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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages) Page 1 of 13 Mentor Research area(s) Internship category Internship description Andrei Bakin, PhD Dept. of Cancer Genetics www.roswellpark.edu/andrei- bakin Cancer bioinformatics Cancer genetics Cancer molecular and cellular biology Scientific Research ADAM family in Cancer progression and Metastasis Tumor microenvironment promotes breast cancer invasion and progression. The anti-inflammatory TGFβ and the pro-inflammatory TNF cytokines are major drivers of invasion and metastasis in the tumor microenvironment. Our published studies show that the pro-invasive activities of TGFβ and TNFα depend on TAK1, an ubiquitin- dependent protein kinase that activates NFκB and mitogen-activated protein kinase (MAPK) signaling in response to TGFβ and TNF cytokines. Recent studies suggest that TAK1 engages ADAM metalloproteinases promoting tumor invasion and metastases, including bone-destroying metastatic lesions. How TGFβ and TNF cytokines cooperate in the regulation of ADAMs is largely unknown. The current project will investigates the mechanism by which TGFβ and TNF cytokines regulate expression and activity of ADAM proteases and their contribution to metastatic potential of breast carcinomas in pre-clinical cancer models. Successful completion of the project may lead to a new treatment paradigm for patients with breast cancer. Dhyan Chandra, PhD Dept. of Pharmacology and Therapeutics www.roswellpark.edu/dhyan- chandra Cancer experimental diagnostics Cancer genetics Cancer molecular and cellular biology Cancer pharmacology & therapeutics Scientific Research Molecular mechanism of therapy resistance in cancer The overall goal of my laboratory is to understand how mitochondria-mediated cell death is regulated in cancer and normal cells. Investigating how cancer cells abrogate the mitochondrial cell death machinery will allow new avenues to restore cell death in cancer. We use biochemical, cellular, and molecular approaches to identify and define novel targets and/or agents for cancer prevention and treatment.

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Page 1: 2015 Internship Directory: High School Summer Research ... · 2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages) Page 1 of 13 Mentor

2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

Page 1 of 13

Mentor Research area(s)

Internship category

Internship description

Andrei Bakin, PhD Dept. of Cancer Genetics www.roswellpark.edu/andrei-bakin

Cancer bioinformatics Cancer genetics Cancer molecular and cellular biology

Scientific Research

ADAM family in Cancer progression and Metastasis Tumor microenvironment promotes breast cancer invasion and progression. The anti-inflammatory TGFβ and the pro-inflammatory TNF cytokines are major drivers of invasion and metastasis in the tumor microenvironment. Our published studies show that the pro-invasive activities of TGFβ and TNFα depend on TAK1, an ubiquitin-dependent protein kinase that activates NFκB and mitogen-activated protein kinase (MAPK) signaling in response to TGFβ and TNF cytokines. Recent studies suggest that TAK1 engages ADAM metalloproteinases promoting tumor invasion and metastases, including bone-destroying metastatic lesions. How TGFβ and TNF cytokines cooperate in the regulation of ADAMs is largely unknown. The current project will investigates the mechanism by which TGFβ and TNF cytokines regulate expression and activity of ADAM proteases and their contribution to metastatic potential of breast carcinomas in pre-clinical cancer models. Successful completion of the project may lead to a new treatment paradigm for patients with breast cancer.

Dhyan Chandra, PhD Dept. of Pharmacology and Therapeutics www.roswellpark.edu/dhyan-chandra

Cancer experimental diagnostics Cancer genetics Cancer molecular and cellular biology Cancer pharmacology & therapeutics

Scientific Research

Molecular mechanism of therapy resistance in cancer The overall goal of my laboratory is to understand how mitochondria-mediated cell death is regulated in cancer and normal cells. Investigating how cancer cells abrogate the mitochondrial cell death machinery will allow new avenues to restore cell death in cancer. We use biochemical, cellular, and molecular approaches to identify and define novel targets and/or agents for cancer prevention and treatment.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

Page 2 of 13

Mentor Research area(s)

Internship category

Internship description

Sreenivasulu Chintala, PhD Dept. of Pharmacology and Therapeutics N/A

Cancer molecular and cellular biology Cancer pharmacology & therapeutics Urology

Scientific Research

Drug Resistance mechanisms and combination therapy in Genitourinary Cancers Our research goal is to understand the molecular mechanism(s) responsible for drug resistance and develop effective combination therapy for genitourinary cancers of kidney, bladder and prostate. The current project is to investigate the mechanism(s) how cystine transporter xCT, contributes the drug resistance and evaluate the xCT inhibitors combination to reverse the drug resistance in genitourinary malignancies. We will use the pre-clinical models of in vitro cells and in vivo xenografts for the studies. Internship will provide the opportunity to learn various cell and molecular biology techniques in the research field of experimental cancer therapeutics.

Steven De Boer, MSc medical physics Dept. of Radiation Medicine www.roswellpark.edu/steven-de-boer

Radiation Oncology

Clinical Research Scientific Research

Radiotherapy dose calculations Tissue density corrections for radiotherapy dose calculations Dose calculations Project may include implementation of tissue density corrections for dose calculations

Vita Golubovskaya, PhD Dept. of Surgical Oncology www.roswellpark.edu/vita-golubovskaya

Cancer molecular and cellular biology

Scientific Research

Targeting Focal Adhesion Kinase in cancer The project will be focused on studying of novel inhibitors of Focal Adhesion Kinase in different types of cancer.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

Internship category

Internship description

Maciej Goniewicz, PharmD, PhD Dept. of Cancer Prevention and Population Sciences www.roswellpark.edu/maciej-goniewicz

Cancer prevention and epidemiology Tobacco control

Scientific Research

Safety of electronic cigarettes. Harm reduction. Research projects focus on new nicotine-containing 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.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

David Goodrich, PhD Dept. of Pharmacology and Therapeutics www.roswellpark.edu/david-goodrich

Cancer experimental diagnostics Cancer genetics Cancer molecular and cellular biology Urology

Scientific Research

Thoc1 and Prostate Cancer Progression Prostate cancer is diagnosed increasingly at an early stage due to widespread screening using the PSA test. Most newly diagnosed men do not require treatment because their disease will remain indolent. A few men would benefit from potentially curative treatment like prostatectomy because their prostate cancer is destined to progress to life threatening disease. Currently it is difficult to predict which patients should receive immediate treatment and which should simply be monitored carefully. We have observed that the ribonucleoprotein encoded by the THOC1 gene is up regulated in clinically aggressive prostate cancer. We have begun an effort to test whether THOC1 expression may be a clinically useful biomarker for identifying which newly diagnosed prostate cancer patients should receive immediate treatment because their disease is likely to progress. A scientific internship on this project would involve analyzing specimens from human prostate cancer patients and mouse models of prostate cancer for expression of THOC1 using techniques like immunohistochemical staining, enzyme linked immunosorbent assay, and polymerase chain reaction. Data will then be correlated with clinical outcome to test the hypothesis.

Katerina Gurova, PhD Dept. of Cell Stress Biology www.roswellpark.edu/katerina-gurova

Cancer genetics Cancer molecular and cellular biology Cancer pharmacology & therapeutics

Scientific Research

Study of the mechanism of action of novel anti-cancer agents We have several candidate anti-cancer agents, discovered in the lab. Intern will test their activity against tumor and normal cells and their effect on different signaling pathways in cells.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

Francisco Hernandez-Ilizaliturri, MD Dept. of Medicine www.roswellpark.edu/francisco-hernandez-ilizaliturri

Cancer molecular and cellular biology Cancer pharmacology and therapeutics Tumor immunology & immunotherapy

Medical Oncology

Scientific Research

Lymphoma Translational Research Program Our group of investigators is actively involved in clinical, translational and laboratory-based research projects, in an attempt to gain a better understanding of pathogenesis, prognostic factors, and cellular/molecular features associated with the development of “resistance” in lymphoid neoplasms. Our research focuses in 1) improving the biological activity of monoclonal antibodies against b-cell lymphoma; 2) overcoming rituximab-chemotherapy resistance in b-cell lymphoma; 3) evaluate novel small molecule inhibitors targeting key-regulatory pathways in lymphomas; 4) identification of biomarkers of response to current available therapies in patients with B-cell lymphoma; and 5) applying our pre-clinical work in the rational design of clinical trials for patients with lymphomas. Dr. Francisco J Hernandez-Ilizaliturri’s projects: (1) Identifying and targeting key-regulatory pathways responsible for resistance to chemo-immunotherapy in B-cell lymphoma. the inhibitory of apoptosis proteins (IAP) in B-cell lymphoma. We are evaluating IAP antagonists, such as LCL-161, are peptidic or non-peptidic small molecules developed to target aberrant IAP expression in cancer cells. (2) Identification of biomarkers of response to current available therapies in patients with B-cell lymphoma.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Steven Hochwald, M.D Dept. of Surgical Oncology www.roswellpark.org/steven-hochwald

Cancer biostatistics Cancer experimental diagnostics Cancer molecular and cellular biology Surgical Oncology

Clinical Research Scientific Research

Biomarkers of esophageal cancer: analyze the correlation between focal adhesion kinase (FAK)/pyruvate kinase M2 (PKM2) levels and clinical outcome.Rapidly growing cells take up glucose at a high rate and undergo glycolysis to produce building blocks for synthetic reactions and energy. Normal tissues such as fetal cells only switch to this state upon growth factor stimulation, whereas esophageal cancer cells are locked in the glycolytic mode to function like fetal cells by promoting incorporation of glucose metabolites into macromolecules rather than burning them to produce CO2. Loss of normal control of key glycolytic enzymes contributes to excessive glucose consumption by tumor cells. PKM2, the penultimate glycolytic enzyme that catalyzes the irreversible conversion of phosphoenolpyruvate to pyruvate, is deregulated in esophageal cancer cells and has been shown to be an important prognostic factor for survival in esophageal cancer patients. PKM2 re-expression can allow esophageal cancer cells to sustain excessive glucose turnover and proliferation. We will perform esophageal cancer tissue microarray analyses and the levels of FAK and PKM2 protein in the EC specimens will be quantified (the RPCI microarray core facility). Statistical analysis will be carried out to determine correlations between the levels of FAK and PKM2, tumor differentiation and stage of esophageal cancer. FAK modulation of PKM2 and aerobic glycolysis in esophageal cancer Esophageal cancer causes over 400,000 deaths worldwide every year. Normal cells use glucose as a fuel to maintain basic functions such as muscle movement. When they receive environmental signals including growth factor stimulation, normal cells such as fetal cells take up excessive glucose to produce building blocks and energy for their rapid growth or to support cell proliferation. When organ construction or tissue repair is completed, cells return to the normal state upon withdrawal of extracellular stimuli. Esophageal cancer cells are locked in the growth mode with high glucose consumption in an environment which is independent of stimulation. Environmental factors can change the function of glucose-processing proteins and cause excessive glucose consumption. Current therapeutic strategies targeting a single gene may benefit a small fraction of cancer patients who harbor the altered gene. However, tumor cells often use another alternative route to become drug resistant and maintain high glucose consumption. Therefore, we examined whether blocking a common tumor phenomena such as glucose metabolism inhibits growth of esophageal cancer. Our studies demonstrate that a key protein of glucose metabolism, named pyruvate kinase M2 or PKM2, contributes to excessive glucose consumption in esophageal cancer cells. We will use sophisticated gene manipulation techniques to define the role of PKM2 binding with FAK in modulation of glucose metabolism in esophageal

cancer cells (project 1).

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

Yurij Ionov, PhD Dept. of Cancer Genetics www.roswellpark.edu/yurij-ionov

Cancer experimental diagnostics Cancer genetics

Scientific Research

Role of natural IgM antibodies in cancer immune surveillance To develop multivalent scFv antibody phage display to analyze IgM antibody genes involved in cancer immune surveillance. To test in mouse model the efficiency of recombinant antitumor antibodies to prevent cancer

Fengzhi Li, PhD Dept. of Pharmacology and Therapeutics www.roswellpark.edu/fengzhi-li

Cancer molecular and cellular biology Cancer pharmacology & therapeutics

Scientific Research

Anticancer drug mechanism studies Candidate will be involved in lab bench work.

Harish Malhotra, PhD Dept. of Radiation Medicine www.roswellpark.edu/harish-malhotra

Radiation Oncology

Scientific Research

Evaluation of the accuracy of various dose computation algorithms for lung Stereotactic Body Radiotherapy Treatment planning in radiotherapy is a process which lets a clinician preview the radiation dose distribution in a patient using various mathematical models. The accuracy of these dose computation algorithms depend on various factors and are often inversely related to the needed computation needed. However, computation power of the computers has increased significantly in recent times and hence it is now possible to employ more sophisticated algorithms. In this study, we will use different algorithms for a number of lung patients and evaluate their differences in estimating dose to the tumor and organs at risk.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

Internship category

Internship description

Mateusz Opyrchal, MD, PhD Dept. of Medicine www.roswellpark.edu/mateusz-opyrchal

Cancer molecular and cellular biology Cancer pharmacology & therapeutics

Scientific Research

Mechanisms of resistance to standard therapies in breast cancer Our lab has several projects that would be suitable for a summer student involving novel mechanisms of resistance to chemotherapy or endocrine therapy in breast cancer. The students would work under the supervision of a senior technician or a post-doc with at least weekly meetings with me to evaluate progress. The project would involve tissue culture, proliferation assays, western blots, transfections ... We will structure the projects to have achievable results by the end of the internship. Our last student won the best oral presentation so the bar is set high.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

Santosh Patnaik, MD, PhD Dept. of Surgical Oncology www.roswellpark.edu/santosh-patnaik

Cancer bioinformatics Cancer biostatistics Cancer experimental diagnostics Cancer genetics Cancer molecular and cellular biology Cancer molecular epidemiology Cancer pharmacology and therapeutics Cancer prevention and epidemiology Clinical genetics Tumor immunology & immunotherapy Medical Oncology Surgical Oncology Tissue microenvironment in cancer

Scientific Research

Genetics and epigenetics in cancer and development We are interested in genetics (gene mutations, expression, etc.) and epigenetics (microRNAs, RNA editing, etc.) as it pertains to cancer and the human host's 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, 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: 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 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.

Matthew Podgorsak, PhD Dept. of Radiation Medicine www.roswellpark.edu/matthew-podgorsak

Radiation Oncology Medical Physics

Clinical Research

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.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

Mukund Seshadri, DDS, PhD Dept. of Pharmacology and Therapeutics www.roswellpark.edu/mukund-seshadri

Cancer biophysics Cancer pharmacology& therapeutics Radiation Oncology

Scientific Research

Multimodality Imaging of Cancer My research 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.

Gal Shafirstein, DSc (PhD) Dept. of Cell Stress Biology www.roswellpark.edu/gal-shafirstein

Cancer biophysics Surgical Oncology

Clinical Research Scientific Research

PDT for patients with head and neck or lung cancer We focus on the implementation of treatment planning and light dosimetry in interstitial PDT for patients with head and neck cancer, and intraoperative PDT for patients with lung cancer. 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.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

Ashwani Sood, PhD Dept. of Immunology www.roswellpark.edu/Ashwani-Sood

Cancer experimental diagnostics

Scientific Research

Role of PDEF in breast cancer Many biologic risk factors including old age, family history, prior breast cancer and higher breast density have been described as risk factors for breast cancer development. However, the underlying molecular mechanisms remain unknown. Our lab has identified PDEF-CEACAM6 as a novel oncogenic axis in breast cancer. The goal of this project is determine whether activation of this oncogenic axis explains one or more biologic risk factors in breast cancer. Specifically for this project PDEF and CEACAM6 expression will be determined in breast tissue from women age 60 years or older versus those from age <35 years by immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Mark Travers, PhD Dept. of Cancer Prevention and Population Sciences www.roswellpark.edu/mark-travers

Cancer prevention and epidemiology

Scientific Research

Evaluating 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. Dr. Travers has validated a novel real-time particle monitor for measuring exposure to tobacco smoke pollution (TSP). This method accurately measures people’s exposure to TSP and predicts their body-burden of tobacco smoke-related carcinogens. Dr. Travers has shown that U.S. smoke-free air policies result in 90% reductions in fine particle air pollution in hospitality venues and 92% reductions in carcinogen levels of previously exposed individuals. Current projects are measuring exposure to particulate air pollution in different environments including workplaces, homes, cars, outdoors, and multi-unit housing with collaborators in over 65 countries. Dr. Travers is leading an R01 community intervention trial examining exposures to TSP in multi-unit housing and testing interventions to increase the adoption of smokefree multi-unit housing policies. Dr. Travers’ Air Pollution Exposure Research Laboratory (APERL) is examining pollution from new and emerging tobacco products including waterpipe (hookah) and electronic cigarettes (e-cigs). This translational research is used to reduce exposure to airborne carcinogens by directly informing effective public health policies and by educating individuals to change their personal health behaviors. Work for this internship may be based in the laboratory and/or involve data collection in the field. An emphasis is always placed on gathering data that informs public health policy debates.

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2015 Internship Directory: High School Summer Research Internship Program in Cancer Science (13 pages)

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Mentor Research area(s)

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Internship description

Eunice Wang, MD Dept. of Medicine www.roswellpark.edu/eunice-wang

Cancer molecular and cellular biology Cancer pharmacology & therapeutics Tumor immunology & immunotherapy

Medical Oncology

Scientific Research

Targeting the Bone Marrow Microenvironment in Acute Leukemia Our research 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, leukemia patient samples, flow cytometry, in vitro assays and whole animal bioluminescent preclinical mouse models

Lourdes Ylagan, MD Dept. of Pathology www.roswellpark.edu/lourdes-ylagan

Cancer experimental diagnostics Cancer Pathology

Clinical Research

Evaluation of Urothelial Lesions of the Bladder using p16/Ki-67 on Urine Specimens The laboratory is interested in the evaluation of bladder cancers thru urine cytology using markers of differentiation using a unique double staining methodology to detect high grade lesions of the urinary tract. The student will be expected to help in the organization and preparation of the slides, working with a technologist to understand staining techniques and incorporate what one sees in the microscope with clinical findings. He/She should also be able to review the literature on what has been written with regards to using p16/Ki-67 in the detection of bladder carcinoma in urine specimens. In addition, the student will be expected to write an abstract and prepare a poster for presentation and be able to speak about their project. This project will be in collaboration with the Cytopathology Fellow.