{"629081":{"#nid":"629081","#data":{"type":"event","title":"MS Defense by Kirti Karunakaran","body":[{"value":"\u003Cp\u003EIn partial fulfillment of the requirements for the degree of\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EMaster of Science in Biology\u003C\/p\u003E\r\n\r\n\u003Cp\u003Ein the\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EKirti Karunakaran\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EWill defend her thesis\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003E\u0026ldquo;\u003C\/strong\u003E\u003Cstrong\u003EAnalysis of the impact of a p53 mutation in a homogeneous genetic background\u0026rdquo;\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ET\u003C\/strong\u003E\u003Cstrong\u003Euesday, November 26th, 2019\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E12:00 PM\u003C\/p\u003E\r\n\r\n\u003Cp\u003EKrone Engineered Biosystems Building\u003C\/p\u003E\r\n\r\n\u003Cp\u003EChildren\u0026rsquo;s Healthcare Seminar Room 1005\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EThesis Advisor:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. John F. McDonald\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDr. Matthew Torres\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESchool of Biological Sciences\u003C\/p\u003E\r\n\r\n\u003Cp\u003EGeorgia Institute of Technology\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJ. Leonard Lichtenfeld, MD, MACP\u003C\/p\u003E\r\n\r\n\u003Cp\u003EDeputy Chief Medical Office\u003C\/p\u003E\r\n\r\n\u003Cp\u003EAmerican Cancer Society\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAbstract:\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECancer, known for its uncontrollable growth and spread of abnormal cells, has been associated with 10 specific hallmarks. Of the 10, two hallmarks (uncontrolled growth, inhibition of apoptosis or programed cell death) directly relate to p53, known as the guardian of the genome. P53, a tumor suppressor gene, works as a transcriptional regulator for cell cycle arrest and apoptosis. In more than 50% of cancers, p53 has been found to be heavily mutated making it an important gene to study.\u0026nbsp; While there have been several studies on p53 and its role in cancer, these studies do not recognize the potential impact of genetic background in which the p53 mutation occurs. Most studies on P53 function have been carried out in heterogeneous genetic backgrounds.\u0026nbsp; This is a potentially significant omission because previous studies have shown that genetic background can have a significant effect on the phenotypic consequences of cancer driver mutations. For example, several cancer driver mutations previously identified as biomarkers of cancer (e.g., BCR-ABL) have recently been found to be present in normal healthy individuals. Other more recent studies indicate that genetic background can have a\u003C\/p\u003E\r\n\r\n\u003Cp\u003Esignificant effect on the phenotypic impact of p53 mutations. The goal of my study was to utilize the CRISPR Cas 9 system to create a loss of function mutation in the p53 gene in a well characterized ovarian cancer cell line (HEY) and to evaluate the impact of this mutation on cell growth and apoptotic function in identical genetic backgrounds.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThis was done by creating a deletion in Exon 4 of p53 with the CRISPR Cas9 system, to establish p53 mutated but otherwise\u0026nbsp; \u0026ldquo;genetically identical\u0026rdquo; cell lines. Cell lines with functionally significant mutations using were identified and growth rates and drug sensitivity between the wildtype p53 (original cell line) and mutation p53 (CRISPR Mutated Cell Lines) were compared. The CRISPR-induced mutation was a deletion in codons 33-36 of exon 4 which decreased the length of the protein from 393 to 389 amino acids. Using the cell lines with the specified deletion, I compared the growth rates over 96 hours which demonstrated a significantly higher growth rate for the wildtype cells\u0026nbsp; relative to the mutated strains. Sensitivity assays to the chemotherapeutic drug cisplatin (a standard of care for ovarian cancer) demonstrated that the mutant cell lines had higher cell viability in comparison to the wildtype. The overall results demonstrated that mutations in p53 increase resistance to chemotherapy but a decrease cell proliferation. My results indicate that that mutations in p53 can have a significant effect on the cellular phenotype- even when genetic backgrounds are identical. Analysis of the cellular properties of these cells in subsequent generations may provide valuable insight into changes in genetic background that occur over time as an adaptive response to mutations in key cancer diver genes like p53.\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Analysis of the impact of a p53 mutation in a homogeneous genetic background\u201d"}],"uid":"27707","created_gmt":"2019-11-18 19:15:43","changed_gmt":"2019-11-18 19:15:43","author":"Tatianna Richardson","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2019-11-26T12:00:00-05:00","event_time_end":"2019-11-26T14:00:00-05:00","event_time_end_last":"2019-11-26T14:00:00-05:00","gmt_time_start":"2019-11-26 17:00:00","gmt_time_end":"2019-11-26 19:00:00","gmt_time_end_last":"2019-11-26 19:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"221981","name":"Graduate Studies"}],"categories":[],"keywords":[{"id":"111531","name":"ms defense"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}