Philosophy of Scholarship

Cellular and Molecular Neurobiology Research with Undergraduates at Agnes Scott

One of the exciting aspects of science is that scientific research can be made accessible to learners at various stages of their academic career. With an observable phenotype, such as a disease model, my research project can a 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. Through inquiry-based research in my lab, students can acquire necessary scientific skills while we answer interesting questions about how vesicle trafficking impacts brain development and how alterations in that trafficking are implicated in neurodevelopmental disorders such as Autism Spectrum Disorders and Schizophrenia.

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The scientific details of my research project can be found here. In short, we exploring the effects of the loss of BLOC-1 subunits (a vesicle coat-associated protein complex) and interacting proteins on the excitatory/inhibitory (E/I) balance in the hippocampus. Loss of BLOC-1 proteins result in alterations of endosomal trafficking and dendritic spine morphology as well as a change in the population of parvalbumin interneurons in the hippocampus. Our work continues to explore changes in cellular function when BLOC-1 is removed. This research is necessary as subunits of BLOC-1 and interacting proteins have been implicated in several neurodevelopmental disorders, such as Schizophrenia, Rett Syndrome, and Autism Spectrum Disorders. This research project incorporates transcriptional biology, behavioral analysis, primary cell cultures, confocal microscopy, biochemical techniques, and mouse genetics. 

Personal Lab Research

Research with students is such a high priority that even in my first semester, I worked with three students. From that semester forward, I have been working with students in my lab every academic year. During the week, I spend 4-6 hours with my research students in lab as we continue researching the role of BLOC-1 and vesicle trafficking in neurodevelopmental disorders. Some of these students have been volunteers and some have been part of BIO440: Mentored Research. Over my 5 years at Agnes Scott, I have worked with 24 students in my lab. The students who have participated in research in my lab and their final products can be viewed here.

Of those 24 students I have worked with:

  • 9 students are authors on a manuscripts, and 3 of those students are an author on 2 manuscripts
  • 2 students gave poster presentations in the main meeting at the annual Society for Neuroscience meeting
  • 1 student gave an oral presentation (nanosymposium) at the annual Society for Neuroscience meeting
  • 15 students gave an oral presentation at Agnes Scott's student research day, SpARC
  • 3 students gave a poster presentation at Agnes Scott's student research day, SpARC

During my 5 years at Agnes, I have published 9 peer-reviewed articles based on my research (article reference hyper links are found here) and research with my collaborators. My research projects have generated four peer-reviewed primary articles and 1 peer-reviewed review article with students as co-authors on the paper. There are an additional 4 peer-reviewed primary articles published on collaborative projects with the Faundez lab at Emory and the Pozzo-Miller lab at UAB. 

From My Research Students:

"I worked with Dr. Larimore identifying a common molecular pathway between Rett syndrome and schizophrenia for 3 semesters. I am in medical school, and I am currently applying for psychiatry residencies. Working with Dr. Larimore fostered my interest in neuroscience, mental health, and neurodevelopment disorders.  Through my research with Dr. Larimore and the classes I took with her, I was able to develop critical thinking skills and public speaking skills. " Alex Ambrose (Class of 2013, currently in medical school)

"As a current doctoral candidate in the interdisciplinary program in neuroscience at Georgetown University, my work in Dr. Jennifer Larimore's lab during my senior year at ASC propelled my neuroscience graduate career. Together we have published 3 research manuscripts and 1 review, presented research at local and national conferences, and maintained a successful mentor and mentee relationship years after my graduation in 2014. The combination of Dr. Larimore's training both inside and outside the lab shaped my career in unprecedented ways. With her training, guidance, and recommendation letters I have won 3 research fellowships funded by NIH and Society for Neuroscience, 5 presentation awards from national conferences, and continued to build my neuroscience skill set at Georgetown. Without her mentorship, teaching abilities and infectious love of neuroscience - there is no way I would be the successful and productive member of the scientific community that I currently am. Her love of research has shaped my current career goals and future plans to enter academia teaching at a small college that focuses on training undergraduate students for graduate school. To date, Dr. Larimore remains my professional and personal role model, and her contributions to ASC's biology department and Neuroscience major have forever impacted the way I conduct research, mentor students, and succeed in science. Without a single doubt in my mind, I owe her all of my success and passion for neuroscience research to her and our time time together at ASC." Kaela Singleton (Class of 2014, currently a PhD candidate at Georgetown)

"Her unwavering support has resulted in my selecting her as my academic advisor, enrolling in over 5 courses she teaches, and considering her a true role model and mentor. Dr. Larimore has, time and time again, gone out of her way to find or suggest opportunities for me to gain experience in my chosen field of neuroscience research. Not only has she given me the opportunity to continue to work, grow, and learn in her lab at Agnes Scott, but she has also demonstrated an incredible dedication to preparing me as best I can to achieve the goals I’ve shared with her. We talk almost daily about some aspect of neuroscience, and she knows better than anyone else what kind of research I am hoping to do. Because of this, she has pushed me out of my comfort zone in order to prepare me as well as possible to succeed in my goals. This has included encouraging me to present work at conferences, giving me the opportunity to publish multiple papers as an undergraduate, emailing me countless research opportunities she finds, and allowing me opportunities such as attending and presenting at SfN. In addition, she is also my biggest source of inspiration, support, and guidance. My experience of Dr. Larimore’s support and mentorship is not isolated. I would venture to say that every student at Agnes Scott who is, or is considering, pursuing a career in neuroscience has sought her guidance on more than one occasion. Her door is always open, and consequently, she can be found taking countless time out of her days to advise, mentor, guide, and even comfort students overwhelmed by courses, graduate school applications, career decisions, and everything in between. It is no exaggeration to say Dr. Larimore has consistently affirmed my love of research, made me immeasurably more comfortable with knowing what steps I will have to take in pursuing my career, and is one of the most incredible and supportive women in science I have ever had the privilege of knowing."  Hannah Rudolph (Class of 2018, currently applying to graduate programs in Neuroscience)

Fall 2012 - Spring 2013

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During my first year at Agnes Scott, with the support of an external grant from the International Rett Syndrome Foundation, I published a manuscript examining the roles of MeCP2 (a gene mutated in Rett Syndrome) in synaptic expression of BLOC-1 subunits using animal models and human pluripotent stem cells with an Agnes Scott student, Laurel Alex Amrbose, who is currently in medical school.

I continued a collaboration with Dr. Pozzo-Miller examining the TRPC signaling and BDNF release in the hippocampus of a Rett Syndrome mouse model, which resulted in a publication as well.

In my third publication that year, also in collaboration with Dr. Pozzo-Miller, we published a review on the recent progress of Rett Syndrome research, analyzing potential new therapeutic targets.

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.

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 Neurology, Jan 2013, Vol. 8, No. 1, Pages 21-28.

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.

 

Fall 2013 - Spring 2014

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During my second year, with the support of an external grant from the International Rett Syndrome Foundation, I published a manuscript that examined dosage dependent phenotypic observations due to a loss of one of the BLOC-1 subunits with an Agnes Scott student, Kaela Singleton who is currently in a Neuroscience PhD program at Georgetown.

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 8.

 

Fall 2014 - Spring 2015

During my third year, I collaborated with the Faundez lab at Emory on some of their cell biology papers. I am co-author on two papers that were published in my third year. One reported on copper sensitivity in dysbindin null animals, suggesting copper toxicity may play a role in schizophrenia. The other paper reported on NSF and dysbindin interactions as they pertain to synaptic plasticity.

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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.

 

 

 

Fall 2015 - Spring 2016

During my fourth year, with the support of internal grant money, I was on pre-tenure leave in the Spring and was working on an educational book about neuroscience, which is now published.

J. Larimore. Neuroscience Basics: A guide to the Brain’s Involvement in Everyday Activities. Academic Press, 2017.

 

Fall 2016 - Spring 2017

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During my fifth year at Agnes, with the support of internal grant money from generous donors to Agnes Scott, I published a manuscript with Agnes Scott students that examined the role of BLOC-1 expression on GABAergic interneuron expression in the hippocampus. These students are Miranda Arnold, Rebecca Cross, Kaela Singleton, Hannah Rudolph, Martha Vorder Bruegge, Andrea Sweatmen, Cecilia Garza, and Eli Whisnant.

I also worked with Hannah Rudolph (Class of 2018) as well as Rebecca Cross, Laura Segura and Kaela Singleton to publish a review of similar genetic mutations in the endosomal pathway observed between Autism Spectrum Disorder and Schizophrenia.  Hannah is currently applying to graduate school, Rebecca is an assistant in a doctor's office, Kaela and Laura are both PhD candidates in Neuroscience programs.

Finally, I published my third manuscript of the year describing the role of BLOC-1 assoiated neuronal AGAP1 in endosomal trafficking and dendritic morphology and outgrowth with students, Miranda Arnold, Kaela Singleton, and Rebecca Cross. Miranda Arnold is currently earning her masters of biomedical sciences.

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.

 

Future Plans for Personal Research

As I move forward in my career, I am committed to continuing independent research in my lab, as well as using that research to generate peer-reviewed publications and scientific meeting presentations. Experiences like this not only allow me to continue research in neurodevelopmental biology, but these experiences allow students to identify what they want out of their future careers and prepare them for additional experiences that are necessary for further education. I will continue to offer Mentored Research (BIO 440) sections with at least one section offered each academic year, allowing students the opportunity for inquiry-based research. I will also continue to publish my results in respected peer-reviewed journals enhancing the scientific profile of Agnes Scott College.

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