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Browsing by Author "Cruz, Leigh-Ann"

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    11039 Indiana CTSI High-School STEM Summer Research Program: Future opportunities from a 2020 virtual program
    (Cambridge University Press, 2021) Sanders, Elmer; Cruz, Leigh-Ann; Speidell, Emily; Schnabel, Rose; Balaji, Adhitya; Hogarth, Elise; Miller, Jade; Vaides, Sofia; Allen, Matthew R.; Medicine, School of Medicine
    ABSTRACT IMPACT: The Indiana Clinical and Translational Sciences Institute K-12 STEM Outreach Program’s pivoted to a virtual program in summer 2020 which yielded novel approaches that could be retained in future years to extend the reach/impact of our pipeline program. OBJECTIVES/GOALS: Provide students with a meaningful and safe research experience during the COVID Pandemic. Develop new modules and approaches that could be delivered virtually. Engage students from communities that were not possible in previous years when in person meetings were required. METHODS/STUDY POPULATION: The program has historically supported over 100 high school students per year in a summer research internship for the last 5 years. Students are placed with academic research mentors in various Schools and Departments across the IUPUI campus, and also with industry laboratories. COVID-related restrictions required development of 100% virtual program. Key aspects of the virtual program included: cohort-based research mentor assignments with 1-4 mentees matched per research mentor, research projects that could be conducted virtually, heavy engagement of high-school teachers to facilitate the research experience with cohorts of mentees, a more rigorous virtual seminar series that included new modules such as COVID-specific programming and thus enhancing public education about COVID. RESULTS/ANTICIPATED RESULTS: The program served 130 students in summer 2020. We were able to recruit new faculty and industry mentors involved in data science research. As a result, we have now increased our mentor pool to serve more students in the future. Because student participation was virtual, we were able to accept students from further distances (up to 120 miles away) across the state. We were also able to accept local economically disadvantaged students that may have not been able to participate because of lack of reliable transportation. A positive unanticipated outcome was that mentees relationships with the mentors was established virtually thus increasing the potential for students to remain engaged in their research. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adapting to a virtual platform provided research experience to high school students during a time when traditional approaches were not possible. Given some research experiences do not require in-person activities, this newly established model could be used moving forward to allow more statewide engagement in research experiences.
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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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    HOXB13 Mediates Tamoxifen Resistance and Invasiveness in Human Breast Cancer by Suppressing ERα and Inducing IL-6 Expression
    (American Association for Cancer Research, 2013-09-01) Shah, Nilay; Jin, Kideok; Cruz, Leigh-Ann; Park, Sunju; Sadik, Helen; Cho, Soonweng; Goswami, Chirayu Pankaj; Nakshatri, Harikrishna; Gupta, Rajnish; Chang, Howard Y.; Zhang, Zhe; Cimino-Mathews, Ashley; Cope, Leslie; Umbricht, Christopher; Sukumar, Saraswati
    Most breast cancers expressing the estrogen receptor α (ERα) are treated successfully with the receptor antagonist tamoxifen (TAM), but many of these tumors recur. Elevated expression of the homeodomain transcription factor HOXB13 correlates with TAM-resistance in ERα-positive (ER+) breast cancer, but little is known regarding the underlying mechanism. Our comprehensive evaluation of HOX gene expression using tiling microarrays, with validation, showed that distant metastases from TAM-resistant patients also displayed high HOXB13 expression, suggesting a role for HOXB13 in tumor dissemination and survival. Here we show that HOXB13 confers TAM resistance by directly downregulating ERα transcription and protein expression. HOXB13 elevation promoted cell proliferation in vitro and growth of tumor xenografts in vivo. Mechanistic investigations showed that HOXB13 transcriptionally upregulated interleukin (IL)-6, activating the mTOR pathway via STAT3 phosphorylation to promote cell proliferation and fibroblast recruitment. Accordingly, mTOR inhibition suppressed fibroblast recruitment and proliferation of HOXB13-expressing ER+ breast cancer cells and tumor xenografts, alone or in combination with TAM. Taken together, our results establish a function for HOXB13 in TAM resistance through direct suppression of ERα and they identify the IL-6 pathways as mediator of disease progression and recurrence.
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    HOXB7 is an ERα cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance
    (American Association for Cancer Research, 2015-09) Jin, Kideok; Park, Sunju; Teo, Wei Wen; Korangath, Preethi; Cho, Sean Soonweng; Yoshida, Takahiro; Győrffy, Balázs; Goswami, Chirayu Pankaj; Nakshatri, Harikrishna; Cruz, Leigh-Ann; Zhou, Weiqiang; Ji, Hongkai; Su, Ying; Ekram, Muhammad; Wu, Zhengsheng; Zhu, Tao; Polyak, Kornelia; Sukumar, Saraswati; Surgery, School of Medicine
    Why breast cancers become resistant to tamoxifen despite continued expression of the estrogen receptor alpha (ERα) and what factors are responsible for high HER2 expression in these tumors remains an enigma. HOXB7 ChIP analysis followed by validation showed that HOXB7 physically interacts with ERα, and that the HOXB7-ERα complex enhances transcription of many ERα target genes including HER2. Investigating strategies for controlling HOXB7, our studies revealed that MYC, stabilized via phosphorylation mediated by EGFR-HER2 signaling, inhibits transcription of miRNA-196a, a HOXB7 repressor. This leads to increased expression of HOXB7, ER-target genes and HER2. Repressing MYC using small molecule inhibitors reverses these events, and causes regression of breast cancer xenografts. The MYC-HOXB7-HER2 signaling pathway is eminently targetable in endocrine-resistant breast cancer.
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