Bio

Honors & Awards


  • Predoctoral Individual National Research Service Award (F31), National Institute of Health, NINDS (2016-2017)
  • BRAINS Fellow, University of Washington (2019)
  • Neuroscience Scholars Program Associate, Society for Neuroscience (2019-2020)

Boards, Advisory Committees, Professional Organizations


  • Postdoc Representative, Stanford SOM Diversity Cabinet (2019 - Present)
  • Co-Chair, Stanford SURPAS Diversity Advisory Committee (2019 - Present)

Professional Education


  • Doctor of Philosophy, University of Virginia (2018)
  • Bachelor of Science, Florida State University (2011)

Publications

All Publications


  • A three-dimensional dementia model reveals spontaneous cell cycle re-entry and a senescence-associated secretory phenotype. Neurobiology of aging Porterfield, V., Khan, S. S., Foff, E. P., Koseoglu, M. M., Blanco, I. K., Jayaraman, S., Lien, E., McConnell, M. J., Bloom, G. S., Lazo, J. S., Sharlow, E. R. 2020; 90: 125?34

    Abstract

    A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72+ (C9+) ALS patients to derive neuronal progenitor cells. We demonstrated that C9+ and neurotypic neuronal progenitor cells differentiate into neurons. The C9+ neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9+ neurons. Moreover, C9+ neurons expressed high levels of mRNA for CXCL8, a chemokine overexpressed by senescent cells, while media from C9+ neurons contained significant levels of CXCL8, CXCL1, IL13, IP10, CX3CL1, and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia.

    View details for DOI 10.1016/j.neurobiolaging.2020.02.011

    View details for PubMedID 32184029

    View details for PubMedCentralID PMC7166179

  • Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons. Acta neuropathologica Khan, S. S., LaCroix, M., Boyle, G., Sherman, M. A., Brown, J. L., Amar, F., Aldaco, J., Lee, M. K., Bloom, G. S., Lesné, S. E. 2018; 136 (4): 589?605

    Abstract

    ?-Synuclein (?Syn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble ?Syn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted ?Syn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by ?Syn. Overexpression of human wild-type ?Syn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory. It also increased extracellular amyloid-? oligomers (A?Os), ?Syn oligomers, exacerbated tau conformational and phosphorylation variants associated with AD, and enhanced neuronal cell cycle re-entry (CCR), a frequent prelude to neuron death in AD. Conversely, ablation of the SNCA gene encoding for ?Syn in APP mice improved memory retention in spite of increased plaque burden. Reminiscent of the effect of MAPT ablation in APP mice, SNCA deletion prevented premature mortality. Moreover, the absence of ?Syn decreased extracellular A?Os, ameliorated CCR, and rescued postsynaptic marker deficits. In summary, this complementary, bidirectional genetic approach implicates ?Syn as an essential mediator of key phenotypes in AD and offers new functional insight into ?Syn pathophysiology.

    View details for DOI 10.1007/s00401-018-1886-z

    View details for PubMedID 29995210

    View details for PubMedCentralID PMC6329667

  • mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association Norambuena, A., Wallrabe, H., McMahon, L., Silva, A., Swanson, E., Khan, S. S., Baerthlein, D., Kodis, E., Oddo, S., Mandell, J. W., Bloom, G. S. 2017; 13 (2): 152?67

    Abstract

    A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-? oligomers (A?Os) and tau, the precursors of plaques and tangles. We now report that CCR results from A?O-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. A?Os were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by A?Os unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death.

    View details for DOI 10.1016/j.jalz.2016.08.015

    View details for PubMedID 27693185

    View details for PubMedCentralID PMC5318248

  • Tau: The Center of a Signaling Nexus in Alzheimer's Disease. Frontiers in neuroscience Khan, S. S., Bloom, G. S. 2016; 10: 31

    Abstract

    Tau is a microtubule-associated protein whose misfolding, hyper-phosphorylation, loss of normal function and toxic gain of function are linked to several neurodegenerative disorders, including Alzheimer's disease (AD). This review discusses the role of tau in amyloid-? (A?) induced toxicity in AD. The consequences of tau dysfunction, starting from the axon and concluding at somadendritic compartments, will be highlighted.

    View details for DOI 10.3389/fnins.2016.00031

    View details for PubMedID 26903798

    View details for PubMedCentralID PMC4746348

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