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Browsing by Author "Olson, Jacob"

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    4539 Building a Translational Science pipeline: The Indiana CTSI STEM K-12 Program
    (Cambridge University Press, 2020-07-29) Sanders, Elmer; Barth, Vanessa; Cruz, Leigh-Ann; Sherrer, Ilesha; Olson, Jacob; Speidell, Emily; Solis, Elvia; Harrison, Sharon; Hinshaw, Amy; McAteer, James A.; Anatomy, Cell Biology and Physiology, School of Medicine
    OBJECTIVES/GOALS: Develop strong network of science teachers interested in promoting scientific research to their students. Place students in an immersive summer research internship that, when possible, matches their career interests. Expose students to the numerous career paths within the STEM field. METHODS/STUDY POPULATION: The program recruits socio-economically disadvantaged students and provides them a stipend, and also accepts students who can participate unpaid. Local school teachers are engaged in a summer fellowship to learn biotechnologies and research. In Spring these teachers help recruit students and during the subsequent Fall help students with college and scholarship applications. Students are placed in a variety of laboratories within the Schools of Medicine, Science, Dentistry, Public Health, Informatics, Health and Human Sciences, Engineering and Technology, especially in biomedical engineering. Students are also placed in industry laboratories such as Eli Lilly and the Indiana Bioscience Research Institute. Long-term program follow-up is done through post-internship surveys to assess impact on graduate and professional school admission. RESULTS/ANTICIPATED RESULTS: Since the Indiana CTSI was established in 2008, 872 students have participated in the summer internship. 71% of past interns are underrepresented minorities in science or classified as disadvantaged by NIH criteria. 17% of students interned during grade 10, 72% during grade 11, and 11% during grade 12. 21% of students engage in the program for more than one year. 100% of past interns are currently enrolled in or have graduated college. Over 60% of those with a bachelors degree proceed to graduate and professional schools and over 80% stay in STEM related fields. These rates are equal for interns from underrepresented minorities or those classified as disadvantaged by NIH criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: Students engaged in the Indiana CTSI STEM program are progressing through the translational science pipeline based on their graduating from college and remaining in the STEM field.
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    Building a virtual summer research experience in cancer for high school and early undergraduate students: lessons from the COVID-19 pandemic
    (BMC, 2021-08-09) Corson, Timothy W.; Hawkins, Shannon M.; Sanders, Elmer; Byram, Jessica; Cruz, Leigh-Ann; Olson, Jacob; Speidell, Emily; Schnabel, Rose; Balaji, Adhitya; Ogbeide, Osas; Dinh, Julie; Hinshaw, Amy; Cummings, Laura; Bonds, Vicki; Nakshatri, Harikrishna; Ophthalmology, School of Medicine
    Abstract Background The COVID-19 pandemic posed a unique challenge for summer research programs in 2020, particularly for programs aimed at hands-on experience for younger trainees. The Indiana University Melvin and Bren Simon Comprehensive Cancer Center supports two pipeline programs, which traditionally immerse high school juniors, seniors, and early undergraduate students from underrepresented populations in science in hands-on projects in cancer biology labs. However, due to social distancing policies during the pandemic and reduction of research operations, these students were not physically allowed on campus. Thus, the authors set out to strategically pivot to a wholly virtual curriculum and evaluate the Virtual Summer Research Experience in Cancer outcomes. Methods The virtual program included four components: 1. a core science and professional development curriculum led by high school teachers and senior undergraduates; 2. faculty-delivered didactic sessions on cancer science; 3. mentored, virtual research projects with research faculty; and 4. online networking events to encourage vertical mentoring. Outcomes data were measured using a locally created 11-item Research Preparation Scale, daily electronic feedback, and weekly structured evaluation and feedback via Zoom. Results Outcome data suggested high self-reported satisfaction with the virtual program. Outcome data also revealed the importance of coordination between multiple entities for seamless program implementation. This includes the active recruitment and participation of high school teachers and further investment in information technology capabilities of institutions. Conclusions Findings reveal a path to educate and train high school and early undergraduate students in cancer research when hands-on, in-person training is not feasible. Virtual research experiences are not only useful to engage students during public health crises but can provide an avenue for cancer centers to expand their cancer education footprints to remotely located schools and universities with limited resources to provide such experiences to their students.
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    TONSL is an immortalizing oncogene and a therapeutic target in breast cancer
    (American Association for Cancer Research, 2023) Khatpe, Aditi S.; Dirks, Rebecca; Bhat-Nakshatri, Poornima; Mang, Henry; Batic, Katie; Swiezy, Sarah; Olson, Jacob; Rao, Xi; Wang, Yue; Tanaka, Hiromi; Liu, Sheng; Wan, Jun; Chen, Duojiao; Liu, Yunlong; Fang, Fang; Althouse, Sandra; Hulsey, Emily; Granatir, Maggie M.; Addison, Rebekah; Temm, Constance J.; Sandusky, George; Lee-Gosselin, Audrey; Nephew, Kenneth; Miller, Kathy D.; Nakshatri, Harikrishna; Surgery, School of Medicine
    Study of genomic aberrations leading to immortalization of epithelial cells has been technically challenging due to the lack of isogenic models. To address this, we utilized healthy primary breast luminal epithelial cells of different genetic ancestry and their hTERT-immortalized counterparts to identify transcriptomic changes associated with immortalization. Elevated expression of TONSL (Tonsoku Like, DNA Repair Protein) was identified as one of the earliest events during immortalization. TONSL, which is located on chromosome 8q24.3, was found to be amplified in ~20% of breast cancers. TONSL alone immortalized primary breast epithelial cells and increased telomerase activity, but overexpression was insufficient for neoplastic transformation. However, TONSL-immortalized primary cells overexpressing defined oncogenes generated estrogen receptor-positive adenocarcinomas in mice. Analysis of a breast tumor microarray with ~600 tumors revealed poor overall and progression free survival of patients with TONSL overexpressing tumors. TONSL increased chromatin accessibility to pro-oncogenic transcription factors including NF-κB and limited access to the tumor suppressor p53. TONSL overexpression resulted in significant changes in the expression of genes associated with DNA repair hubs, including upregulation of several genes in the homologous recombination (HR) and Fanconi Anemia pathways. Consistent with these results, TONSL overexpressing primary cells exhibited upregulated DNA repair via HR. Moreover, TONSL was essential for growth of TONSL-amplified breast cancer cell lines in vivo, and these cells were sensitive to TONSL-FACT complex inhibitor CBL0137. Together, these findings identify TONSL as a regulator of epithelial cell immortalization to facilitate cancer initiation and as a target for breast cancer therapy.
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