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Helen Zhao, Ph.D.

My current research project is focused on investigating the underlying mechanisms of Alzheimer's disease (AD)-like neuropathology using Down syndrome (DS) patient derived iPS cells. All Down syndrome patients at age of 40 have AD-like neuropathological changes including accumulation of plaque and tangle, most of them develop cognitive decline and exhibit sign of dementia at late 60s. Besides the extremely high prevalence of AD in DS individuals during adulthood, many AD-like pathological signatures such as endosome abnormality, impaired neurogenesis, neural connectivity and excessive astrocyte genesis can be traced back to the prenatal stage. By using DS specific iPSC-derived brain organoid as a model, we are able to investigate early stages of AD neuropathology and observe the disease progression in action. iPSC technology offers us a unique opportunity to better understand the AD-like neuropathology in DS patients and may eventually shed light on developing therapeutic strategies to prevent or lower the high prevalence of AD in DS patients. We have been able to recapitulate some of AD-like neuropathology in DS brain organoids and observed abnormal amyloid beta metabolisms and Tau aggregation.

My previous projects are focused on 1) investigating the underlying mechanisms of neuropathology in Andeans with Chronic mountain sickness (CMS). For the first time, we demonstrated that iPSC-derived neurons from CMS subjects had neuronal abnormality and mitochondrial dysfunction. CMS neurons are more susceptible to hypoxia-induced cell death and the impaired adaptive mechanism is due to lack of protective mechanism such as Akt activation; 2) investigating the mechanism of hyperoxia adaptation in hyperoxia-selected Drosophila Melanogaster. We studied gene expression profiles in hyperoxia-selected flies and identified a group of genes, such as antimicrobial peptide genes, that play an important role in the survival under extreme high oxygen environments.  

Chronic mountain sickness patient-specific iPSCs-derived neurons expressing glutamatergic neuronal markers including MAP2 and VGLUT1.


  1. Zhao HW, Lin J, Sieck G, and Haddad GG. Neuroprotective Role of Akt in Hypoxia Adaptation in Andeans. Front Neurosci. 2021 Jan 15;14:607711. doi: 10.3389/fnins.2020.607711. PMID: 33519361; PMCID: PMC7843528. 
  2. Zhao HW, Perkins G, Yao H, Callacondo D, Appenzeller O, Ellisman M, La Spada A.R., Haddad G.G. Mitochondrial dysfunction in iPSC-derived neurons of subjects with chronic mountain sickness. J Appl Physiol (1985). 2018 Sep 1;125(3):832-840. doi: 10.1152/japplphysiol.00689.2017. Epub 2017 Dec 21. PMID: 29357502; PMCID: PMC6734077. 
  3. Zhao HW, Gu XQ, Chailangkarn T, Perkins G, Callacondo D, Appenzeller O, Poulsen O, Zhou D, Muotri AR, Haddad GG. Altered iPSC-derived neurons' sodium channel properties in subjects with Monge's disease.  Neuroscience. 2015 Mar 12;288:187-99. doi: 10.1016/j.neuroscience.2014.12.039. Epub 2015 Jan 3. PMID: 25559931; PMCID: PMC4323892. 
  4. Zhao HW, Zhou D, Nizet V, and Haddad GG. Experimental selection for Drosophila survival in extremely high O2 environments. PLoS One. 2010 Jul 23;5(7):e11701. doi: 10.1371/journal.pone.0011701. PMID: 20668515; PMCID: PMC2909141.