Listed below are current participating mentors in the Student
Intern Program . Click on the Principal Investigator's name
for a more detailed description about their laboratory and research
goals. For a full list of NCI-Frederick laboratories click
here.
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Current Student Intern Program
Mentors for 2007 - 2008 School Year
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| Principal Investigator |
Lab Information |
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| NATIONAL CANCER INSTITUTE |
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Ding Jin |
GENE REGULATION CHROMOSOME BIOLOGY LABORATORY |
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Phone: (301) 846-7684 or 301-846-1532 |
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Email: djjin@helix.nih.gov |
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Regulation of transcription is a key step in controlling gene expression in all cells. Many diseases and cancers are the results of defects in transcription machinery and gene expression. The basic structure and function of RNA polymerase (RNAP) and RNAP-associated proteins are conserved throughout evolution. Sophisticated genetics and advanced biochemistry make E. coli an ideal model system to study the transcription machinery and the influence of transcription factors on gene expression and regulation. Currently, we focus on: (i) RNAP of E. coli and the RNAP-associated proteins RapA and SspA; and (ii) the mechanism of the global change in the transcription pattern associated with nutrient starvation known as the stringent response. Also, (iii) we have initiated a research project on the transcription control in Helicobacter pylori, the causative agent of gastric cancer. |
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David Derse |
HIV DRUG RESISTANCE PROGRAM |
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Phone: (301) 846-5611 |
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Email: derse@ncifcrf.gov |
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Retroviral Replication Laboratory/ Retrovirus Gene Expression Section
Our main focus is characterizing the molecular virology of human T cell leukemia virus type 1 (HTLV-1) and translating these studies into a better understanding of retroviral pathogenesis. HTLV-1 infects approximately 20 million people worldwide and a fraction of those infected go on to develop either adult T cell leukemia/lymphoma or a degenerative neurological disease that resembles multiple sclerosis. We are studying the mechanisms by which the virus is transmitted between lymphocytes, replicates its genome, and then changes the behavior and functions of that cell. We are comparing HTLV-1 with other retroviruses such as HIV-1 to better understand how retroviruses are transmitted from cell to cell and how cells restrict the spread of these viruses.
The SIP candidate will be involved in projects using state-of-the-art recombinant DNA, cell and molecular biology, and biochemistry technologies.
For more information http://www.retrovirus.info/Derse.html
Email David Derse with questions about this sponsorship derse@ncifcrf.gov. |
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Jairaj Acharya |
LABORATORY OF CELL AND DEVELOPMENTAL SIGNALING |
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Phone: (301) 846-7051 |
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Email: acharyaj@mail.ncifcrf.gov |
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We use Drosophila and mouse as model organisms to study the in vivo function of enzymes of sphingolipid metabolic signaling and proteins implicated in phospholipid distribution. |
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Ira Daar |
LABORATORY OF CELL AND DEVELOPMENTAL SIGNALING |
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Phone: (301) 846-1667 |
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Email: daar@ncifcrf.gov |
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Our laboratory uses the frog as a model system to determine how cell adhesion and cell movement is regulated. Understanding these processes is important because it is the movement and spread of cancer cells which most often leads to mortality, rather than the primary tumor. |
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Lucy Anderson |
LABORATORY OF COMPARATIVE CARCINOGENESIS |
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Phone: (301) 846-5600 and (301) 846-1246 |
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Email: andersol@ncifcrf.gov |
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The qualified student will participate in identifying molecular mechanisms linking cancer development in offspring to paternal exposure to environmental carcinogens using an animal model. In humans, this preconceptional or transgenerational carcinogenesis has been suggested by epidemiological studies; however, the cause-effect relationship cannot be determined experimentally. Animals provide advantages for controlled treatments and for sample collection at specific time points. The project will focus on gene modification in the sperm nuclear DNA and differential gene expression between carcinogen-treated and control mice. |
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Veronique PASCAL |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301) 846-1547 |
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Email: pascalv@mail.nih.gov |
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The primary goal of the laboratory is to achieve a more complete understanding of the cellular and molecular mechanisms of natural killer (NK) cell function—in particular, the ability to recognize and lyse tumor cells. A large portion of modern cancer research has focused on the ability of the immune system to destroy cancer cells using tumor-specific antibodies and immunomodulatory agents. A better understanding of the mode of NK cell tumor recognition will allow us to design novel antitumor therapies. The majority of our effort is directed toward the characterization of the murine Ly49 and human KIR families of NK cell class I MHC receptors. There are 14 Ly49 genes identified in the C57BL/6 (B6) mouse genome. Ten of these (Ly49a-j) have been shown to produce mRNAs with a complete coding region, and the rest are pseudogenes (Ly49k-l). Our laboratory has found that the Ly49l gene produces a novel activating Ly49 protein in CBA/J mice, which demonstrates that Ly49 family members may be silenced via germline mutations in certain mouse strains. The observed differences in Ly49 expression between strains indicated the need to survey several strains of mice in order to identify the full Ly49 gene repertoire. Extensive screening of a 129/J cDNA library by our group led to the discovery of 10 distinct full-length Ly49-related coding sequences (Ly49e, g, i, o, p, r, s, t, u, v). Although 129/J mice share the same class I MHC haplotype with B6 mice, only one Ly49 is identical in the two strains (Ly49E). Three novel activating Ly49 proteins were discovered, Ly49P, R, and U. The MHC specificity of the total 129/J-Ly49 repertoire was evaluated with soluble class I MHC tetramers. Ly49V bound to many types of class I MHC, including the nonclassical Qa-1b protein, suggesting that Ly49V+ NK cells may monitor host cells for a global downregulation of MHC molecules. Our lab has determined the organization of the 129 Ly49 cluster, and in addition to the 10 Ly49 genes identified by cDNA cloning, 9 new genes were identified in the 129 Ly49 cluster. These results demonstrate that Ly49 gene numbers can be significantly different between inbred mouse strains, analogous to the haplotype differences observed in the human KIR genes.
Our group has discovered a probabilistic transcriptional switch that controls Ly49 gene activation, and it appears that the separately evolved human KIR gene family uses the same type of switch, indicating that probabilistic switches will likely be involved in many systems where genes are selectively activated in a subset of the cells in a given tissue. This discovery has important implications for the control of stem cell differentiation, and may one day allow us to modify cell fate in differentiating systems such as bone marrow cultures.
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Robin Winkler-Pickett / Rosalba Salcedo |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301)-846-6274 |
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Email: salcedor@mail.nih.gov |
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Chronic inflammation is associated with high increase in epithelial cancer, since tumors arise in sites of chronic inflammation and tumors themselves can secrete a large profile of proinflammatory mediators within the tumor microenvironment. Today several inflammatory mediators have been implicated in cancer promotion. In our lab, we are currently studying the roles of tumor necrosis factor-alpha (TNF-a) and Lymphotoxin-alpha and beta (LT-a, LT-b) towards tumor progression by using knockout mice for TNF-a and/or LT-a,b, as well as conditional knockout mice in which these genes were deleted in specific cell types. We are using chemically induced cancer models including DMBA/TPA-induced skin carcinogenesis and AOM/DSS-induced colon carcinogenesis.
The role of the student in this project will be helping with the isolation and purification of murine DNA, performing PCR reactions, running agarose gels, keeping organized records of the experimental data that he/she will generate. This student will be trained and supervised to perform all these activities. We hope this will be a great learning experience for the student and a great help for our lab.
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Howard Young / Deborah Hodge |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301) 846-5700 |
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Email: hodged@mail.nih.gov |
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A student intern in the Cellular and Molecular Immunology Section of the Laboratory Experimental Immunology will be instructed in the basic techniques of molecular biology and cell biology in order to perform experiments designed to understand how the expression of genes is regulated in the immune system. These techniques will include purification and cloning of plasmids and specific DNA fragments, characterization of DNA through the use of restriction enzymes, purification of cellular RNA and genomic DNA, electrophoresis of RNA and DNA, handling and growth of mammalian cells in tissue culture, introduction of DNA into mammalian cells, Western blot and immunoprecipitation analysis of proteins and other techniques which may be applicable to the ongoing studies within this section. Upon mastering these techniques, the intern will assist Dr. Deborah Hodge, the Staff scientist in the laboratory, in carrying out experiments designed to understand the how the immune system functions. The student will be given an independent project dealing with the cellular and molecular aspects of gene expression in natural killer cells and T cells and how this gene expression may affect the ability of the immune system to fight cancer and infectious diseases. |
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Sher Hendrickson |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301) 846-7244 |
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Email: shendrickson@ncifcrf.gov |
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There are many forces in nature which shape the genetics of a population through Natural Selection. An individual with a gene mutation that gives it "an advantage" in its environment will leave behind more offspring than others that lack this mutation, and therefore, a greater proportion of individuals in future generations will have the mutation. However, if the mutation also occurs in another environment, but it is not advantagous, it may disappear from the population over time. By making comparisons between populations, we can begin to look for evidence of selection of particular gene mutations.
At present, I have two on-going research projects--one on carnivores and another on humans--to look for mutations that may be avantageous under certain conditions. The carnivore project focuses on genes from the mitochondria, which is "the power house" of the cell. By comparing species of big cats, bears, and foxes from different environments, I hope to identify gene mutations which influence efficiency of energy production in different climates. I am looking for a student who would like to learn how to isolate DNA, sequence genes and look for mutations in the carnivores. This student should be inspired and self-sufficient such that they can work with only moderate guidance (after being trained of course!) on days when I am pre-occupied with other projects. Further, although this student would work mainly on the carnivore project, broad interests and an open mind are desirable! There may be opportunities to work with my other human (or potentially even bird!) projects as well. |
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Warren Johnson |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301) 846-7483 |
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Email: johnsonw@ncifcrf.gov |
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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. 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. |
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Marilyn Menotti-Raymond |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301) 846-7486 |
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Email: raymond@ncifcrf.gov |
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A goal of the Animal Genetics section at the Laboratory of Genomic Diversity is to characterize genetic organization in the domestic cat and to develop genomic resources facilitating and establishing Felis catus as a powerful animal model and adjunct to improve human health. Specifically, the cat holds particular promise to contribute to our understanding of human hereditary disease analogues, neoplasia, genetic factors associated with host response to infectious disease and mammalian genome evolution. My research over the past several years has focused on developing genetic maps of the cat. Our maps have now reached a resolution that we are able to apply them towards the mapping and identification of disease genes segregating in cat pedigrees maintained by collaborators. Recently, we identified the gene and characterized the mutation for feline spinal muscular atrophy (SMA), a model for human spinal muscular atrophy. The bench-work for this mapping was accomplished by one of our SIP students! In the future, student projects will be focused on other mapping projects, including identifying genes segregating in hereditary disease pedigrees and other genes of biological interest in the cat.
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Steve O'Brien / Mary McNally |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301)-846-7520 |
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Email: mjmcnally@ncifcrf.gov |
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The Laboratory of Genomic Diversity’s Core Genotyping Facility carries out studies on 10 major published genes. Some of the genes are CCR5, CCR2, SDF1-3UTR, IL10-592, CCR5MP and various RANTES. These genes are on chromosomes 1, 3, 10, and 17. The purpose of this typing is to give our scientists insight into the association between these genes and diseases in cohorts of interest. We also have a ongoing Mitochondrial DNA Study which involves 30 SNPS typed on 3,000 patients. The lab manages inventory and distribution of all genomic DNA to all principal investigators’ labs for research. Our lab also makes a panel of DNA plates, which are instrumental in genotyping for most of the principal investigators. These plates consist of 2 water blanks per plate, 4% in plate duplicates and 8% across the panel duplicates for quality control. The lab provides samples for scientists by extracting DNA from whole blood, cell pellets, WBC buffy coat, mouthwash, cheek swabs, and other tissues. The core facility also provides high throughput genotyping service to outside labs. This means that labs outside of the core facility design and optimize primers. Then the primers and protocols are provided to the core lab, which in turn types samples either by RFLP or Taqman analysis. URL http://rex.nci.nih.gov/lgd/front_page.htm |
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Steve O'Brien / Joan Pontius |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301)846-1761 |
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Email: pontiusj@ncifcrf.gov |
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Data management, webpage development and
eventually programming for a laboratory
interested in comparative genomics of mammals
and its applications towards both evolution and
disease. We are currently working on the cat genome
and need help organizing results into a website and
writing new tools to organize the data. Position
entails computational work on an Apple computer,
but will also entail learning a lot of biology.
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Steve O'Brien / Efe Sezgin |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301)-846-7125 |
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Email: sezgine@ncifcrf.gov |
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As part of Genetic Epidemiology laboratory under the supervision of Dr. Michael W. Smith, the project focuses on the genes that increase or decrease susceptibility to HIV-1 and progression to AIDS, susceptibility to Hepatitis B and C viruses. Special attention is given to the Y chromosome and its genes. Main molecular techniques such as PCR, high throughput genotyping, DNA sequencing and other related methods will be applied. The data generated will be analyzed with a variety of statistical software.
Interested student will have the chance of working both on the wet lab and computer application side of the projects. Our laboratory provides an excellent environment for advancing on the topics of genetics, biochemistry, genomics, bioinformatics and immunology.
This position will be in close interaction with Dr. Taras Oleksyk and other parallel projects in the lab.
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Jill Slattery |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301) 846-5882 |
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Email: slattery@mail.ncifcrf.gov |
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My research investigates how genes evolve and change. This is important information that can be used to study disease and how we adapt to disease. I have two major areas of interest: 1) how genes in retroviruses change over time and 2) the evolution of genes located on the X and Y (sex chromosomes).
The first project is genetic analysis of viruses harmful to humans such as human T-cell leukemia virus (HTLV) and HIV which causes AIDS. But we use a comparative approach that looks at how related viruses such as STLV (found in monkeys) and FIV (found in cats) change within those species. The reason for this is that often we can learn a lot more about the genetics of particular genes by comparing them across species rather than looking at just one single species.
The second project concerning the evolution of genes on the sex chromosomes also uses a comparative approach by looking at genes within the cat family. Next to our house cat pet, there are 37 other species of cat. At LGD, we have DNA from these cats stored away and we use that for genetic analysis. We have numerous research projects ongoing concerning cat evolution that have proven to be very important in understanding molecular changes in genes involved with disease in humans as well. My work with sex chromosomes has been very interesting and uncovered some unusual and novel patterns possible in genetic change.
We have started a new initiative to use comparative methods to determine the structure and function of sex-linked cancer genes. These genes are located on the sex chromosomes and have been associated with several different human cancers. We are creating a candidate list of genes to examine in species other than human to infer how the gene works under normal circumstances, and compare with mutations that might lead to cancer.
As a SIP within my lab, you would be given all opportunities to advance into a role in research that fits your talents. We will train you in basic techniques of DNA analysis such as: Extraction of DNA, PCR, and sequencing. You will be exposed to computer programs and methods of analysis that we use to examine the data. Your project would be an aspect of describing genetic changes within candidate genes-the specific details would be decided upon after the training period. |
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Jennifer Troyer |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301)-846-7478 |
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Email: jtroyer@ncifcrf.gov |
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My laboratory studies the intereaction between viruses and their host species. We currently are involved in research projects that include investigating genes that may effect HIV/AIDS treatment efficacy, and looking at the effect that various host (human) proteins have on the ability of HIV to grow and mutate. We are also using closely related viruses that are found in many cat species, called feline immunodeficiency viruses (FIV), to understand how these viruses can move from one host species to another and how some of these host species, particularly lion and puma, can be infected with the virus without getting sick.
In our lab you will learn molecular genetic techniques such as DNA and RNA extraction, PCR, sequenceing, and cloning. You will also be involved in data analysis and will eventually be expected to have input into your project design. Depending on your project and preferences, you may also learn cell culture techniques and/or bioinformatics and computer modeling. Student projects will focus on FIV as a model for HIV. |
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Naoya Yuhki |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301) 846-5290 and (301) 846-5295 |
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Email: yuhki@ncifcrf.gov |
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The student will work on a comparative genome project which aims to research "what is genome". Studies of comparative genomics of immune systems using computational and biological methods will be conducted in order to unveil the function and evolutionary process of many complex genetic systems of immunity, including the major histocompatibility complex (MHC), the leukocyte receptor complex (LRC)and others. DNA sequencing of these complex and transcripts will be determined using a high throughput system, automated sequencing, and high speed computer analyses. He/she will isolate DNA/RNA, set up sequencing reactions with fluorescent dye based chemicals, operate a robotic system, an automated DNA sequencer and data-mining nucleotide sequences. Lectures of current knowledge of biology, mathematical applications, languages & tools for computational biology, such as Perl, BioPerl modules, Ruby and Data Base Management System, MySQL will be given every morning in summer. |
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Teizo Yoshimura |
LABORATORY OF MOLECULAR IMMUNOREGULATION |
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Phone: (301)846-5518 |
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Email: yoshimut@mail.nih.gov |
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There is a clear link between chronic inflammation and cancer. Monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, is a chemoattractant regulating the recruitment of blood monocytes into sites of the inflammatory responses. MCP-1 also regulates the recruitment of tumor-associated macrophages that provide a microenvironment favorable for cancer cells to grow; thus, MCP-1 is a molecular target for cancer treatment. During cancer development, MCP-1 is produced by not only cancer cells but also myeloid cells infiltrating cancer tissues. I am attempting to define the role for MCP-1 produced by these two cell types by using mice in which the gene for MCP-1 is deleted in either epithelial cells or myeloid cells. I am also studying the mechanisms by which cancer cells constitutively produce a high level of MCP-1. |
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Tawnya McKee |
MOLECULAR TARGETS DEVELOPMENT PROGRAM |
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Phone: (301)846-1943 |
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Email: mckee@ncifcrf.gov |
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The MTDP designs and implements screens to find compounds that can directly impact molecular targets thought to be important in cancer. Many of the targets we look at do not have any compounds or chemicals known to change how the target behaves in a cancer cell. We try to find compounds that change the target's behavior. Many of the compounds we use are natural products, that is they are not synthsized in the lab, but are made by things like plants, fungii and marine organisms. We test extracts of these organisms in our screens and then, like a detective work to identify the individual chemicals that have the acitivity and figure out the chemical structure. As a SIP student working with me you would learn how to isolate the active compounds and work with us to identify the compound's structure using a variety of instruments like NMR and MS. |
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Barry O'Keefe |
MOLECULAR TARGETS DEVELOPMENT PROGRAM |
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Phone: (301) 846-5332 |
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Email: okeefe@ncifcrf.gov |
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The Molecular Targets Development Program (MTDP) provides leadership for converting CCR's basic sciences advances into drug leads, bioprobes, and reagents for molecular target evaluation. The MTDP exploits chemical and biodiversity repositories, including the NCI Natural Products Repository, for molecularly targeted lead discovery.
The MTDP also facilitates the discovery of natural products and synthetic compounds that may serve as bioprobes for chemical genetics, proteomics, target validation, and potential lead compounds for clinical development. Compounds of interest include classical drug-like organic small molecules, and peptides, proteins, and other bioactive chemical classes. |
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Pradman Qasba |
NANOBIOLOGY PROGRAM |
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Phone: (301) 846-1934 |
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Email: qasba@helix.nih.gov |
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Structural Glycobiology Section (SGS)
Structure - Function Relationship of Glycosyltransferases
At the cell surface complex carbohydrates, linked to proteins or lipids that are embedded in the cell membrane, are involved in cell interactions, cellular, bacterial and viral adhesions. These oligosaccharides clearly serve as recognition markers and take part in a wide range of biological functions. For example, they are involved in forming the extracellular matrix with collagen to which growth factors bind with a high degree of specificity and thus regulate the growth factor activity. The initial interaction between the carbohydrate and the protein is a priori condition for the initiation of the biological response. Since these interactions occur with a unique conformer of the oligosaccharide, the precise information about all the conformers which are accessible by the oligosaccharide is essential. Such an information is important in the studies on the modulation of protein?protein interactions by carbohydrate moieties.
The assembly of the complex carbohydrates on glycoproteins and glycolipids require the concerted action of a large number of Golgi resident glycosyltransferases, which catalyze the transfer of a single sugar residue to a specific oligosaccharide acceptor, and by glycosidases, the processing enzymes. The exact processing depends on the species, tissue developmental stage and the availability of the repertoire of glycosyltransferases and glycosidases. Mutations in the glycosyltransferase genes, resulting in the altered glycosyltransferase activities and changes in the oligosaccharide structures have to be cause of several diseases. A knowledge of the three-dimensional (3-D) structure of the glycosyltransferases, glycosidases and their complexes with the oligosaccharides is highly desirable for understanding the biosynthesis and functions of glycoproteins.
Research work of my laboratory has focused on the structure-function studies of Golgi-glycosyltransferases, the enzymes involved in the synthesis of oligosaccharide moieties (glycans) of glycoconjugates (glycoproteins, glycolipids and glycosaminoglycans), and analysis of the conformational preferences of oligosaccharide acceptors and their interactions with the proteins. This structural information has led to the design of new glycosyltransferases, and use of these enzymes in the synthesis of oligosaccharides for vaccine development and assembly of bio-nanoparticles for the development of the targeted-drug delivery system.
Having first cloned and expressed a-lactalbumin and b-1,4-galactosyltransferase, the studies that initiated the cloning of other glycosyltransferases in various other laboratories, our research group investigated the structural aspects of members of galactosyltransferase subfamily. We are using genetic engineering, crystallographic and molecular modeling methods, to identify the regions and residues involved in the interaction of these enzymes with the metal-ion, sugar-nucleotide donors and oligosaccharide acceptors. The structural work on the galactosyltransferase family members from our laboratory, and on other glycosyltransferases from various laboratories, have shown that, upon binding the sugar-nucleotide donor substrate, flexible loops at the substrate binding site of these enzymes undergo a marked conformational change, from an open to a closed conformation. This creates an oligosaccharide acceptor binding site in the enzyme that did not exist before. The loop then acts as a lid covering the bound donor substrate. After the transfer of the glycosyl unit to the acceptor, the saccharide product is ejected, and the loop reverts to its native conformation to release the remaining nucleotide moiety. This conformational change also creates the binding site for a-lactalbumin and other cellular proteins like Ovalbumin. The interaction of a-lactalbumin with galactosyltransferases then modulates the acceptor specificity of the enzyme. The specificity of the sugar donor is determined by a few residues in the sugar-nucleotide binding pocket of the enzyme, which are conserved among the family members from different species. Furthermore, the conformational analysis of oligosaccharides by molecular dynamics simulations in our laboratory has provided information about all the possible conformations an oligosaccharide can access, the information which is vital for understanding the carbohydrate-protein interactions in general, and specifically the interactions between oligosaccharide substrates and glycosyltransferases.
Based on the structural information of glycosyltransferases and conformational analysis of oligosaccharide chains, we have been able to design novel glycosyltransferases with broader or requisite donor and acceptor specificities. This detailed structural information has also enabled other investigators to synthesize specific inhibitors for these enzymes. The reengineered recombinant glycosyltransferases are making it possible to (1) to synthesize oligosaccharides for vaccine development, (2) remodel the oligosaccharide chains of glycoprotein drugs, and (3) modify the glycan moieties of glycoproteins. Our current goal is to modify the oligosaccharide moieties of glycoproteins with mutant glycosyltransferases so that they can be linked via glycan chains, thereby assisting in the assembly of bio-nanoparticles that are useful for the development of the targeted-drug delivery system and contrast agents for MRI.
Also student may refer to our web sites:
http://glycores.ncifcrf.gov/
http://www-lecb.ncifcrf.gov/~qasba/
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Bruce Shapiro |
NANOBIOLOGY PROGRAM |
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Phone: (301) 846-5536 |
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Email: bshapiro@ncifcrf.gov |
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The study of the structure and function of ribonucleic acids (RNA) is an important and exciting 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 a cell's normal function are tRNA, mRNA, and rRNA. 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 structure/function relationships and also the development of computational methodologies and tools to help unravel these relationships.
Included in our research are algorithms for RNA folding and analysis of the folding results. Our lab was the first to develop a massively parallel (1000's of computer processors) genetic algorithm (GA) for searching the very large RNA conformational space. In addition we have developed a unique RNA 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 use these computational tools and others to analyze HIV and other retroviruses as well as other RNA related diseases.
In addition, our lab has been studying the three-dimensional behavior of RNA and RNA/Protein complexes using techniques such as molecular dynamics and elastic network interpolation. These very computationally intense problems work with all atom and/or reduced atomic representations on state-of-the-art high performance parallel computers.
Most recently our group has been investigating the design of RNA based nanostructures. This is a relatively new field which holds great potential for drug delivery, diagnosis and molecular machine design.
Research goals/Purpose:
Student will begin work this summer. There are several possible projects that he/she will be working on related to computational approaches to RNA structure prediction, analysis and nanodesign. Once he/she arrives and we have a chance to discuss some of the details of these projects and learn some of the biological, mathematical, as well as computer concepts required, we will find mutual interests and determine the specifics of the project. Some potential projects include:
1) Helping to carry out molecular mechanics and molecular dynamics simulations using the supercomputer facilities for studying structural aspects of the RNA. This may ultimately lead to findings useful for drug design.
2) Helping to develop WEB code for the computer RNA structure analysis system we have developed in our laboratory.
3) 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.
4) Assisting in structural searches for interesting RNA features present in RNA related biological systems using our software.
5) Helping to find and understand RNA folding pathways using the genetic algorithm running on our massively parallel supercomputers and the RNA structure analysis workbench STRUCTURELAB.
6) Studying how RNA structure/function impacts the control of various biological systems and diseases.
7) Helping to design and implement an RNA structural database that will tie in with our software systems.
8) Helping to develop new computer algorithms that assist in defining RNA nanostructures with functional properties.
9) Writing and publishing papers related to the above work. |
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Susan Mertins |
SCREENING TECHNOLOGIES BRANCH |
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Phone: (301) 846-7245 |
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Email: smertins@ncifcrf.gov |
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The Screening Technologies Branch (STB) is the organizational component of the Developmental Therapeutics Program responsible for the development and operation of in vitro drug screening tools and detailed investigation and development of novel therapeutic agents for the treatment of cancer, AIDS opportunistic infections, and AIDS related malignancies. This is accomplished through research contracts, projects conducted by Operations and Technical Support Contractor (SAIC) at NCI-Frederick and efforts of staff scientists. |
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Nadya Tarasova |
STRUCTURAL BIOPHYSICS LABORATORY |
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Phone: (301) 846-5225 |
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Email: tarasova@ncifcrf.gov |
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We are a drug development group, with the majority of our group members having backgrounds in chemistry. The major goal of our work is the development of new approaches to anti-cancer chemotherapy, with a particular emphasis on the design and synthesis of a new generation of less toxic but more effective drugs. Students who choose to join our lab will be involved in all stages of drug development from design to synthesis, to activity testing of new anti-cancer compounds. |
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Yun-Xing Wang |
STRUCTURAL BIOPHYSICS LABORATORY |
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Phone: (301)-846-5985 |
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Email: wangyu@ncifcrf.gov |
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Our lab studies structural biology of a number of important biological molecules and systems using nuclear magnetic resonance (NMR) spectroscopy and various other biophysical and biochemical tools. Our general goal of studies is to understand biological processes at atomic level and interpret atomic coordinates in terms of biology.
Our daily research activity involves cloning genes, over-expressing/purification of proteins, transcribing RNA molecules,setting up NMR experiments on spectrometers, analysis/interpret of NMR data and calculations of structures of bio-macromolecules etc. |
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| SCIENCE APPLICATIONS INTERNATIONAL CORPORATION
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Stan Burt / Raul Cachau |
ADVANCED BIOMEDICAL COMPUTING CENTER |
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Phone: (301) 846-6062 |
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Email: cachau@ncifcrf.gov |
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At the hearth of every life process are molecules (three dimensional arranges of atoms) interacting with each other. These interactions control the traffic of information in and out of the cell, the cell metabolism; modulate the expression of genes etc. Scientists take advantage of knowledge of the cell control mechanisms to design drugs, nanoparticles or modified biomacromolecules that interfere with them. At the ABCC we apply and develop software packages and strategies to better understand the mechanisms of function of molecules from small drugs to nanoparticles. At the ABCC we use a range of tools including computer graphics, computer simulations and statistical analysis methods for the computational characterization of molecules of biological interest. A student working at the ABCC will participate in projects to develop, validate or apply methods to simulate and analyze molecular properties in areas of Nanotechnology, Bioinformatics, and, in general, Molecular Modeling, applied to problems in Cancer biology. These efforts will be used to support other groups at the NCI interested in the development of new treatments to thwart the progression of illness. |
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Mary Carrington / Maureen Martin |
BASIC RESEARCH PROGRAM |
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Phone: (301)-846-5318 |
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Email: martinm@ncifcrf.gov |
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Dr. Mary Carrington heads the HLA Typing Laboratory. The lab is currently in the process of genotyping the Killer cell Immunoglobulin-like receptors (KIR) found on natural killer cells in a number of disease cohorts including individuals infected with human papilloma virus (which predisposes to cervical cancer), HIV, Hepatitis B virus and hepatitis C virus. In addition, we are genotyping the KIRs in several ethnic populations in order to determine the frequency of the KIR genes in these populations. Our goal is to type the KIRs in the various populations and analyze these data for potential association with disease outcome. A student intern would be involved in the development of protocols and in the actual KIR typing process, and their responsibilities would include PCR amplification of the KIR genes, agarose gel electrophoresis and DNA sequencing on an Applied Biosystems automated sequencer.
In our lab, the student will learn and perform the following procedures:
1. Extraction of DNA from peripheral blood lymphocytes and cell lines.
2. Setting up Polymerase chain reactions (PCR)
3. Performing agarose gel electrophoresis.
4. Setting up sequencing reactions for the Applied Biosystems automated sequencer
5. Analysis and interpretation of the data generated.
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Jonathan Keller / Ming Ji |
BASIC RESEARCH PROGRAM |
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Phone: (301) 846-1461 and (301) 846-5992 |
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Email: mji@ncifcrf.gov |
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The Hematopoiesis and Stem Cell Biology Section is currently engaged in studies to define the molecular regulation of hematopoietic stem cell quiescence, survival, self-renewal, lineage commitment and differentiation. In this regard, transcription factors are essential for stem cell and lineage development by regulating the expression of hematopoietic growth factors (HGF), HGF receptors, other transcription factors, and lineage specific genes. Thus, our current efforts are aimed at defining the function of specific transcription factors and transcriptional regulators as mediators of these processes using stem cell line models; knock out mice and normal hematopoietic cells. It is anticipated that the student will be engaged in studies to define the function of specific transcription factors in hematopoietic cell growth and differentiation. As part of these studies, the student will learn how to set up experiments, understand positive and negative controls and learn to interpret the data. Finally, it is anticipated that the student will learn about hematopoiesis and the biology of stem cells. |
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Dennis Michiel / Daniel Stoughton |
BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM |
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Phone: (301) 846-5274 |
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Email: dstoughton@ncifcrf.gov |
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The Biopharmaceutical Development Program (BDP) is a unique facility for the production and testing of biological therapeutics for use in clinical trails in humans. The BDP manufactures biopharmaceuticals, including monoclonal antibodies, recombinant proteins, immunoconjugates, peptide and DNA vaccines, viruses, and other biologicals to explore novel therapeutic concepts. More information on the GMP manufacture of biopharmaceuticals is available at http://web.ncifcrf.gov/research/brb/BDP/index.html . A student working in the Purification Development Laboratory will participate in laboratory projects to develop large-scale purification methods to manufacture the drugs being made by the BDP. The laboratory techniques include small to large-scale chromatographic purification methods, systematic approaches to optimization and scale-up of chromatographic processes, protein refolding methods, and analytical studies using chromatography. |
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Dennis Michiel / Man-Shiow Jiang |
BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM |
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Phone: (301) 846-1825 & (301) 846-1608 |
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Email: mjiang@ncifcrf.gov |
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The Biopharmaceutical Development Program (BDP) is a unique program to explore novel therapeutic concepts for the treatment or prevention of cancer, AIDS and other diseases. The BDP has facilities for the production and testing biopharmaceuticals, including monoclonal antibodies, recombinant proteins, immunoconjugates, peptide and DNA vaccines, viruses, and other biologicals. These biological therapeutics are produced under FDA guidelines for use in clinical trails in humans. More information on the GMP manufacture of biopharmaceuticals is available at http://wwwbdp.ncifcrf.gov/.
A student working in the Purification Development Laboratory will participate in laboratory studies to develop large-scale purification methods to manufacture the drugs being made by the BDP. As part of these studies, the student will learn how to design and set up experiments for the characterization of the biologicals. The laboratory techniques include small to large-scale chromatographic purification methods with computer control and monitoring, systematic approaches to optimization and scale-up of chromatographic processes, protein refolding methods, and characterization studies using chromatography, electrophoresis and other analytical techniques.
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Jianwei Zhu / Yueqing Xie |
BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM |
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Phone: (301) 846-1469 and (301) 846-5511 |
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Email: yxie@ncifcrf.gov |
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A student working in the Bioprocess Development Laboratory will participate in developing and optimizing methods to fermentation, cell culture, and recovery for a variety projects including monoclonal antibody, therapeutic recombinant proteins, protein and plasmid vaccines. The laboratory techniques include cellular biochemistry and biochemical engineering, protein biochemistry, process engineering, and systematic approaches to optimization of fermentation processes, growth of mammalian cells producing monoclonal antibodies, small-scale chromatographic purification methods, and analytical studies using HPLC systems. |
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Jianwei Zhu / Vinay Vyas |
BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM |
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Phone: (301) 846-1469 and (301) 846-1036 |
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Email: vvyas@ncifcrf.gov |
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A student working in the Bioprocess Development Laboratory will participate in developing and optimizing methods to fermentation, cell culture, and recovery for a variety projects including monoclonal antibody, therapeutic recombinant proteins, protein and plasmid vaccines. The laboratory techniques include cellular biochemistry and biochemical engineering, protein biochemistry, process engineering, and systematic approaches to optimization of fermentation processes, growth of mammalian cells producing monoclonal antibodies, small-scale chromatographic purification methods, and analytical studies using HPLC systems.
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Ligia Pinto / Troy Kemp |
HPV IMMUNOLOGY LABORATORY (CLINICAL SERVICES PROGRAM)
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Phone: (301) 846-1766 and (301) 846-6383 |
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Email: tkemp@ncifcrf.gov |
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Cervical cancer is the second most common cancer diagnosed among women worldwide, with approximately 500,000 new cases each year and over 200,000 deaths per year. Genital human papillomavirus (HPV) infections are the most common viral sexually transmitted diseases worldwide and have been found to be the central etiological risk factor for cervical cancer. A prophylactic vaccine against infection with HPV and cervical cancer was recently approved by FDA. The HPV Immunology Laboratory is involved with clinical trials of human papillomavirus-like particles (VLP), analyzing immune responses to HPV VLP in vaccine recipients. It is our goal to better understand determinants of long term protection against infection. We are also analyzing immune responses to HPV in natural history studies of HPV-induced cervical lesions, with the goal of identifying putative correlates of immune protection against infection and disease progression.
Students will have the opportunity to participate in projects analyzing systemic and mucosal immune responses to HPV antigens. Approaches used in our laboratory include cytokine multiplex profiling systems, ELISA, pseudovirus neutralization assays, flow cytometry and RT-PCR. |
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Ven Natarajan |
LAB OF MOLECULAR CELL BIOLOGY (CLINICAL SERVICE PROGRAM) |
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Phone: (301) 846-1248 |
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Email: vnatarajan@niaid.nih.gov |
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Role of Vitamin A Signaling in Immune Function
Vitamin A and its biologically active derivatives (collectively known as retinoids) have a wide variety of effects on development, cellular differentiation, immune function, and cell death. How can these relatively simple molecules exert such diverse effects? Research has shown that retinoids control the activity of a group of proteins known as retinoic acid receptors (RAR) and retinoid X receptors (RXR). These proteins are transcription factors that bind to specific DNA sequences present in certain genes. Retinoids bind to these proteins and affect their transcriptional activity.
This laboratory has been interested in the role of RAR and RXRs in specialized immune cells called T cells. T cells are produced in thymus and are circulated in blood and these cells fight viral and bacterial infections. T lymphocytes are stimulated to grow and secrete cytokines when they encounter antigens. We have shown that the levels of retinoid receptors (RAR and RXR) are changed during T cell activation. We are interested in identifying the role of these changes in T lymphocyte function.
Selected student will have the opportunity to learn the following techniques: DNA isolation, quantitation by spectrophotometer, restriction enzyme digestion, gel electrophoresis, mutagenesis, bacterial transformation, cell culture, eukaryotic cell transfection, and luciferase enzyme assay. Selected student is encouraged to work on a research project incorporating these techniques.
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James Cherry |
LABORATORY OF MOLECULAR TECHNOLOGY |
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Phone: (301) 846-5304 |
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Email: jcherry@ncifcrf.gov |
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Interviews may be conducted at Tollhouse, Rm 209 also (check with the interviewer for location). The Gene Expression Laboratory (GEL) is provides scientific and technical expertise in the area of gene expression, including mRNA isolation and purification from a variety of biological specimens for different species. Nucleic acids are characterized by size fractionation on chips using a Bioanalyzer and quantified by real-time polymerase chain reactions (PCR). The laboratory also provides scientific and technical expertise necessary to generate and purify recombinant adenoviruses for gene expression students. The student intern will be working with Real-Time PCR Group. Student will be trained in different technology platforms designed to monitor and quantitate gene expression. |
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David Munroe / Martin White |
LABORATORY OF MOLECULAR TECHNOLOGY |
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Phone: (301) 846-1773 and (301) 846-5676 |
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Email: whitem@ncifcrf.gov |
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Project #1: Molecular Biology Based Science Project: Intern will be involved in utilizing DNA sequencing and Micro array technologies directed toward cancer gene discovery for applications in gene therapy and/or drug intervention in cancer treatment applications. Candidate will also be exposed to computerized data analysis packages.
Project #2: Student will be involved in assisting with the development of 2D gel systems and computer based analysis packages for protein arrays. These systems will be a valuable tool in identifying proteins involved in various disease processes.
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Timothy Veenstra |
LABORATORY OF PROTEOMICS AND ANALYTICAL TECHNOLOGY |
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Phone: (301)-846-7286 |
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Email: veenstra@ncifcrf.gov |
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Our laboratory utilizes separations and state-of-the-art mass spectrometry tools for investigating the proteome - the sum total of gene expression in a cell or tissue. Since cancer is ultimately a disease manifested at the level of the proteome, our investigations enable key mechanistic insights into this disease. These insights are derived from characterizing the proteome at many different levels, including determining protein flux, post-translational modifications and protein-protein interactions. |
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Cheryl Winkler / Elizabeth Binns-Roemer |
MOLECULAR GENETIC EPIDEMIOLOGY (INTRAMURAL RESEARCH SUPPORT PROGRAM) |
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Phone: (301) 846-5747 and (301) 846-6730 |
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Email: ebinns@mail.ncifcrf.gov |
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My research investigates the role of host genetic factors in infectious diseases, kidney diseases, and cancers associated with hepatitis viruses. We study how genetic variation within genes influences or modifies a person's susceptibility to infection and pathogenesis following exposure to pathogens such as HIV-1 or the hepatitis viruses. The differences we see within a population in response to viral pathogens in resistance to infection and severity of disease can usually be attributed to both differences in the virus and in the host. The goal of our project is to identify those human genes that make a difference in how an individual is affected by different viruses.
Students in my lab are treated as research equals and are given responsibilities corresponding to their skill levels. We are a nurturing group and provide our students with the support they need to be independent and successful participants in our research team. The student will learn many skills, including DNA analysis, genotyping, using computer databases and software. |
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| INTERNSHIPS IN SUPPORT OF SCIENCE/RESEARCH
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Ken Michaels |
SCIENTIFIC PUBLICATIONS, GRAPHICS & MEDIA |
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Phone: (301) 846-1055 |
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Email: kvm@ncifcrf.gov |
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Scientific Publications, Graphics & Media (SPGM) is a service organization of communications experts that supports the mission of the National Cancer Institute, the Center for Cancer Research, and SAIC-Frederick, Inc. Our mission is to optimize and facilitate the effective communication of NCI-Frederick investigators, administrators and staff within the company, within the scientific community, and to the general public. To achieve that mission, SPGM people provide a full range of specialized products and services to best serve the publication, presentation, and other communication needs of our clientele.
The department staff includes professional photographers, videographers, multi-media developers, writers, graphic designers and illustrators. All staff members are professional communicators regardless of specialty, and talent diversification is promoted. Typical work assignments include design and production of scientific posters, slide presentations, illustrations, Web-based graphics, animations, digital image capture and enhancement, and design and production of a wide range of materials for the print media. Staff writers create and edit newsletters, reports, scientific publications, and manuscripts. Depending on the student’s particular interests, the internship curriculum will be tailored to one of the following areas of emphasis or a blend of two or more:
Scientific writing and editing
Scientific illustration and graphic design
Biological photography, videography and multi-media development
The type of projects involved will depend on the exact curriculum, and may cover the full range of services the department offers. In any case, it will involve working on actual jobs in production for the department’s customers. The student may function independently on relatively simple assignments under guidance and supervision, and will participate collaboratively with staff professionals on more challenging projects. The student will assemble and present a portfolio of work performed over the course of the internship at completion. |
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