Indiana University
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The Gill Center for Biomolecular Science

Yousuf O. Ali | Gill Research Scientists

Assistant Research Scientist

Office: MSBII 112
TEL: 215-543-4993
Email: yoali@indiana.edu

Education

  • 2011, Ph.D., University of Miami
  • 2005, B.A., Ohio Wesleyan University

Research Interests

My main research interests lie in understanding some of the underlying mechanisms that disrupt cellular homeostasis and serve as a basis of disease in different proteinopathies, specifically Alzheimer’s disease and tauopathies. Specifically, my current scientific endeavors diverge in two interesting directions:

  1. First, following my past training, I am interested in understanding the intrinsic maintenance mechanisms in neurons required to sustain neuronal health and repair damages upon various insults. Specifically, I study how such maintenance mechanisms are hampered in Alzheimer’s disease and proteinopathies, with the goal of utilizing the underlying mechanisms to harness novel neuroprotective therapeutics. One such molecule discovered to impart robust neuroprotection is called NMNAT2. NMNATs play roles in neuronal maintenance and their overexpression provides neuroprotection in various neurodegenerative conditions. Deleting NMNAT2 function in mice causes significant axonal deterioration and neuronal loss. Supporting its role as a neuronal maintenance factor in humans, nmnat2 mRNA expression is reduced in many neurodegenerative diseases, including tauopathy and AD. In rTg4510 transgenic mice, a Frontotemporal Dementia and Parkinsonism-17 (FTDP-17) tauopathy model, NMNAT2 abundance declines prior to the onset of neurodegeneration or memory deficits. Most importantly, elevating NMNAT2 levels in rTg4510 mice reduces Tau burden and ameliorates neurodegenerative phenotypes. NMNAT2 levels are also reduced in mouse brains harboring familial APP/PS1 mutations. Recently, I have shown that NMNAT2 imparts neuroprotection in proteinopathies by functioning as a chaperone that aids in removing toxic protein aggregates. It does so by interacting with HSP90 and functioning as a foldase in various proteotoxicity models. My ongoing research efforts include understanding novel protein-protein interactions of NMNAT2 to better understand how it functions as a neuronal maintenance factor, and to develop a feasible drug discovery effort targeting upregulation of this protein as a therapy for such debilitating neurological disorders.
  2. Second, I am interested in understanding if heart disease is an early catastrophe in Alzheimer’s disease that accelerates dementia later in life. Afflictions of the heart and brain share common triggers and biochemical characteristics, including inflammation, oxidative stress, and hypoxia, and oxygen deficit caused by impaired blood flow. Growing evidence supports a strong and likely causal association between cardiovascular disease (CVD), and its risk factors, with incidence of cognitive decline and Alzheimer’s disease. It is not clear however, whether this relation may be due to shared risk factors, or due to direct or indirect influences of CVD on the pathological processes, which cause AD. My interest lies in understanding whether an Alzheimer’s heart functions any differently from a normal heart. Although preliminary, my current work reveals that in two different AD mouse models, heart dysfunctions can occur as a consequence of the expression of APP in the brain, leading to an age-dependent accumulation of amyloid oligomers in the AD heart. This raises the possibility that amyloid oligomers can be released into the circulation and get into the heart, resulting in cardiac amyloidosis and heart dysfunction. Such work has translational value, with the ongoing work on amyloid specific antibody therapy, which can be beneficial for improving heart functions in pre-AD patients. Currently, I am characterizing the nature and timing of such oligomeric deposition in the AD heart and if these indeed compromise heart function.

Representative Publications

  • Ali YO et al. (2015) A Novel NMNAT2:HSP90 Complex Mediates Proteostasis in Protein Misfolding Disorders (In Revision).
  • Ciupek, S.M., Ali YO et al. (2015) Progressive functional impairments of hippocampal neurons in a tauopathy mouse model. (Accepted) Journal of Neuroscience (March).
  • Majid T, Ali YO, Venikraramani D, Jang MK, Lu H-C, Pautler RG. (2014) In Vivo Axonal Transport Deficits in a Mouse Model of Fronto-Temporal Dementia. NeuroImage: Clinical. Mar 31; 4:711-7.
  • Ali YO, Li-Kroeger D, Bellen HJ, Zhai RG, Lu, H-C (2013). Sustaining a Healthy Brain: NMNAT Functions as an Essential Endogenous Neuronal Maintenance Factor. Trends Neurosci. 2013, 36 (11), 632-640. PMCID:PMC3857727 (Featured Cover Article).
  • Zang S*, Ali YO*, Ruan K, Zhai RG. (2012) Drosophila NMNAT maintains the dynamic presynaptic active zone structure through interaction with BRP. EMBO Reports, 14(1): 87-92. PMCID:PMC3537136. *Co-First Authors (Featured Cover Article) Highlighted in EMBO Reports in Chaperoning the synapse-NMNAT protects Bruchpilot from crashing
  • Ljunberg C*, Ali YO*, Zhu J, Oka K, Zhai RG, Lu HC. (2011) CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy. Human Molecular Genetics. 21(2):251-67. PMCID:PMC3276285.
    *Co-First Authors.

    For full list of Publications, visit:
    http://www.ncbi.nlm.nih.gov/pubmed/?term=Ali+YO