- B.Sc. in Neuroscience, University of Pittsburgh, Pittsburgh, PA.
- B.A. in Political Science. Minor Chemistry (Magna Cum Laude) University of Pittsburgh, Pittsburgh, PA.
- Ph.D. in Neuroscience, University of Miami: Miller School of Medicine, Miami, FL.
I am fascinated by and committed to understand how and why neurons become vulnerable during disease states. This intrigue has persisted throughout my research career starting with my undergraduate work at the University of Pittsburgh with Drs. Robert Hickey and Steven H. Graham examining the role of Bcl-2 family members in apoptosis. After obtaining my B.S. in Neuroscience, I performed my graduate work in Dr. Carlos T. Moraes’ laboratory (University of Miami: Miler School of Medicine). During my graduate training, I used mouse models to study how mitochondrial dysfunction contributed to the selective degeneration of certain neuronal populations in the central nervous system. Although mitochondria provide energy for all neurons, each neuronal subtype withstands different degrees of mitochondrial dysfunction. To complement these skills, I sought a postdoctoral position with Dr. Richard J. Youle (National Institutes of Health/NINDS) to gain additional experience in biochemistry and cell biology. My postdoctoral efforts were among the first reports to validate the importance of mitochondrial quality control in the survival of dopaminergic neurons in vivo.
Mitochondrial dysfunction and mutated mitochondrial DNA (mtDNA) are key pathophysiological features of all major neurodegenerative diseases. With over 600 neurological disorders affecting an estimated 50 million Americans, the need for understanding the events preceding and contributing to neurodegeneration are crucial for our increasingly growing aged population. My past, current, and future work implies that even though mitochondria provide the energy required for all neurons in the brain, this requirement and tolerance for dysfunction are different depending on the neuron subtype explaining some of the neurodegenerative patterns seen in disease.
Considerable efforts in the mitochondrial research field are currently focused on understanding the basic mechanisms of how mitochondrial processes work, such as mitophagy (the selective removal of damaged mitochondria) and the mitochondrial unfolded protein response. Newly developed transgenic reporters mouse models are currently underway to study these newly defined mitochondrial processes. I am now working to define the function of these processes in neurons to define their importance in neurodegenerative disease. Although all neurons are highly reliant on oxidative phosphorylation as well as mitochondrial function for ATP generation, the diversity and heterogeneity of neurons indicates that something as simple as energy demand is likely very complex. My graduate and postdoctoral research has touched upon and supported this idea, and I would like my research to continue in this same vein. My prospective research projects will focus on: 1) to what degree mitochondrial dysfunction is tolerated by different neuron subtypes, 2) mechanisms that contribute to the accumulation of mutated mtDNA in neurons, and 3) to what extent mitochondrial function is affected by aggregates that accumulate in neurodegenerative disease, such as aIpha-synuclein.
- Fritsch LE, Ju J, Gudenschwager Basso EK, Soliman E, Paul S, Chen J, Kaloss AM, Kowalski EA, Tuhy TC, Somaiya RD, Wang X, Allen IC, Theus MH, Pickrell AM. Type I Interferon Response Is Mediated by NLRX1-cGAS-STING Signaling in Brain Injury. Front Mol Neurosci. 2022 Feb 25;15:852243. doi: 10.3389/fnmol.2022.852243. PMID: 35283725; PMCID: PMC8916033. Type I Interferon Response Is Mediated by NLRX1-cGAS-STING Signaling in Brain Injury.
- Paul S, Pickrell AM. Hidden phenotypes of PINK1/Parkin knockout mice. Biochim Biophys Acta Gen Subj. 2021 Jun;1865(6):129871. doi: 10.1016/j.bbagen.2021.129871. Epub 2021 Feb 9. PMID: 33571581. Hidden phenotypes of PINK1/Parkin knockout mice.
- Sarraf SA, Sideris DP, Giagtzoglou N, Ni L, Kankel MW, Sen A, Bochicchio LE, Huang CH, Nussenzweig SC, Worley SH, Morton PD, Artavanis-Tsakonas S, Youle RJ, Pickrell AM. Cell Rep. 2019 Oct 1;29(1):225-235.e5. doi: 10.1016/j.celrep.2019.08.085. PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis.
- *Pinto, M., *Pickrell, AM., *Wang, X., Bacman, S.R., Yu, A., Hida, A., Dillon, L., Morton, P.D., Malek, T., Williams, S.W., and Moraes, C.T. "Transient mitochondrial DNA double strand breaks in mice cause accelerated aging phenotypes in a ROS-dependent but p53/p21-independent manner." Cell Death and Differentiation. 2017 24(2): 288-299.
- *Pickrell, AM., *Huang, C.H., Kennedy, S.K., Ordureau, A., Sideris, D.P., Hokestra, J.G., Harper, J.W., and Youle, R.J. “Endogenous Parkin Preserves Dopaminergic Substantia Nigral Neurons Following Mitochondrial DNA Mutagenic Stress.” Neuron. 2015. 87(2): 371-81.
- Pickrell, AM. and Youle, R.J. “The Role of PINK1, Parkin and Mitochondrial Fidelity in Parkinson’s Disease.” Neuron. 2015 85(2): 257-273.
- *Pinto M., *Pickrell AM., Fukui H., and Moraes C.T. Neurobiology of Aging. “Mitochondrial DNA damage in a mouse model of Alzheimer's disease decreases A plaque formation.” 2013 34(10): 2399-407.
- *Pickrell, AM., *Pinto, M, Hida, A., and Moraes, C.T. "Striatal dysfunctions associated with mtDNA damage in dopaminergic neurons of a mouse model of PD." J. Neuroscience 2011 31(48): 17649-58.
- Pickrell, AM., Fukui, H., Wang, X., Pinto, M., Moraes, C.T. “The Striatum is Highly Susceptible to Mitochondrial Oxidative Phosphorylation Dysfunctions.” Journal of Neuroscience. 2011 31(27): 9895-904.
* denotes equal contribution
For a full list of Dr. Pickrell's publications, visit PubMed