Potential Mentors for 2010-2011


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Jairaj Acharya

LABORATORY OF CELL AND DEVELOPMENTAL SIGNALING

Email: acharyaj@mail.nih.gov
Phone: (301) 846-7051
Bldg/Room: 0560 / 22-6
 
Research Goals/Purpose:
Our long-term objective is to understand the complex interrelationship between phospholipid and sphingolipid metabolism and metabolic signaling in vivo. Intermediates of phospholipid (PL) and sphingolipid (SL) metabolism serve as second messengers for a number of signaling cascades including activation of G-protein-coupled receptors such as adrenaline and thrombin as well as receptor tyrosine kinases by growth factors. They mediate a number of processes ranging from protein secretion to activation of apoptosis. We have initiated studies to understand several aspects of lipid signaling in Drosophila.
 
Training Plan:
Our long-term objective is to understand the complex interrelationship between phospholipid and sphingolipid metabolism and metabolic signaling in vivo. Intermediates of phospholipid (PL) and sphingolipid (SL) metabolism serve as second messengers for a number of signaling cascades including activation of G-protein-coupled receptors such as adrenaline and thrombin as well as receptor tyrosine kinases by growth factors. They mediate a number of processes ranging from protein secretion to activation of apoptosis. We have initiated studies to understand several aspects of lipid signaling in Drosophila.

Rachel Bagni

PROTEIN EXPRESSION LABORATORY

Email: bagnir@mail.nih.gov
Phone: (301) 846-5469
Bldg/Room: 0535 / 428
 
Research Goals/Purpose:
The Molecular Detection Group in the Protein Expression Laboratory provides expert support in the development and execution of platforms designed to assess the role of infectious agents in cancer etiology. Our group is particularly interested in viruses that cause cancer, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV) and hepatitis B virus (HBV). Two major areas of research that our work covers are (1) epidemiology of a virus and its associated disease(s) (prevalence, incidence and transmission) and (2) the evaluation of whole-viral-genome gene expression of herpesviruses under different conditions (at diagnosis, during treatment, post-treatment). Interns in our laboratory will have the opportunity to learn/utilize the following technologies and techniques: DNA and RNA extractions, PCR, cloning, quantitative PCR, Western blots, ELISAs, immuno-fluorescence assays.
 
Training Plan:


Kelley Banfield

LABORATORY OF MOLECULAR TECHNOLOGY

Email: banfieldk@mail.nih.gov
Phone: (301) 846-6114
Bldg/Room: Toll House / 915 TH
 
Research Goals/Purpose:
Real-Time qPCR is a sensitive method to answer numerous genetic questions. The student will learn, run, optimize, and analyze fluorescence-based assays detecting RNA and DNA. These experiments aim to qualify and quantify nucleic acids helping define their role in cancer biology in various studies. The student will work under the direct supervision of Myla Spencer, M.S., with direction by Kelley Banfield, Ph.D., and Dan Soppet, Ph.D.
 
Training Plan:
During the training period, the student will be taught all the fundamental aspects of laboratory research as well as qPCR specific techniques, including but not limited to the following: 1) Keeping a detailed and organized notebook 2) Accurate experimental measurement and quality control procedures 3) Use of computer analysis software 4) RT-PCR, Real-Time PCR and qPCR 5) Relative and absolute expression analysis 6) Quality control using the Bio-Analyzer 7) Primer and probe design 8) Cell culture and RNA extraction from cells and tissues Utilizing these techniques, the student will help to efficiently quantify RNA transcripts and potential biomarkers of cancer.

Elizabeth Boeggeman

Email: eeb@helix.nih.gov
Phone: (301) 846-7564
Bldg/Room: 0469 / 221
 
Research Goals/Purpose:
Studies on the Structure and Function of Glycosyltransferases
 
Training Plan:
Involved in the cloning of recombinant enzymes. Expression of the recombinant proteins in bacterial cells. Isolation of plasmid DNA and anlysis on agarose gels. PCR amplifications. Re-folding of proteins by In vitro methods

Jianbo Chen

HIV DRUG RESISTANCE PROGRAM

Email: chenjia@mail.nih.gov
Phone: (301) 846-1841
Bldg/Room: 0535 / 324
 
Research Goals/Purpose:
We study the replication mechanisms of retroviruses such as human immunodeficiency virus 1 and murine leukemia virus using fluorescent microscopy imaging, molecular, biochemical techniques.
 
Training Plan:
Student will be initially trained on basic molecular cloning techniques such as plasmid vector construction, sequencing and sequence analysis, PCR cloning. Mentor will design appropriate project for student to complete under mentor's supervision. Through such research experiences, the student will learn in design experiment, executing the experiment plan, and trouble-shoots and solve technical difficulties. The student will also learn how to record their data and present their work.

Ira Daar

LABORATORY OF CELL AND DEVELOPMENTAL SIGNALING

Email: daar@ncifcrf.gov
Phone: (301) 846-1667
Bldg/Room: 0560 / 22-3
 
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 EphrinB1 transmembrane Eph ligand. 1) EphrinB1 mutants will be expressed in developing embryos to determine structural motifs that are important for EphrinB1-induced developmental effects. 2) EphrinB1 will be co-expressed with proteins found to be associated with EphrinB1. The ability of these proteins to physically interact with EphrinB1 will be assayed. The ability to modulate EphrinB1-induced developmental effects will also be assessed. 3) The ability of EphrinB1 to modulate the protein’s activity will also be tested.

Cathy Hixson

AIDS and Cancer Virus Program

Email: hixsoncv@mail.nih.gov
Phone: (301) 846-5621
Bldg/Room: 0535 / 424
 
Research Goals/Purpose:
This lab area purifies recombinant viral proteins. Specific mutations of the various proteins are created to provide tools for researchers to use in determining a protein's activity and function. Proteins that enable or increase infectivity are good targets for vaccines or medical intervention. In this lab area we purify the proteins, quantitate them and determine their purity. The SIP student that works in this lab will use analytical instruments and computer software for operating those instruments. They will use many standard software programs for the analysis of data, and generation of reports. They will become accomplished in general chemistry techniques and basic laboratory skills. When the program has ended, the student will have taken recombinant proteins from the beginning stages of production to being fully purified, quantitated, and aliquotted for shipment. Dr. Robert Gorelick, the principle investigator of this research area, will provide an overview of the HIV-1 virus and how these recombinant viral proteins are used in research.
 
Training Plan:
1. SAIC new employee safety training 2. Safety training specific for this lab 3. Make solutions, run SDS PAGE gel electrophoresis equipment, prepare western blots. 4. Learn the operation of laboratory instruments: UV Spectrophotometer, HPLCs, Amino Acid Analyzer, MALDI-TOF Mass Spec, and Protein Sequencer. 5. Learn protein research techniques: Sample preparation, quantitation, characterization, percent purity determination. 6. Organize and evaluate data to determine what the next step in the process will be. 7. Log sample information and data, and prepare reports of results obtained. 8. Organize sample storage and retrieval - the samples will need to be stored, removed for processing and then stored again in a different format for each step in the purification of a protein. 9. Prepare samples for shipment to research scientists at other labs. When the purified protein is ready for use as a reagent, it will need to be aliquotted and labeled for easy retrieval and positive identification.

Deborah Hodge

LABORATORY OF EXPERIMENTAL IMMUNOLOGY

Email: hodged@mail.nih.gov
Phone: (301) 846-6501
Bldg/Room: 0560 / 31-16
 
Research Goals/Purpose:
Our research is focused on the molecular mechanisms involved in regulation of interferon gamma gene expression. Recent work has concentrated on post-transcriptional control mechanisms. For these studies, we have created a knock out mouse that has 162 nt ARE element deleted in the 3'UTR of the interferon gamma gene. This mouse has changes in immune cellular function and location. Current studies are targeted at the characterization of this mouse.
 
Training Plan:
The student will be involved in the genotyping and characterization of the interferon gamma ARE-deleted mouse. This will involved DNA isolation from tissues with PCR analysis of the DNA. The student will also use molecular biology techniques to examine interferon gamma RNA levels in cells that express the gene.

O.M.Zack Howard

LABORATORY OF MOLECULAR IMMUNOREGULATION

Email: howardz@mail.nih.gov
Phone: (301) 846-1348
Bldg/Room: 0560 / 31-19
 
Research Goals/Purpose:
An in vivo increase in myeloid derived suppressor cells (MDSC) often occurs following infection or with tumor progression. This increase appears to be dependent on hematopoietic growth factors, e.g., G-CSF and/or GM-CSF, induced by trauma or produced by tumor, and inflammatory factors, e.g., IL-1, PGE2 and IL-6. MDSC have been successfully generated from mouse bone marrow cells (BMCs) in vitro using G-CSF or GM-CSF plus an inflammatory factor. As melanoma tumors increase in size there is an increase in serum levels of the tumor associated antigen gp100 (Pmel). Since our earlier studies showed that administration of gp100 induces both myeloid cell migration and the production of IL-6, we investigated the ability of gp100 to influence the in vitro production of MDSC. The effect on mouse BMCs cultured with 25 ng/ml of mGM-CSF or mG-CSF and 10 ng/ml of mIL-6 was compared to cells cultured with either growth factor and gp100. BMC’s cultured with G-CSF and IL-6 or gp100 produced GR1+CD11b+ cells with the ability to suppress antigen specific proliferation of CD8 cells. Addition of GM-CSF to G-CSF cultures actually reduced the suppressive function of the GR1+CD11b+ cells, suggesting that GM-CSF therapy could overcome MDSC driven immune suppression. These studies allow us to conclude that in vitro culture with G-CSF and gp100 leads to the generation of phenotypic and functional MDSC and allow us to speculate that gp100 and perhaps other tumor associated antigens (TAA) contribute to immune suppression by inducing MDSC setting up a feed-back loop whereby larger tumors produce more TAA that in turn induce more MDSC.
 
Training Plan:
The student will learn basic lab techniques for the in vitro culture of mouse myeloid. This project will expand to include transfection of mouse bone marrow with expression vectors to determine if specific genetic fragments will drive myeloid cell development and function. In short this is a cellular immunology project.

Mohammad Ishaq

LAB OF MOLECULAR CELL BIOLOGY (CLINICAL SERVICE PR

Email: mishaq@mail.nih.gov
Phone: (301) 846-1500
Bldg/Room: 0550 / 120
 
Research Goals/Purpose:
Project Title: Role of adapter protein Vav in nuclear receptor-mediated function in T lymphocytes. The Vav family of Rho-guanine nucleotide exchange factors (GEFs) control a diverse array of signaling pathways following T cell activation by antigen receptors although the exact mechanism by which Vav exerts its function is only beginning to emerge. Nuclear receptors are a family of transcription factors that play an important role in the development and homeostasis both by ligand-dependent activation and active repression of target genes. Our previous studies with nuclear retinoid receptors have provided important insights in the functioning of these receptors and have revealed the importance of epigenetic mechanisms in modulating their function during T cell signaling. The role of Vav family of proteins in the regulation of nuclear receptor function in T lymphocytes is not known. Our preliminary findings suggest that Vav-1, an isoform of of Vav proteins that is highly expressed in T cells and involved in regulating Ca++ fluxes, modulates nuclear receptor function in Jurkat T cells. This study will examine in detail the role of Vav-1 in the regulation of nuclear receptor function in Jurkat cells and normal human peripheral blood T cells.
 
Training Plan:
The following plan will be followed to initiate and complete the project. 1. Initial training for cell culture, T cell isolation , routine molecular biology, and biochemical techniques. 2. Grow and maintain Jurkat T cell lines in proper medium. Isolate and grow T cells from normal human blood. 3. Transfect Jurkat and normal T cells with reporter plasmids to study the activity of nuclear receptors. 4. Using reporter assays study the effect of expression of wild type and mutant Vav on the receptor function in Jurkat and normal T cells. 5. Knockdown Vav-1 protein levels in Jurkat and normal T cells using RNA interference (RNAi) and study the effect of this knockdown on nuclear receptor function.

Warren Johnson

LABORATORY OF GENOMIC DIVERSITY

Email: johnsonw@ncifcrf.gov
Phone: (301) 846-7483
Bldg/Room: 0560 / 11-10
 
Research Goals/Purpose:
Comparative Genomics, the evolution-based method of studying genome organization, is an increasingly important field of research that is being empowered by the rapidly growing amount of genomic sequence from a wide range of species. Interpreting and utilizing this information is a necessary step towards being able to fully take advantage of these resources. Among our goals in comparative genomics are to 1) discover evolutionarily conserved sequence motifs that are responsible for regulatory and other critical genomic functions, particularly outside of protein coding genes; 2) provide a framework for reconstruction of genome organization, content and dynamics that have occurred during the mammalian radiations; 3) empower new animal models of human disease and heritable phenotypes; and 4) provide a starting point for assessment of the expansion, contraction and adaptation of gene families in different evolutionary lineages. Several species and populations of wild animals, including the cat and other carnivores, primates, and camelids are our main focues due to their extensive biomedical surveillance by the veterinary research community and their utilization as important comparative biochemical models in pharmacology and medicine.
 
Training Plan:
Student projects will focus around the burgeoning field of comparative genomics. The student will be learning basic techniques of processing biological samples extraction of DNA, and using molecular genetic markers to describe patterns of molecular genetic variation and interpret these in an evolutionary context. He/she will become familiar with computer software packages used to analyze their results. The student will also learn to interpret those results and be exposed to basic aspects of study design. Specifically, he/she will be learning the basic skills involved with polymerase chain reaction (PCR) amplification, sequencing, STR amplification and cloning. Typical student projects involve the use of domestic and non-domestic animals and wild populations as models for the study of evolution, infectious disease, and comparative genomics and these studies often have application to conservation initiatives and biomedical applications.

Chang Kim

LABORATORY OF MOLECULAR TECHNOLOGY

Email: kimcha@mail.nih.gov
Phone: (301) 846-6343
Bldg/Room: Toll House / 209
 
Research Goals/Purpose:
MicroRNAs are small RNAs that regulate gene expression. They are good candidates as biomarkers because they are aberrantly expressed in many cancers. Our research goal is to develop a molecular diagnostic 1) to detect cancers early and 2) to determine the prognosis of cancer so that treatment decisions can be made. The achievement of these goals could lower the cost of healthcare.
 
Training Plan:
The student intern will first be trained in the diverse molecular biology techniques such as pipetting, extraction and purification of microRNA and RNA, and the analysis of RNA/DNA. Next, the student will be trained on more sophisticated instruments which are used to analyze RNA and DNA such as the Agilent Bioanalyzer, Affymetrix Genechip microarrays, and the Agilent microRNA microarrays. Upon mastery of these technologies, the student will take practice clinical samples to do pilot experiments on microRNA expression analysis using microarrays. Subsequent to completing the pilot studies, the student will obtain presentable and publishable data on real clinical samples. Specifically, we will profile microRNAs of gastric cancers (second highest mortality worldwide) and prostate cancers (which affects 1/6 men in their lifetime) using high-throughput microarray technology.

Douglas Kuhns

NEUTROPHIL MONITORING LAB (NML) SAIC-FREDERICK, IN

Email: dkuhns@mail.nih.gov
Phone: (301) 846-6378
Bldg/Room: 0310 / 107
 
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, our SIP 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 her knowledge base progresses, she will be tasked with two independent projects 1) determine the optimum commercial antibody and optimum blotting conditions for western blot analysis of specific phagocyte proteins and 2) acquire the skills necessary for maintenance of the THP1 cell cultures, a acute monocytic leukemia cell line, and analysis of functional responses of those cells, i.e., O2- production, western blot analysis, etc.
 
Training Plan:
Description of 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, spectro-photometers, sterile technique, monitoring of bacterial cell growth. 5) Basics of SDS-PAGE gel electrophoresis and western blotting 6) Comparison study of commercial antibodies to be used for western blot analysis of NADPH oxidase components; optimization of conditions for selected antibodies – blocking conditions, dilution, etc. 7) Basics of THP1 cell culture; cell identification and counting 8) Analysis of THP1 cells responses - O2- production, western blot analysis

Mark Lewandoski

Cancer and Developmental Biology Lab

Email: Lewandom@mail.nih.gov
Phone: (301) 846-5510
Bldg/Room: 0539 / 135
 
Research Goals/Purpose:
The overall goal is to understand the role of Fibroblast Growth Factor (FGF) signaling during early development, with, in this case, a special focus on FGF3 during embryonic axis extension.
 
Training Plan:
The student will begin with assisting Dr. Matt Anderson, a post-doctoral fellow, in his studies of FGF3 in axis extension. The student will assist with genotyping mice and embryos, preparing plasmids and performing RNA in situ hybridization. Depending on the student's abilities and work ethic, this effort may result in a branching off of a related, but more independent project.

Mark Lewandoski

Cancer and Developmental Biology Lab

Email: Lewandom@mail.nih.gov
Phone: (301) 846-5510
Bldg/Room: 0539 / 135
 
Research Goals/Purpose:
The overall goal is to understand the role of Fibroblast Growth Factor (FGF) signaling during early development, with, in this case, a special focus on FGF4 and 8 during somitogensis.
 
Training Plan:
The student will begin with assisting Dr. Naiche Adler, a post-doctoral fellow, in her studies of FGF4 and 8 in somite formation. The student will assist with genotyping mice and embryos, preparing plasmids and performing RNA in situ hybridization. Depending on the student's abilities and work ethic, this effort may result in a branching off of a related, but more independent project.

Christopher McLeland

NANOTECHNOLOGY CHARACTERIZATION LABORATORY

Email: mclelandc@mail.nih.gov
Phone: (301) 846-6974
Bldg/Room: 0469 / 246
 
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.

Mary McNally

LABORATORY OF GENOMIC DIVERSITY

Email: mjmcnally@ncifcrf.gov
Phone: (301) 846-7520
Bldg/Room: 0560 / 21-14
 
Research Goals/Purpose:
The LGD Core Genotyping Facility does mass genotyping using both the Illumina and Affymetrix platforms. The purpose of this typing is to give our scientists insight into the association between certain genes and diseases in cohorts of interest. The lab manages inventory and distribution of all genomic DNA to all principal investigators’ labs for research. Our lab also makes panels of DNA plates, which are instrumental in genotyping for most of the principal investigators. The lab provides samples for scientists by extracting DNA from whole blood, cell pellets, WBC buffy coat, mouthwash, cheek swabs, and other tissues.
 
Training Plan:
The students will learn DNA aliquoting, genotyping using both Illumina & Affymetrix platforms, how to use databases and programming of robotic equipment. DNA extractions methods will also be a possibility.

Marilyn Menotti-Raymond

LABORATORY OF GENOMIC DIVERSITY

Email: raymondm@mail.nih.gov
Phone: (301) 846-7486
Bldg/Room: 0560 / 11-38
 
Research Goals/Purpose:
The goal of the LGD cat genome project over the years has been to facilitate the development of the cat model for human gene annotation and for human disease etiology through development of feline genomic resources for the cat, building a full genome map, and annotating the cat’s genome sequence. At the present time we are applying these genomic resources to identify genetic factors associated with phenotypic variation in the cat which can would have direct application to improve human health.
 
Training Plan:
I think that we have an ideal learning situation for anyone interested in genetics and genomics. Students and interns working with us are becoming expert at genetic linkage mapping, fine mapping using comparative genomics tools and the available 2X whole genome sequence of the cat, sequencing of candidate genes for causative mutations- all the "steps" in the "teasing apart" process to understand the genetic basis behind phenotypic variation, and the basis for mapping in any organism. It’s an exciting time to be studying genetics in the domestic cat. Students will learn to design and execute polymerase chain reaction (PCR), sequence DNA, trouble-shoot experiments, become proficient in multiple software applications pertinent to their research. Our students have a research project. They will not be involved in performing a repetitive task.

David Nellis

BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM

Email: nellisd@mail.nih.gov
Phone: (301) 846-6792
Bldg/Room: 0320 / 4
 
Research Goals/Purpose:
The Biopharmaceutical Development Program (BDP) manufactures therapeutic materials for first-in-human clinical trials of innovative therapeutic concepts for the treatment or prevention of cancer and other diseases. Many new BDP projects are selected based on a semi-annual, competitive, proposal review process (NeXT). To support these projects, the BDP has facilities for the production and testing biopharmaceuticals, including monoclonal antibodies, recombinant proteins, immunoconjugates, peptide and DNA vaccines, therapeutic viruses, and other biologicals. These biological therapeutics are produced under FDA guidelines for use in clinical trials in humans. More information on the GMP manufacture of biopharmaceuticals is available at http://wwwbdp.ncifcrf.gov/. This internship offers inquisitive and motivated science/engineering students an intensive applied biotechnology laboratory training opportunity. The student working in the Early Process Sciences Department will participate in laboratory studies to develop large-scale, controlled purification methods for the manufacture of investigational new drugs being made by the BDP. As part of these studies, the student will first master practical laboratory skills for the design, set up and execution of experiments aimed at characterizing biological products using spectroscopy, electrophoresis, analytical chromatography and specialized techniques. This work will be supplemented with guided-studies to understand the science foundations supporting the methods. The student will subsequently learn micro-to-large scale production techniques including chromatographic purification, computer process control, and process scale-up. The student will design and execute a laboratory-study focusing on a current area of biotechnology.
 
Training Plan:
The student will be assigned directly to the Early Process Sciences Department (EPS) within the Biopharmaceutical Development Program (BDP). To provide the student with a valuable and enjoyable internship experience, in depth training will be provided. Training will progress incrementally from general-to-specific, practical-to-abstract, and simple-to-complex. Training will include: Required lab safety training for new employees (OHS), General laboratory-specific safety training (BDP), Lab documentation, methods and instrumentation training by (EPS), Continuing involvement in laboratory activities, Participation in laboratory and project team meetings. Directed-readings, tapes, videos and on-line resources will be provided to the student. These studies will convey concepts necessary for understanding laboratory activities. During the Students will have the opportunity to periodically interact with staff and students from a variety of BDP departments including quality control, quality assurance and manufacturing. During the summer SIP appointment, the student will attend scientific lectures, training sessions and workshops on selected topics. This background will prepare the student for application of routine laboratory methods to solve common problems and successfully complete an outstanding student project.

David Newman

NATURAL PRODUCTS BRANCH/DEVELOP THERAPEUTICS PROGR

Email: dn22a@nih.gov
Phone: (301) 846-5387
Bldg/Room: 0431 / 202
 
Research Goals/Purpose:
To help develop robotic analytical systems used in the Natural Products Support Group and to aid in their "debugging and operation".
 
Training Plan:
Provided a suitable student can be identified (a love of working with computerized systems, and / or modification of electromechanical devices), they will work very closely with the IT manager in the NPSG in improving and building lab robotic system.

Barry O'Keefe

MOLECULAR TARGETS DEVELOPMENT PROGRAM

Email: okeefeba@mail.nih.gov
Phone: (301) 846-5332
Bldg/Room: 0562 / 101
 
Research Goals/Purpose:
The MTL works on bioassay development, high throughput screening and the isolation and characterization of novel compounds from plants, marine invertebrates, algae and microorganisms with activity against cancer or HIV. The purpose of the research is to identify new molecules with the potential to advance science and have a therapeutic benefit.
 
Training Plan:
The student will be training ini the Protein Chemistry and Molecular Biology Group and will work on the isolation, identification and characterization of proteins and peptides of interest to the NCI. These may include potential anti-cancer or anti-viral targets as well as bioactive proteins with activity against HIV. The student will learn proteins purification and recombinant expression and all of the techniques therein required.

Joan Pontius

LABORATORY OF GENOMIC DIVERSITY

Email: pontiusj@mail.nih.gov
Phone: (301) 846-1761
Bldg/Room: 0560 / yes
 
Research Goals/Purpose:
To assist in bioinformatics needs for laboratory interested in comparative mammalian genomics.
 
Training Plan:
Student will learn computational tools such as use of Linux/UNIX operating system, text processing, webpage design and programming in Perl.

Anu Puri

NANOBIOLOGY PROGRAM

Email: apuri@helix.nih.gov
Phone: (301) 846-5069
Bldg/Room: 0469 / 217
 
Research Goals/Purpose:
Research program in the Membrane Structure and Function section (CCRNP) focuses on the strategic development of biologically viable lipid-based nanoparticles (liposomes) for directed delivery of anti-cancer and anti-AIDS agents. The long-term goal is to develop these state-of the art liposomes compatible for delivery of anti-cancer agents for treatment of patients. This includes optimization of the targeting potential, tunable drug release properties, and imaging capabilities of liposomes. The project will meet these goals by developing thermo-sensitive and polymerizable liposomes, which will bear infrared fluorescent markers. Specifically, the focus is on treatment of HER2-positive breast cancer and B-cell lymphoma. HER2-affibody molecules and CD22 ScFv will be used as recognition markers. Thermosenstive liposome formulations (that are already in clinical trials) will be used to tag affibody molecules. For CD22 targeting, various liposome formulations will be tested. Using focused ultasound, local hypertheria strategy will be used to trigger drug release from these liposomes. These features of the liposomes will improve targeted drug delivery
 
Training Plan:
The student will be involved in the development of liposomes, optimize methods for hydrophobic and hydrophilic drug encapsulation and antibody conjugation to the liposome surface. He will perform in vitro screening of these delivery vehicles. The candidate will learn various techniques which include tissue culture; FACS, cell toxicity assays, video enhanced fluorescence microscopy, lipid handling, and ELISA assays. This training will enable him/her to understand the relationship of fundamental research with the clinical applications and will be valuable in developing road map of his future career in biological sciences.

Karlyne Reilly

MOUSE CANCER GENETICS PROGRAM

Email: kreilly@ncifcrf.gov
Phone: (301) 846-7518
Bldg/Room: 0560 / 32-20
 
Research Goals/Purpose:
The Genetic Modifiers of Tumorigenesis Section is focused on using mouse models of human cancer to understand tumor biology and the role of genetic background on initiation and progression of tumors. Cancer is a complex disease that involves the interaction of many factors, such as diet, environmental mutagens, and genetic background. In patients it is difficult to dissect the relative contributions of different factors to cancer, because of the heterogeneity of the human population; however, mouse models of cancer afford the opportunity to control for variables in diet and environment and to focus on the role of genetics in tumorigenesis. We are interested in how naturally occurring polymorphisms can affect tumorigenesis and how they may interact with the mutations that accumulate during tumor initiation and progression. For this reason we focus on identifying modifier genes in different inbred strains of mice. Project 1: Identification of modifier genes affecting resistance or susceptibility to nervous system tumors. Aim 1) To characterize candidate modifier genes for Nerve Sheath Tumor Resistance loci, looking for changes in expression, splicing, and activity between susceptible and resistant mouse strains. Aim 2) To map modifiers of astrocytoma in backcross mice and examine the relationship between parental inheritance, gender, and polymorphisms on tumor resistance. Aim 3) To examine the role of imprinted genes on mouse chromosome 11 in tumorigenesis, with a focus on Grb10. Project 2: Characterization of the molecular genetics of initiation, progression, and infiltration of astrocytoma Aim 1) To study the intracellular signal transduction pathways that control proliferation and migration of astrocytomas, as potential target for therapeutic intervention, with a focus on Egfr, Pdgfr, Pi3K/Akt/mTor, and Bmi1. Aim 2) To examine the role of genes implicated in neural stem cell maintenance and astrocyte differentiation in astrocytoma tumorigenesis, as they relate to theories about neural stem cells and the development of brain cancer, with a focus on Bmi1, Sox11, and NcoR1. Aim 3) To identify the potential spectra of tumor initiating cells for astrocytoma and peripheral nerve sheath tumors by developing a reporter of spontaneous loss of heterozygosity in vivo. Project 3: Developing the Nf1-/+;Trp53-/+cis mouse model for preclinical testing of candidate drugs for astrocytoma and neurofibromatosis type 1 Aim 1) To develop in vivo imaging techniques for brain tumors in mice using bioluminescence and magnetic resonance imaging. Aim 2) To use cell-based high throughput screening techniques to identify anti-astrocytoma agents. Aim 3) To identify the mechanism underlying the inhibition of astrocytoma and neurofibromatosis cell growth by the natural product Schweinfurthin and its synthetic analogs.
 
Training Plan:
The student will aid in the characterization of modifier genes for brain cancers and nerve cancers using basic molecular biology and cellular biology techniques.

Melody Roelke-Parker

LABORATORY OF GENOMIC DIVERSITY

Email: melodyr@mail.nih.gov
Phone: (301) 846-7479
Bldg/Room: 0560 / 11-10
 
Research Goals/Purpose:
Goals: Animal models are important as tools for understanding human health. As a veterinarian, I investigate infectious diseases of wild and domestic cat species - I am particularly concerned with genetic variation of both the disease agent and the host and how this variation effects the disease outcome. My work has a particular emphasis on the impact of feline immunodeficiency virus in free ranging Florida panthers and African lions. I am also involved with several hands-on domestic cat projects which involve anesthesia, physical exams, blood drawing and reproductive evaluation.
 
Training Plan:
Plan: The student will learn to process blood products, grow animal cells in tissue culture, extract DNA, learn PCR and sequencing techniques. In addition they will learn to trouble shoot and analyze their results in each step of the process. The students will also be exposed to basic clinical examination and blood collection procedures and laboratory techniques such as flow cytometry. Typical projects may involve pedigree construction within prides of wild lion, evaluation of immune system status of wild cats infected with FIV, investigation of feline papilloma virus, and isolation and identification of novel feline pathogens.

Bruce Shapiro

NANOBIOLOGY PROGRAM

Email: shapirbr@mail.nih.gov
Phone: (301) 846-5536
Bldg/Room: 0469 / 150
 
Research Goals/Purpose:
The study of the structure and function of ribonucleic acids (RNA) is an important area of biological and computational research. In recent years the understanding of the role that these molecules play in a cell's life cycle has become even more important. The various types of RNAs that control cell functions are tRNA, mRNA, and rRNA and RNAi. Other 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/DNA structure function relationships and also the development of computational methodologies and tools to help unravel these relationships. Included are algorithms for RNA/DNA folding and analysis of the folding results. Our lab was the first to develop a massively parallel genetic algorithm (GA) for searching the very large RNA conformational space. In addition we have developed a unique RNA/DNA structure analysis workbench, STRUCTURELAB, which is a heterogeneous computer system that is used to analyze the results of the GA, as well as other folding algorithms. We also developed one of the currently best algorithms for RNA structure prediction based on RNA sequences alignments, KnetFold. Our group also does molecular mechanics and molecular dynamics simulations on RNA and RNA/protein complexes to understand the atomic scale interactions that determine the functionality of these molecules. Our group has also been exploring ways of using RNA structure/function relationships to define RNA nanobiology entities including RNA tectoshapes. These RNA based structures have the potential for developing functional nanoarrays, drug delivery vehicles amongst other possibilities. One important component for the development of these RNA nanoparticles involves the recent implementation of a database of RNA motifs for nanostructure design, RNAJunction, as well as the development of software tools to speed and simplify the design process.
 
Training Plan:
Student will be working on projects related to computational approaches to RNA structure analysis. Some potential projects are enumerated below. Other projects may materialize based on further discussions. 1) Helping to carry out molecular mechanics and molecular dynamics simulations using the supercomputer facilities for studying the structural aspects of the RNA. This will ultimately lead to the design of RNA nanoparticles.. 2) Helping in the development of computer algorithms for improving RNA structure prediction and analysis methods for both secondary and tertiary structure. This includes two-dimensional and three-dimensional modeling and the prediction of nanobiology constructs. 3) Assisting in structural searches for interesting functional features in RNA sequences and their structures. 4) Exploring the general problem of RNA structure and its relationship to gene expression and nanobiology. 5) Helping to find and understand RNA folding patterns using various algorithms running on parallel supercomputers and the RNA/DNA structure analysis workbench STRUCTURELAB. 6) Helping to enhance and develop new algorithms for STRUCTURELAB and NanoTiler. This may include added 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 and computational approaches to studying these structures. 2) Familiarizing oneself with the computers and the software available in our lab and their relationship to RNA structural biology. 3) Learning more about the software development methods used in our laboratory. 4) Writing and/or modifying software as the need arises. 5) Running various software to analyze and discover structural features. 6) Attending seminars when possible.

Shyam Sharan

MOUSE CANCER GENETICS PROGRAM

Email: sharans@mail.nih.gov
Phone: (301) 846-5140
Bldg/Room: 0560 / 32-04
 
Research Goals/Purpose:
Mutation in the BRCA1and BRCA2 gene accounts for majority of all early-onset familial breast cancer cases. Based on the recent studies, these genes act as tumor suppressors by maintaining the genomic integrity. A major goal of the Genetics of Cancer Susceptibility Group is the functional analysis of the murine homolog of human breast cancer susceptibility genes, BRCA1 and BRCA2 to uncover their novel biological functions.
 
Training Plan:
The student will participate in the project aimed at understanding the functional significance of missense mutations identified in the breast cancer susceptibility gene, BRCA1. S/he will generate missense mutations the human BRCA1 gene in a bacterial artificial chromosome (BAC) and introduce these modified BACs into mouse embryonic stem cells lacking endogenous Brca1 and examine their effect on cell survival, DNA repair, cell cycle regulation, and apoptosis. In addition, the student will examine the effect of some of these missense mutation in mouse models. This training will improve the student's understanding of various molecular biology techniques and provide an opportunity to learn about cancer genetics.

Jill Slattery

LABORATORY OF GENOMIC DIVERSITY

Email: slatterj@mail.nih.gov
Phone: (301) 846-5882
Bldg/Room: 0560 / 11-10
 
Research Goals/Purpose:
As more whole genome information becomes available, we are now able to conduct studies to describe genome evolution, re-arrangment, and adaptation in humans. Research projects are focused on comparative genomic analyses of mammalian species to investigate how genes change and evolve. We conduct large-scale sequencing projects of selected genes targeted in human health. We compare how these genes change among different species and can interpret those patterns in an evolutionary context
 
Training Plan:
The SIP is trained in basic molecular genetic methods such as PCR, cloning and sequencing. The SIP is then assigned to a particular project ongoing within the lab, and will be responsible for a specific area of research. The SIP will be directly supervised at all times, but is encouraged to be independent and learn to be an investigative scientist.

Nadya Tarasova

CANCER AND INFLAMMATION PROGRAM

Email: tarasovn@mail.nih.gov
Phone: (301) 846-5225
Bldg/Room: 0538 / 147
 
Research Goals/Purpose:
Synthesis and chracterization of novel targeted anti-cancer agents
 
Training Plan:
The student will learn how to design, synthesize, purify and characterize new anti-tumor agents. He/she will learn how to determine the purity and structure of resulting compounds with the help of mass-spectrometry, circular dichroism, fluorescence and UV spectroscopy. He or she will learn how to grow tumor cells in culture and determine anti-cancer activity of new compounds.

Terry Van Dyke

MOUSE CANCER GENETICS PROGRAM

Email: vandyket@mail.nih.gov
Phone: (301) 846-1988
Bldg/Room: 0560 / 32-24
 
Research Goals/Purpose:
Our research goal is to understand the molecular mechanisms of prostate cancer and glioblastoma progression in genetically engineered mouse models.
 
Training Plan:
The student will work with Dr. Yurong Song, a Research Fellow in my lab, on her project. He/she will closely work under Dr. Song's guidance and assist her on characterizing the mouse models she generated in the lab, which involves making solutions, organizing paraffin embedded blocks and slides, genotyping the mice via PCR (involving DNA extraction, PCR, casting a gel, electrophoresis, imaging, and data interpretation and data entry into a mouse colony database. The student will also examine the genetic manipulations (e.g. disruption of Rb and Pten pathway) on cell proliferation by Ki-67 staining and apoptosis by TUNEL staining on tissue slides obtained from tumor tissues and normal controls. In addition, he/she will characterize the tumor by immunohistochemistry (IHC) marker staining on tissue slides. Primary tumor cells are great tools to dissect the molecular pathways involved in the tumorigenesis. The student will be involve in the cell maintenance and cell based assays. Aseptic techniques are required for most of the techniques described here. He/she will also have an opportunity to learn how to make a PowerPoint poster and present scientific data.

Abdul Waheed

HIV DRUG RESISTANCE PROGRAM

Email: awaheed@ncifcrf.gov
Phone: (301) 846-1739
Bldg/Room: 0535 / 124
 
Research Goals/Purpose:
The goal of the research in Dr. Eric Freed's lab is to understand the molecular biology of HIV-1 replication, in particular mechanisms of HIV-1 assembly and release. Understanding the molecular mechanisms of HIV-1 assembly and release will eventually help to design drugs that inhibit the late stages of the HIV-1 replication cycle. Several drugs have been tested in the lab that showed antiviral activity for HIV-1. Since live HIV-1 work is not possible for a student intern, we will test these compounds for their anti-viral activity against 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 in a variety of techniques in the fields of molecular and cell biology, biochemistry, bioimaging, and virology. These include 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 general laboratory equipment, 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 potential problems. The student will learn how to maintain records of the data, and present the work in both formal and informal lab meetings and poster presentation at scientific meetings.

Stephanie Watkins

CANCER AND INFLAMMATION PROGRAM

Email: watkinssk@mail.nih.gov
Phone: (301) 846-6871
Bldg/Room: 0567 / 209
 
Research Goals/Purpose:
Our lab focuses on the suppression of tumor infiltrating immune cells and ways to enhance or sustain their activation to improve cancer therapies. The goal for the student would be to teach them to identify and characterize immune cells of interest (particularly T cells and Dendritic cells) that are isolated from a mouse with prostate cancer. This would include teaching the student basic immunology and laboratory techiques commonly used in immunological research such as cell culture systems, cytokine quantification, and real-time PCR.
 
Training Plan:


Jami Willette-Brown

LABORATORY OF EXPERIMENTAL IMMUNOLOGY

Email: willettj@mail.nih.gov
Phone: (301) 846-6028
Bldg/Room: 0567 / 274
 
Research Goals/Purpose:
The research interests of The Inflammation and Tumorigenesis Section at the LEI are to understand the physiological activities of IKKα in skin tumorigenesis and inflammation and reveal the mechanisms of how IKKα regulates these function by using genetic animal models, including Ikkα conditional knockout, Ikkα kinase inactive knockin, and IKKα transgenic mice, and molecular biology approaches.
 
Training Plan:
Description of Training Plan: Characterize the functional expression of 14-3-3 sigma in skin tissues of transgenic mice OBJECTIVES: a. To screen for positive transgenic mice. b. To develop enzymatic assays for measurement of kinase pathway proteins . c. To perform protein analysis assays on skin tissue preparations from transgenic animals. METHOD OF INVESTIGATION: a. Perform genotyping on tail samples from transgenic animals. b. Prepare skin tissue lysates from transgenic animals and determination of protein concentration. c. Determine optimal kinase assay conditions. d. Perform western blot analysis of proteins from preparations

Dr.Cheryl Winkler

MOLECULAR GENETIC EPIDEMIOLOGY (INTRAMURAL RESEARC

Email: winklerc@mail.nih.gov
Phone: (301) 846-5747
Bldg/Room: 0560 / 21-19
 
Research Goals/Purpose:
The project will involve looking at candidate genes that confer resistance and/or susceptibility to the HIV virus. We also use this same approach to look into genetic implications with regard to the kidney disease FSGS.
 
Training Plan:
The student will be trained in the necessary molecular genetic techniques that will enable him/her to complete a project. He/She will learn skills such as taqman, RFLP-PCR, sequencing, DNA extraction, and possible RNA work. The student will learn to solve problems, participate in experimental design, work in a database, and keep an organized reproducible account of his/her experiments.

Yili Yang

Cancer and Developmental Biology Lab

Email: yiliyang@mail.nih.gov
Phone: (301) 846-6396
Bldg/Room: 0538 / 224
 
Research Goals/Purpose:
Understand principles of biological experiments; Learn essential knowledge in cancer and developmental biology; Mast basic techniques in molecular cloning, cell culture, and animal typing; Use the knowledge and techniques to study the role of STAT1 in cell transformation
 
Training Plan:
Step 1: Learn basic laboratory techniques; Step 2: Design and carry out experiments; Step 3: Participate proposed project; Step 4: Summarize results and write report.

Howard Young

LABORATORY OF EXPERIMENTAL IMMUNOLOGY

Email: younghow@mail.nih.gov
Phone: (301) 846-5700
Bldg/Room: 0560 / 31-16
 
Research Goals/Purpose:
To investigate the molecular mechanisms regulating the expression of interferon-gamma and the consequences of chronic interferon-gamma expression on host immune function. The Young laboratory has observed that the IFN-gamma gene is a sentinel gene marker for hyperactivation of NK gene expression as multiple signals synergistically converge to activate IFN-gamma gene expression. However, the molecular mechanisms involved in this gene activation and the biochemical pathways activated when the NK cells see multiple signals are incompletely defined. It is a hypothesis that NK cells respond to diverse extracellular signals through the activation of distinct biochemical pathways that affect IFN-gamma through transcriptional and post-transcriptional control mechanisms. Therefore the goal of this project is to understand how specific extracellular signals trigger complimentary biochemical pathways that result in synergistic activation of IFN-gamma gene expression.
 
Training Plan:
The student will perform Western blots, cell culture, multiplex cytokine analyses, ELISAs and DNA purification in order to characterize IFN-gamma gene expression. The student will also isolate cells from a transgenic mouse developed in the lab that expresses chronic interferon gamma in order to examine the effects of this expression on the development and maturation of NK and T cells.

Matthew Zustiak

BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM

Email: zustiakm@mail.nih.gov
Phone: (301) 846-6061
Bldg/Room: 0432 / 208
 
Research Goals/Purpose:
Evaluation of genetically engineered mammalian cell lines for enhanced growth and biotherapeutic protein production
 
Training Plan:
The student will need to learn basic cell culture techiques and assays required for the evaluation of cell growth and productivity


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