Faculty

Research Summary

Dr. Skildum's research interests are in understanding the basic molecular biology of cancer cells, with the goal of decreasing the often devastating impact cancer has on the lives of patients and their families. Dr. Skildum moved to the University of Minnesota Medical School, Duluth campus in the fall of 2004. He worked in the laboratory of Dr. Kendall Wallace, where he initiated a study of potential links between mitochondrial infidelity and antiestrogen resistance in human breast cancer. He was appointed Assistant Professor in 2011 and teaches in the areas of metabolism and microbiology.

Teaching Summary

Biochemistry, metabolism, and virology. Course director for gastrointestinal medicine

Mentoring & Advising: undergraduate researchers 

Service Summary

Member, National Research Mentoring Network. (2012 - Present)

Mentor
Bridges to Baccalaureate. (2011 - Present)
McNair Scholars. (2011 - Present)
Pathways to Advanced Degrees in Life Science. (2011 - Present)
 

Research Summary

Whole genome sequencing has become increasingly straightforward in recent years, though our understanding of the regulatory genome – the noncoding portion of the genome dictating where, when, and to what level genes are expressed – remains incomplete. Research in the Slattery lab explores the mechanisms by which transcription factors interact with noncoding regulatory DNA elements, also known as enhancers, to influence cell fate decisions. We use an integrative approach centered on three major themes – DNA binding specificity, context-specific genomics, and cis-regulatory element dissection – to characterize gene regulatory networks controlling the response to environmental stress. Importantly, this approach also allows us to identify and test noncoding DNA variants linking the response to cell stress with various disease states.

Teaching Summary

Pharmacology (Neuropharmacology)

Mentoring/Advising: undergraduate students, graduate students, and post doctoral researchers

Research Summary

Toxicology; My primary research focus is on the mitochondrion as a primary target or a critical factor in the pathogenesis of various chemical exposures. Current projects focus on modulating cancer causation or chemical toxicity by manipulating mitochondrial homeostasis and the role of mitochondrial epigenetics in the reprogramming of metabolic homeostasis as a compensatory survival response to mitochondrial toxicity. Dr. Wallace is past president of the Society of Toxicology, the American Board of Toxicology, the Academy of Toxicological Sciences, the Mitochondrial Research Society and the ILSI Health and Environmental Sciences Institute and has served on various scientific panels for the National Institutes of Health, the U.S. Food and Drug Administration, and the U.S. Environmental Protection Agency. He served 20 years as Editor-in Chief of the journal Toxicology.

Research Summary

Synapses are the fundamental units of neural communication in the brain. Using multidisciplinary approaches, we study how synaptic structure and function are precisely shaped during development and how their dysfunctions lead to neurological disorders. By understanding the physio-pathological roles of critical synaptic proteins and ion channels at the cellular, circuitry and system levels, we aim to identify novel targets and further develop pharmacological and genetic therapies for neurodevelopmental disorders, such as autism spectrum disorder (ASD). ASD is characterized by defective social interactions, impaired communication and restricted patterns of repetitive behaviors. Although ASD involves many brain areas, emerging evidence suggests that aberrant activity of the cerebellum in the early developmental stage can lead to ASD. Employing various autistic mouse models to simulate the complex etiology of ASD, we investigate the cellular and molecular mechanisms underlying the cerebellum pathology. By selectively manipulating the excitability of cerebellar neurons, we ask how dysfunction of the cerebellum affects the brain circuitry and generates the autistic phenotypes over development.

Selected Publications

Chao, O. Y., Pathak, S. S., Zhang, H., Augustine, G. J., Christie, J. M., Kikuchi, C., Taniguchi, H., Yang, Y. M. (2023). Social memory deficit caused by dysregulation of the cerebellar vermis. Nature Communications, 14 6007: 1-19. PMID: 37752149. doi: https://doi.org/10.1038/s41467-023-41744-2 

Levings, D. C., Pathak, S. S., Yang Y. M., Slattery M. (2023). Limited expression of Nrf2 in neurons across the central nervous system. Redox Biology, 65 102830: 1-8. PubMed ID: 37544245. doi: https://doi.org/10.1016/j.redox.2023.102830

Rudolph S., Badura A., Lutzu S., Pathak S. S., Thieme A., Verpeut J. L., Wagner M. J., Yang Y. M., Fioravante D. (2023). Cognitive-affective functions of the cerebellum. The Journal of Neuroscience, 43 (45): 7554-7564. PMID: 37940582. doi: https://www.jneurosci.org/content/43/45/7554

Chao, O. Y., Nikolaus, S., Yang, Y. M.*, Huston, J. P. (2022). Neuronal circuitry for recognition memory of object and place in rodent models. Neuroscience & Biobehavioral Reviews, 141 (104855): 1-30. PMID: 36089106. doi: https://doi.org/10.1016/j.neubiorev.2022.104855 (*Co-corresponding author)

Fang, K., Liu, D., Pathak, S. S., Yang, B., Li, J., Karthikeyan, R., Chao, O. Y., Yang, Y. M.*, Jin, V. X., Cao, R. (2021). Disruption of circadian rhythms by ambient light during neurodevelopment leads to autistic-like molecular and behavioral alterations in adult mice. Cells, 10 (12), 3314-3333. PMID: 34943821. doi: https://doi.org/10.3390/cells10123314 (*Co-corresponding author)

Chao, O. Y., Zhang, H., Pathak, S. S., Huston, J. P., Yang, Y. M. (2021). Functional convergence of motor and social processes in lobule IV/V of the mouse cerebellum. Cerebellum, 20: 836–852. PMID: 33661502. doi: https://doi.org/10.1007/s12311-021-01246-7 

Chao, O. Y., Pathak, S. S., Zhang, H., Dunaway, N., Li, J. S., Mattern, C., Nikolaus, S., Huston, J. P., Yang, Y. M. (2020). Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism. Molecular Brain, 13: 1-16. PMID: 32778145. doi: https://doi.org/10.1186/s13041-020-00649-7 

Chao, O. Y., de Souza Silva, M. A., Yang, Y. M.*, Huston, J. P. (2020). The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties. Neuroscience and Biobehavioral Reviews, 113: 373-407. PMID: 32298711. doi: https://doi.org/10.1016/j.neubiorev.2020.04.007 (*Co-corresponding author)

Chao, O. Y., de Marron Fernandez Velasco, E., Pathak, S. S., Maitra, S., Zhang, H., Duvick, L., Wickman, K., Orr, H. T., Hirai, H., Yang, Y. M. (2020). Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism. Neuropsychopharmacology, 45 (7): 1159-1170. PMID: 32179875. doi: https://doi.org/10.1038/s41386-020-0656-5 

Lesperance, L. S., Yang, Y. M., Wang, L. Y. (2020). Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse. Molecular Brain, 13: 1-18. PMID: 31941524. doi: https://doi.org/10.1186/s13041-019-0536-2 

Chao, O. Y., Yang, Y. M. (2019). Timing constraints of action potential evoked Ca2+ current and transmitter release at a central nerve terminal. Scientific Reports, 9: 1-14. PMID: 30872753. doi: https://doi.org/10.1038/s41598-019-41120-5 

Fekete, A., Nakamura, Y., Yang, Y. M., Herlitze, S., Mark, M. D., DiGregorio, D. A., Wang, L. Y. (2019). Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules. Nature Communications, 10 (1): 826-842. PMID: 30778063. doi: https://doi.org/10.1038/s41467-019-08452-2 

Chao, O. Y., Yunger, R., Yang, Y. M. (2018). Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism. Behavioural Brain Research, 347: 140-147. PMID: 29545145. doi: https://doi.org/10.1016/j.bbr.2018.03.014 

Yang, Y. M.*, Arsenault, J., Bah, A., Krzeminski, M., Fekete, A., Chao, O. Y., Pacey, L. K., Wang, A., Forman-Kay, J., Hampson, D. R., Wang, L. Y. (2020). (Epub 2018) Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain. Molecular Psychiatry, 25 (9): 2017-2035. PMID: 30224722. doi: https://doi.org/10.1038/s41380-018-0240-0 (*Co-corresponding author)

Yang, Y. M., Wang, W., Fedchyshyn, M. J., Zhou, Z., Ding, J., Wang, L. Y. (2014). Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents. Nature Communications, 5: 1-13. PMID: 25078759. doi: https://doi.org/10.1038/ncomms5564 .

Yang, Y. M., Aitoubah, J., Lauer, A. M., Nuriya, M., Takamiya, K., Jia, Z., May, B. J., Huganir, R. L., Wang, L. Y. (2011). GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse. The Journal of Physiology, 589 (17): 4209-4227. PMID: 21690196. doi: https://doi.org/10.1113/jphysiol.2011.208066 

Zhang, B., Sun, L., Yang, Y. M., Huang, H. P., Zhu, F. P., Wang, L., Zhang, X. Y., Guo, S., Zuo, P. L., Zhang, C. X., Ding, J. P., Wang, L. Y., Zhou, Z. (2011). Action potential bursts enhance transmitter release at a giant central synapse. The Journal of Physiology, 589 (9): 2213-2227. PMID: 21486773. doi: https://doi.org/10.1113/jphysiol.2010.200154 

Yang, Y. M., Fedchyshyn, M. J., Grande, G., Aitoubah, J., Tsang, C. W., Xie, H., Ackerley, C. A., Trimble, W. S., Wang, L. Y. (2010). Septins regulate developmental switching from microdomain to nanodomain coupling of Ca²⁺ influx to neurotransmitter release at a central synapse. Neuron, 67 (1): 100-115. PMID: 20624595. doi: https://doi.org/10.1016/j.neuron.2010.06.003 

Wang, L. Y., Fedchyshyn, M. J., Yang, Y. M. (2009). Action potential evoked transmitter release in central synapses: Insights from the developing calyx of Held. Molecular Brain, 2: 1-11. PMID: 19939269. doi: https://doi.org/10.1186/1756-6606-2-36 

Joshi, I., Yang, Y. M.*, Wang, L. Y. (2007). Coincident activation of metabotropic glutamate receptors and NMDA receptors (NMDARs) downregulates perisynaptic/extrasynaptic NMDARs and enhances high-fidelity neurotransmission at the developing calyx of Held synapse. The Journal of Neuroscience, 27 (37): 9989-9999. PMID: 17855613. doi: https://doi.org/10.1523/JNEUROSCI.2506-07.2007 (*Co-first author)

Yang, Y. M., Wang, L. Y. (2006). Amplitude and kinetics of action potential-evoked Ca²⁺ current and its efficacy in triggering transmitter release at the developing calyx of Held synapse. The Journal of Neuroscience, 26 (21): 5698-5708. PMID: 16723526. doi: https://doi.org/10.1523/JNEUROSCI.4889-05.2006

Bio

I am a biological anthropologist and field researcher interested broadly in how climate change affects social-environmental systems, both past and present. My research broadly focuses on how climate change affects humans – their mobility, access, and health.

Currently, I have two main projects. First the Alaska Social-Environmental Systems Project (AkSES) seeks to understand how ongoing climate change will affect rural communities in Alaska under various Representative Controlled Pathway models (RCPs) representing the future of carbon emissions. We model how thawing permafrost increases risks for communities from environmental hazards, infrastructure damage, and thawing historical cemeteries from past epidemics using GIS, remote sensing methodologies, and multivariate statistics. This project prioritizes multiple forms of data use including public climate data and climate projections, archival and historical primary source data, as well as community created data. This project is currently recruiting research assistants. To find out more: https://arcg.is/jru1v

My second project focuses on human evolutionary anatomy, paleoecology, and human dispersal patterns in Southeast Asia during the past 80,000 years. Specifically, I investigate how past climate change and competition for resources may have influenced human dispersal pathways in Southeast Asia. I use paleoclimate niche modeling and GIS with the goal of increasing the success of traditional fossil survey methods. I am a National Geographic Explorer for this research and, since 2014, a member of an international team of researchers doing human origins excavations in the Lao PDR in concert with the Lao Ministry of Heritage, Culture, and Tourism, the University of Illinois at Urbana-Champaign, the French National Centre for Scientific Research (CNRS), and the Musée de l’Homme, Paris.

My area of expertise are: human gross anatomy, human evolutionary anatomy, climate change modeling/species distribution modeling, and GIS/remote sensing.

Research Summary

The focus of our molecular parasitology laboratory is trypanosomes. Species of these vector-borne protozoan parasites cause World Health Organization-designated Neglected Tropical Diseases that are endemic to poor, rural populations and for which new drug targets are urgently needed. The laboratory studies aspects of their metabolism and mitochondrial gene expression, looking not only for vulnerabilities that may serve as new drug targets but also at processes that can inform our fundamental understanding of eukaryotic evolution.

Teaching Summary

Microbiology and Parasitology
Mentoring/Advising: undergraduates, graduate & post-doctoral fellows