Potential Mentors for 2018 - 2019

A

Jairaj Acharya

Laboratory of Cell and Developmental Signaling

Research Goals/Purpose:

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

Training Plan:

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

Jairaj Acharya

Research Goals/Purpose:

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

Training Plan:

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

Roxanne Angell

Research Goals/Purpose:

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

Training Plan:

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

B

Kajal Biswas

Research Goals/Purpose:

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

Training Plan:

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

Frank Blanchard

Research Goals/Purpose:

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

Training Plan:

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

C

Ravindra Babu Chalamalasetty

Research Goals/Purpose:

Wnts are powerful secreted signaling molecules required for stem cell potency and cell-fate decisions in embryonic stem cells, early embryonic development and tumorigenesis. The current focus of our laboratory is to identify the key lineage determinants downstream of Wnt signaling pathway during embryonic stem cell differentiation.

Training Plan:

The Student will be trained under my supervision and will learn the concepts of the project. They will be taught basics of Molecular Biology, Biochemistry, Cell Biology, Embryonic stem cell culture system and bioinformatics. They will then participate in independent projects with the expectation of experimental set-up, data analysis and record keeping.

D

Ira Daar

Laboratory of Cell and Developmental Signaling

Research Goals/Purpose:

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

Training Plan:

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

Chengkai Dai

Research Goals/Purpose:

Elucidation of proteomic instability of cancer and tumor-associated amyloids, and explore novel anti-cancer therapeutic strategy---disrupting cancer proteome homeostasis, or proteostasis.

Training Plan:

Visualization of HSF1 activation in cancer cells by Proximity Ligation Assay.

Natalia De Val Alda

Research Goals/Purpose:

CMM offers investigators access to unique expertise and EM technologies that allow our partners to explore new avenues of research in order to enhance the knowledge of biological systems. Our lab provides high-resolution Transmission Electron Microscopy (TEM) with the use of our 300kEV Titan Krios electron microscope coupled with a direct detector k2 camera. Supporting equipment includes 2 FEI Vitrobot, as well as several FEI scopes to access sample quality. The research goals for the WHK student will be to be able to understand all the EM pipeline, from sample preparation to data collection. The purpose will be for the student to become an independent user in our lab.

Training Plan:

The training plan is to become familiar with all the main procedures used in Electron Microscopy. He or she will be mainly working with myself as well as Htet Khant. He or she will learn how to work with cells, viruses as well as protein-protein complexes. This will give him/her a broad spectrum of the type of samples we work with at the CMM. He or she will focus mainly in the TEM technique. After the two months training, he or she will be able to do some of the sample preparations and data collection by himself/herself. Of course, he or she will be always monitored by me or Htet. He or she will start with some theoretical training about what is a TEM scope (this will take one or two days) and after that he or she will start working on the bench with Htet. At the end of his/her training, he or she will understand the main points of the EM technique and being able to prepare some of the easy samples by himself/herself.

James Dunleavey

Research Goals/Purpose:

Student will learn molecular biology techniques including DNA isolation and PCR analysis, protein biology techniques including Western blotting, and will assist mentor in understanding tumor biology with an emphasis on the stromal contribution to tumor growth. Student will learn about mouse genetics, tumor biology, mouse cell tissue culture, and a variety of molecular biology techniques.

Training Plan:

Student will learn basic laboratory practice and techniques, following which will be expected to transition to cell culture and protein biology, with an emphasis on protein-protein interaction and Western blotting. Student will also be given opportunity to learn advanced techniques, including microscopy, following mastery of initial protocols.

E

Rebecca Erwin-Cohen

Research Goals/Purpose:

Infertility (either for first births or second births) is rising in the US. Using our mouse model of chronic inflammation, we are looking at ways that inflammation may be impacting infertility.

Training Plan:

As a contributing member of our team, the student will learn and routinely perform PCR (including DNA and RNA extraction/purification) to verify genotype of transgenic mice. The student will learn tissue culture and several assays including assays for nitric oxide production, cytokine, and sex hormone detection, using state of the art equipment and techniques.

F

John Fenimore

Research Goals/Purpose:

We have been working on various aspects of the immune system’s relationships with other biological systems including the tumor environment, brain, musculature, liver and the host microbiome. Our lab's primary area of interest is the interactions of IFN-gamma and host tissues in an attempt to understand the processes and mechanisms that affect immunity. We are interested in using IFN-g as a potential immunotherapeutic treatment of cancers and increasing the efficacy of these therapies with other treatments. We wish to examine the effects of interferon gamma and examine the mechanisms and effects of elevated constitutive exposure of pro-inflammatory cytokines while that emulate those of patients with a lupus like disease.

Training Plan:

We would like to have our student learn DNA and RNA extraction techniques, PCR, as well as cell culture methods. Learn microbead separation techniques and assay techniques such as ELISA.

H

Megan Hess

Research Goals/Purpose:

We study the relationship between the immune system and other biological systems such as the tumor environment, brain, musculature, liver and the host microbiome. The primary focus of the lab is the cytokine IFN-gamma. IFN-gamma is a protein that modulates the immune system and has roles in intracellular infections and inflammation as well as autoimmunity. We are interested in the mechanisms IFN-gamma uses to alter host immunity and how constant expression of IFN-gamma leads to a lupus-like disease in our mouse model. We are also interested in using IFN-gamma as a potential treatment for cancers in combination with existing therapeutic drugs.

Training Plan:

We would like to have our student learn DNA and RNA extraction techniques, PCR, as well as cell culture methods. Learn microbead separation techniques and assay techniques.

Sarah Hooper

Research Goals/Purpose:

1. The CRTA student will have opportunities to learn about occupational health medicine and learn the following skills including: administrative duties include: answering telephones, greeting patients, updating and filing patients' medical records, filling workers compensation insurance forms, handling correspondence, scheduling appointments, arranging for referrals and laboratory services.Clinical duties include: taking medical histories and recording vital signs, explaining treatment procedures to patients, preparing patients for examination, and assisting the nurse practitioner during the examination.

Training Plan:

In addition to reviewing and practicing skills, the CRTA will choose one of the occupational health medicine topics below and research the evidence based medicine surrounding the practice to improve the current occupational practice. They will present to the professional staff at a staff meeting. A. Travel Medicine Topic B. Assessment Topic C. Evidence Based Medicine on occupational health topic 2. Explore continuous quality improvement and learn and complete a audit of the electronic medical record. 3.Become more confident about decision making and triage under the direct supervision of licensed nursing staff. 4. Writing an occupational health article for the Poster. 5. Plan and execute a Wellness event for the campus.

Xiaojun Hu

Research Goals/Purpose:

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

Training Plan:

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

J

Brad Jakubison

Research Goals/Purpose:

The research objective is to train students in hematology, molecular biology, and cancer biology. Student will learn techniques utilizing DNA, RNA, and protein based assays. The focus of the project is on hematopoietic stem cell maintenance and biology. Specifically, this project studies the molecular mechanisms of ID2.

Training Plan:

The student will initially learn the basics of molecular biology. The student will eventually transition into cell based assays and histology. Lastly, the students will perform immunofluorescence and flow cytometry assays. Collectively, this opportunity will give the students a well-rounded experience of a research laboratory.

Xiaoli Jiao

Research Goals/Purpose:

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

Training Plan:

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

K

Suhas Kharat

Research Goals/Purpose:

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

Training Plan:

Similar to Research goals.

Kimberly Klarmann

Research Goals/Purpose:

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

Training Plan:

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

Jay Knight

Research Goals/Purpose:

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

Training Plan:

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

L

Moonsup Lee

Research Goals/Purpose:

Ciliogenesis is a critical process in early development and organogenesis. Using Xenopus laevis (African Clawed frog) as a model system, I study on molecular mechanism of ciliogenesis and signaling pathway required for ciliogenesis. I expect this study contributes to understanding ciliogenesis in terms of mechanistic aspects.

Training Plan:

A student will learn experiments releted to biochemistry and molecular biology such as co-immunoprecipitation, immuno-blotting, PCR, bacterial transformation, cell culture and DNA prep.

M

Buyong Ma

Research Goals/Purpose:

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

Training Plan:

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

Chris McLeland

Research Goals/Purpose:

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

Training Plan:

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

Wendell Miley

Research Goals/Purpose:

Developing, optimizing, and validating a test for detecting human IgM antibodies against Kaposi Sarcoma Herpes Virus (KSHV) antigens.

Training Plan:

Kaposi Sarcoma Herpes Virus (KSHV), also known as HHV-8, is the causitive agent for a cancer called Kaposi Sarcoma. Our laboratory, the Viral Oncology Section (VOS), does basic research on KSHV. The successful student will contribute to developing, optimizing, and validating a multiplex assay for the detection of human IgM antibodies against KSHV. IgM is a class of antibodies made during the earliest stages of viral infection.

N

Kedar Narayan

Research Goals/Purpose:

At the Center for Molecular Microscopy, high-resolution 3D ultrastructural imaging of large cellular and tissue samples is carried out primarily by Focused Ion Beam Scanning Electron Microscopy (FIB-SEM). Recent and continuing technological developments in FIB-SEM now allow us to image a wide variety of biological specimens in 3D and at nanoscale resolutions. Segmentation of these large image datasets to extract features of interest reveals new biology and helping confirm hypotheses in a variety of systems, however, this is a manual and limiting step. In this research goal, we aim to set up streamline manual and semi-automated segmentation of FIB-SEM datasets with the aim of visualizing biological structures in 3D. Additionally, we aim to feed these "ground truthed" segmentation datasets to train a separately designed neural network, with the ultimate goal of accurate automated segmentation of FIB-SEM data.

Training Plan:

The WHK SIP students will be trained by CMM personnel to use segmentation software, and will be given training FIB-SEM datasets to practice and sharpen their skills. The CMM is highly collaborative, so there is a variety of interesting projects that require segmentation of specific cellular features, such as mitochondria, nuclei, etc. The students will be expected to segment out these features as required, both for direct analysis, as well as for training the neural network.

O

Barry O'Keefe

Research Goals/Purpose:

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

Training Plan:

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

P

Lorena Parlea

Research Goals/Purpose:

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

Training Plan:

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

Melissa Porter

Research Goals/Purpose:

Goals The overall goal of this internship is for the WHK intern to obtain an appreciation for communicating scientific discovery in plain language to the larger public. He/she will leave the internship with a greater understanding of how to communicate complex scientific topics to a lay audience. The intern will develop specific skills sets throughout the course of the internship to achieve this goal. The skills will include but are not limited to the following: • Written communication o The intern will write a series of articles highlighting various researchers at the NCI at Frederick for the Poster which will help the WHK intern experience the variety and breadth of science at the NCI at Frederick. He/she will have the opportunity to explore various areas and interests in science. Additionally, this will also help the student develop writing skills, including writing in plain language. • Oral Communication o The WHK intern will be responsible for developing and presenting a scientific research poster to a public audience several times through the course of the internship. These occurrences will give him/her the opportunity to orally present the various ways of communicating scientific discoveries to the public. It will also give the intern an opportunity to accept constructive feedback from peers and mentors about his/her presentation skills. • Public Affairs & Outreach o The WHK intern will assist with various outreach events throughout the course of his/her time in the internship. The intern will gain experience with developing programs, handling professional interactions with the public, and advocating and promoting the proper communication of complex scientific discoveries and STEM education for Frederick County youth. The opportunities will enhance experiential learning for the WHK student in his/her develop in scientific communication. Timeline 1st quarter ( May/June – August/Sept) – learn the various tools for communicating with the public and within the NCI at Frederick. Develop a poster for presentation at various poster days. 2nd quarter (Sept/Oct. – Nov/Dec) – Examine the effect of mis-information on health outcomes. For example, the HPV vaccination rates or anti-vaccination autism connection and the impact on vaccination rates. 3rd quarter (Dec/Jan.- March/April) – examine potential collaborators to help identify and examine the data collected (for example, the scientific library or bioinformatics groups) 4th quarter (March/April- May/June) – give final presentation on outcomes of project, examine any potential publication forums.Help to develop the WHK student incoming/outgoing ceremony for enhancing the student experience in the WHK program.

Training Plan:

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

Anu Puri

Research Goals/Purpose:

Main Goal: "Development of Tunable & On-demand Deliverable RNAi-based Nanotherapeutics for Treatment of Cancer" Specific Aims: -Development and characterization of siRNA-loaded nanoparticles (siRNA-NPs) -Development of photoactivatable siRNA-NPs -Evaluation of efficacy of siRNA-NPs in cell culture systems

Training Plan:

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

S

Bruce Shapiro

Research Goals/Purpose:

The study of the structure and function of ribonucleic acids (RNA) is an important area of biological and computational research. Understanding of the role that these molecules play in a cell's life cycle has become very important. The various types of RNAs that control a cell's normal function are tRNA, mRNA, rRNA and most recently discovered RNAi. RNAs, such as the viruses HIV, polio and the common cold, to name a few, are detrimental to living organisms. Our research deals with the basic biological concepts associated with RNA structure function relationships and also the development of computational and experimental methodologies and tools to unravel these relationships. Included are algorithms for RNA folding and analysis of the folding results. We also do molecular mechanics and molecular dynamics simulations on RNA and RNA/protein complexes to understand atomic scale interactions that determine the functionality of these molecules. We also explore ways of using RNA structure/function relationships to define RNA-based nanobiology entities. These RNA based structures have the potential for therapeutic uses amongst other possibilities. Several software approaches are being explored and developed to assist in the design of these RNA-based therapeutic nanoparticles.

Training Plan:

Student intern will be working on projects related to computational approaches to RNA structure analysis. Some potential projects are enumerated below: 1) Apply several software tools developed by our laboratory, and others to explore RNA structure and function. 2) Carry out molecular mechanics and molecular dynamics simulations of RNA using high performance computing facilities. 3) Develop computer algorithms for improving RNA structure prediction and analysis methods for both secondary and tertiary structure. 4) Searches for interesting functional features in RNA sequences and their structures. 5) Find and understand RNA folding patterns using various algorithms. 6) Enhance and help develop new algorithms for our computational RNA-based software. This includes adding features for prediction and characterization of our RNA nanobiology structures for potential therapeutic use. 7) Apply coarse-grained simulation techniques to RNA nano constructs to understand their dynamic behavior. 8) Help to develop and maintain our web servers. Specific steps in the project will involve: 1) Library work to find and read relevant papers on RNA structure, nanobiology, computational and experimental approaches. 2) Familiarization with computers and software in our lab and experimental techniques. 3) Learn about software development methods and experimental techniques used in our laboratory. 4) Writing and/or modifying software as the need arises. 5) Running various software packages to analyze and characterize structural features. 6) Attending seminars when possible. 7) Collaboration with other scientists. 8) Writing results in scientific papers.

Dhirendra Simanshu

Research Goals/Purpose:

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

Training Plan:

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

Shweta Singh

Research Goals/Purpose:

The Student will have the opportunity to learn about genetically modified mouse models along with basic techniques for handing DNA, RNA and protein. He/She will also be able to learn about basic molecular biology techniques and hematopoietic stem and progenitor cells regulation.

Training Plan:

The Student will start by performing molecular biology techniques like DNA isolation and PCR and then exposed to cells isolation from mouse bone marrow, flow cytometry and immunoflorescence.

Shree Ram Singh

Research Goals/Purpose:

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

Training Plan:

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

Hongyan Sui

Research Goals/Purpose:

LHRI (Laboratory of Human Retrovirology and Immunoinformatics) has collaborated with the National Institute of Allergy and Infectious Diseases (NIAID) in NIH and supported antiviral clinical trials for patients infected with HIV or other viruses by performing immunological, virological and bioinformatics methods. The immune system is typically divided into two categories: innate and adaptive immune responses. The innate immune responses are the first line of defense encountered by invading infectious agents, e.g. DNA, RNA, polysaccharide or proteins derived from bacteria or viruses. To detect the invading agents (pathogens), cells in our body possess sensors (receptors) for the agents on the cell surface or in the cytosol of the cells. Upon infection, the pathogens are detected by the sensors and trigger the innate immune responses such as the secretion of type-I interferon (IFN), an anti-viral protein. LHRI has discovered for the first time that Ku70 (a known nuclear protein which plays a key role to repair damaged DNA in the nucleus) is a novel cytosolic DNA sensor that produces Type-III IFN rather than Type-I IFN from virus infected cells [X. Zhang, et al. and T. Imamichi, The Journal of Immunology 186 (2011)] and in the last year, we reported that Ku70 relocates from the nucleus to the cytosol upon virus infection and induces the Type-III IFN [H. Sui, et. al and T. Imamichi, Science Signaling 10, (2017)]. We have currently investigated the molecular mechanism of this change in the location of Ku70. The finding from this study may shed light on a new physiological cell-signaling pathway in innate immune responses and biological cell responses.

Training Plan:

The student will be trained to learn how to perform general lab experiments such as western blot, RNA extraction, real time RT-PCR, DNA gel electrophoresis, cell culture and confocal fluorescence microscopy and will be involved in the current projects to assist us in completion of some basic experiments. The student will get a chance to present his/her work and participate in lab meetings. The goal is to help the student gain insight into biology research, enhance critical scientific thinking and learn to scientific interpretation of experimental results.

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Nadya Tarasova

Research Goals/Purpose:

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

Training Plan:

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

Pedro Torres-Ayuso

Research Goals/Purpose:

Identification of novel druggable alterations in lung squamous cell carcinoma. Lung squamous cell carcinoma is the second most frequent form of lung cancer, treatments for this disease are limited to chemotherapy and radiotherapy. The goal of this project is to investigate novel protein kinases that could become potential pharmacological targets for lung squamous cell carcinoma patients.

Training Plan:

The student will get insight into the field of cancer cell signaling. In partnership with a postdoctoral fellow, the student will participate in bench top molecular biology (such as molecular cloning, mutagenesis, sequencing, and plasmid preparation, RNA extraction and qPCR), followed by cell biology (cell culture, cell growth assays, DNA transfections and western blot analysis). The student will be also trained to present their work in lab meetings and in written format.

Yien Che Tsai

Laboratory of Protein Dynamics and Signaling

Research Goals/Purpose:

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

Training Plan:

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

Yien Che Tsai

Research Goals/Purpose:

Some pathogenic proteins are extremely stable in cells, causing prolonged disease. One example is the catalytic subunit of botulinum toxins. Based on recent understanding of how these proteins achieve their extraordinary stabilty, this project explores a novel approach to speed up their degradation using targeted nanobodies.

Training Plan:

Students will learn cloning, protein chemistry and cell biology.

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Abdul Waheed

Research Goals/Purpose:

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

Training Plan:

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

Jiming Wang

Research Goals/Purpose:

The student is expected to learn the concept of the initiation of inflammatory responses, which are associated with cancer. Leukocyte infiltration is a hallmark at the sites of inflammation and is mediated by pathogen and host produced cell motility inducers, namely chemoattractants. These molecules are recognized by a family of G-protein coupled receptors expressed on leukocytes. The student is expected to understand the interaction of chemoattractants and receptors determines the degree of host responses.

Training Plan:

The student will learn how to measure leukocyte motility on bench top and understand that each chemoattractant will activate one or more receptors transfected into cell lines, thereby experiencing the concept of specificity of chemattractants and receptors and their ability to mediate the migration of specific cell types.

Rex Warnert

Research Goals/Purpose:

The NCI at Frederick Information Security & Compliance Office (ISCO) addresses information security for all of the information and information systems that support the operations of NCI at Frederick, including those managed by contractors and other organizations. It provides a foundation for the management of NCI at Frederick security operations, and it provides organization-wide common security controls that complement security controls in place for individual information systems and information assets.

Training Plan:

The student will assist with various operational and continuous monitoring security tasks. The projects will include being hands on with some of the security tools and interacting with system owners with the assistance of the mentor.

Christopher Westlake

Research Goals/Purpose:

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

Training Plan:

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

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Acong Yang

Research Goals/Purpose:

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

Training Plan:

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

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Paul Zakrevsky

Research Goals/Purpose:

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

Training Plan:

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