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.

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.

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.

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.

H

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.

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

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

Melissa Porter

Research Goals/Purpose:

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

Training Plan:

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

Anu Puri

Research Goals/Purpose:

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.

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.

T

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.

W

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.

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).