Current Mentors for 2017 - 2018

A

Jairaj Acharya

Laboratory of Cell and Developmental Signaling

Research Goals/Purpose:

Our group studies sphingolipid/phospholipid signaling using Drosophila and mouse as model organisms. We use a combination of genetic, biochemical and cell biological approaches to evaluate the role of genes of sphingolipid metabolism/signaling in physiologcial and pathological conditions

Training Plan:

The student will be trained in all basic methodologies required in our studies. The student will work under the supervision of a post-doctoral fellow. The student will have the opportunity to pursue small independent projects.

Jairaj Acharya

Research Goals/Purpose:

Our group studies sphingolipid/phospholipid signaling using Drosophila and mouse as model organisms. We use a combination of genetic, biochemical and cell biological approaches to evaluate the role of genes of sphingolipid metabolism/signaling in physiologcial and pathological conditions

Training Plan:

The student will be trained in all basic methodologies required in our studies. The student will work under the supervision of a post-doctoral fellow. The student will have the opportunity to pursue small independent projects.

Jairaj Acharya

Research Goals/Purpose:

Our group studies sphingolipid/phospholipid signaling using Drosophila and mouse as model organisms. We use a combination of genetic, biochemical and cell biological approaches to evaluate the role of genes of sphingolipid metabolism/signaling in physiologcial and pathological conditions

Training Plan:

The student will be trained in all basic methodologies required in our studies. The student will work under the supervision of a post-doctoral fellow. The student will have the opportunity to pursue small independent projects.

Matthew Anderson

Research Goals/Purpose:

Fibroblast growth factors are secreted signaling molecules that are important in human embryonic development and disease. In both of these contexts they have been implicated in the cellular processes of proliferation, survival/death, migration, and differentiation. Mouse loss of function genetic studies have been crucial to our understanding of FGF function in both development and disease. The goal of this project is to assess the effect of removing several genes encoding members of the fibroblast growth factor signaling family on limb and hip girdle development during mouse embryonic development. Previous results suggest redundancy between these family members however we intend to do a more specific deletion of the genes. Redundancy will be assessed at the levels of signaling during embryogenesis and skeletal development at the end of gestation.

Training Plan:

Students will learn to dissect mice to remove mid- and late-gestation embryos, PCR genotype these embryos, and perform in situ RNA analysis and skeletal preparations.

Roxanne Angell

Research Goals/Purpose:

Project Management (PM): PM of Data Science Information Technology Program (DSITP) and Information Technology (IT) Projects using Project Management best practices based on the Project Management Body of Knowledge (PMBOK). Current IT projects will be included in addition to new DSITP projects or initiatives. These projects will be built out and followed through the processes and techniques for initiation, planning, implementation, monitoring and controlling, and closing. IT Service Improvement: The purpose is to improve upon processes and practices within the Information Systems Program (ISP)/IT Operations Group (ITOG) by using the Information Technology Infrastructure Library (ITIL) methodology of service strategy, service design, service transition, service operations and continual service improvement.

Training Plan:

Project Management (PM): The student intern will work with an ITOG Project Manager on current and new IT centric project initiatives. Student will be exposed to the 47 processes, the 5 process groups, and the 10 knowledge areas of project management. Training includes biweekly Operational Goal Meetings, independent reading, and other project management training opportunities. IT Service Improvement: The student intern will work with the project manager on exploring and improving existing incident management, change management, configuration management, and problem management processes and procedures based on ITIL standards for continuous service improvement. Includes independent reading of best practices for IT Service Management, weekly ITOG meetings, incident triage meetings, monthly change management meetings, configuration management meetings and communication meetings with different groups aimed at preventing problems. He/she will work with ITOG technicians transitioning to the new IT software for maximum utilization in conjunction with incident, change, configuration and problem management.

B

Joe Barchi

Research Goals/Purpose:

Student will learn the basics of organic chemistry, organic synthesis, proper procedure for lab experimentation and safety. Specifically, the student will learn the basics of the importance of cellular glycans and how to prepare various sugars or sugar analogues/peptides in the lab. Furthermore, the student will become proficient in designing experiments that lead to novel immunogenic and/or therapeutic glycopeptides that can be used as vaccine components or antimetastatic agents

Training Plan:

-Obtain basic knowledge of Organic chemistry -Obtain working knowledge of equipment in a standard chemical biology lab -Begin to use said equipment in the implementation of basic organic reactions -Shadow experienced chemists who can show them proper technique and laboratory skills. -Student will learn the basics of glycoconjugate chemistry and probe design that is the foundation of chemical biology research -Learn basics of bioassays used to evaluate the compounds prepared in their synthetic endeavors. -Become proficient bin record keeping, proper notebook maintenance and archiving of data. -Learn the basics of writing and presenting scientific data in a concise but logical and comprehensive way

John Beutler

Research Goals/Purpose:

Potential drugs are hiding in every leaf and root, and our lab attempts to find them. We will purify compounds from a Chinese spice known as Sichuan Pepper for potential use in cancer. Then we will analyze the structure of the compounds with modern techniques, compare compounds with others and estimate the amounts using NMR spectroscopy. Finally, we will test biological activity in several different models of cancer using biochemistry and cells.

Training Plan:

Training will include extraction of plant material, use of high performance liquid chromatography and other chromatographic techniques to purify alkamides for analysis, as well as exposure to basic NMR methods of analysis. Training will also include how to read scientific papers, how to communicate results, and how to participate in a scientific team.

Kajal Biswas

Research Goals/Purpose:

BRCA2 is a known tumor suppressor and presence of mutations are associated with predisposition to breast, ovarian and pancreatic cancers. Many variants with unknown significance has been identified in this gene from genetic screening of susceptible families. In an attempt to identify the pathogenic significance of those variants, our lab has developed an mouse embryonic stem cell based technology. We are now improving that technology using recently developed CRISPR-Cas method to generate variants. The students will use this technology to generate mutations in mouse ES-cells using CRISPR-Cas method. Besides that, we have identified a several BRCA2 functional interactor gene using retroviral mediated screen. Two of the genes are NCOA1 and NCOA3, members of the steroid family receptors. The student will also work to validate these genes as a functional interactor of BRCA2 using CRISPR mediated gene activation system.

Training Plan:

The student will learn basic laboratory safety and basic biological techniques. The student will then be exposed to various molecular biological techniques like PCR, cloning, gel-electrophoresis, sequencing, western blot as well as cell culture techniques. In addition, the student will also be trained to obtain scientific information as well as maintaining and presenting experimental data in laboratory and scientific meetings.

Frank Blanchard

Research Goals/Purpose:

1. Project Description – The WHK Intern will be stationed in the Office of Public Affairs, Frederick National Laboratory for Cancer Research. The intern will work closely with the director of public affairs to become acquainted with institutional public outreach in a national laboratory environment. The intern will interact with staff at all levels of the organization and with constituents in the Frederick community. The intern will gain experience in planning and executing outreach projects to support institutional goals, crafting institutional messages for various audiences, writing, editing, using visuals to communicate, face-to-face community interactions, and interacting and working with a creative services staff. Goal – The project is designed to give the WHK intern an understanding of how a public affairs office operates within a national laboratory environment and how communications can be used strategically to support the mission, and enhance the reputation, of a biomedical research organization. The intern will develop specific skill sets through writing for a mass audience; writing for a website; writing and producing visuals for social media; business communication; tailoring messages for target audiences; converting scientific jargon into everyday language; researching and writing a news story; working with designers, photographers, and other creative individuals to produce successful outreach projects; and preparing materials for a trade show exhibit.

Training Plan:

2. Student Plan – The WHK intern will receive assignments as they arise throughout the year. For a general overview: Jun – Aug: Introduction to staff, community contacts. Writing exercises with a focus on the fundamentals of news-writing. Write 2-3 stories for Insite, including at least one scientific article, and explore multimedia options to accompany texts. Repurpose/recast as warranted to the Poster, FNL website, social media, handout, etc. Sep – Nov: Assist in preparing for In The Street exhibit and Chamber of Commerce Business Expo from concept to production to display. Develop talking points / elevator speech for the events. Opportunity to attend and participate in both events. Continue to pursue writing assignments as they arise. Dec – Feb: Work on integrated communications to support institutional goals. Write profile articles on WSK interns for publication in Insite and the Poster. Continue writing assignments. Mar – May: Assist in preparing exhibit, handout, and talking points for Frederick Day in Annapolis. Work on design for a sponsorship advertisement, such as the YMCA magic show at the Weinberg, and work with SPGM on production. Continue writing assignments.

Xavier Bofill De Ros

Research Goals/Purpose:

We are interested in studying the processing and maturation of miRNAs. The final goal of our research is to translate the knowledge on miRNA biogenesis to an improved design of shRNAs that could be used as a gene therapy tool. In particular, the student will explore how different structural features of the pri-miRNA influence the processing.

Training Plan:

The student will learn the basic concepts of miRNA/shRNA biology such as the canonical biogenesis pathway and mRNA targeting. The project will involve the design and construction of plasmids containing different miRNAs or shRNAs. The student will gain skills in general techniques in molecular biology such as DNA isolation, cloning and mutagenesis, as well as the use of specific programs for DNA sequence manipulation and analysis.

Xavier Bofill De Ros

Research Goals/Purpose:

We are interested in studying the processing and maturation of miRNAs. The goal of this research project is to identify structural elements of RNA in pri-miRNA processing. In particular, the student will be using standard bioinformatic tools as well as programs developed in the our lab to analyze publicly available datasets.

Training Plan:

The student will learn the basic concepts of miRNA biology such as the canonical biogenesis pathway and mRNA targeting. The project will involve the use of different bioinformatic tools, and depending on the capabilities of the student writing its own scripts (R programing will be a plus). The position will requires certain degree of self-teaching skills and passion both for the biological meaning of the data and the computer science.

C

Raul Cachau

Research Goals/Purpose:

The overall goal of our research is to improve our understanding on the basic mechanisms of bio and nanomaterials function and the specific interactions that modulate their properties in the biological matrix.

Training Plan:

The student will learn the basic modeling techniques for the structure characterization of bio and nanomaterials including the basic elements of three dimensional reconstruction methods from experimental data and statistical methods used to explore the correlation of the bio and nanomaterial three dimensional (structural) properties with experimental (toxicity) data. The student will also have the opportunity to get familiarized with imaging methods used for the characterization of biomedical samples and bio and nanomaterials.

Ravindra Babu Chalamalasetty

Research Goals/Purpose:

We are interested in understanding the role of Wnt signaling in cancer and development. Our projects are geared towards delineating mechanisms of Wnt signals in self-renewal and differentiation of stem cells. In particular we will explore the roles of transcription factors required for Neuro-mesodermal progenitor maintenance and commitment.

Training Plan:

Student will first learn the concepts of Wnt signaling in general followed by hands on experiments in molecular biology, biochemistry and stem cell culture. Some of the common techniques students are expected to do routinely in the lab are PCR genotyping, quantitative-PCR, isolation of DNA and RNA, agarose gel electrophoresis etc. Students are the taught concepts of bio-informatics, for example DNA and protein sequence analysis, designing Q-PCR oligos, microarray analysis. Students are trained to make figures for research articles and participate in the preparing the manuscript.

Jiji Chen

Research Goals/Purpose:

Super resolution and single molecule imaging holds great promise for biomedical research. One of the major challenges in live cell application relies on time-consuming acquisition. Newly emerging algorithm that capable of resolving dense localization spots on sCMOS camera has the potential to overcome the issue. This research project aims on development and adaption of new algorithm to super resolution imaging in cells.

Training Plan:

The student will be trained to gain programming skills and understand the critical principles of optics and physics for a modern microscopy and imaging system. The data acquired with super resolution microscopy will be analyzed with newly developed algorithm. Training with biological sample preparation and data acquisition is expected as well.

Alex Compton

Research Goals/Purpose:

Work in the Antiviral Immunity and Resistance Section is guided by integrative approaches combining experimental virology, cell biology, and evolutionary biology to reveal dynamic host-virus interactions. A focus is placed on the cell-intrinsic innate immune response, as well as the strategies employed by HIV and emerging viruses to evade or overcome these immune barriers.

Training Plan:

The student, in partnership with a postdoctoral fellow, will participate in bench top molecular biology (such as molecular cloning, mutagenesis, sequencing, and plasmid preparation) followed by cell biology (cell culture, DNA transfections, immunolabeling for microscopy and western blot analysis). A portion of the work will entail computational analysis of DNA sequences and genomics. The student will be involved in discussions about experiments using HIV, but will not directly manipulate virus during the internship.

D

Ira Daar

Laboratory of Cell and Developmental Signaling

Research Goals/Purpose:

The mechanisms controlling morphogenetic movements during development involve modifications of cell-cell and cell-matrix adhesion. Abnormal modifications of these adhesion systems are often associated with metastatic progression. Our present focus is on a subset of the Eph family of molecules that are de-regulated in a wide variety of metastatic cancers.

Training Plan:

The student will be taught to use the Xenopus system under my supervision or that of a postdoctoral fellow in the Laboratory of Cell and Developmental Signaling. The project will involve completing the functional characterization of the cellular and developmental effects mediated by the intracellular portion of the EphrinB transmembrane Eph ligand. 1) EphrinB mutants will be expressed in developing embryos to determine structural motifs that are important for EphrinB-induced developmental effects. 2) EphrinB will be co-expressed with proteins found to be associated with EphrinB. The ability of these proteins to physically interact with EphrinB will be assayed. The ability to modulate EphrinB-induced developmental effects will also be assessed. 3) The ability of EphrinB to modulate the protein’s activity will also be tested.

Lisheng Dai

Research Goals/Purpose:

MicroRNAs comprise a novel class of small, non-coding endogenous RNAs that regulate gene expression by directing their target mRNAs for degradation or translational repression. Current project is to understand the mechanisms of microRNA biogenesis.

Training Plan:

Student will do regular and/or challenge experiments to gain the insight of biology research. Student will also read relevant literatures and participate in scientific discussions in the lab meeting once a week. Student will also present his/her work in group meetings and listen to the presentations of others. The goal is to help student to accumulate the knowledge of biology, and learn most RNA biology related techniques. Moreover, the student will get training for improving his/her critical thinking skill and efficiently plan the experiments, as well as scientific interpretation of the results.

Angela Dinardo

Research Goals/Purpose:

Our lab primarily studies miRNA biogenesis, modification, and turnover in the context of cancer. Our research goal for this project is to understand the implications of expressing miRNA by an RNA polymerase I promoter, which is normally involved in ribosomal RNA transcription. Our findings may provide a novel pathway for miRNA biogenesis with applications in cancer therapeutics. In addition to this goal, we hope to gain insight on the effect of knocking out DGCR8, a protein involved in the cleavage of primary miRNA transcripts. Analysis of deep sequencing data may uncover an intimate link between miRNA and rRNA pathways.

Training Plan:

The student working with me will become deeply immersed in the principles of molecular biology and learn a variety of techniques including cell culture, q-RT PCR, Northern blotting, luciferase assays, library construction, and more. The student will be encouraged to ask curious questions, expose themselves to relevant literature, and participate in scientific discussions with any members of the lab. This experience is primarily for the student to gain real experience in cancer research, which may guide his or her path toward a future career in the sciences.

Xia Ding

Research Goals/Purpose:

Breast cancer susceptibility gene 2 (BRCA2) mutation is a high risk factor for developing breast and ovarian cancer. The research goal is to understand the molecular mechanism of how BRCA2 mutation leads to cancer development, how BRCA2-mutated tumor acquire drug resistance, and furthermore how to cure BRCA2-mutated cancers based on this understanding.

Training Plan:

By using genome-wide screening, we identified several genetic interactors that can potentially cooperate with BRCA2 to facilitate tumorigenesis. Student plan is to follow up on these molecules and perform extensive molecular and cellular experiments to validate their biological functions in regards to BRCA2 and their implications in cancer development and cancer treatment.

F

John Fenimore

Research Goals/Purpose:

I have been working on various aspects of the immune system’s relationships with other biological systems including the brain, musculature, liver and the host microbiome. Our lab's primary area of interest is the interactions of IFN-gamma and host tissues in an attempt to understand the processes and mechanisms that effect immunity.

Training Plan:

I would like to have our student learn DNA and RNA extraction techniques, PCR, as well as cell culture methods. Learn microbead separation techniques and help us establish an effective CRISPR system for our cell lines.

Matt Fivash

Research Goals/Purpose:

Develop systems an software to support the research efforts at NCI-Frederick.

Training Plan:

* Extend HPC systems in support of NCI-Frederick data analysis requirements. Learn how to interact with multiple micro-computers using the Linux OS. * Develop a personal search engine to track large amounts of lab electronic data. Learn how a search engine works, and experiment using FOSS software.

G

Jeffrey Gildersleeve

Research Goals/Purpose:

Carbohydrates are one of the major classes of biomolecules found in living organisms. While many people associate carbohydrates with simple sugars or structural materials (e.g. cellulose), cells make a complex assortment of carbohydrate molecules that are involved in a wide range of biological processes. The set of carbohydrate molecules produced by a cell, referred to as the glycome, changes significantly with the onset and progression of cancer, resulting in expression of a variety of tumor associated carbohydrate antigens. Our group studies immune responses to carbohydrate antigens and the role of these responses in the development, progression, and treatment of cancer. We use a combination of chemical synthesis, molecular biology, protein expression, and microarray technology in our studies. The primary focus of this project is to study and develop monoclonal antibodies to carbohydrates. Antibodies that bind carbohydrate antigens are very useful in basic research and have numerous applications as diagnostics and therapeutics. Unfortunately, they are difficult to obtain. Our approach is to learn how the immune system develops and evolves carbohydrate binding antibodies and then use that information to develop new antibodies and/or better antibodies. Our studies focus on antibodies that target tumor associated carbohydrate antigens with diagnostic or therapeutic relevance for cancer.

Training Plan:

The project will involve construction of plasmids containing antibody genes, expression of the corresponding antibodies, and characterization of the resulting antibodies. The student will learn molecular biology techniques for isolating DNA, cloning and manipulating genes, and introducing mutations into genes. Next, the student will learn how to express, purify, and characterize a protein (antibody). Finally, the student will learn about glycan microarray technology developed in our laboratory and how to use this tool for high-throughput profiling of antibody binding properties.

H

Stephanie Halling

Research Goals/Purpose:

C&SS Goals

Training Plan:

C&SS Goals

I

Taisuke Izumi

Research Goals/Purpose:

LHRI (Laboratory of Human Retrovirology and Immunoinformatics) has a contract with National Institute of Allergy and Infectious Diseases (NIAID) in NIH and supports their clinical trials for HIV-infected patients by performing applied basic research and clinical research. LHRI has demonstrated that IL-27, a member of the Interleukin 12 (IL-12) family cytokine, plays a pleiotropic role in the immune system, by exhibiting antiviral activity against Human Immunodeficiency virus type I (HIV-1) and other virus, e.g. Herpes virus and influenza virus in multiple immune cells, such as CD4 T cells, Dendritic cells, and Macrophages. Our research goal is to clarify the detail mechanisms of IL-27-mediated resistance against HIV-1 infection. MicroRNA (miRNA), small 19-22 nucleotides long non-protein coding RNAs, are a critical regulator of mRNA turnover, deadenylation, and translation. We have previously identified seven novel microRNAs (miRNAs) in Macrophage treated with IL-27, One of the miRNAs has been defined to be a potent antiviral activity throughInterferon production in Macrophages.We have concluded that this interferon production may play a fundamental role in the antiviral mechanism of IL-27 in macrophages. On the other hand, it is known that Interferon is not generally produced from CD4 T cells, indicating that the mechanism of antiviral activity in CD4 T cells stimulated by IL-27 would be different from that in macrophages. We have recently discovered fifteen novel miRNAs in IL-27-treated CD4 T cells, suggesting that this particular miRNA expression may be involved in the resistance against HIV-1 infection in IL-27-treated CD4 T cells. To achieve our research goal, we focus on these novel miRNAs to reveal IL-27 mediated anti-HIV 1 activity in CD4 T cells.

Training Plan:

Our inquiry for the summer student who will dedicate functional analysis of the novel miRs and determine which miRNAs possesses the anti-viral activity in CD4 T cells. The student will be expected to perform experiments independently with minimum supervision by a staff scientist. The student will be instructed on the proper operation of the laboratory and biological tools, equipment and materials. Specific laboratory operations will primarily include RNA isolation from disinfected cell lysates and quantitation, RT-PCR, Immunoblotting, ELISA and operation of the fluorescent and confocal microscope. The position will include the manipulation of human non-virulent HIV-1 virus (No replication-competent) and primary immune cells in a BSL2* Laboratory. The student will be expected to present their data during a laboratory meeting and Student Internship program conference and may have their data published in a scientific paper in an academic journal.

J

Randall Johnson

BSP CCR Genetics Core

Research Goals/Purpose:

Support DSITP scientific projects.

Training Plan:

Students will be given general instruction on project management. Prior knowledge is helpful but not required.

K

Suhas Kharat

Research Goals/Purpose:

Student will learn basic molecular biology techniques such as plasmid isolation, primer designing, PCR reaction setup, restriction digestion, DNA ligation, bacterial transformation. Apart from molecular biology students will also work on some bioinformatic assignments such as analyzing DNA and protein sequences in BLAST and ClustalO tools.

Training Plan:

Similar to Research goals.

Kimberly Klarmann

Research Goals/Purpose:

Students will have the opportunity to learn about blood cell development, hematology, and basic molecular biology in this lab. Students will have the opportunity to learn about genetic modification, genetically modified mouse models and cell line models as well basic techniques for handling DNA, RNA and proteins. The focus of the lab is on the genetic regulation of early blood cell and bone marrow maturation (as it occurs in the adults, as opposed to the developing embryo). The genes studied by the lab include the Id family, Gfi-1 and POGZ.

Training Plan:

The students who join our lab will start by learning the basics of molecular biology and then transition to working with cells isolated from mouse tissues as well as cell lines. This laboratory will also teach the students about immunofluorescence and flow cytometry as well as how to handle and manage mouse models of hematopoietic (blood cell) development.

Jay Knight

Research Goals/Purpose:

The WHK SI intern will work with the Information Technology Operations Group (ITOG) and the previous interns to gain knowledge of the best practices according to the IT infrastructure Library (ITIL).

Training Plan:

The student will be exposed to the foundations of ITIL including Service Strategy, Service Design, Service Transition, Service Operation and Continual Service Improvement. On the job training includes, but is not limited to, Incident Management, Change Management, Problem Management, Triage of Service Requests, Configuration Management, Reports, Asset Management, IT Service Management workflows, and Metrics. Additionally, the WHK SI intern will work with the previous interns and the Program Administration and Operations Office to gain knowledge of Documentation Control including expose to the various processes involved including Standard Operating Procedures (SOPs), Service Level Agreements (SLAs), and Operational Level Agreements (OLAs) preparation and review. Self-paced training will involve reviewing current documents, independent reading, and Health and Human Services (HHS) learning portal on-line training. Training may extend to other areas including programming, networking, storage, and systems administration on LINUX or Windows operating systems depending on time, projects, operational work, and students skills and level of interest.

L

Kyeongeun Lee

HIV Drug Resistance Program

Research Goals/Purpose:

The nuclear pore complex (NPC) is a macromolecular machine that acts as a gatekeeper regulating the transit of molecules between the cytoplasmic and nuclear compartments of the cell. Newly synthesized proteins in the cytoplasm which act in the nucleus are actively transported through the NPC, whereas mRNAs transcribed in the nucleus egress through the NPC such that they can be translated in the cytoplasm. Viruses that co-opt nuclear proteins for their replication have evolved mechanisms to enable their transport through NPCs. This project will seek to elucidate the role of different proteins that comprise the NPC in aiding transport of cellular proteins as well as retroviruses.

Training Plan:

The student intern will work with a senior staff member in the group to develop fluorescent tag-labeled nuclear pore proteins to be expressed in living cells. The intern will also label cell cargo and viral proteins with different fluorescent markers. With these tools, the student will compare the transport of proteins from cytoplasm to the nucleus through the NPC using cells expressing authentic NPCs to those expressing genetically modified NPCs. By comparing and contrasting the transport of different cargo, we hope to develop an understanding of the contribution of specific NPC components to the transport process.

Mark Lewandoski

Research Goals/Purpose:

Molecular signaling is an integral part of biology and is a key factor in both cancer, which is the focus of our institute and embryonic development, which is the focus of our lab. Due to the highly dynamic nature of embryonic development, establishing the relationship between different genes and signaling molecules can be challenging. In order to address this, reporter constructs for different signaling pathways have been created. Reporter constructs give a real time readout of signaling activity in different living systems, from cell cultures to adult mice. Although there have been reporter constructs made for many different signaling pathways, a reporter for Fibroblast Growth Factor (FGF) signaling, which our lab studies, has not yet been made. Due to the importance of (FGF) in tumor formation and metastasis as well as in embryonic development, this reporter construct would be very valuable to the research community

Training Plan:

The successful candidate will receive hands on laboratory experience. The generation of the reporter construct will involve molecular biology, including performing restriction digests, ligation reactions and polymerization chain reactions. Once this is done, the reporter construct will be inserted into mouse embryonic stem cells and clones will be screened for FGF responsiveness. Ultimately, a successful ES cell line will be used to create a genetically modified mouse colony. As well as practical experience, the student will receive training in critical thinking, designing scientific experiments and interacting with scientific literature.

Yanling Liu

Research Goals/Purpose:

The ABCC Imaging and Visualization Group (IVG) collaborates with multiple FNL laboratories and provides direct support on infrastructure, software, algorithm, and visualization solutions to FNL imaging community. Student interns will work on full project lifecycle of identifying software solutions and algorithms (primarily from the open source imaging community), installing and testing these solutions with test data, comparing these software packages and algorithms for use within FNL, develop applications for imaging and visualization tasks, and providing summary reports on the best candidates for adoption by FNL. The project aims to enhance IVG quantitative imaging analysis and information capability to accelerate biomedical reserach at FNL. Also the project will help to inform students' decisions in college and a possible career in computer science by being actively involved in an end-to-end life experience on a complete project. These experiences will help train students to be better prepares and informed for college and professional life.

Training Plan:

Student interns will work on full project lifecycle of identifying software solutions and algorithms (primarily from the open source imaging community), installing and testing these solutions with test data, comparing these software packages and algorithms for use within FNL, develop applications for imaging and visualization tasks, and providing summary reports on the best candidates for adoption by FNL.

Yanling Liu

Research Goals/Purpose:

The ABCC Imaging and Visualization Group (IVG) collaborates with multiple FNL laboratories and provides direct support on infrastructure, software, algorithm, and visualization solutions to FNL imaging community. Student interns will work on full project lifecycle of identifying software solutions and algorithms (primarily from the open source imaging community), installing and testing these solutions with test data, comparing these software packages and algorithms for use within FNL, develop applications for imaging and visualization tasks, and providing summary reports on the best candidates for adoption by FNL. The project aims to enhance IVG quantitative imaging analysis and information capability to accelerate biomedical reserach at FNL. Also the project will help to inform students' decisions in college and a possible career in computer science by being actively involved in an end-to-end life experience on a complete project. These experiences will help train students to be better prepares and informed for college and professional life.

Training Plan:

Student interns will work on full project lifecycle of identifying software solutions and algorithms (primarily from the open source imaging community), installing and testing these solutions with test data, comparing these software packages and algorithms for use within FNL, develop applications for imaging and visualization tasks, and providing summary reports on the best candidates for adoption by FNL.

Stephen Lockett

Research Goals/Purpose:

In biological research, cells are generally studied in the culture dish, but it is known that the phenotype of cells in artificial culture is different to cells in tumor tissue. Consequently, a major challenge in cancer biology is understanding individual cells in the spatial context of other cells in tumor tissue. The Optical Microscopy and Analysis Laboratory (OMAL) provides the NCI with a range of technologies for acquiring and quantitatively analyzing 3D images of tumor tissue. A key component of OMAL's research is developing methods to prepare samples for image acquisition with 3D microscopes and developing and utilizing software for segmenting (delineating) individual cells from the 3D images. Once segmented, measurements are made of the size and shape of individual cells, the spatial organization of individual (fluorescence labeled) macro-molecules in each cell and the spatial context of each cell to neighboring cells.

Training Plan:

The student will learn a variety of biological, microscopy and image analysis techniques in support of the research goals. They are: 1) Learn how to make tissue optical clear through chemical treatment. 2) Fluorescence label cleared tissue. 3) Acquire 3D images of the labeled - cleared tissues using 3D microscopy: confocal, two photon and light sheet. 4) Analyze the images with existing software available in ImageJ / Fiji, previously built in house by OMAL, or other available software. 5) Statistically interpret the quantitative measurements from the analysis. 6) Communicate the results to OMAL staff and scientists from collaboration NCI labs. 7) Understand how the results augment the understanding of cancer biology. 8) Present the aforementioned methods, results from utilizing the methods and the biological context in poster and oral format at NCI - Frederick. 9) The plan may include the opportunity to develop further the in house built image analysis software. The plan may not include all of steps 1 through 4 and 9.

Debra Long-Priel

Research Goals/Purpose:

The Werner H. Kirsten Student Intern Program (SIP) at the National Cancer Institute (NCI) at Frederick is designed to expose high school seniors to research in a health care environment. The scientific interns experience the basic methods of cancer research through “hands-on” laboratory training. In the Neutrophil Monitoring Lab, the student will be taught many of the basic skills necessary to function in a laboratory setting. This will include safety in the laboratory, pipetting, sterile technique, preparation of buffers, proper use of balance and pH meter, centrifugation, monitoring of bacteria growth curves, etc. As his/her knowledge base progresses, the intern will be tasked with two independent projects 1) measure ROS production in differential HL-60 cells using either spectrophotometric or luminescence assay and 2) measure the NADPH oxidase components by immunoblotting.

Training Plan:

Training Plan: 1) Basics of laboratory safety – safety eyewear, gloves, lab coats 2) Importance of accurate, detailed laboratory notebook 3) Basics laboratory skills (A) – proper use of microscope, balance, pH meter, pipettes, preparation of solutions, buffers, etc. 4) Basics laboratory skills (B) – proper use of centrifuges, spectrophotometers, sterile technique, monitoring of bacterial cell growth, ROS production by spectrophotometry and luminometry. 5) Basics of SDS-PAGE gel electrophoresis and western blotting

M

Buyong Ma

Research Goals/Purpose:

Computational Investigation of sequence and structural aspect of the key molecules involved in immunology

Training Plan:

(1) Using computational biology / Bioinformatics approaches, such as sequence alignment, protein structure prediction, and molecular dynamics simulation tools to investigate the structure and function relationship of proteins involved in immunological pathways. (2) study the complex protein–protein interactions and networks to get insight into immune responses. (3) analyzing protein structures of antibody-antigen complex

Vickie Marshall

Research Goals/Purpose:

The mission of the Viral Oncology Section is the development of assays and procedures to identify and study pathogens associated with the development of human cancers.

Training Plan:

Student will be trained in the essentials of real time and digital PCR technologies. Several assays will be developed to identify pathogens associated with cancer. Student will become familiar with bioinformatic software and genetic analysis programs.

Chris McLeland

Research Goals/Purpose:

Gain working knowledge of laboratory instrumentation. Learn hands-on skill sets and laboratory techniques unique to the NCL. Gain understanding of cancer biology and nanotechnology. Become familiar with tissue culture and sterile technique. Learn to summarize research data and present to NCL staff. Participate in summer student activities, such as student seminar series.

Training Plan:

The summer student plan is divided into 3 phases. The first phase covers laboratory safety topics, and familiarization with basic equipment, such as balances and autoclaves, as well as common tools, such as pipets and centrifuges. The second phase entails more advanced laboratory techniques such as tissue culture and media and reagent preparation. Upon completion of these first 2 phases (at the end of the summer), the student will work with NCL scientists to execute their own research project aimed at elucidating the details of interactions between nanoparticles and biological matrices.

Jordan Meier

Research Goals/Purpose:

Dysregulated metabolism is a hallmark of many cancers. New methods to detect aberrant metabolic features thus have considerable potential in biomarker discovery, imaging, and diagnostics. The goal of this project is to develop and characterize small molecules that can detect the presence of the cancer-associated metabolite fumarate.

Training Plan:

The project will involve the synthesis and characterization of a fluorogenic probes. The student will work a postdoctoral fellow to learn techniques in synthetic chemistry and characterization required to define the structure of fluorescent probes., and develop a core skill set useful for this project and related chemistry/drug discovery projects. Additional training includes the potential to learns techniques in spectroscopic characterization and kinetics that will be useful to determine which of these fluorescent reporters may be most useful for studying aberrant cancer metabolism in pre-clinical and clinical settings.

Stephanie Mellott

Research Goals/Purpose:

Microarray technology enables you to monitor the activity of all the genes in the genome in a high-throughput manner. Our student will have the opportunity to learn about the new Nanostring technology and Affymetrix microarray platforms for gene expression as well as be introduced to the world of processing clinical patient samples.

Training Plan:

During our student's internship, s/he will be taught all of the general aspects of a laboratory as well as microarray specific skills, including but not limited to the following: use of Agilent Bioanalyzers and Nanodrop instruments for Q.C. purposes, keeping a detailed lab notebook to include various projects, operation and application of the Nanostring platform, operation and application of Affymetrix platform, fluidics and scanner, and operation and application of Sanger sequencing as time permits. S/He will be introduced to DNA and RNA extraction techniques and methods, how to handle and processing clinical patient samples as well as the necessary paperwork.

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Barry O'Keefe

Research Goals/Purpose:

The research goals of this project are the cloning, expression and unification of proteins of interest for the Molecular Targets Laboratory from recombinant E.coli. The proteins include enzymes and antiviral natural products. The goal is to produce proteins of sufficient quantity and purity to be used in the screening and drug discovery efforts in the MTL.

Training Plan:

The student will become familiar with safe handling techniques for recombinant organisms as well a safe general laboratory procedures. They will then learn how to clone a gene into E. coli and how to induce expression of the gene product in culture. They will also learn how to scale up culture volume, centrifuge and collect cell pellets and lyse the resulting cell pellets to release soluble proteins The student will then learn techniques for the purification of proteins including several types of chromatography including metal chelation affinity. size exclusion, hydrophobic interaction and ion exchange. These techniques will be used to purify expressed proteins. The student will also learn to assess protein purity by SDS-PAGE and LC/MS techniques. The student will also learn how to quantify protein and assess their primary amino acid sequence by automated amino acid sequencing. Finally, the student will become familiar with various assays to determine the biological activity of the purified proteins produced.

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Lorena Parlea

Research Goals/Purpose:

As scientific understanding of human diseases and their treatments expands, there is an ever-increasing focus on developing therapeutics that function on the smallest of scales. Nanomedicine can be used to fight afflictions from the moment they are expressed using gene-silencing therapy. The discovery of RNA interference (RNAi) served as a key to open the door for human gene therapy based on small interfering RNAs (siRNAs). Ever since, harnessing the silencing functions that siRNAs carry out within cells has become an endeavor of great importance; RNA itself may offer the most convenient method of delivering therapeutics to cells through the construction of functionalized RNA-based nanostructures. Student intern will be part of projects related to experimental RNA nanobiology working in conjunction with the computational RNA structure nano design component of our laboratory. Some potential projects are enumerated below. Final decisions on specific topics will be made after detailed discussions with the intern after arrival.

Training Plan:

1) Develop and use experimental techniques to verify our computational predictions of RNA-based nanostructures and to enhance the computational rules for these predictions; 2) Experimentally test RNA nanoparticle self-assembly. Specific steps in the project will involve: 1) Independent work with the literature to find, read and possibly present some relevant papers on RNA structure, nanobiology, computational and experimental approaches; 2) Learn experimental techniques used in our laboratory; 3) Aid in running experimental protocols used in RNA nano design; 4) Run various experiments to analyze and determine the structural features and functionalities of the designed nanoparticles; 5) Attend seminars when possible; 6) Collaborate with other scientists; 7) Write results in scientific papers.

Melissa Porter

Research Goals/Purpose:

Goals The overall goal of this internship is for the WHK intern to obtain an appreciation for communicating scientific discovery in plain language to the larger public. He/she will leave the internship with a greater understanding of how to communicate complex scientific topics to a lay audience. The intern will develop specific skills sets throughout the course of the internship to achieve this goal. The skills will include but are not limited to the following: • Written communication o The intern will write a series of articles highlighting various researchers at the NCI at Frederick for the Poster which will help the WHK intern experience the variety and breadth of science at the NCI at Frederick. He/she will have the opportunity to explore various areas and interests in science. Additionally, this will also help the student develop writing skills, including writing in plain language. • Oral Communication o The WHK intern will be responsible for developing and presenting a scientific research poster to a public audience several times through the course of the internship. These occurrences will give him/her the opportunity to orally present the various ways of communicating scientific discoveries to the public. It will also give the intern an opportunity to accept constructive feedback from peers and mentors about his/her presentation skills. o The WHK intern will also be responsible for developing and presenting a presentation at the NICBR teachers NECSES event. This presentation should include input from other students in the WHK intern program and potentially interns in other NICBR partner programs on scientific education. • Public Affairs & Outreach o The WHK intern will assist with various outreach events throughout the course of his/her time in the internship. The inter will gain experience with developing programs, handling professional interactions with the public, and advocating and promoting the proper communication of complex scientific discoveries and STEM education for Frederick County youth. The opportunities will enhance experiential learning for the WHK student in his/her develop in scientific communication. Timeline 1st quarter ( May/June – August/Sept) – learn the various tools for communicating with the public and within the NCI at Frederick. Develop a poster for presentation at various poster days. 2nd quarter (Sept/Oct. – Nov/Dec) – Select a scientist or professional at the NCI at Frederick to profile and work with communications staff on developing interview questions, setting up and conducting the interview, doing background research and writing an article to be published in the Poster. Write the beginning in a series of posts on the WHK student experience incorporating self-experience as well as experiences from other WHK students. 3rd quarter (Dec/Jan.- March/April) – conduct the second individual profile to be published in the Poster. Continue to develop student experience series. Research and suggest new potential articles or outreach activities for communicating scientific information. Develop a presentation incorporating input from WHK interns and interns from other NICBR agencies on scientific education to be presented at the NICBR Teacher’s NECSES. 4th quarter (March/April- May/June) – conduct the third individual profile for publication in the Poster. Help to develop the WHK student incoming/outgoing ceremony for enhancing the student experience in the WHK program.

Training Plan:

Project Description The WHK Intern will work at the Office of Scientific Operations (OSO) within the NCI at Frederick. The WHK intern will spend time working with the public affairs specialist, administrative officer, and educational outreach specialist on his/her primary goal of communicating scientific and health information from the NCI at Frederick. Official projects will include 1) developing articles for the NCI at Frederick online newsletter The Poster, 2) creating and presenting a scientific research poster at the NCI at Frederick Poster Day, NIH Student Poster Day, and the NICBR Spring Research Festival and 3) additionally assisting in various internal and external outreach events that focus on communicating health and well-being, the NCI mission, and advantages of STEM education for Frederick County youth 4) attending various lectures and seminar series to learn about the science that is done at the NCI at Frederick, 5) find and read various research papers to understand the science and background of the individual scientists the student will intern.

Anu Puri

Research Goals/Purpose:

Research program in the RNA Biology Laboratory focuses on the strategic development of biologically viable lipid-based nanoparticles for directed delivery of nucleic acids and/or anti-cancer agents. The long-term goal is to develop state-of the art nano-tools that will be compatible for delivery of drugs or nucleic acids to treat patients. This includes optimization of the targeting potential, tunable drug release properties, and imaging capabilities of nanoparticles.

Training Plan:

The student will be involved in the development of liposomes, optimize methods for hydrophobic and hydrophilic drug encapsulation. She/he will perform in vitro screening of these delivery vehicles. The candidate will learn various techniques which include tissue culture; FACS, cell toxicity assays, fluorescence microscopy, lipid handling, and ELISA assays.

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Brad Robertson

Research Goals/Purpose:

Computer & Statistical Services (C&SS) is responsible for providing a wide array of information science related services to the National Cancer Institute at Frederick (NCI-Frederick) and Frederick National Laboratory for Cancer Research (FNL) communities. Within the Web Development group, and more specifically the User Experience Team (where the intern will be focused), we strive to optimize the user experience for web based applications. Our mission is to continually optimize, design and redesign new and existing web applications that will service the scientific mission here at the NCI at Frederick. Web applications can range anywhere from public facing websites to specific mission critical, interactive services that collect and analyze data for scientists.

Training Plan:

Dependent on the strengths of the selected student, interns will be involved in a variety of activities including: Improving existing web applications for optimal user experience. Design and implementation of responsive layouts for existing application infrastructure. Wireframing/designing new applications or subsections of applications. User testing. Prototyping. Brainstorming. Providing feedback and support to User Experience team. Tasks could fall on a more technical side as well, for students showing interest and strength in programming.

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Tanya Sappington

Research Goals/Purpose:

This is an administrative position with the Frederick Administrative Resource Center (ARC) in support of the CCR scientists located at the NCI-Frederick campus. The incumbent will receive an introduction to Federal policy and procedures in various areas of administration. The goal is for this to be an educational experience for the student and a great introduction to Federal service.

Training Plan:

The student will learn multiple areas of administration including personnel, financial management, travel, and procurement. Responsibilities will include answering phones, greeting visitors, taking minutes, creating agendas, inventory maintenance, procurement submissions, database entry, and special projects. Projects may include assisting the travel core with travel packages, budget review including policy and multiple financial reports, maintenance service agreement review, personnel review, and other projects as identified.

Bruce Shapiro

Basic Research Program

Research Goals/Purpose:

The study of the structure and function of ribonucleic acids (RNA) is an important area of biological and computational research. Understanding of the role that these molecules play in a cell's life cycle has become very important. The various types of RNAs that control a cell's normal function are tRNA, mRNA, rRNA and most recently discovered RNAi. RNAs, such as the viruses HIV, polio and the common cold, to name a few, are detrimental to living organisms. Our research deals with the basic biological concepts associated with RNA structure function relationships and also the development of computational and experimental methodologies and tools to unravel these relationships. Included are algorithms for RNA folding and analysis of the folding results. Our lab was the first to develop a massively parallel genetic algorithm for searching very large RNA conformational spaces. We have developed a unique RNA structure analysis workbench, STRUCTURELAB, which is a heterogeneous computer system that is used to analyze folding results. We developed some of the best algorithms for RNA structure prediction based on RNA sequence alignments and pseudoknot prediction as exemplified by KNetFold and CyloFold. We also do molecular mechanics and molecular dynamics simulations on RNA and RNA/protein complexes to understand atomic scale interactions that determine the functionality of these molecules. We recently discovered a new type of translational enhancer by using these techniques. We also explore ways of using RNA structure/function relationships to define RNA nanobiology entities. These RNA based structures have the potential for therapeutic uses amongst other possibilities. Important for the development of these RNA nanoparticles is the recent implementation of a database of RNA motifs for nanostructure design, RNAJunction, as well as the development of software tools, NanoTiler and NanoFolder, to speed and simplify the design process. Using these methods we designed and experimentally verified the self-assembly of a functional RNA nanocube and nanoring as well as other nano-architectures. The experimental component in our group merges together our computational designs with experimental verification. This has led to successful cell culture and mouse model experiments.

Training Plan:

Student intern will be working on projects related to computational and experimental approaches to RNA structure analysis and RNA nanobiology. Some potential projects are enumerated below. Final decisions on specific topics will be made after detailed discussions with the intern after arrival. 1) Carry out molecular mechanics and molecular dynamics simulations of RNA using high performance computing facilities. 2) Develop computer algorithms for improving RNA structure prediction and analysis methods for both secondary and tertiary structure. 3) Searches for interesting functional features in RNA sequences and their structures. 4) Find and understand RNA folding patterns using various algorithms running on parallel computers. 5) Enhance and develop new algorithms for STRUCTURELAB and NanoTiler. This includes adding features for prediction for nanobiology structures and datamining. Specific steps in the project will involve: 1) Library work to find and read relevant papers on RNA structure, nanobiology, computational and experimental approaches. 2) Familiarization with computers and software in our lab. 3) Learn about software development methods used in our laboratory. 4) Writing and/or modifying software as the need arises. 5) Running various software packages to analyze and discover structural features. 6) Attending seminars when possible. 7) Collaboration with other scientists. 8) Writing results in scientific papers.

Brad Sherman

Research Goals/Purpose:

LHRI (Laboratory of Human Retrovirology and Immunoinformatics) has a contract with National Institute of Allergy and Infectious Diseases (NIAID) in NIH and supports their clinical trials for HIV-infected patients by performing applied basic research and clinical research. The mission of the LHRI is to investigate the mechanism of immune and viral responses in infected individuals utilizing microbiological, biochemical, and immunological techniques, and bioinformatics analysis. The student will be trained to apply bioinformatics techniques to study human and viral genomes and variations in relationship with infectious and allergy diseases.

Training Plan:

Specific instructions will be given to support the development, implementation and maintenance of bioinformatics tools for use in genetic studies using next generation sequencing (NGS) technologies. The student will be expected to present his/her work in bioinformatics group meetings and student Internship program conferences, and may have the opportunities to contribute to scientific papers.

Dhirendra Simanshu

Research Goals/Purpose:

RAS mutations are found in one-third of all human cancers. NCI established the RAS initiative in the fall of 2013 to explore innovative approaches for attacking the proteins encoded by mutant forms of RAS genes and to ultimately create effective, new therapies for RAS-related cancers. Our group leads the structural biology efforts within the RAS Initiative. Our aim is to gain structural insights into wild-type and oncogenic mutants of KRAS in complex with various effectors/regulatory/partner proteins, which may identify novel binding pockets or interfaces amenable to attack with small molecules. Recently, our group has solved the first structure of KRAS4b protein in complex with PDEdelta, a protein that plays an important role in targeting KRAS4b to cellular membranes. This protein-protein complex structure shows every amino acid of full-length, fully processed KRAS protein for the first time. Working to gain structural insights into KRAS mutations, we have solved the first structures of multiple oncogenic mutants of KRAS4b in the GTP-bound form. The GTP-bound forms of these mutants are the most common drivers of human cancers. For more information, please visit RAS Structural Biology group web page: https://www.cancer.gov/research/key-initiatives/ras/target-identification/structural-biology

Training Plan:

During the internship period, the student will learn basic protein biochemistry, biophysics, and structural biology techniques. Our goal will be to train the student in designing the experimental plan, performing various structural biology experiments and troubleshooting the potential problems. The student will work under the supervision of a scientist and will have the opportunity to pursue small structural biology projects. Additionally, the student will be trained to present their work in laboratory meeting and poster presentation in scientific meetings.

Shree Ram Singh

Research Goals/Purpose:

Our current research is directed toward understanding the molecular genetic mechanisms by which stem cells regulate tissue homeostasis, regeneration, and tumorigenesis. We are utilizing Drosophila model to understand the above mechanisms. Specifically, we are using adult testis, kidney, and gastrointestinal tissues to characterize the genes/signaling pathways that regulate stem cell behavior and tumor formation. The knowledge gained from investigating stem cell regulation in Drosophila model will provide a basis for understanding how human adult stem cells respond during normal and pathological conditions.

Training Plan:

At the beginning of the internship, the student will be trained in the basic methodologies of laboratory research. The student will be working on specific projects related to Drosophila adult stem cells. The student intern will be exposed to various techniques in genetics, cell biology, developmental biology, and molecular biology. The student will participate in laboratory seminars and will present their research work in meetings. The student intern will collaborate with other members in the laboratory and will participate in writing their scientific work.

Lei Sun

Research Goals/Purpose:

Hematopoiesis is a multi-stage developmental process that is maintained throughout life by a limited number of hematopoietic stem cells (HSC), which proliferate, self renew, and differentiate into mature blood cells of all lineages. Central questions about the molecular events that regulate HSC quiescence, survival, self-renewal, and lineage commitment remain to be answered. A significant effort in this field is focused on learning to direct these processes to expand and maintain hematopoietic stem cells (HSC) for the treatment of leukemia and other hematological disorders. Transcription factors are the ultimate downstream mediators of extrinsic signals received by the micro environment and cell intrinsic signals. Our current focus is to define how transcriptional regulators promote HSC self renewal and cell specification to multiple hematopoietic cell lineages using stem cell line models; knock-out mice and normal hematopoietic cells. Since transcription factors are frequently deregulated or mutated in leukemia, we will also evaluate if specific transcriptional regulators represent potential therapeutic targets. We believe that knowledge of the molecular and cellular regulation of HSC will contribute to 1) an improved understanding of the mechanism(s) that regulate normal HSC development, 2) if deregulation of these processes contributes to hematopoietic malignancies, 3) the development of biopharmaceuticals to treat leukemia, 4) improved methods of bone marrow transplantation, regenerative medicine, and gene therapy.

Training Plan:

The student will be instructed in all basic techniques required in our studies. Finally, he/she will learn to plan an experiment and analyze data.

Jian Sun

Research Goals/Purpose:

The student will be using the Xenopus system to understand how Eph/ephrinB signaling regulates Wnt co-receptor LRP6 protein level and determine the intersection between Wnt signaling and Eph/ephrin signaling during development.

Training Plan:

In the three months, the students will be trained to learn how to do the general lab experiments such as western blot, keeping and manipulating animals (frog), gel electrophoresis, cell culture and confocal Fluorescence Microscopy. In the second three months, the students will get involved into some current projects to assist the mentor to finish some basic experiments which they learned in the first period. For the last six months, the students will have their own project to be trained to learn how to design and perform experiments in an independent project.

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Nadya Tarasova

Research Goals/Purpose:

Development of drug leads and candidates that target common mutations found in tumor cells

Training Plan:

The student will use several computer-based approaches for the design of compounds "in silico". He/she will synthesize them, purify and characterize the structure of new compounds. The student will perform biophysical studies aimed at characterization of interactions of the drug leads with intended protein target and evaluate the effects of compounds on the growth of tumor cells.

Yien Che Tsai

Laboratory of Protein Dynamics and Signaling

Research Goals/Purpose:

Metastasis is the major obstacle for cancer treatment. The goal of this project is to understand the mechanisms that allow cancer cells to spread so better strategies for preventing metastasis can be developed. This study will focus on how changes in protein regulation contribute to cancer progression.

Training Plan:

Students will learn basic molecular cloning, biochemistry, cell biology and data analysis.

Tommy Turbyville

Research Goals/Purpose:

RAS is a gene that is mutated in about 30% of cancers, and there are no current therapies available for patients who have cancer with this mutation. The RAS Image-based screens group uses optical microscopy techniques to understand how RAS molecules move and signal in living cells. And we use that understanding to develop assays to screen for molecules that disrupt RAS activities in cells. The goal is to identify molecules that could lead to an improved understanding of RAS and drugs that treat RAS-driven cancers.

Training Plan:

The student will develop a cell line that contains a fluorescent biosensor that can be used to detect RAS activation in live cells, and use optical microscopy and image analysis to quantify RAS activity under different conditions.

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Julio Valencia

Research Goals/Purpose:

Evaluate the Cellular and Molecular mechanisms of Interferon gamma (IFNg)-based immunotherapies. Characterize IFNg-based immunotherapy strategies

Training Plan:

Learn DNA and RNA extraction techniques. Master polymerase chain reaction (PCR) techniques. Master protein based molecular biology techniques such as Western blot Use above tools to examine the impact of IFNg over tumor development in 2D and 3D environments.

Cris Vera

Research Goals/Purpose:

To learn about some of the basic concepts and tools within the field of bioinformatics and genomics. To come up with and complete a bioinformatics project of the student's choosing, depending on interests.

Training Plan:

exploring the CCR-SF fundamental concepts in genomics bioinformatics approaches/best practices and current tools designing pipelines researching a project

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Abdul Waheed

Research Goals/Purpose:

The goal of the research in our lab is to understand the molecular biology of HIV-1 replication, in particular mechanisms of HIV-1 assembly and release. Several host-factors are involved in the process of virus assembly and release. Understanding the molecular mechanisms of HIV-1 assembly and release would eventually help to design the drugs that inhibit the late stages of HIV-1 replication cycle. Several drugs have been tested in the lab that showed antiviral activity for HIV-1. Since the live HIV-1 work is not possible for the student intern, we would test these compounds for its anti-viral activity in other viruses like MLV, EIAV, FIV, etc. The ultimate goal of our research is to identify novel targets for the development of anti-HIV therapies that can be used to treat infected patients.

Training Plan:

The student will be trained to learn a variety of techniques in the fields of molecular and cell biology, biochemistry, bioimaging, and virology. These includes recombinant DNA techniques involving cloning of genes in plasmid vectors, mammalian cell culture maintenance, transfection of plasmids in mammalian cells, immunoblot analysis, fluorescent microscopy, etc. The student will learn how to use of general laboratory equipments, and the basics of many of the assays used in the laboratory. The student will gain experience in designing the experimental plan, performing the experiments and trouble-shooting the potential problems. The student will learn how to maintain their records of their data, and trained to present their work in both formal and informal lab meetings and poster presentation in scientific meetings.

Kylie Walters

Research Goals/Purpose:

Participate in experiments to solve the structure, target and provide mechanistic information on the proteasome and its accessory proteins.

Training Plan:

Students will learn how to make samples for biochemical or biophysical analyses as well as have exposure towards running such experiments.

Greg Warth

Research Goals/Purpose:

Learn how to document a change control, setup VoIP devices, develop and record metrics, learn how to use a network discovery tool and enter results in a IT service management system

Training Plan:

Take IT service management course Take IT Service management software tech course Enter data into IT Service Management system Gaither monthly metrics and learn how to put data in monthly report

Christopher Westlake

Research Goals/Purpose:

Ultrastructure Analysis of Primary Cilium assembly Almost every cell in the human body contains at least one cilium. While some cilia in human cells function in locomotion, not unlike cilia on the surface of the single celled organism paramecium, most of our bodies cilia are immotile and function in cellular signaling. Hence the cilium is often referred to as the cell’s antennae. In humans cilia are critical for reproduction and embryonic development and are needed for vision and for our sense of smell. Defects in cilia function are associated with more than 20 genetic disorders and cancer. We are investigating how membrane transport regulators function in the building of the cilium, a process termed ciliogenesis. Through the use of various genetic approaches in cells and zebrafish embryos and cellular imaging we are able to understand how ciliogenesis occurs and to determine what proteins regulate this process.

Training Plan:

Students will use computer based analysis programs to map and identify structures involved in the assembly of the primary cilium. Electron microscopy images captured from cells will be converted into three-dimensional representations of the developing cilium. Students will become proficient at using imaging software to generate 2D and 3D animation structure models for presentations and publications. Through this work students will be gain a deeper understanding of various aspects of cell biology. Students will also have the opportunity to gain wet laboratory experience in cell biology techniques, including cell culture and microscopy imaging (epifluorescence and confocal microscopy).

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Acong Yang

Research Goals/Purpose:

Research in our lab aims to find out the mechanism of how microRNAs (miRNA), as gene regulators, are being regulated. miRNA plays essential roles in gene regulation, dysregulation of miRNA involved in various human diseases, including cancer. We are interested in understanding the mechanisms of miRNA biogenesis, post-transcriptional modifications, and miRNA stability in mammalian systems. These information will be applied in testing novel RNA-based approaches designed to alter gene expression with improved safety, which can be used as tools for biological discovery and therapeutics.

Training Plan:

The student will be trained to master a variety of molecular biology, cell biology, and RNA biology techniques. They will also learn the principle of next generation sequencing (NGS) and do the library construction for NGS. In detail, they will design and do molecular cloning, culture mammalian cell line and transfection of plasmids into cells, then examine the results by immunoprecipitaion, reporter assay and NGS analysis, etc.

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Paul Zakrevsky

Research Goals/Purpose:

The research being conducted in the RNA structure and design section focuses on the characterization of rationally designed RNA structures, with an emphasis on RNA nanotechnology and nanomedicine applications. The RNA interference pathway (RNAi) has become a powerful tool that can be used to knockdown the expression of a target gene in mammalian cells. This RNAi response can be triggered by the introduction of short RNA molecules called small interfering RNAs (siRNAs) to cells. Rather than simply delivery these siRNAs to cells by themselves, current research in our lab involves the design of RNA nanostructures to package siRNAs in such a way that the nanostructure provides additional advantageous properties for cellular delivery. A student intern in the lab will be involved in projects that aim to characterize RNA nanostructures through the use of various experimental techniques.

Training Plan:

1.) Develop common laboratory skills such as pipette technique, buffer preparation, etc. 2.) Learn techniques required for RNA preparation such as polymerase chain reaction (PCR), enzymatic RNA synthesis, and purification methods 3.) Learn, develop and improve protocols for the assembly of RNA nanoparticles. 4.) Characterize the assembly and function of RNA structures using various techniques including gel electrophoresis and cell culture. 5.) Collaborate with computational scientists to design new, or improve existing, RNA structures. 6.) Read, share and discuss relevant scientific papers. 7.) Maintain good documentation of lab work and results.

Ming Zhou

Research Goals/Purpose:

hormone enrichment and extraction from biological samples Quantitative analysis by using UPLC-TSQMS instrument statistical data analysis

Training Plan:

The trainee will learn the skills how to extract and enrich various classes of biologically important molecules from complex biological samples. He will be involved in additional sample preparation and chemical analyses using liquid chromatography and mass spectrometry techniques to obtain qualitive and quantuantive results for ongoing research/clinical studies. The trainee will also learn to use statistical skills to analyze the research/clinical data to identify important molecules that related to certain mechanisms of human diseases

Jianjian Zhu

Research Goals/Purpose:

Identification of signals regulating digit identity by comparison of vertebrates with adaptive evolutionary limb modifications. As a consequence of evolutionary adaptations, the digits of different vertebrates have distinct features such as different lengths, numbers and shapes of the digit (phalangeal) elements that give them unique ‘identities’ (for example, thumb vs. pinkie). In bats adapted for flight, some of the forelimb digit elements become extremely long, but with few joints, to form the struts for the wing membrane. In birds, such as chicks, the hindlimb digits have many elements and many joints, for grasping branches and perching. Previous work has shown that, in chick, signaling from interdigits at early limb bud stages plays an important role in specifying different digit identities and has implicated Bmp signaling factors in this regulation. To screen for potential interdigit regulators of digit identity, we have performed expression array analyses and compared the interdigit expression profiles of fruit bat (Carollia perspicillata), chick, and mouse. Based on these results, we have identified a small group of candidate signaling factors with expression differences that may play roles in interdigit-mediated regulation of digit morphogenesis.

Training Plan:

The student will be involved in validating differential expression of the candidate signaling factors across the limb bud in mouse, chick, and bat embryos using whole mount in situ hybridization. For those signaling factors whose expression is confirmed to be different between interdigit regions, the student will implant beads containing the signaling factors in chick limb buds to investigate the effect of those factors on digit identity determination and morphogenesis. The student will get training and experience in critical scientific thinking, designing and synthesizing RNA probes, collecting mouse/chick embryos, carrying out in situ hybridization, skeletal analysis, and micro-manipulating chick embryos in ovo.

Jianghai Zhu

Research Goals/Purpose:

Studying and programing a new algorithm to improve the alignment of Cryo-EM images, to de-blur the Cryo-EM movies.

Training Plan:

To learn basic image analysis and manipulation. To lean scientific programing, especially for HPC and GPU computing.