Brigham and Women's Hospital
Description GENERAL SUMMARY\/OVERVIEW STATEMENT: As a motivated technical research assistant level 1 (TRA1), the candidate will work closely with Dr. Ben Gewurz, Assistant Professor in the Brigham and Women\u2019s Hospital Department of Medicine\/Division of Infectious Disease and Associate Chair of the Graduate Program in Virology of Harvard Medical School. Dr. Gewurz is also an associate member of the Broad Institute of Harvard and MIT. The candidate will work closely with Dr. Gewurz to perform CRISPR genetic and proteomic analysis of Epstein-Barr virus (EBV) driven B cell cancers. Epstein\u2013Barr virus (EBV) was the first human tumor virus to be identified. EBV causes ~200,000 human cancers annually. EBV is associated with multiple human malignancies, including lymphomas of patients with HIV or who have had organ transplantation, Burkitt lymphoma (BL), Hodgkin lymphoma, T- and NK-cell lymphomas, nasopharyngeal and gastric carcinomas [56\u201361]. Many EBV-driven cancers remain incurable, and improved diagnostic and therapeutic approaches are needed. Key aspects of EBV cancer biology can be modeled in the lab. EBV transforms resting, human B cells into rapidly growing, immortalized lymphoblastoid cell lines (LCL), which are models for EBV-driven lymphomas. Studies of how EBV causes this dramatic transformation have lead to major breakthroughs in immunology and virology. Yet, many fundamental aspects of EBV biology remain to be molecularly defined. The candidate will join ongoing studies to study how EBV promotes human cancers, and how we can exploit this knowledge to treat EBV-associated cancers. They will join ongoing efforts to use CRISPR genetic and proteomic approaches to study key aspects of the EBV lifecycle, including efforts to reprogram EBV genome expression programs. CRISPR is a powerful tool for genetic analysis in EBV-transformed cells that has recently become available. CRISPR genome engineering is for the first time allowing us to use genetic analysis to ask fundamental questions in EBV biology. We enjoy a close collaboration with the Broad Institute of Harvard and MIT, where pioneering discoveries in CRISPR technology are being made at a rapid pace. This relationship is allowing us to use cutting-edge CRISPR\/Cas9 tools for genetic analysis of the EBV and host genomes. We are at the leading edge of applying new CRISPR technologies to studies of the EBV\/host relationship. We are using genome-wide CRISPR screens to study how host factors control key aspects of the EBV lifecycle and to identify new therapeutic targets. These include investigation of EBV-induced host dependency factors that enable transformed B-cell growth and survival, that reprogram EBV latency states, and that control the latency\/lytic switch. We are also using CRISPR to identify mechanisms by which EBV evades key immune pathways, including subversion of the PDL1\/PD1 T-cell immune checkpoint pathway, which is proving to be an important therapeutic target. We also use CRISPR-activation and CRISPR-inhibition approaches to reprogram the viral and host genome. We also use multiplexed tandem-mass spectrometry to identify how EBV remodels the B-cell proteome during lytic versus latent B-cell infection. We are interested in defining EBV rewires host metabolic pathways to support lytic replication versus B-cell growth transformation. More information is available at http:\/\/gewurzlab.bwh.harvard.edu\/ and https:\/\/www.hms.harvard.edu\/dms\/virology\/fac\/Gewurz.php and http:\/\/www.dfhcc.harvard.edu\/insider\/member-detail\/member\/ben-gewurz-md-phd\/ The candidate will perform laboratory techniques, including tissue culture of cell lines, transient DNA and RNA transfection of cell lines, immunoprecipitation, Western Blot, recombinant DNA work. The candidate will take on increasing independence. A two-year commitment is strongly preferred. Prior trainees who have held this position have co-authored multiple manuscripts, including as first authors. They have had the opportunity to present their work at our group meetings and at national meetings. The last four individuals who held this position have matriculated at: 1) Harvard Medical school Graduate Program in Virology; 2) Tri-institutional (Cornell\/Rockefeller\/Sloan Kettering) MD-PhD program; 3) University of Pennsylvania Biological Sciences Graduate Program; 4) Yale Medical School MD program. PRINCIPAL DUTIES AND RESPONSIBILITIES:\u00a0 The following will be taught and then performed independently: 1. Tissue culture of cell lines 2. Transfection of cell lines with DNA and RNA 3. Immunoprecipitation and Western Blot 4. Recombinant DNA work 5. CRISPR\/Cas9 genetic analysis, including construction of knockout cell lines and participation in genome-wide CRISPR screens. 6. Biochemical purification of proteins from cells 7. Construction of cell lines that stably express epitope-tagged proteins 8. Laboratory jobs, as assigned by the Gewurz laboratory. 9. Attend weekly laboratory and floor meetings, and present data to the group The following will be performed with Dr. Gewurz: 1. Experimental design 2. Taking on increasing independence in performing biological experiments 3. Assist with analysis of experimental data using basic statistical methods 4. Discuss progress of work on a daily basis. Qualifications Must have completed an undergraduate degree program in biological sciences, biochemistry, or chemistry at the time of starting this position. Prior laboratory experience in molecular biology or biochemistry is preferred. SKILLS\/ABILITIES\/COMPETENCIES REQUIRED: \u2022 Excellent organizational skills \u2022 Detail oriented \u2022 Highly motivated, enjoys multi-tasking \u2022 Computer literacy, including Microsoft Excel, Powerpoint \u2022 Ability to methodically record data and to analyze data using basic statistics \u2022 Ability to perform a variety of outine tests and prioritize work \u2022 Good interpersonal and communication skills \u2022 Ability to demonstrate professionalism WORKING CONDITIONS : Candidate will be working on the 8th floor of the 181 Longwood Avenue MCP building, in the heart of the Longwood Medical area. There will be opportunities to attend science seminars at Harvard and the Broad. The work environment is a biological lab. Safety protocols are closely followed. Candidate will have their own desk, bench and computer.\u00a0EEO Statement Brigham and Women\u2019s Hospital is an Equal Opportunity Employer. All qualified applicants will receive consideration for employment without regard to race, sex, color, religion, national origin, sexual orientation, protected veteran status, or on the basis of disability.
Brigham and Women's Hospital
Website : http://www.brighamandwomens.org
Boston's Brigham and Women's Hospital (BWH) is an international leader in virtually every area of medicine and has been the site of pioneering breakthroughs that have improved lives around the world. A major teaching hospital of Harvard Medical School, BWH has a legacy of excellence that continues to grow year after year. Brigham and Women’s Health Care – the parent corporation for Brigham and Women’s Hospital, Brigham and Women’s Faulkner Hospital and the Brigham and Women’s Physician Organization – includes 150 outpatient practices with over 1,200 physicians. We serve patients from New England, throughout the United States, and from 120 countries around the world.BWH is an internationally-known referral center for the most complex cases in nearly all areas of medicine. In fact, US News and World Report consistently ranks us among the nation’s top ten hospitals and in the top ten for specific specialty areas that in 2015 include cancer, cardiology and heart surgery, diabetes and endocrinology, geriatrics, gynecology, nephrology, neurology and neurosurgery, orthopedics, pulmonology, and rheumatology. The BWH name is a reflection of our history. In 1980 three of Boston’s oldest and most prestigious Harvard Medical School teaching hospitals - the Peter Bent Brigham Hospital, the Robert Breck Brigham Hospital, and the Boston Hospital for Women – merged to form Brigham and Women’s Hospital. As a national leader in improving health care quality and safety, we have helped to develop some of the industry’s best practices including computerized physician order entry (CPOE) to prevent medication errors. The CPOE is now a nationally-accepted safety practice. The BWH Research Institute (BRI) is one of the most powerful biomedical research institutes in the world and the second largest recipient of National Institutes of Health (NIH) funding among independent hospitals in the United States. With over $640 million in total research funding and over 1,000 principal investigators, BWH has long had great success in research as measured by the number of important discoveries made, the size and scope of its research portfolio and the volume of publications annually.