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 2008 - 2009 School Year
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| Principal Investigator |
Lab Information |
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| NATIONAL CANCER INSTITUTE |
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Mark Fortini |
Cancer and Developmental Biology Lab |
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Phone: (301)-846-7599 |
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Email: fortini@ncifcrf.gov |
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Studying cell communication pathways involved in normal development and cancer, using the fruit fly Drosophila as an experimental model organism. |
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Ding Jin / Julie Torruellas Garcia |
GENE REGULATION CHROMOSOME BIOLOGY LABORATORY |
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Phone: (301)-846-1648 |
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Email: garciajul@mail.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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Ding Jin / Cedric Cagliero |
GENE REGULATION CHROMOSOME BIOLOGY LABORATORY |
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Phone: (301)-846-7684 or (301)-846-1532 |
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Email: caglieroc@ncifcrf.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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Sandra Ruscetti / Xiujie Li |
LABORATORY OF CANCER PREVENTION |
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Phone: (301)-846-5662 |
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Email: lixiu@ncifcrf.gov |
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The Retroviral Molecular Pathogenesis Section of the LCP uses retroviruses to understand the molecular basis for various diseases. We have been studying retroviruses that cause leukemia or neurological disease in rodents to obtain information on the molecular changes in normal cells that result in pathological consequences. By providing important information about the cause of disease, these animal models are invaluable for identifying molecular targets relevant to human cancers for their prevention and treatment, the main research goal of the LCP. |
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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 / Yih-Horng Shiao |
LABORATORY OF COMPARATIVE CARCINOGENESIS |
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Phone: (301) 846-5600 and (301) 846-1246 |
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Email: shiao@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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Michael Dean / Colm O'Huigin |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301)-846-1717 |
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Email: colmoh@ncifcrf.gov |
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Nature subjects the key genes of the immune system in humans to a ongoing improvement process. We learn about the forces driving the improvement by studying the gene sequences themselves, comparing between individuals or species. Rapid change of sequences is commonly seen as a response to disease or competition. Using the analytical tools of population genetics, epidemiology and molecular evolution I have been working to identify genes from the genomic and DNA databases that are involved in keeping individuals healthy. Then I can apply the techniques of molecular genetics to understand the processes driving the changes in the gene. The molecular techniques primarily involve DNA extraction, PCR reactions, gel electrophoresis, sequencing and sequence comparison. The genes studied are primarily those of the immune system, including members of the TRIM, MHC and KIR families. A student can expect to become involved initially in the molecular aspects of the work. The teaching phase will see the student learn how to handle DNA for PCR through to sequencing. As the student becomes capable of handling the molecular aspects, it will become possible to spend time learning the analytical methods including sequence alignment and handling as well as phylogenetic tree construction and identification of sites under selection. |
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Daniel McVicar / Selinda Orr |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301)-846-6471 |
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Email: orrse@mail.nih.gov |
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Our laboratory studies many different receptor systems involved in the immune system. Receptors enable cells to detect and respond to a variety of signals that control the fate of the cell. Our goal is to understand the signal transduction of these receptors: how the information, or signal, is passed along throughout the cell. We are interested in receptor systems found in Natural Killer cells which respond to viral diseases such as HIV and Hepatitis. These studies also help us learn more about the immune system and how it can be harnessed for the prevention of and/or treatment of cancer.
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Jonathan Weiss / Tim Chan |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301)-846-6684 |
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Email: chantim@mail.nih.gov |
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Our lab focuses on understanding mechanisms of the immune system and exploiting these mechanisms to develop more powerful immunotherapeutic strategies for the treatment of renal cell carcinoma. We are currently interested in the use of cytokines such as interleukin-12 (IL-12) and interleukin-15 (IL-15) as a cancer therapeutic potential. The designed therapies attempt to modulate the interplay between the innate immune response (such as dendritic cells, natural killer (NK) and NKT cells) and the adaptive immune response (such as CD4 and CD8 T cells).
The student will gain valuable basic molecular biology, cell biology and immunology techniques throughout their project. These techniques include cloning and purification of DNA vectors, DNA typing of mice, setting up polymerase chain reactions (PCR), DNA electrophoresis, western blotting for proteins and other techniques including running ELISAs to detect cytokines expression. The student will also learn basic tissue culture techniques for culturing a variety of tumor cell lines and dendritic cells. As the student progresses, he/she will be given a project that examines how one of the cytokine therapies allow for improved therapeutic responses against cancer. |
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Robin Winkler-Pickett |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301)-846-1328 |
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Email: winklerr@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. These are very complex mouse models. This student will be trained and supervised to perform all these activities. We hope to include the student in additional aspects of the project, including data analyses and other hands-on experimental work as the project progresses. This will be a great learning experience for the student in a friendly learning environment. |
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Howard Young / Ram Savan |
LABORATORY OF EXPERIMENTAL IMMUNOLOGY |
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Phone: (301)-846-6500 |
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Email: savanr@mail.nih.gov |
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A second 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 with a focus on Natural Killer cells. 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 one of the current postdoctoral fellows in carrying out experiments designed to understand the how NK cells function. The student will be given an independent project dealing with the cellular and molecular aspects of gene expression and how this gene expression may affect the maturation, development and function of NK cells. |
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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 / Victor David |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301)-846-7487 |
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Email: david@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 is focused on the identification and characterization of hereditary disease genes in the cat. 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! Our present SIP student is focused on mapping the gene causative of silver coat color in the cat. 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 / 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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Steve O'Brien / Melody Roelke-Parker |
LABORATORY OF GENOMIC DIVERSITY |
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Phone: (301)-846-7479 |
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Email: roelke@ncifcrf.gov |
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This job has two main aspects; one deals with domestic cat oocyte (egg) collection for stem cell research and the other involves work on conservation genetics, infectious disease (FIV, FeLV), and immunology projects with wild, non-domestic cats. Specifically, would you be working with fresh and frozen blood and tissue samples from cats, lions, pumas, Iberian lynx, Siberian tigers and/or leopards. Techinques you will learn include blood processing and hematology procedures, DNA extraction, PCR and molecular genetic analysis, and lymphocyte flow cytometry. You will have contact with live cats, so you should not be alergic to them. Also, you must not be squimish about working with blood and other dead tissues. The PIs on this project is a veterinarian. |
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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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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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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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Arthur Hurwitz |
LABORATORY OF MOLECULAR IMMUNOREGULATION |
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Phone: (301) 846-5443 |
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Email: hurwitza@ncifcrf.gov |
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Our laboratory studies the immune response to self-antigens as it pertains to tumor immunity and autoimmune disease. As it develops, the immune system tries to eliminate lymphocytes that recognize its own proteins or 'self-antigens' (referred to as self-tolerance). However, some T cells do escape this process and exist in the blood and lymph as tolerant T cells. We are studying how these T cells can become activated to elicit an anti-cancer immune response. We are also studying how these cells become aberrantly activated in autoimmune diseases like multiple sclerosis. |
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Anu Puri |
NANOBIOLOGY PROGRAM |
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Phone: (301) 846 5069 |
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Email: apuri@helix.nih.gov |
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Mission and Goals of CCRNP-Membrane Structure and Function(CCR Nanobiology Program)
Our research revolves around two major research areas.
(A) Viral Entry and Pathogenesis: Our goal is to find out how viruses "negotiate" the entry of their genetic material into the cell. Cells are surrounded by cell membranes, which impose insurmountable barriers for passage of undesirable molecules and particles into the cell. Viruses are enveloped by similar membranes. The virus has developed strategies to overcome these insurmountable barriers by designing envelope glycoproteins, which catalyze the fusion of viral and cellular membranes. We are specifically studying the mode of action of the envelope glycoproteins of retroviruses including the Human Immunodeficiency Virus (gp120-gp41). Using quantitative fluorescence spectroscopy and video microscopy we monitor kinetics of fusion between pairs consisting of intact virions or viral envelope glycoprotein-expressing cells and target cells bearing appropriate receptors. Using FRAP (fluorescence recovery after photobleaching) technique; we investigate receptor mobility in the plasma membrane and factors that restrict receptor movement. We examine role of receptor mobility on viral glycoprotein-mediated fusion. We are pursuing the molecular characteristics of fusion kinetics using a variety of biophysical, virological, molecular and cell biological techniques. The knowledge gained concerning fusion mechanisms is helpful in our endeavors to design reagents, which block fusogenic activity and delivery of the HIV-1 genome into the cell.
(B) Lipid based Nanoparticles for Targeted and Triggered Drug delivery of Anti-Cancer and anti-AIDS Drugs: Lipid-based nanoparticles (Liposomes) have been under investigation for decades for site-directed delivery of anti-cancer agents. However, application of liposomes for treatment of patients is limited due several factors including (a) poor understanding of mode of interactions of liposomes ex/in vivo, (b) their sub-optimal bio-distribution profile, and (c) unavailability of viable methods of liposome-disintegration for site-specific drug release. We are developing liposomes with targeting, imaging and optimal drug release capabilities to combat breast cancer and B-lymphomas. Our formulations will be labeled with optical or radioactive beacons for imaging of their distribution, and contain tumor-specific targeting agents for selective delivery. These nanoparticles will release the active drug “on demand� - at optimal time defined by real-time imaging and within a target volume only - by focused ultrasound-produced increase of the temperature in the tumor tissue. Such a drug delivery system will provide an innovative means for tumor specific delivery of therapeutic agents optimized for the breast cancer patient.
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Pradman Qasba / Marta Pasek |
NANOBIOLOGY PROGRAM |
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Phone: (301)-846-1934 or (301)-846-1933 |
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Email: pasekm@ncifcrf.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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Sudhir Kondapaka |
SCREENING TECHNOLOGIES BRANCH |
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Phone: (301) 846-1126 |
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Email: kondapakas@ncifcrf.gov |
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Cancer is treated by surgery, radiation, chemotherapy, hormones, and immunotherapy. Although surgery and radiation therapy destroy or damage cancer cells in a specific area, chemotherapy works throughout the body. Drugs used in chemotherapy can destroy cancer cells that have metastasized or spread to parts of the body far from the primary (original) tumor. At Screening Technologies Branch, one of the research goals is to identify the drug candidates for chemotherapy. In order to screen and identify the most effective anti cancer drugs among the several thousands of candidates, we develop or use existing drug screening models. In my laboratory, I employ various biochemical and molecular techniques to understand the effect of the selected drugs on various cancer cell lines. These drugs may stop or slow the growth or kill the cancer cells. These changes can be documented by measuring subtle changes in gene expression or protein levels. The intern would be exposed to various cell culture and biochemical methods to measure and identify these changes. The methods employed in lab range from simple as making reagents to complex molecular /biochemical techniques. My goal is to train the intern to understand the basic concepts of research and to gain hands on experience with techniques such as cell propagation/maintenance, protein extraction/estimation, gel electrophoresis (separation of proteins, or DNA or RNA), immunoblotting (identifying the protein of interest using immunological techniques), kinase assays (enzymatic reactions in-vitro), and data presentation. In addition to the exposure to various research techniques mentioned, the intern would be able to understand the biology of cancer. |
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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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Anne Monks / Nicole Reifsnider |
SCREENING TECHNOLOGIES BRANCH |
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Phone: (301)-846-5528/((301)) 846-(301)-846-1338 |
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Email: reifsnidern@ncifcrf.gov |
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The Laboratory of Functional Genomics, Screening Technologies Branch
This laboratory is focused on moving potential new anticancer compounds towards the clinic by trying to understand the mechanism underlying their ability to kill or prevent the growth of human tumor cells. We use a variety of gene-based techniques as tools to determine which genes are changed in response to a compound, and use this information to develop a hypothesis about how it is working, then design experiments to test the hypothesis. Techniques employed in the lab include whole genome microarrays, polymerase chain reaction assays,reporter gene assays and RNA inhibition, plus mmunofluorescent assays to visualize target proteins and western blots to quantitate them. A student working in the LFG will have the opportunity to learn several of the techniques and use them to assist with ongoing laboratory projects, and with experience, will collaborate with their mentor to develop an independent project commensurate with their skills and proficiency. |
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Robert Shoemaker / Giovanni Melillo |
SCREENING TECHNOLOGIES BRANCH |
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Phone: (301)-846-6845 and (301)-846-5050 |
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Email: melillog@ncifcrf.gov |
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My laboratory, Tumor Hypoxia Laboratory, Screening Technologies Branch, Developmental Therapeutics Program, SAIC Frederick, Inc, is involved in the discovery and development of novel approaches targeting hypoxic cell signaling for cancer therapy. |
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| SCIENCE APPLICATIONS INTERNATIONAL CORPORATION
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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. Chemists and biologists take advantage of the molecular based fine control mechanisms of the cell to design drugs that interfere with them. At our program we apply and develop software packages and strategies to better understand the mechanisms of function of biomolecules. To do this we use a range of tools including computer graphics, computer simulations and statistical analysis for the functional characterization of the molecules. These efforts are used to support the NCI to develop new treatments (e.g. new drugs) that by interacting with the biomolecules and interfere with their function may provide mechanisms of control that can thwart the progression of illness.
A student working in the ABCC will participate in projects to develop, validate or apply methods to simulate and analyze biomolecular properties in areas of Bioinformatics, Structural Genomics and Proteomics, Molecular Modeling, Homology Modeling, Molecular Dynamics or Quantum Chemistry applied to problems in Cancer biology in which the center plays a role supporting other groups at the NCI. |
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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 / Andrew Burnette |
BIOPHARAMACEUTICAL DEVELOPMENT PROGRAM |
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Phone: (301)-846-1469 and (301)-846-6064 |
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Email: aburnette@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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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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Ester Rozenblum / Lorraine Covell |
LABORATORY OF MOLECULAR TECHNOLOGY |
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Phone: (301)-846-5676 or (301)-846-1773 |
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Email: lcovell@ncifcrf.gov |
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Project #1: Molecular Biology Based Science Project: Intern will be involved in utilizing DNA sequencing and Microarray technologies directed toward cancer gene intervention in cancer treatment applications. Candidate will also be exposed to computerized data analysis.
Project #2: Scientific and technical expertise in the area of gene expression including mRNA isolation and purification from a variety of biological specimens for different species. The student will be trained in different technology platforms designed to monitor and quantitate+ gene expressions.
Project #3: Involves genetic mutation detection studies. The student will utilize PCR, gel chip electrophoresis, and DNA sequencing technologies to assist in identifying mutations in both cancer and immunodeficiency genes.
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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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Scott McNeil / Lisa Sheffield |
NANOTECHNOLOGY CHARACTERIZATION LABORATORY |
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Phone: (301)-846-6939 |
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Email: sheffieldl@mail.nih.gov |
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The NCL serves as a national resource and knowledge base for all cancer researchers to facilitate the translation of basic nanoscale particles and devices into clinical applications, thereby reducing suffering and death from cancer. As a part of its knowledge sharing mission, the NCL provides training opportunities to cancer researchers and students. In the past two years, the NCL has trained two summer students, one of whom obtained the training during two consecutive years. Both students are applying knowledge gained during internship at NCL in their current studies. Training at NCL was an important factor for one of the students in making the decision to apply for medical school and continue his research in clinical cancer nanotechnology. By providing comprehensive training to students, the NCL is contributing to the education of the next generation of nanotechnology researchers. |
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Douglas Kuhns |
NEUTROPHIL MONITORING LAB (NML) SAIC-FREDERICK, INC. |
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Phone: (301) 846-6378 |
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Email: dkuhns@mail.nih.gov |
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The Neutrophil Monitoring Laboratory (NML; Clinical Services Program) provides both clinical and basic research support to investigators in the Laboratory of Host Defenses (LHD) and Laboratory of Clinical Infectious Diseases (LCID), NIAID, NIH. The NML’s primary mission is to provide CLIA-certified studies of phagocytic cell function on samples isolated from patients with recurrent bacterial, mycobacterial and fungal infections (chronic granulomatous disease (CGD), Job’s syndrome, leukocyte adhesion deficiency, IFN-g receptor deficiency) as well as patients with abnormal inflammatory responses (patients with pyogenic sterile arthritis, pyoderma gangrenosum, and acne, i.e., PAPA syndrome). Included in NML’s repertoire of functional assays are determinations of reactive O2 species, staphylocidal activity, neutrophil adherence, release of granular proteins, alteration in surface marker expression, and chemotaxis. In addition, the NML performs Western blot analysis of neutrophil extracts to characterize the specific protein defect in CGD. |
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Dominic Esposito |
PROTEIN EXPRESSION LABORATORY |
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Phone: (301) 846-7376 |
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Email: domespo@ncifcrf.gov |
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The Protein Expression Laboratory is part of the Advanced Technology Program at SAIC-Frederick, Inc. Our job is to clone, express, and purify proteins of interest to NCI, NIH, and USAMRIID researchers. As part of this mandate, we are also continually in search of new technologies for producing active, well-behaved proteins, and interns in the lab will assist in projects designed to meet this goal. Our lab consists of multiple groups responsible for the various protein production activities, from cloning and bacterial expression at small scale, to insect and mammalian expression, to large-scale fermentation of yeast and bacteria, and finally, purification of the many proteins that come through our lab. Interns will have a chance to explore one or more of these areas and focus on a particular technology improvement to one of these processes. |
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| INTERNSHIPS IN SUPPORT OF SCIENCE/RESEARCH
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Galen Mayfield |
COMPUTER & STATISTICAL SERVICES |
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Phone: (301) 846-7361 |
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Email: gmm@css.ncifcrf.gov |
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Computer & Statistical Services (C&SS)provides comprehensive computer support for the NCI-Frederick.
The Web Design & Development Group within C&SS provides web programming, graphic design, and database development services to the NCI-Frederick. We develop a wide variety of web sites and applications ranging from graphic-design intensive "brochure" sites to full blown applications in C#.NET. The Web Design & Development Group works in ASP, ASP.NET, C#, Microsoft Visual Studio 2005, Dreamweaver, and Photoshop. We welcome any interns interested in learning or expanding their skills in web-based graphic design and/or application development. |
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