Translational Anatomy of Neurodegenerative Disease & Developmental Disorder

Lab Director : Jonathan J. Wisco, Ph.D.

Basic Science Research

The Laboratory for Translational Anatomy of Degenerative Diseases and Developmental Disorders is interested in the anatomical validation of innovative neuroimaging and surgical techniques. Merging the techniques of structural MRI with detailed clinical anatomy dissection and quantitative histopathology, we have two major scientific research interests.

Alzheimer’s Disease

First, we have been investigating the relationship between gradient echo imaging, which is sensitive for the presence of iron in the brain, and oxidative stress pathophysiology of neurodegenerative disease. Since iron binds to neuropathological proteins in Alzheimer’s disease (AD), frontotemporal dementia, Parkinson’s disease, cerebrovascular disease, and chronic traumatic encephalopathy, for example, it should be visible in MRI. We recently showed that T2* mapping of iron deposits of the hippocampus corresponded to AD pathophysiology.

Vocal Fold Imaging and Histology

Second, we have been studying the association of vocal fold mucosa MRI signal intensity with underlying tissue architecture to inform the creation of better synthetic vocal fold vibration models for patients with subglottic stenosis of the larynx. Recently we have acquired high resolution MR images of the porcine larynx in various hydration conditions to delineate mucosa from muscle.

In addition, we have started segmenting vocal fold MR images and examining underlying histological structure.

Medical Education Research

Anatomy Academy

In addition to basic science research, members of the Wisco Lab are encouraged to participate in Anatomy Academy. The program was established in 2012 to teach anatomy, physiology and nutrition concepts as an effort to combat the obesity epidemic through educational intervention, and inspire kids to pursue science as a career.  The program is a multi-institutional and multi-disciplinary collaboration for pre-professional students between the disciplines of medicine, dentistry, nursing, public health, public policy and education at Brigham Young University, University of Utah, Utah Valley University, UCLA, Valencia College (Orlando, FL), New Mexico State University (Las Cruces, NM), San Jacinto College (Houston, TX), Briar Cliff University (Sioux City, IA), and Mesa Community Colleges (Mesa, AZ).  We serve 22 elementary school partners in over 43 classes. School sites for the Boston area will be established soon!

Volunteers in Anatomy Academy learn how to communicate complex medical information to a level appropriate for elementary school kids; prepare and deliver lessons on anatomy, physiology and nutrition that help kids understand the importance of establishing and maintaining a healthy lifestyle; teach groups of children in didactic and active learning environments; serve as role models for pursuing higher education; demonstrate the utmost professional demeanor; and become exposed to an experiential learning environment that results in immediate, quantifiable behavioral change in students.  Thus, Mentors are exposed to at least one component of each of the six Accreditation Council for Graduate Medical Education (ACGME) Core Competencies – Patient Care, Medical Knowledge, Practice-based Learning and Improvement, Interpersonal and Communication Skills, Professionalism, Systems-based Practice.

For more information on Anatomy Academy, you can view our Anatomy Academy videos at http://youtu.be/r6bN073FGOs, and/or a recent feature of the program at http://education.byu.edu/news/2013/07/15/the-science-of-hands-on-learning/.

Here is Dr. Wisco’s radio conversation with Julie Rose of Top of Mind:

https://www.byuradio.org/episode/2e80e368-63c4-4f15-8f76-7e1cc947b6b4?playhead=2412&autoplay=true.

We have studied the effect of Anatomy Academy on inspiring life-long learning in pre-professional and professional students that we call Mentors. In recent studies, we examined 1) Mentor self-efficacy in the ACGME Core Competencies of Interpersonal and Communication Skills; and 2) how Mentors improved their learning environments by incorporating feedback to their students.

 

 

Grounded Theory Thematic Meta-Analysis

We have developed a qualitative research approach and analysis called Grounded Theory Thematic Meta-Analysis (GTTMA). We combined grounded theory’s iterative coding approach with thematic analysis pattern delineation in the context of a meta-analysis involves the following steps. The coding process is often described as phases of data collection, open coding (initial coding), axial coding (intermediate coding), and selective coding (advanced coding) that lead to a singular or multifaceted grounded theory (see figure below). In summary:

1. Formulating a research question from which broad concepts can be organized (i.e. in a concept map) and used in a series of Boolean searches of databases to discover relevant published literature. We considered the construction of broad concepts as part of the data collection phase, and the Boolean search terms as open coding for the data collection phase. For each broad concept, we aimed to analyze ~50-100 papers.
2. Each paper served as a singular “voice” akin to an interview. We elected to perform a thematic analysis for each phase of coding, which looked for cohesive patterns in the diction of the papers. A content analysis would have been too granular, and a narrative analysis would have been too restrictive. We considered the coding of themes from each paper as part of the open coding phase.
3. Groups of papers served as “voices” akin to focus groups whose data on the broad concepts were similar and re-coded for themes that were confirmatory or unique as a result of combining data from groups of papers. We considered this coding of groups of papers as the axial coding phase.
4. Finally, we analyzed the data from all of the groups of papers and re-coded for themes that again were confirmatory or unique as a result of considering intersections between groups. We considered this coding of intersectionality as the selective coding phase.
5. At each phase of coding we allowed our analysis to add papers (akin to “adding voices” to the analysis), and bridge across all three types of coding, which ensures thorough analysis of the data.

Grounded theory method that we employed in GTTMA. This figure is purposely constructed in a circular fashion to show that coding that informs new themes and experimental questions can jump to any of the coding stages and in forward or reverse direction from the initial data collection phase.

Recent Publications: (For more publications, please see Dr. Wisco’s CV.)

Note: Throughout this biographical sketch, graduate student authors are in italics & undergraduate student authors are underlined

Adhikari R, Steed KS, Hutchinson B, Wang B, Mendoza M, Staudte R, Atmojo M, Cox P, Hancock T, Barkdull K, Harris M, Watt R, Bangerter N, Wisco JJ. Hippocampal T2 Signal Loss and Decreased Radial Arm Maze Performance in Transgenic Murine Model for AD. Brain and Nerves 2020; doi: 10.15761/JBN.1000127.

Cieslak SG, Hutchinson B, Adhikari R, Steed KS, Staudte RS, Cox P, Rasch A, Black E, Araujo A, Wisco JJ. The effects of L-Cysteine on Alzheimer’s disease pathology in APOE2, APOE3, and APOE4 homozygous mice. Brain and Nerves 2020; doi: 10.15761/JBN.1000128.

Holley SL, Hill SL, Ottesen TD, Vance PK, Challyandra L, Katrikh AZ, Whiting DC, Stark ME, Wisco JJ. Dissectional investigation: variations in morphology of the teres minor tendon and muscle-tendon junction. Rheumatol Orthop Med, 2020 doi: 10.15761/ROM.1000170.

Taylor EN, Huang N, Wisco JJ, Wang Y, Morgan KG, Hamilton JA. The brains of aged mice are characterized by altered tissue diffusion properties and cerebral microbleeds. J Transl Med. 2020;18(1):277. Epub 2020/07/10. doi: 10.1186/s12967-020-02441-6. PubMed PMID: 32641073.

Adams JS, Nelson HM, Strong E, Wisco JJ, Klappa S. A Mentors’ Experience in Teaching Basic Science Concepts in the Community Outreach Program, Anatomy Academy: A Phenomenological Study. HAPS Educator 2020; 24(2):27-35. https://doi.org/10.21692/haps.2020.017.

Araujo AG, Park D, Steed KS, Ajijola OA, Shivkumar K, Mahajan A, Fishbein M, Hageman N, Stark ME, Wisco JJ. An Assessment of Stellate Ganglion Neuronal Remodeling in Association with Cardiovascular Disease. ISCIENCE-D-20-00399. 2020; Available at SSRN: https://ssrn.com/abstract=3564981.

Szarpak L, Wisco JJ, Boyer R. How healthcare must respond to Ventilator-Associated Pneumonia (VAP) in invasively mechanically ventilated COVID-19 patients. Am J Emerg Med 2021 Oct;48:361-362. doi: 10.1016/j.ajem.2021.01.074. Epub 2021 Feb 2.

Sedlmayr JC, Bates KT, Wisco JJ, Schachner ER. Revision of hip flexor anatomy and function in modern humans, and implications for the evolution of hominin bipedalism. Anat Rec 2021 Sep 26. doi: 10.1002/ar.24769. Online ahead of print.

Lee A, Wisco JJ, Shehan JN, Basa K, Spiegel JH. Dysphagia After Gender Affirming Chondrolaryngoplasty (Tracheal Shave): A Survey Study. Facial Plast Surg Aesthet Med 2021; Nov 9. doi: 10.1089/fpsam.2021.0214.

Lin D, Bunch B, Zuim Dantas De Souza R, Chen D, Zhou J, Zumwalt A, Wisco JJ. Effectiveness of Pedagogical Tools for Teaching Medical Gross Anatomy During the Covid-19 Pandemic. Med Sci Edu 2022 Feb 24;1-12. doi: 10.1007/s40670-022-01524-x.

Mori JO, Shafran JS, Stojanova M, Katz MH, Gignac GA, Wisco JJ, Heaphy CM, Denis GV. Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins. The Prostate 2022; Apr 11. 82(10):1005-1015. doi: 10.1002/pros.24351. Epub 2022 Apr 11.

Lee A, Wisco JJ, Shehan JN, Basa K, Spiegel JH. Dysphagia after gender affirming chondrolaryngoplasty (tracheal shave): An anatomic cadaver study. Facial Plast Surg Aesthet Med 2022 DOI: 10.1089/fpsam.2022.0021

Wisco JJ. 2022. Design, implement, and disseminate a medical sciences educational scholarship project. In Wisco JJ (Ed.), A toolkit for explorers in medical sciences educational scholarship: From ideas to dissemination. International Association of Medical Science Educators (IAMSE) Publications. http://www.iamse.org/wp-content/uploads/2022/06/ESC-IAMSE-Toolkit-1.pdf

Wisco JJ, Huggett KN. 2022. Identifying sources of funding. In Wisco JJ (Ed.), A toolkit for explorers in medical sciences educational scholarship: From ideas to dissemination. International Association of Medical Science Educators (IAMSE) Publications. http://www.iamse.org/wp-content/uploads/2022/06/ESC-IAMSE-Toolkit-1.pdf

Wisco JJ, Huggett KN. 2022. Analyzing data. In Wisco JJ (Ed.), A toolkit for explorers in medical sciences educational scholarship: From ideas to dissemination. International Association of Medical Science Educators (IAMSE) Publications. http://www.iamse.org/wp-content/uploads/2022/06/ESC-IAMSE-Toolkit-1.pdf

Wisco JJ. 2022. A checklist of objectives. In Wisco JJ (Ed.), A toolkit for explorers in medical sciences educational scholarship: From ideas to dissemination. International Association of Medical Science Educators (IAMSE) Publications. http://www.iamse.org/wp-content/uploads/2022/06/ESC-IAMSE-Toolkit-1.pdf

Landau-Taylor J, Cassidy B, Claus LA, Prasad M, Shi J, Barrett J, Shaffer K, Wisco JJ. Integration of Clinical Skills into Preclinical Curriculum via a Low-Cost Femoral Triangle Ultrasound Model. Med Sci Edu 2022; Sep https://doi.org/10.1007/s40670-022-01629-3.

Kania B, Sotelo A, Ty D, Wisco JJ. The Prevention of Inflammation and the Maintenance of Iron and Hepcidin Homeostasis in the Gut, Liver and Brain Pathologies. J Alzheimers Dis. 2023;92(3):769-789. doi: 10.3233/JAD-220224. PMID: 36846996; PMCID: PMC10116142.

Black E, Rasch A, Wimmer T, Li A, Cieslak S, Steed KS, Adhikari RD, Wisco JJ, Hutchinson B. The Effects of Age, Genotype, and an Oxidative Stress-Inducing Diet on Hippocampal Subfield Biomarkers in an ApoE Mouse Model. Eur J Neurosci 2023 Feb 12; doi: 10.1111/ejn.15933.

Lai ER*, Rukavina NA*, Wisco JJ, Zumwalt AC. Comparing the emotional experiences of students in similar dissection- and prosection-based medical gross anatomy courses: A mixed-methods study. Anat Sci Edu 2023 Apr 15; https://doi.org/10.1002/ase.2281.

Filimonov A, Gates A, Allos AN, Billings HJ, Goldina A, Wisco JJ. A Call to Action for Improving LGBTQIA+ Inclusive Policies and Practices in Educating Science and Medical Professionals. Med Sci Edu 2023; In press.

Harris ML, Bennion E, Magnusson KR, Howard VJ, Wadley VG, McClure LA, Levine DA, Manly JJ, Avila JF, Glymour MM, Wisco JJ, Thacker EL. Rural versus urban residence in adulthood and incident cognitive impairment. Neuroepidemiology 2023; In press.