolism will be tested in vitro and in this mouse model to determine whether kidney cancer growth can be blocked. The second project investigates the existence of circulating cancer cells in the bloodstream of patients with kidney or prostate tumors. These cells exist at very rare concentrations in the bloodstream along with the patient s healthy blood cells. This project is exploring various technologies to identify and ultimately isolate these cancer cells from amid the numerous healthy blood cells analogous to identifying a single grain of sand in an entire sandbox! The clinical goal is to use our understanding of these rare cancer cells in the blood to better guide treatment decisions of kidney and prostate cancer patients. Page 8 of 21

9 2017 Internship Directory: Summer Experience Mentor area(s) Internship Anm Nazmul Khan, MBBS, PhD Medicine /Anm Nazmul-Khan Role of neutrophil extracellular traps (NETs) in ovarian tumor progression Cellular necrosis is associated with release of damageassociated 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, and elicit neutrophil-mediated inflammation. Our lab found that advanced epithelial ovarian cancer (EOC) is associated with accumulation of neutrophils and 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 and ovarian tumor growth is unknown. Furthermore, we have also shown that purified mtdna and cell-free ascites from EOC stimulate ex vivo generation of neutrophil extracellular traps (NETs). NETs promote metastasis in tumor-bearing mice and 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 and NETs can augment tumor growth and metastasis. To achieve this aim in vitro cellular assay and flowcytometry will be used involving human ovarian tumor cell lines. Sergei Kurenov, MS Surgical Oncology /Sergei-Kurenov Cancer biostatistics Surgical Oncology Liver Surgery Preplanning Using Virtual Reality (VR) Simulation System There are two goals for project: 1.Create modifications into existing preplanning VR surgical simulation system for liver specific surgical oncology cases such as hepatocellular carcinoma (HCC). 2.Continue to develop a liver specific surgical risk calculator based on national datasets. Both goals of work require intermediate skills in C# programming. Fengzhi Li, PhD Pharmacology and Therapeutics /Fengzhi-Li Study the novel anticancer drug FL118 mechanism of action in pancreatic cancer The student will be trained for basic technology (e.g. cell culture, western blots, etc.) for studying drug action mechanism. the goal is for the student to be family with lab anticancer drug research. Page 9 of 21

10 2017 Internship Directory: Summer Experience Mentor area(s) Internship Xiang Ling, PhD Pharmacology and Therapeutics /Xiang-Ling Anticancer drug evaluation and mechanism study Our current research focuses on: the molecular mechanisms of action of FL118, the DMPK profile and 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 and animal experiment. Song Liu, PhD Bioinformatics/ Biostatistics /song-liu Cancer bioinformatics Cancer biostatistics Cancer experimental diagnostics Cancer molecular epidemiology Cancer prevention and epidemiology Clinical genetics Clinical Decipher the genetic and epigenetic landscape of cancer Developing statistically sound and computationally effective methods for analyzing data from modern biology and medicine is the long-term research interest of my group. For the last 6 years, my research group has been working very closely with cancer genomics researchers, and has accumulated extensive experience in statistical and bioinformatics method development and application of highthroughput genomics studies including various platforms of next-generation sequencings (NGS), high-density microarrays, and their integration. Understanding the genetic and epigenetic alternation of haematological and solid tumor genome is currently a main focus of our research, and an ongoing effort is to develop computational approaches that integrate whole-genome, whole-exome sequencing data with epigenome and transcriptome profiling. A number of research opportunities will be provided along this line. Kent Nastiuk, PhD Cancer Genetics /Kent-Nastiuk Cancer experimental diagnostics Urology Signaling in androgen deprivation therapy for prostate cancer My lab is investigating how androgen regulated growth and apoptosis signaling pathways are changed in prostate cells in culture, in mouse models and in patient samples of prostate disease (BPH, inflammation, cancer). Since androgen deprivation therapy (ADT) is the principal treatment for advanced prostate cancer, and when administered for extended periods causes frailty, we are also examining the mechanism of ADT-induced muscle loss. We use a broad range of techniques from whole animal imaging to protein biochemistry to gene expression analysis to determine mechanism in order to develop better therapies for prostate diseases. Page 10 of 21

11 2017 Internship Directory: Summer Experience Mentor area(s) Internship Richard O'Connor, PhD Cancer Prevention and Population Sciences /Richard-O'Connor Cancer prevention and 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 and electronic cigarettes. In the first, participants completed a five week trial of their choice of products, and 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. Joyce Ohm, PhD Cancer Genetics /Joyce-Ohm Epigenetic remodelding in translocation associated soft tissue sarcomas My laboratory is actively investigating how both genetic and environmental determinants may reprogram the epigenome and contribute to tumor initiation and progression. I currently have an NIH RO1 grant focused on epigenomic remodeling in stem cells and differentiated neural cells following exposures to environmental toxicant exposure as well as an ongoing program looking at epigenetic reprogramming in translocation associated soft-tissue sarcomas. My research lab regularly performs omics level molecular analysis of normal, pre-malignant, and malignant cell populations including RNA-sequencing, ChIPsequencing, and global methylation analysis, all of which are key elements of my ongoing research. Our long term goals are to identify novel therapeutic strategies for the treatment of aggressive human cancers based on their molecular profiling. Page 11 of 21

12 2017 Internship Directory: Summer Experience Mentor area(s) Internship Scott Olejniczak, PhD Immunology /Scott-Olejniczak The effect of the removal of PIM2 in the proliferation of multiple myeloma Multiple myeloma is a cancer characterized by plasma cell malignancy and believed to result from a combination of mutation and environmental influence. As with other cancers, multiple myeloma can result in unchecked cell growth and metastasis. Some characteristics of multiple myeloma are: low blood cell count, kidney problems, and bone and calcium problems. In our research experiments, we will be studying the role of the serine kinase family member PIM2 in CD28 and IL6 initiated myeloma cell signal transduction. Activation of the cell membrane expressed CD28 receptor and the presence of the IL6 cytokine are both known to promote myeloma cell proliferation and survival. It is also known that PIM2 lies within the CD28 and IL6 signaling pathways. Therefore, we hypothesize that, the removal of PIM2 from either CD28 or IL6 initiated myeloma cell signaling will result in decreased cellular proliferation and survival. This could mark PIM2 as a potential therapeutic target in the treatment of multiple myeloma. Page 12 of 21

13 2017 Internship Directory: Summer Experience Mentor area(s) Internship Santosh Patnaik, MD, PhD Surgical Oncology /Santosh-Patnaik Cancer bioinformatics Cancer biostatistics Cancer molecular epidemiology Surgical Oncology Experimental and computational examination of genes in cancer and immunology We are interested in genetics (gene mutations, gene expression, etc.) and epigenetics (micrornas, RNA editing, etc.) as it pertains to cancer and the human body's immunological response to it. This is a very broad area, and 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 and 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: largescale 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 and knowledgeable individuals; hypothesization; design, preparation for, and execution of experiments; data collection, analysis, and presentation; and 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 and analysis of. Page 13 of 21

14 2017 Internship Directory: Summer Experience Mentor area(s) Internship Beth Pflug, PhD Urology /Beth-Pflug Targeting Dysregulated Energy Sensing Pathways in Prostate Cancer Changes in energy sensing pathways and cellular metabolism are associated with the ability of prostate tumor cells to escape growth regulation and 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 and growth through DNA and RNA synthesis, and 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 and lipids. The folate pathway is considered a major energy sensing pathway as cell growth and DNA synthesis is regulated by availability of the vitamin. Folate during development and 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 and 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 and pathway activity. We hypothesize that the major energy sensing pathway of AMPK is the direct link that connects he expression and 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) and 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 and 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 21

15 2017 Internship Directory: Summer Experience Mentor area(s) Internship Matthew Podgorsak, PhD Radiation Medicine /Matthew-Podgorsak Radiation Oncology 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, Ph.D. Molecular and Cellular Biology /Steven-Pruitt Cancer bioinformatics Stem/progenitor cell replication in cancer and aging Work under this internship will be directed at understanding how normal and abnormal DNA replication and cell proliferation of stem and progenitor cells contribute to tissue maintenance and genome stability in cancers and 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 and FACS), generation of and/or histological/molecular characterization of transgenic mice, and whole genome bioinformatic analyses. Brahm Segal, MD Medicine /Brahm-Segal Innate Immune Responses in Ovarian Cancer 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. Mukund Seshadri, DDS, PhD Pharmacology and Therapeutics /Mukund-Seshadri Cancer biophysics Radiation Oncology Multi-modal Imaging of Cancer in my laboratory is focused on three main areas: (i) understanding the vascular biology of head and neck cancers and exploiting them for therapeutic benefit, (ii) development of safe and effective bio-adjuvant approaches for the prevention of oral cancers and, (iii) the use of advanced imaging methods such as MRI, CT in preclinical models and in patients to study response of head and neck tumors to chemotherapy and radiation. The work is interdisciplinary in nature and draws on concepts from biophysics, cancer biology, pharmacology and molecular biology. Given my clinical background, I feel strongly about pursuing a research program that addresses clinically-relevant questions in the laboratory setting and potentially translates the knowledge gained into meaningful outcomes for patients. Page 15 of 21

16 2017 Internship Directory: Summer Experience Mentor area(s) Internship Gal Shafirstein, D.Sc. Cell Stress Biology /Gal-Shafirstein Cancer biophysics Treatment Planning and Light Dosimetry in Photodynamic Therapy (PDT) My research team is focused on the development and implementation of treatment planning and light dosimetry in PDT. My group includes, 3 engineers, research scholar and a pre-doctoral student. We do preclinical and clinical studies, and investigate combination therapies. Li Tang, MD, PhD Cancer Prevention and Population Sciences /Li-Tang Cancer molecular epidemiology Cancer prevention and epidemiology Gene-diet interactions in cancer survivorship and treatment outcome Our research program is engaged in molecular epidemiological study of cancer, with focus on cancer recurrence and survival. Our research interest is to understand the interactive roles of genetic and dietary factors in cancer prognosis by utilizing multi-disciplinary approaches. The primary focus is on cruciferous vegetables and their key anti-cancer effectors, the phytochemical isothiocyanates. We have successfully conducted studies on anti-cancer mechanisms, metabolism, and bioavailability of isothiocyanates in both in vitro and in vivo models. We are currently investigating ways to translate findings into clinical settings, in the hope of developing dietary intervention approaches to improve cancer prognosis. Mark Travers, PhD Cancer Prevention and Population Sciences /Mark-Travers Tobacco products and exposure science Examining exposure to tobacco smoke pollution and new and 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 and changing health behaviors. Accurate, easy to communicate, empirical data on exposures is necessary to justify the interventions and 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 and emissions from new and emerging products such as waterpipe (hookah) and 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, and secondary data analysis. Page 16 of 21

17 2017 Internship Directory: Summer Experience Mentor area(s) Internship Xinjiang Wang, PhD Pharmacology and 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 and cell death will be analyzed. Cell culture, cell growth assay, Western blotting analysis of target proteins and biochemical events of apoptosis will be performed. Eunice Wang, MD Medicine /Eunice-Wang Medical Oncology Novel Biological Therapies for Acute Leukemia Our research focuses on the preclinical assessment and development of novel therapeutic strategies for acute leukemia. We are specifically interested in how interactions between tumor cells and other elements of the host marrow microenvironment contribute to cancer cell survival and therapeutic resistance. Current projects in the lab are focused on optimizing for acute myeloid leukemia and evaluation of antibody drug conjugates targeting CD33 and CD123 expressed on leukemia cells. Students will gain experience in sterile cell culture, proliferation assays, colony formation assays using primary leukemia patient samples, flow cytometry, and bioluminescent mouse models. The goal of our research is to identify immunotherapeutic and biological agents for translation into early stage clinical trials. Page 17 of 21

18 2017 Internship Directory: Summer Experience Mentor area(s) Internship Jianmin Wang, PhD Bioinformatics/ Biostatistics /Jianmin-Wang Cancer bioinformatics Cancer biostatistics Cancer experimental diagnostics Cancer molecular epidemiology Cancer prevention and epidemiology Clinical Integrative analysis of large-scale, multi-dimensional genomic data. The primary interests of my group are focused on the analysis of large-scale -omics data from cutting-edge biotechnologies using computational and statistical methods. My research interests include i) sensitive identification of structure variation from next-generation sequencing data; ii) statistical inference and computation variants (isoforms, SNV, SV) identification of RNASeq data; iii) integrated study of genomic, epigenetic and proteomic data. A number of methods and tools have been developed or are in development for computational analysis of nextgeneration data using statistical inference. Also, we have applied those methods into cancer genetics studies that revealed many novel findings. A number of research opportunities will be provided along this line. Clinical genetics Lei Wei, PhD Bioinformatics/Bios tatistics /Lei-Wei Cancer bioinformatics Identifying driver mutations by using next generation sequencing (NGS) Next generation sequencing (NGS) is providing an efficient system for characterizing cancer genomes. By comparing with the matched normal DNA, we can identify additionally acquired mutations, so called somatic mutations in cancers. Certain somatic mutations may directly contribute to tumorigenesis process by disrupting tumor suppressors or activating oncogenes. Identifying such driver mutations is an important step for understanding the mechanism of cancers and facilitating the development of personalized treatments. The current research will work on the somatic mutations found by NGS in various cancer types. The trainee will be expected to: 1) develop a good understanding of cancer NGS data; 2) by doing literature search and data-mining, identify novel mutations/mechanisms that may contribute to tumor initiation, progression and recurrence; 3) contribute to scientific publications. Page 18 of 21

19 2017 Internship Directory: Summer Experience Mentor area(s) Internship Anna Woloszynska- Read, PhD Pharmacology and Therapeutics /Anna -Woloszynska- Read Urology Role of STAG2 in bladder cancer High grade and high stage muscle-invasive bladder cancer (MIBC) is one of the most aggressive human cancers. Less than 20% of patients with advanced MIBC survive past 5 years due to lack of curative treatment. Thus, investigating the mechanisms of bladder cancer invasion is of paramount importance. Numerous factors are involved in recurrence, progression, and patient survival given bladder cancer s diverse biological and functional characteristics. Due to the heterogeneous nature of BC, pathologically similar tumors may behave differently, making progression to MIBC highly unpredictable. The unpredictable aggressiveness of high-risk non-muscle invasive (NMI) bladder tumors often leads to over-treatment with radical cystectomy, which in turn is associated with significant morbidity. Yet few options remain, since misrecognition and under-treatment of potentially aggressive, life-threatening NMI bladder tumors most often results in death. To date, the molecular alterations that transform NMI bladder cancer into MIBC have not been identified. MIBC patients with refractory disease have severely limited treatment options, making development of improved prognostic markers and treatment strategies a very high priority for this group of patients. The purpose of this project is to investigate the role of STAG2 in bladder cancer. The hypothesis guiding this research is that STAG2 in muscle-invasive bladder cancer has a predictive value and acts as an oncogenic transcriptional factor regulating genes involved in tumor cell invasion. To delineate the mechanism by which STAG2 enhances invasion in muscle-invasive bladder cancer cells our laboratory is working to establish the functional role of novel STAG2 target genes in STAG2-dependent regulation of invasion in muscle-invasive bladder cancer cells and identify prognostic significance of STAG2 alone or in combination with its downstream targets in bladder cancer progression. Page 19 of 21

20 2017 Internship Directory: Summer Experience Mentor area(s) Internship Yue Wu, PhD Urology /Yue-Wu Cancer molecular epidemiology Cancer prevention and epidemiology Understanding Progression of Prostate Cancer to Castration Re-Current Disease My research interest is in androgen metabolism and androgen receptor signaling in prostate cancer. Specifically, his research projects are focused on prostatic androgen trafficking and metabolism by prostatic epithelial cells and cancer cells, and how androgen metabolism affects biology and clinical characteristics of prostate cancer. The ultimate goal is to delineate mechanisms underlying the progression of prostate cancer to castration recurrent disease, and to identify novel modalities to prevent or treat castration recurrent prostate cancer. Y.Eugene Yu, PhD Cancer Genetics Genetic modeling and analysis of human diseases Genetic modeling and analysis of human diseases /Y.Eugene-Yu Page 20 of 21

21 2017 Internship Directory: Summer Experience Mentor area(s) Internship Qianqian Zhu, PhD Bioinformatics/ Biostatistics /Qianqian-Zhu Cancer bioinformatics Cancer biostatistics Cancer experimental diagnostics Cancer molecular epidemiology Cancer prevention and epidemiology Clinical genetics Clinical Dissecting the contribution of genetic factors to complex diseases Many common human diseases are known to have a major genetic component. Understanding the genetic basis of these diseases will enable effective disease prevention, diagnosis and treatment. My group has developed a number of novel computational methods to elucidate the genetic factors of complex human diseases and traits through integrating highthroughput genomics and genetics data. In addition to method development, my group has conducted multiples genome-wide association studies (GWAS) including steatosis and related phenotype in patients with genotype 1 chronic hepatitis C infection, and tamoxifen resistance in breast cancer patients. We are currently conducting a number of cutting-edge studies in dissecting genetic contributors to human diseases including pemphigus vulgaris, therapyrelated acute myeloid leukemia, unrelated donor blood or marrow transplant (BMT)-related mortality, and familial ovarian cancer. Page 21 of 21