Internship Directory: Summer Research Experience Program in Cancer Sciences (13 Pages)

Transcription

1 Andrei Bakin, PhD Dept. of Cancer Genetics TAK1 signaling in cancer recurrence and metastasis Breast and Ovarian cancers (BRCA, OVCA) are among the deadliest cancers for women in the United States, largely due to recurrence and metastasis. Both cancer types have tendency to become refractory to conventional therapies, whereas hormone-receptor and HER2- negative BRCAs (TNBCs) do not have a targeted therapy. Our program is focused on better understanding of the molecular underpinnings of cancer progression metastasis, and on developing of more effective anti-cancer therapeutics. Two projects are available for this internship: project 1 is to define how and why TAK1 facilitates cancer progression and metastasis. Bioinformatics and experimental (genetic and chemical) tools will be used to define the role of specific TAK1 signaling components in cancer. Project 2 is to examine pharmacological activities of novel chemical probes against TAK1 in pre-clinical models. Breast metastatic cell lines and primary tumors will be used in preclinical models with anti-tak1 agents alone and with conventional agents. Matthew Barth, MD Dept. of Pediatrics Pediatrics Targeted therapeutic approaches in B-cell lymphoma We are characterizing differences in intra-cellular signaling in sensitive and resistant B-cell non-hodgkin lymphoma cell lines and attempting to reverse resistance using targeted inhibition of pathways found to have altered activation in resistant cells. Page 1 of 13

2 Dhyan Chandra, PhD Cancer prevention and epidemiology Cancer cell death The focus of Dr. Chandra s laboratory is to: understand the underlying mechanisms of cell death including apoptosis, autophagy, and necroptosis in cancer; study heat-shock proteins and their role in cancer cell survival and death; target mitochondria for cancer prevention and therapy. Gokul Das, PhD Estrogen Receptor & Tumor Suppressor 53 in Cancer Research in my laboratory focuses on interaction between estrogen receptors and tumor suppressor p53 signaling in cancer. Our strategy integrates basic, translational, and clinical approaches to understand mechanisms that drive the cancer process. We use various cellular and molecular techniques in our experimental strategy. Experimental systems include cancer cell culture, xenograft tumors in mice, and cancer patient tissues. Potential Summer Research Projects are: (1) Analyze the role of mutant p53 and estrogen receptor-beta in triple negative breast cancer (TNBC). TNBCs are very aggressive tumors. Currently available endocrine and chemotherapeutic agents are not effective to treat these cancers. Information on the signaling pathways is expected to facilitate development of new therapeutic strategies against this cancer. (2) Investigate mechanisms responsible for resistance to tamoxifen therapy for breast cancer. (3) Analyze how interaction between estrogen receptor and p53 signaling affect cancer cell metabolism (4) Determine mechanisms underlying the role of estrogen receptors and p53 in hard-to-treat non-small cell lung cancer (NSCLC). Page 2 of 13

3 Kevin Eng, PhD Dept. of Bioinformatics & Biostatistics Cancer biostatistics Cancer molecular epidemiology Tumor immunology & immunotherapy Gynecology Ovarian cancer statistical modeling Statistics, as the study of how to make quantitative inferences, is at the heart of scientific : every high-quality study at the institute must involve a biostatistician. While I am trained as a statistician, my specialization is in genomics and ovarian cancer. In the following projects, the candidate intern will develop technical skills in basic statistics, statistical programming, simulation and computational techniques. Project 1. Studying treatment trends in relapsed ovarian cancer. I am interested in the process behind the selection of treatments for relapsed ovarian cancer. By modeling how these decisions are made and how effective they are, we will establish whether we can discriminate between good and poor therapies. Project 2. Modeling signaling pathways. Ovarian cancers are genetically heterogenous: different cancers show different responses and characteristics that can be traced back to their genetic diversity. This project will involve simulating data to reflect a variety of signaling models and testing the performance of existing methods. Project 3. Modeling autocrine and paracrine signaling. It has been hypothesized that correlation between known ligand and receptor pairs reflects an autocrine signaling mechanism. In addition, signal transduction from some receptors involves an algebra of homoand heterodimers. With data from a variety of tissues from the same patient, this project will prototype an analysis of candidate signaling models and determine the effect of transductive signals on prognosis. Page 3 of 13

4 Irwin Gelman, PhD Dept. of Cancer Genetics Genomics and pathways controlling cancer metastasis My lab seeks to identify novel metastasis-regulating genes and pathways using genetic and genomic screens. Our major focus is on the Src- FAK tyrosine kinase pathways as applied to both prostate and breast cancers. The internship consists of projects to identify and characterize such genes using cell culture, animal tumor models (including transgenics) or analysis of human clinical cancer samples in order to determine whether they function as drivers of metastasis, and thus, whether they can be targeted therapeutically. Vita Golubovskaya, PhD Dept. of Surgical Oncology Inhibitors of Focal Adhesion Kinase in cancer Focal Adhesion Kinase (FAK) is highly overexpressed in many types of cancer. We will develop novel inhibitors of FAK. Maciej Goniewicz, PhD Dept. of Cancer Prevention and Population Sciences Cancer prevention and epidemiology Tobacco addiction Safety of electronic cigarettes. Harm reduction. Research projects focus on new nicotinecontaining products and alternative forms of tobacco. Aim of the projects is to 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 and smoking cessation. Other projects evaluate implementation of new tobacco control laws and role of community pharmacists in smoking cessation. Page 4 of 13

5 Pamela Hershberger, PhD Effects of vitamin D in lung cancer Our laboratory uses primarily molecular and cellular approaches to understand how vitamin D impacts the biology of lung cancer. We are also interested in understanding how lung cancer cells become resistant (avoid) the growth suppressive effects of vitamin D. Yurij Ionov, PhD Dept. of Cancer Genetics Cancer experimental diagnostics Tumor immunology & immunotherapy Natural antibodies in cancer immune surveillance Working on finding evidences that the repertoire of natural antibodies can control cancer occurrence. Identifying rearranged human immunoglobulin genes of natural antibodies involved in cancer immune surveillance. Aimin Jiang, PhD Dept. of Immunology Tumor immunology & immunotherapy Beta-catenin and DC-based cancer vaccine Will investigate whether and how modulating beta-catenin signaling improves efficacy of DC-based cancer vaccines. Eugene Kandel, PhD Dept. of Cell Stress Biology Stress signaling pathways in cancer We use various gene-discovery tools to identify the mechanisms, which determine how normal and cancer cells respond to various stresses. This knowledge should increase safety and efficacy of existing therapies and pave the way for the new ones. An intern will have an opportunity to learn about gene discovery technologies, culture and genetic engineering of mammalian cells, and other laboratory techniques, while helping in characterizing the roles of various putative modulators of stress response pathways. Page 5 of 13

6 Eric Kauffman, MD Dept. of Urology Urology Clinical Clinical features and outcomes of kidney cancer This project involves investigation of clinical features and outcomes of kidney cancer and prostate cancer patients treated at Roswell Park Cancer Institute, using clinical databases. Examples of specific prostate cancer questions currently being investigated include: i) the role of active surveillance as an alternative option to prostatectomy surgery in low or intermediate risk prostate cancer patients, ii) the role of MRI imaging in prostate cancer diagnosis and staging, and iii) the metastatic status of low grade prostate cancers removed by surgery and implications for postoperative patient surveillance. Examples of specific kidney cancer questions currently being investigated include i) clinical and pathologic features of kidney tumors with the potential to metastasize despite small size, and implications for active surveillance as an alternative to surgery, ii) significance of kidney tumor growth rate in predicting metastatic potential, iii) clinical features to differentiate benign and malignant kidney tumors prior to surgery, iv) comparison of risk factors and clinical features/outcomes among different kidney cancer biologic subtypes. Students will gain experience in clinical database entry and analysis, and acquire basic knowledge and background in prostate and/or kidney cancer biology and clinical management. Individual projects will be tailored to the student s level of training and interest. Page 6 of 13

7 Eric Kauffman, MD (continued) Dept. of Urology Laboratory in kidney cancer biomarkers My lab is involved in multiple projects primarily related to kidney cancer biomarkers. Our main focus is currently the molecular characteristics and clinical significance of circulating tumor cells (CTC)-- cells shed from the primary kidney tumor into the bloodstream in the absence of metastasis. Current work aims to determine the molecular markers on CTCs which enable their reliable detection in kidney cancer patients using flow-cytometry based approaches; this work additionally involves cancer cell fluorescent imaging analysis, with future plans to explore single-cell PCR for CTC characterization. Additional projects ongoing include the use of immunohistochemistry to investigate protein markers in patient tumors for a) differentiating renal cell tumor histologic subtypes, including malignant vs. benign, and b) assessing risk level for kidney cancer patients, in order to guide decisions for surgery. Fengzhi Li, PhD Anticancer drug development and mechanism of action Our lab focuses on anticancer drug discovery and development toward clinical trials. Interns will focus on this area to study drug action mechanisms and drug efficacy. Page 7 of 13

8 Asoke Mal, PhD Dept. of Cell Stress Biology Targeting oncogenic fusion PAX3- FOXO1 protein Our is aimed to develop molecularly targeted therapy for children malignant cancer alveolar rhabdomyosarcoma (ARMS). The modern multimodality treatment approaches are ineffective in patients with this disease and many children die. Therefore, there is a critical need to develop new therapeutic strategies to improve the survival of children with ARMS. Oncogenic PAX3-FOXO1 fusion protein is implicated in the poor prognosis and molecular basis of ARMS pathogenesis. Therefore, abrogation of PAX3-FOXO1 oncoprotein protein is a viable targeted therapeutic approach against ARMS. This proposal involves the characterization and validation of small molecule inhibitors of PAX3- FOXO1 in the development of novel ARMS-specific therapeutics. Daryl Nazareth, PhD Dept. of Radiation Medicine Cancer biophysics Radiation oncology Computational radiation physics Use computational tools, including MATLAB and a supercomputer cluster, to develop better optimization methods in radiation therapy. Mateusz Opyrchal, MD, PhD Dept. of Medicine Medical oncology Testing new theuraputic compounds in breast cancer The project would involve testing new promising drugs to determine if they have activity in breast cancer cells and to determine the predictors of activity. Page 8 of 13

9 Matthew Podgorsak, PhD Dept. of Radiation Medicine 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. Elizabeth Repasky, PhD Dept. of Immunology Cancer biophysics Radiation oncology Physiology & immunology of tumor microenvironment To understand how host physiology impacts tumor growth and effects of novel cancer therapies. Mukund Seshadri, DDS, PhD Cancer biophysics Cancer imaging My program is focused on the use of advanced imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT) and optical molecular imaging techniques in preclinical and clinical studies to assess the biological characteristics of tumors and their response to traditional and novel anticancer treatments. The program is also focused on the development of novel multifunctional and multimodal (MRI and optical imaging) nanoparticles for targeted imaging and therapy through active inter- and intradepartmental collaborations at Roswell Park and the University at Buffalo. Page 9 of 13

10 Gal Shafirstein, D. Sc. Dept. of Cell Stress Biology Surgical oncology Photodynamic therapy Thermal therapy Bioengineering internship in photodynamic therapy Goal: Learn how to utilize image based treatment planning software and spectroscopy in photodynamic therapy. Nature of the work: Laboratory work with physical models that mimics tissue (phantoms). Working with software package, including: Matlab (Mathworks), Comsol (finite element packages) and Medical imaging software for image analysis of CT, MR scans and ultrasound. You will be collaborating with other teams that do pre-clinical. Participate in the write up of abstract and paper (as a coauthor). Present abstracts in international meetings. Ashwani Sood, PhD Dept. of Immunology Tumor immunology & immunotherapy Vaccine potential of PDEF oncogene in cancer The aim here is to determiine whether PDEF can induce HLA-A2 dependent T cell responses. Overlapping PDEF peptides spanning the coading region of PDEF will be used to immunize HLA- A2/Kb transgenic mice. Spleen cells will be isolated from the immunized and control mice and tested for activation of PDEF specific T cells. Quantititative RT/PCR and ELIspot assays will be used to assess the cytokine IF-N gamma secretion by activated T cells. Joseph Spernyak, PhD Dept. of Cell Stress Biology Cancer biophysics Imaging sciences Development of MRI imaging agents The project will involve some basic chemical synthesis of MR contrast agents and characterization of their imaging potential. The student will learn how magnetic resonance imaging works and be exposed to its multiple medical applications. Page 10 of 13

11 Nicoleta Voian, MD, MPH Dept. of Medicine Genetic counseling Clinical Genetics counseling Shadow genetic counseling sessions, case presentations, literature review, small project Xinjiang Wang, PhD Role of Mdm2 in cancer metabolism This project is to assess the role of oncogenic Mdm2 in metabolic reprograming in favor of cancer cell survival under metabolic stress. Eunice Wang, MD Dept. of Medicine Medical oncology Targeting the marrow microenvironment in leukemia Our focuses on the role of acute leukemia cells within the bone marrow microenvironment. We are specifically interested in how interactions between tumor cells and other elements of the marrow microenvironment contribute to leukemia cell survival, expansion, and therapeutic resistance. The overarching goal of our studies is to identify novel approaches and pharmacologic agents capable of targeting these interactions for translation into early stage clinical trials. Our work involves leukemia cell lines, primary patient samples, flow cytometry, in vitro assays and in vivo xenograft models. Meir Wetzler, MD Dept. of Medicine Medical oncology Investigate the role of vitamin D in leukemia Study the effect of vitamin D on the interaction between the bone marrow stroma and the leukemia cells. Page 11 of 13

12 Anna Woloszynska-Read, PhD Cancer epigenetics DNA methylation in bladder cancer The goal of the internship in my laboratory is to learn about cancer epigenetics specifically DNA methylation in cancer biology. We have utilized RNA sequencing and DNA methylation arrays to determine the role of subtoxic concentrations of DNA demethylating agents on the transcriptome and methylome, respectively, in muscle-invasive bladder cancer. We have identified several targets that require laboratory validation by quantitative RT-PCR and DNA methylation pyrosequencing. The summer intern will learn molecular biology techniques and will also be exposed to bioinformatics approaches used in analysis of data from highthroughput genomic assays. Song Yao, PhD Dept. of Cancer Prevention and Population Sciences Cancer biostatistics Cancer molecular epidemiology Cancer prevention and epidemiology Molecular and genetic cancer epidemiology To perform population-based epidemiologic work to understand the roles of molecular and genetic factors in cancer etiology, prognosis and response to treatment. Yuejin Yu, PhD Dept. of Cancer Genetics Molecular genetic studies of human disease Our lab is interested in molecular genetic studies of human disease in order to enhance our understanding of disease processes with the goals of developing more effective preventiion and treatment strategies. The students will have opportunities to work directly with the postdoctoral ers to carry out the experiments using contemporary methodologies in molecular and. Page 12 of 13

13 Jianmin Zhang, MD, PhD Dept. of Cancer Genetics Dysfunction of Hippo pathway in cancer The Hippo signaling pathway has been uncovered to play an essential role in organ size control; and dysregulation of this pathway leads to massive overgrowth and tumorigenesis. We will investigate how YAP/TAZ, the central components of Hippo pathway, oncogenic functions are being regulated. We believe that in the future, a better understanding of the YAP/TAZ biological functions and their dysfunction in cancer will lead to new therapeutic strategies to treat malignant cancer. Yuesheng Zhang, PhD Dept. of Cancer Prevention and Population Sciences Cancer prevention and epidemiology Urology Cancer biology, carcinogenesis, drug development Potential students have an opportunity in participating in one of the several ongoing projects in the lab. First, we are working to understand the molecular basis of why men have approximately 4 fold higher risk than do women in developing bladder cancer. Second, we are working to find agents, particularly those in food, to prevent bladder cancer and bladder cancer recurrence. Third, we are learning novel cancer signaling, involving oncogenic ErbB family tyrosine kinase receptors and p53 tumor suppressor. This may also lead to development of novel cancer therapeutic approaches in bladder cancer, breast cancer and other cancers. Page 13 of 13