Philosophy of Scholarship
Cellular and Molecular Neurobiology Research with Undergraduates at Agnes Scott
Outline:
1. Introduction
2. Research in Class Laboratory – Course-based Undergraduate Research Experiences (CUREs)
3. Personal Lab Research
4. Scientific Publications while at Agnes Scott College
5. Research Project
6. Research Training
1. Introduction
The engagement of students in scientific research not only enhances the project itself but, it also enhances the educational experience of the students involved in the project, imparting critical thinking skills and a deeper understanding of neurobiology through a hands-on approach. There are two ways to include undergraduates in research: utilizing the lab times associated with our lectures – Course-based Undergraduate Research Experiences (CUREs) and incorporating the students into the research time in our laboratory.
With an observable phenotype, such as a disease model, my research project can increase student’s ability to transfer the science knowledge from lectures and data gained in each experiment to a greater understanding of what happens when neurons are not functioning properly. This research project incorporates transcriptional biology, behavioral analysis, primary cell cultures, confocal microscopy, biochemical techniques, and mouse genetics.
My research supports several projects for students in my lab or in my classes. Some examples are: what regulates vesicle trafficking within neurons? How do molecules affect animal/human behavior? And how do changes in neuronal cell populations impact neuronal development? For careers in science, students need the following skills which are can acquired in CUREs:
· Ability to design an effective experiment, analyze the data with statistics, draw important conclusions, and present the research.
· Critically read scientific literature.
· Apply knowledge learned in order to solve a problem.
· Work in pairs or teams utilizing leadership skills.
· Communicate science effectively both written and orally.
2. Research in Class Laboratory – Course-based Undergraduate Research Experiences (CUREs)
I have taught Molecular Biology Lab as a CUREs 11 times as an inquiry-based research experience as the teaching method in the Molecular Biology Lab. I have taught Cellular Neuroscience and System Neuroscience as a CURE 14 times as an inquiry-based research experience as the teaching method for the Neuroscience Times.
In Molecular Biology and Neuroscience, students are assigned into lab research groups based on previous academic performance in science classes so that each lab research group has an equitable division of strong performers. Students are also grouped to ensure diversity. Looking at our students in STEM, Agnes Scott does not have a racial or ethnic group majority. Diversity in these lab research groups yields an overall better educational experience for each of the students. In these assigned groups, students are given background information on the type of research my lab conducts and the techniques we will be using during the semester. The groups then form their independent hypothesis. From this very first lab period, it is evident that the students enjoy creating the hypothesis and setting the direction for what they will explore during the semester. They take part in other aspects of research throughout the semester – writing up their results, presenting scientific data, and working with their lab research group.
As I progress in my career, I firmly believe that experiences like CUREs are necessary for students to understand their own personal strengths and identify potential career options they may not have considered. These experiences also equip students with skills that are necessary in any career – critical thinking, polished presentation skills, enhanced writing ability, knowledge application, understanding scientific literature, and effective teamwork strategies. Because lab work in an inquiry-based setting can impart these skills, inquiry-based research is a high priority for my upper-level science electives. The method of inquiry-based research in labs described above will be a method I continue to practice in my laboratory classes because of its necessity for experiential student learning.
3. Personal Lab Research
Research with students is such a high priority to me that even in my first semester, I worked with three students. From that semester forward, I have been working with students in my lab. During the week, I spend 4-6 hours with my research students in lab. Some of these students have been volunteers and some have been part of a Mentored Research class (BIO 440, BIO 380, BIO 410).
Research in our lab has focused on endosomal trafficking and coat proteins associated with endosomes. Since I started at Agnes Scott College in 2012, I have mentored 47 undergraduate students, 30 are individuals from underrepresented groups in neuroscience. Over the past 10 years, 40 have presented a poster or given a scientific talk in their research, 20 have presented a poster at a national conference, and 14 are contributing co-authors on peer-reviewed manuscripts.
51% have/are pursuing further degrees
12 PhD students, 10 of which are minority women
2 of the PhD women of color earned K99R00 Training awards as NIH DSPAN scholars.
1 of the PhD women of color was a Goldwater Scholar
4 Medical Doctor/ Dental School, 2 of which are minority women
6 Master’s Degrees, 5 of which are minority women
1 Law student
1 Nurse
32% are in STEM related careers
3 Science Educators, 2 of which are minority women
10 Engineer/Data analyst/Lab Tech/manager, 5 of which are minority women
2 NIH Trainees, 2 of which are minority women.
Name. Current career. Time in Lab. Outcome of research in lab.
1. Karima Johnson. Ph.D. in Chinese Medicine at Oregon Health and Science University. Fall 2012 – Spring 2013. SpARC poster presentation.
2. Leila Ibrahim. Master’s in Public Health, Project manager at Brain Health Emory. Fall 2012 – Spring 2013. SpARC poster presentation.
3. Laurel (Alex) Ambrose. Medical Doctor. Fall 2012 – December 2013. SpARC poster presentation *published manuscript.
4. Jessica Resnack. Retail Management. Fall 2013 – May 2014
5. Olivia Bello. Science Teacher, New York City Schools. Spring 2014. SpARC oral presentation *published manuscript.
6. Pamela Guinn. Biology Teacher, St. Gabriel’s College, Thailand. Spring 2014. SpARC oral presentation
7. Jasmine Spraggins. Manager at Chick-fil-A. Spring 2014. SpARC oral presentation
8. Kaela Singleton. Completed a Ph.D. in Neuroscience at Georgetown University current Post-Doc at Emory University. Fall 2013 – Summer 2014. SpARC oral presentation *published 2 manuscripts
9. Laura Segura. Completed a Ph.D. in Neuroscience at University of Illinois Chicago. Spring 2014 – Summer 2014. SpARC oral presentation
10. Katherine Binkowski. OD Medical student. Summer 2014-Fall 2015
11. Rebecca Cross. Secretary at a Medical Clinic. Spring 2014 – Spring 2015. SpARC oral presentation *published manuscript*Honor’s Thesis
12. Eli Whistant. Process Engineer at New WinCup Holdings. Spring 2015. SpARC oral presentation *published manuscript
13. Cecilia Graza. Manager at Doctor’s office. Spring 2015. SpARC oral presentation *published manuscript
14. Kathryn Laprade. Research Tech at Vermont School of Medicine. Spring 2015
15. Martha VoderBrugge. Ph.D. student in Psychology. Spring 2015. SpARC oral presentation *published manuscript
16. Nandi Ramirez. Pediatric Nurse Practitioner, and CEW of Noire Medical Women. Spring 2015. SpARC oral presentation
17. Andi Sweatman. Research Tech. Spring 2015. SpARC oral presentation *published manuscript
18. Miranda Arnold. Masters in Biomedical Sciences from Kennesaw State University and current PhD student in Neuroscience at UGA. Summer 2015 – Spring 2017. Society for Neuroscience, Poster (2015) and talk (2016) * published 2 manuscripts and Honor’s Thesis
19. Megan Do. Dental student at UCSF. Fall 2016
20. Tempist Harris. Fall 2016
21. Alveena Jacks. Ross University School of Medicine. Fall 2016 – Spring 2017. SpARC oral presentation
22. Karina Leung. Master’s Student in Environmental Studies at UNC. Sustainability worker at Agnes Scott College. Spring 2017 – Spring 2018. SpARC oral presentation
23. Anner Harris. Ph.D. student in Neuroscience at the University of Texas. Spring 2017 – Spring 2018. SpARC oral presentation
24. Hannah Rudolph. Ph.D. student in Neuroscience at Oregon Health and Sciences University. Spring 2015 – Spring 2017. SpARC oral presentation, Society for Neuroscience, Poster Presentations, Honor’s Thesis and *published 2 manuscripts
25. Roysheda Tarver. Masters in Applied Behavior, Board Certified. Fall 2017. Scotties with Nerves, Oral Presentation
26. Crystal Burgess. NIH IRTA program. Fall 2017 – Spring 2018. SpARC Oral Presentation and Scotties with Nerves, Oral Presentation and an Honor’s Thesis
27. Susan Cordero Romero. PhD program in clinical research at Clemson. Spring 2018 – Spring 2019. SpARC Oral Presentation, Scotties with Nerves, Oral Presentation, Society for Neuroscience, Poster Presentation and an Honor’s Thesis.
28. Sammi Hatcher. Research Tech. Summer 2019. Summer Symposium presentation
29. Jhodi Webster. Ph.D. student in Neuroscience at UAB. Summer 2018 – Spring 2020. GF-STEM Symposium, Society for Neuroscience, Poster 2018, Society for Neuroscience, Poster 2019, ABRCMS poster presentation 2019, and GURC presentation 2019
30. Alexia Crockett. Ph.D. student in Neuroscience at the University of South Carolina. Summer 2018. GF-STEM Symposium
31. Ruvimbo Dzvurumi. Post-bac research training program. Summer 2018 – Spring 2020. GF-STEM Symposium, Society for Neuroscience, Poster 2018, ABRCMS poster presentation 2019, GURC presentation 2019.
32. Lauren Neal. Goldwater Scholar. Ph.D. student in Neuroscience at Rockefeller University. Spring 2018 – Spring 2020. SpARC Oral Presentation, Society for Neuroscience, Poster 2018, Society for Neuroscience, Poster 2019, ABRCMS poster presentation 2019, GURC presentation 2019
33. Shekinah Phillips. Ph.D. student in Neuroscience at UAB. Fall 2018.
34. Rachel Thompson. Science Teacher with Teach for America. Summer 2019 – Fall 2019. Society for Neuroscience, Poster Presentation, ABRCMS poster presentation 2019
35. Alix Wagner (High School Student). Case Western for Undergraduate! Summer 2019.Summer Symposium presentation
36. Alex Lombardo. NIH IRTA training program for Fall 2021. Summer 2019 – Spring 2020. Summer symposium presentation, Society for Neuroscience Poster Presentation, GURC presentation 2019
37. Camryn Smith. PhD in Neuroscience at Vanderbilt, laboratory research position for Fall 2021 at Baylor College of Medicine. Fall 2019 - Spring 2020. Society for Neuroscience Poster 2019, GURC presentation 2019
38. Clare McDaniel. Applying to medical school. Fall 2021 – Spring 2022. Sparc presentation 2022
39. Anabel Braziel. Samford University Law School. Summer 2021 – Fall 2021. Sparc Presentation 2022
40. 40.Xiomara De La Quinta. Applying to medical school. Fall 2021 – Spring 2022. Sparc presentation 2022
41. Kiki Favors-Gosh. Masters in Medical Sciences. Summer 2021 – Spring 2022. S-STEM student poster presentation Summer 2021
42. Alex Martin. Manager in Retail. Summer 2021 – December 2022. Sparc presentation 2022, SfN presentation November 2022
43. Milo Beauchamp. Spring 2020 - Spring 2023. S-STEM student poster presentation Summer 2020. *published manuscript, Sparc presentation 2022, SfN poster presentation November 2022
44. Yommi Tadesse. NIH IRTA program. Spring 2020 - Spring 2023. S-STEM student poster presentation Summer 2020, *published manuscript Sparc presentation 2022, SfN poster presentation November 2022
45. Rosie Hagel. Junior. Spring 2022 – present. SfN poster presentation November 2022 and November 2023.
46. Delano Bielamowicz. Junior. Spring 2022 – present. SfN poster presentation November 2023.
4. Scientific Publications while at Agnes Scott College
I earned tenure in May 2018 and took Sabbatical in Fall 2018. Over those 7 years, 2 and half years I was not in the lab because of COVID. Despite that, there are 2 research publications since May 2018.
Research Publications since earning tenure in Spring 2018.
Susan Cordero Romero, Ruvimbo Dzvurumi, Alexia Crockett, Alexandra Lombardo, Jhodi Webster, Samantha Hatcher, Alix Wagner, Diana Ghebrezadik, Asiya Abawari, Camryn Smith, Lauren Neal, Yommi Tadesse, M. Beauchamp, Stacey B.B. Dutton and Jennifer L. Larimore. Endosomal trafficking is disrupted in Neurodevelopmental Disorders. J Brain Research. 2021 January.
Frank Y Lee, Jennifer Larimore, Victor Faundez, Esteban C Dell'Angelica, Cristina A Ghiani. Sex-dimorphic Effects of Biogenesis of Lysosome-Related Organelles complex-1 Deficiency on Mouse Perinatal Brain Development. J Neuroscience Research. 2020 May 20. doi: 10.1002/jnr.24620.
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677168/
As a side note, science experiments are lengthy. An entire paper usually includes 7-10 complex experiments that take place over 3-4 years. Based on their complexity, usually 5-10 authors appear on a publication. People who contribute to the figures in the paper are authors. The first author is the person who did the majority of the experiments. The second author is who did the second most work, etc. The last author is the primary professor whose lab the experiments were done in.
On many of these papers, the last author listed is Dr. Victor Faundez, my post-doctoral mentor. Many of the experiments in those papers were conducted with materials from his lab including use of his mouse colonies, or using the microscope his lab has access to. The hypothesis and experimental design in the paper are my own. Dr. Faundez and I continue to collaborate on projects involving the neurobiology of schizophrenia.
8 Publications generated while at Agnes Scott that include Agnes Scott Students:
Susan Cordero Romero, Ruvimbo Dzvurumi, Alexia Crockett, Alexandra Lombardo, Jhodi Webster, Samantha Hatcher, Alix Wagner, Diana Ghebrezadik, Asiya Abawari, Camryn Smith, Lauren Neal, Yommi Tadesse, M. Beauchamp, Stacey B.B. Dutton and Jennifer L. Larimore. Endosomal trafficking is disrupted in Neurodevelopmental Disorders. J Brain Research. 2021 January.
Jennifer Larimore, Stephanie Zlatic, Miranda Arnold, Kaela Singleton, Rebecca Cross, Hannah Rudolph, Martha Vorder Bruegge, Andrea Sweatmen, Cecilia Garza, Eli Whisnant, Victor Faundez. Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus. Frontiers in Genetics, Neurogenomics. Volume 8:28. March 2017. doi: 10.3389/fgene.2017.00028
Hannah Rudolph, Rebecca Cross, Laura Segura, Kaela Singleton, and Jennifer Larimore. Neuronal Endosomal Trafficking: One of the Common Molecular Pathways Disrupted in Autism Spectrum Disorders and Schizophrenia. J Neurol Psychol. 2016 Dec. Vol 4 Issue 2. December 2016.
Miranda Arnold, Kaela Singleton, Rebecca Cross, Christopher Chapleau, Ariana P. Mullin, Isaiah Rolle, Carlene Moore, Anne Theibert, Lucas Pozzo-Miller, Victor Faundez, Jennifer Larimore* The Endosome Localized ARF-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin. Frontiers in Cellular Neuroscience. 2016 Sep 22. 12:218. PMID 27713690.
Frank R and Larimore J. Yoga as a Method of Symptom Management in Multiple Sclerosis. Frontiers in Neurodegeneration, 30 April 2015 | http://dx.doi.org/10.3389/fnins.2015.00133.
Larimore J, Zlatic SA, Gokhale A, Tornieri K, Singleton KS, Mullin AP, Tang J, Talbot K, Faundez V. Mutations in the BLOC-1 Subunits Dysbindin and Muted Generate Divergent and Dosage-Dependent Phenotypes. J Biol Chem. 2014 Apr.
Olivia Bello, Kelsey Blair, Christopher Chapleau and Jennifer L. Larimore. Is memantine a potential therapeutic for Rett Syndrome? Frontiers in Neurosciene. December 2013.
Jennifer Larimore, Pearl V. Ryder, Kun-Yong Kim, L. Alex Ambrose, Christopher Chapleau, Gaston Calfa, Christina Gross, Gary Bassell, Lucas Pozzo-Miller, Yoland Smith, Konrad Talbot, In-Hyun Park, Victor Faundez. MeCP2 Regulates the Synaptic Expression of a Dysbindin-BLOC-1 Network Component in Mouse Brain and Human Induced Pluripotent Stem Cell-Derived Neurons. PLOS-1 Biology. Accepted April 2013.
6 Publications generated while at Agnes Scott that do not have students:
Frank Y Lee, Jennifer Larimore, Victor Faundez, Esteban C Dell'Angelica, Cristina A Ghiani. Sex-dimorphic Effects of Biogenesis of Lysosome-Related Organelles complex-1 Deficiency on Mouse Perinatal Brain Development. J Neuroscience Research. 2020 May 20. doi: 10.1002/jnr.24620.
Gokhale A, Vrailas-Mortimer A, Larimore J, Comstra HS, Zlatic SA, Werner E, Manvich DF, Iuvone PM, Weinshenker D, Faundez V. Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a schizophrenia susceptibility factor. Hum Mol Genet. 2015 Oct 1;24(19):5512-23. doi: 10.1093/hmg/ddv282. Epub 2015 Jul 21.
Gokhale A, Mullin AP, Zlatic SA, Easley CA, Merritt ME, Raj N, Larimore J, Gordon DE, Peden AA, Sanyal S, Faundez V. The N-ethylmaleimide-sensitive factor and dysbindin interact to modulate synaptic plasticity. J Neurosci. 2015 May 13;35(19):7643-53. doi: 10.1523/JNEUROSCI.4724-14.2015.
Christopher A Chapleau, Jane Lane, Jennifer Larimore, Wei Li, Lucas Pozzo-Miller, Alan K Percy. Recent progress in Rett syndrome and MECP2 dysfunction: assessment of potential treatment options. Future Neuro, Jan 2013, Vol. 8, No. 1.
Li W, Calfa G, Larimore J, Pozzo-Miller L. Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17087-92.
Gokhale, A, Larimore, J. Mullin, A., So, L.; Moreno De Luca, A.; Lese-Martin, C.; Brodsky, F.; Lupashin, V., Smith, Y.; Victor Faundez. Quantitative Proteomes of a Schizophrenia Susceptibility Factor Identify Novel Roles of the Endosome-Localized BLOC-1 Complex. Journal of Neuroscience. March 2012.
5. Research Project
Vesicles that traffic through the endosomal pathway are derived from two distinct donor membranes – the Golgi complex or the plasma membrane. Those vesicles originating from the Golgi complex are trafficked directly to the plasma membrane or to an early endosome for further sorting, unless they are mis-folded, in which case they traffic from the Golgi directly to the late endosome. There are specific ADP-ribosylation factors (Arfs), ArfGTPase associated proteins (GAPs), coat proteins, and associated coat proteins that are specific for this anterograde trafficking (Bonifacino and Glick, 2004). The Arf GAPs AGAP1, AGAP2, and AGAP5 have been implicated in several neurodevelopmental diseases (including Autism Spectrum Disorder, schizophrenia, and Trisomy 23), but their exact role in typical neurodevelopment remains unknown. AGAP1, specifically interacts with two other vesicle complexes that are also implicated in several neurodevelopmental disorders: the coat complex AP-3 and the Biogenesis of Lysosome Related Organelles -1 (BLOC1) complex to form vesicles on endosomes. Of the neurodevelopmental disorders that Arf GAPs have been genetically implicated in, one common phenotype is altered abilities in learning and memory. In order for dendritic spines to maintain proper morphology (stubby Type 1 or mushroom Type II) required for synaptic plasticity, recycling endosomes must be fully functional within the dendrite. When endosomes are blocked/unable to traffic, spines shifted from a stable phenotype to an unstable phenotype (thin/filamentous. Type III) (Park et al., 2006a). Further, endosomal recycling of receptors has been demonstrated necessary to maintain a mobile pool of AMPA receptors that are necessary for LTP (Park et al., 2004), the cellular correlation for learning and memory. Additionally, endosomal trafficking is also necessary for the proper trafficking of key receptors to the spines in dendrites in the hippocampus. AMPA receptors require endosomal trafficking in order to maintain the proper number of receptors inserted in the postsynaptic density (PSD). This proposal will examine how AGAP1 protein levels are altered in SHANK3B +/- mice during 1 time point in development.
6. Research Training
In my dissertation research, the lab of my mentor, Dr. Anne Theibert, had a strong emphasis on cell biology, and her lab was in a Neurobiology department, which allowed a natural blending of cell biology in neuroscience. These studies led to ongoing collaborations with Dr. Lucas Pozzo-Miller. The collaboration began as we described the effects on neurite outgrowth of the known genetic mutations in the MECP2 gene that results in Rett Syndrome. My work in graduate school resulted in 5 publications, including a first author publication.
Larimore, J., Chapleau, C., Schanen, C., Kudo, S., Theibert, A., Percy, A., and Pozzo-Miller, L. BDNF Overexpression in Cultured Hippocampal Neurons Prevents Dendritic Atrophy Caused by Rett-Associated MECP2 Mutations. Neurobiology of Disease 2009, (34) 199-211.
Chapleau, C., Larimore, J., Theibert, A., and Pozzo-Miller, L. Modulation of dendritic spine development and plasticity by BDNF and Vesicular Trafficking: Fundamental Roles in Neurodevelopmental Disorders associated with Mental Retardation and Autism. Journal of Neurodevelopmental Disorders 2009 Sep;1(3):185-96.
Chapleau, C., Calfa.G., Lane, M., Albertson, A., Larimore, J., Kudo, S., Armstro, D., Percy, A., Pozzo-Miller, L. Dendritic Spine Pathologies in Hippocampal Pyramidal Neurons from Rett Syndrome Brain and after Expression of Rett-Associated MECP2 Mutations. Neurobiology of Disease 2009, (35) 219-233.
Chapleau, C. A., Carlo, M.E., Larimore, J. L. and Pozzo-Miller, L. The Actions of BDNF on Dendritic Spine Density and Morphology in Organotypic Slice Cultures Depend on the Presence of Serum in Culture Media. Journal of Neuroscience Methods 2008, 169 (1) 182-190.
Moore, C., Thacker, E., Larimore, J., Gaston, D., Underwood, A., Kearns, B., Patterson, S., Jackson, T., Chapleau, C., Pozzo-Miller, L., Theibert, A. 2007. The neuronal Arf GAP centaurin {alpha}1 modulates dendritic differentiation. Journal of Cell Science 2007, 120:2683-2693.
During my post-doctoral fellowship, I trained in the laboratory of Dr. Victor Faundez in the Cell Biology Department of Emory University, an international expert in the vesicle trafficking community. In his lab, I utilized stringent and varied approaches answering focused scientific questions in cell and molecular neurobiology. I used biochemical assays, cellular extractions, and microscopy techniques to investigate the role of vesicular coat complexes in targeting proteins from the cell body to the active zone of the synapse. Work in Dr. Faundez’s resulted in three publications.
Larimore, J. Tornieri, K., Ryder, P., Gokhale, A., Zlatic, S., Craige, B., Lee, J., Talbot, K., Pare, J., Smith, Y., Faundez, V. The Schizophrenia Susceptibility Factor Dysbindin and its Associated Complexes Target Membrane Cargoes to the Synapse. Molecular Biology of the Cell December 2011.* this manuscript was highlighted by the editors and was one of the 50 most read articles in October, pre-print, for MBOC.
Gokhale, A,; Larimore, J.; Mullin, A.; So, L.; Moreno De Luca, A.; Lese-Martin, C.; Brodsky, F.; Lupashin, V., Smith, Y.; Victor Faundez. (2011) Quantitative Proteomes of a Schizophrenia Susceptibility Factor Identify Novel Roles of the Endosome-Localized BLOC-1 Complex. Journal of Neuroscience. March 2012.
Mullin AP*, Gokhale A*, Larimore J*, Faundez V. Cell Biology of the BLOC-1 Complex Subunit Dysbindin, a Schizophrenia Susceptibility Gene. Mol Neurobiol. 2011 Apr 26. These authors contributed equally.