Misiak, Magdalena, Ph.D.
2408D Adams Bldg
Mon-Fri 9:00am-5:00pm (or by appointment)
M. Eng., University of Agriculture, Cracow, Poland (2005)
Postdoctoral Fellow, National Institute on Aging, NIH, Baltimore, USA (2011-2016)
My work in aging extends into olfactory deficits in Alzheimer’s disease (AD). Patients with AD exhibit impaired olfaction, which often occurs early in the disease process; pathology in the olfactory bulb (OB) includes Aβ deposits and neuronal death. Olfactory deficits are evident in patients with mild cognitive impairment (MCI) and may predict conversion to AD. The mechanisms responsible for the degeneration of OB neurons in AD are unknown and understanding the cellular and molecular mechanisms may provide new insight into AD pathogenesis and potential early interventions to predict the disease process. Though oxidative stress increases with age, not all elderly patients suffer neuronal damages associated with increased oxidative stress. Oxidative DNA damage and alterations in cellular DNA repair capacity have been implicated in the aging process and in age-associated neurodegenerative diseases, including AD. My previous work has demonstrated that the capacity of DNA repair enzymes play an important role in the development of mitochondrial, and olfactory dysfunction in our new AD mouse model. DNA repair participates in mediating the mitochondria – nucleus crosstalk, thus DNA repair pathways balance oxidative stress and guard cellular homeostasis.
My current research focuses on the role of DNA repair and oxidative damage pathways in the olfactory system in animal models and human subjects with Alzheimer’s Disease (AD). I would like to study moderating effect of ApoE isoforms on cellular and mitochondrial dysfunctions in olfactory cultures obtained non-invasively from nasal epithelium from elderly patients with and without MCI. Evidence of changes in level of the oxidative stress, DNA damage, and DNA repair capacity in olfactory neuronal cultures between controls, MCI and patients with AD conversion could lead to development of standard molecular tests used for the early disease assessment. Screening for markers such as ROS, nuclear and mitochondrial DNA damage and DNA repair markers in combination with olfactory assessment could be a powerful tool for early recognition of the disease.
My work is by nature interdisciplinary and utilizes the most recent advances in neuroscience to understand the molecular and neural basis of oxidative stress in neurodegenerative diseases and aging. Data-gathering and analysis would provide ample opportunities for undergraduate and graduate students to learn and contribute. The extension of my current work has real-world applications as a potential early identifier of AD, which may lead to improved interventions. By pairing the knowledge and tools I have gained from this work with my desire to utilize novel scientific approaches and expand my research interests, I look forward to continuing my pursuits in the field of neuroscience and aging.
Olfaction and Alzheimer’s disease: mechanism of action and early intervention
Oxidative stress and mitochondrial dysfunction in neurodegeneration
APOE4 as a risk factor in AD
- Misiak M., Singh S., Drewlo S., Beyer C., Arnold S. (2010) Brain region-specific vulnerability of astrocytes in response to 3-nitropropionic acid is mediated by cytochrome c oxidase isoform expression. Cell Tissue Res, 341: 83-93.
- Misiak M., Beyer C., Arnold S. (2010) Gender-specific role of mitochondria in the vulnerability of 6-hydroxydopamine treated mesencephalic neurons. Biochim Biophys Acta, 1797: 1178-1188.
- Misiak M., Vergara Greeno R, Baptiste B.A., Sykora P., Liu D., Ahn J., Cordonnier S., Croteau D.L., Mattson M.P. and Bohr A.V. DNA polymerase β haploinsufficiency triggers death of newly generated olfactory bulb neurons and impairs olfaction in 3xTgAD mice. Aging Cell, 2016: 16(1):162-172.
- Misiak M., Hipolito M.S., Ressom H.W., Obisesan T.O., Manaye K.F., Nwulia E.A. Apo E4 Alleles and Impaired Olfaction as Predictors of Alzheimer's Disease. Clin Exp Psychol. 2017: 3(4). pii: 169.
- Lorenz L., Dang J., Misiak M., Tameh Abolfazl A., Beyer C., Kipp M. (2009) Combined 17beta-oestradiol and progesterone treatment prevents neuronal cell injury in cortical but not midbrain neurones or neuroblastoma cells. J Neuroendocrinol, 21:841-9.
- Pierzchala-Koziec K., Zubel J., Kanitz E., Misiak M. (2006) Grelin modulates the in vitro release of opioids and leptin from the hypothalamus of fed and fasted mice. Front in Neuroendocrinol, 27(1):34-35.
- Singh S., Misiak M., Beyer C., Arnold S. (2009) Cytochrome c oxidase isoform IV-2 is involved in 3-nitropropionic acid-induced toxicity in striatal astrocytes. Glia, 57: 1480-91.
- Singh S., Misiak M., Beyer C., Arnold S. (2010) Brain region specificity of 3-nitropropionic acid-induced vulnerability of neurons involves cytochrome c oxidase. Neurochem Int., 57(3):297-305.
- Canugovi C., Misiak M., Ferrarelli L.K., Croteau D.L., Bohr V.A. (2013) The role of DNA repair in brain related disease pathology. DNA Repair (Amst), 35(6):1293-300.
- Canugovi C., Misiak M., Scheibye-Knudsen M., Croteau D.L., Mattson M.P., Bohr V.A. (2015) Loss of NEIL1 causes defects in olfactory function in mice. Neurobiol Aging., 36(2):1007-12.
- Sykora P., Misiak M., Wang Y., Ghosh S., Leandro G.S., Liu D., Tian J., Baptiste B.A., Cong W.N., Brenerman B.M., Fang E., Becker K.G., Hamilton R.J., Chigurupati S., Zhang Y., Egan J.M., Croteau D.L., Wilson D.M. 3rd, Mattson M.P., Bohr V.A. (2015) DNA polymerase β deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes. Nucleic Acids Res., 43(2):943-59.
- Cheng A., Yang Y., Zhou Y., Maharana C., Lu D., Peng W., Liu Y., Wan R., Marosi K., Misiak M., Bohr V.A., Mattson M.P. Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise, and Metabolic and Excitatory Challenges. (2015) Cell Metabolism.