Meet the Researcher - Faith Prochaska
MEET THE RESEARCHER LIVE ON APRIL 28
Breakout Room: 2
Researcher Name: Faith Prochaska
Title of Research: Effects of Treatment with the DYRK1A Inhibitor CX-4945 on Down Syndrome Phenotypes in Ts65Dn Mice
Division Representing: Social Sciences
Institution: Indiana University-Purdue University Indianapolis
Institution Location: Indiana
Home State: Indiana
District Number: 7
Advisor/Mentor: Randall Roper, Charles Goodlett, Laura Hawley
Funding Source: Summer 2019 IUPUI Undergraduate Research Opportunities Program, Summer 2020 IUPUI Neuroscience Experience and Undergraduate Research Opportunities Program; NIH
I work part time as the Undergraduate Assistant Director of the IUPUI Speaker's Lab through the IU School of Liberal Arts. I started working in January of 2018 and was quickly and frequently promoted. This position involves acting in an administrative capacity to supervise upwards of 20 peers in helping students with communication and public speaking, leading an executive team that creates and manages a worldwide service for those interested in communication and public speaking, as well as directing the longest-running event on IUPUI's campus: The IU School of Liberal Arts' Biannual Speech Night.Since the Spring of 2018 I have been on the Executive Board for Alpha Lambda Delta (ALD) and Phi Eta Sigma (PES), two National Honors Societies, first as Vice President and now as a student advisor.My freshman year (fall 2017-spring 2018) I volunteered with Ronald McDonald House Charities. After moving, I now volunteer at Heaven After Hell Rescue after starting in the spring of 2018. I perform normal kennel duties at least once a week in addition to helping with fundraiser planning, organization, and execution. I also volunteer with members of ALD, PES, IUPUI Honors College Chancellor's Scholars Program, and the IUPUI Cox scholars program. In efforts to continually grow as a person and develop my skillset I also have participated in multiple mentoring programs: Advancing Women Mentoring Program, American Physician Scientists Association Mentoring Program, and the Project Grow: Student Mentoring Program. I have also won the Baccalaureate Outstanding Research Award from the Biology Department at IUPUI.
As a part of ALD I presented at the Annual National Conference over successful strategies implemented at our chapter.In all research presentations I was the lead student author under the supervision of PhD candidate Laura Hawley, M.A. and with the help of my PI Dr. Randall J. Roper and Dr. Charles Goodlett. All of my presentation experience has been focused on my main research study into the Effects of Treatment with the DYRK1A Inhibitor CX-4945 on Down Syndrome Phenotypes in Ts65Dn Mice. I presented preliminary research as a poster twice in 2019, at the Summer IUPUI Undergraduate Center for Research and Learning Symposium and in the Fall IU Undergraduate Research Conference. After developing the study I was able to present posters again in the Spring of 2020 before Covid-19 interrupted conferences: IUPUI Research Day, Indiana Physiological Society Conference, Sigma Xi Virtual Student Research Conference. At the Indiana Physiological Society Conference I was awarded the Second Place Undergraduate Poster Award. I was also selected to give an oral presentation at the Butler Undergraduate Research Conference before it was cancelled due to Covid-19. This fall I was chosen as a virtual oral presenter in the IU Undergraduate Research Conference.Two additional presentations have had my name on them, for a project that I assisted with and analyzed all data for. My results were then separated by sex and split between two other student presenters. I helped create the graphs and posters for both individuals' presentations but presented my own work at that conference.
Significance of Research:
Phenotypic rescue by means of protein inhibition is a possible treatment for the cognitive and physical impairments associated with Down syndrome (DS). The Ts65Dn mouse model exhibits similar phenotypes to individuals with DS as a result of the triplication of approximately one-half of the genes found on human chromosome 21 (Hsa21), one of which is Dual-specificity Tyrosine Phosphorylation-regulated Kinase 1 (DYRK1A), normalization of which could be a valid treatment to correct DS phenotypes. Previous results in our lab have shown DYRK1A overexpression in Ts65Dn compared to euploid mice at postnatal day (P) 15 for male and P18 for female Ts65Dn mice across three brain regions of interest: cerebellum, cerebral cortex, and hippocampus. CX-4945, a casein kinase 2 (CK2) inhibitor, also binds to DYRK1A in an ATP-competitive manner and may reduce excess DYRK1A activity in vivo in Ts65Dn mice. Homing behavior differences were assessed on either P17 or P18 in male and female trisomic and euploid mice given daily injections of either DMSO vehicle or CX-4945 from P14-P18. Preliminary data indicate the Ts65Dn mice show significant reductions in homing behavior as compared to euploid mice. There was a trend for improved performance in the male Ts65Dn mice given CX-4945 compared to vehicle treatment. Additional subjects are needed for final determination of potential sex-dependent effects.This study highlights the neurodevelopmental differences in this mouse model of DS and importance of evaluating potential sex differences and explores a possible treatment that targets a trisomic gene as means to improve for detrimental DS phenotypes.
Uniqueness of Research:
Down syndrome is the leading cause of genetic intellectual disability. If the cognitive deficits associated with Down syndrome are rescued by the DYRK1A CX-4945, as measured with a variety of behavioral tests, it would suggest that the excess levels of DYRK1A are responsible for cognitive defects, and that the treatment with DYRK1A inhibitors might improve these deficits.
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