Nathan Ng

All Publications

• DSC perfusion MRI-derived fractional tumor burden and relative CBV differentiate tumor progression and radiation necrosis in brain metastases treated with stereotactic radiosurgery. American Journal of Neuroradiology ‡Kuo, F., ‡Ng, N. N., Nagpal, S., Pollom, E. L., Soltys, S., Hayden-Gephart, M., Li, G., Born, D. E., Iv, M. 2022; 43 (5): 689-695

  View details for DOI 10.3174/ajnr.A7501

• Brain iron assessment after ferumoxytol-enhanced MRI in children and young adults with arteriovenous malformations: a case-control study. Radiology Iv, M., Ng, N. N., Nair, S., Zhang, Y., Lavezo, J., Cheshier, S. H., Holdsworth, S. J., Moseley, M. E., Rosenberg, J., Grant, G. A., Yeom, K. W. 2020; 297 (2): 438-446

  View details for DOI 10.1148/radiol.2020200378

• Locoregional delivery of stem cell-based therapies. Science Translational Medicine Ng, N. N., Thakor, A. S. 2020; 12 (547): 1-17

  View details for DOI 10.1126/scitranslmed.aba4564

• A deep learning-based system for survival benefit prediction of tyrosine kinase inhibitors and immune checkpoint inhibitors in stage IV non-small cell lung cancer patients: A multicenter, prognostic study eClinicalMedicine Deng, K., Wang, L., Liu, Y., Li, X., Hou, Q., Cao, M., Ng, N. N., Wang, H., Chen, H., Yeom, K. W., Zhao, M., Wu, N., Gao, P., Shi, J., Liu, Z., Li, W., Tian, J., Song, J. 2022; 51: 1-14

  View details for DOI 10.1016/j.eclinm.2022.101541

• Effects of age on white matter microstructure in children with neurofibromatosis type 1. Journal of Child Neurology Tam, L. T., Ng, N. N., McKenna, E. S., Bruckert, L., Yeom, K. W., Campen, C. J. 2021; 36 (10): 894-900

  View details for DOI 10.1177/08830738211008736

• Emerging role of stem cell-derived extravesicular microRNAs in age-associated human diseases and in different therapies of longevity. Ageing Research Reviews Ullah, M., Ng, N. N., Concepcion, W., Thakor, A. S. 2020; 57: 1-14

  View details for DOI 10.1016/j.arr.2019.100979

• Development and validation of a machine learning model to explore tyrosine kinase inhibitor response in patients with stage IV EGFR variant-positive non-small cell lung cancer. JAMA Network Open Song, J., Wang, L., Ng, N. N., Zhao, M., Shi, J., Wu, N., Li, W., Liu, Z., Yeom, K. W., Tian, J. 2020; 3 (12): 1-13

  View details for DOI 10.1001/jamanetworkopen.2020.30442

• Cerebral volume and diffusion MRI changes in children with sensorineural hearing loss. NeuroImage: Clinical Moon, P. K., Qian, J. Z., McKenna, E., Xi, K., Rowe, N. C., Ng, N. N., Zheng, J., Tam, L. T., MacEachern, S. J., Ahmad, I., Cheng, A. G., Forkert, N. D., Yeom, K. W. 2020; 27: 1-9

  View details for DOI 10.1016/j.nicl.2020.102328

• Association of pediatric acute-onset neuropsychiatric syndrome with microstructural differences in brain regions detected via diffusion-weighted magnetic resonance imaging. JAMA Network Open Zheng, J., Frankovich, J., McKenna, E. S., Rowe, N. C., MacEachern, S. J., Ng, N. N., Tam, L. T., Moon, P. K., Gao, J., Thienemann, M., Forkert, N. D., Yeom, K. W. 2020; 3 (5): 1-15

  View details for DOI 10.1001/jamanetworkopen.2020.4063

• Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associated SCN1A mutation. Neurobiology of Disease Xie, Y., Ng, N. N., Safrina, O. S., Ramos, C. M., Ess, K. C., Schwartz, P. H., Smith, M. A., O'Dowd, D. K. 2020; 134: 1-16

  View details for DOI 10.1016/j.nbd.2019.104627

• Mesenchymal stem cells confer chemoresistance in breast cancer via a CD9 dependent mechanism. Oncotarget Ullah, M., Akbar, A., Ng, N. N., Concepcion, W., Thakor, A. S. 2019; 10 (37): 3435-3450

  Abstract

  The development of chemotherapy drug resistance remains a significant barrier for effective therapy in several cancers including breast cancer. Bone marrow-derived mesenchymal stem cells (BMMSCs) have previously been shown to influence tumor progression and the development of chemoresistance. In the present study, we showed that when GFP labelled BMMSCs and RFP labelled HCC1806 cells are injected together in vivo, they create tumors which contain a new hybrid cell that has characteristics of both BMMSCs and HCC1806 cells. By labelling these cells prior to their injection, we were then able to isolate new hybrid cell from harvested tumors using FACS (DP-HCC1806:BMMSCs). Interestingly, when DP-HCC1806:BMMSCs were then injected into the mammary fat pad of NOD/SCID mice, they produced xenograft tumors which were smaller in size, and exhibited resistance to chemotherapy drugs (i.e. doxorubicin and 5-fluorouracil), when compared tumors from HCC1806 cells alone. This chemoresistance was shown to associated with an increased expression of tetraspanins (CD9, CD81) and drug resistance proteins (BCRP, MDR1). Subsequent siRNA-mediated knockdown of BMMSC-CD9 in DP-HCC1806:BMMSCs resulted in an attenuation of doxorubicin and 5-fluorouracil chemoresistance associated with decreased BCRP and serum cytokine expression (CCL5, CCR5, CXCR12). Our findings suggest that within the tumor microenvironment, CD9 is responsible for the crosstalk between BMMSCs and HCC1806 breast cancer cells (via CCL5, CCR5, and CXCR12) which contributes to chemoresistance. Hence, BMMSC-CD9 may serve as an important therapeutic target for the treatment of breast cancer.

  View details for DOI 10.18632/oncotarget.26952

  View details for PubMedID 31191817

  View details for PubMedCentralID PMC6544397

• Astrocyte-enriched feeder layers from cryopreserved cells support differentiation of spontaneously active networks of human iPSC-derived neurons. Journal of Neuroscience Methods ‡Schutte, R. J., ‡Xie, Y., ‡Ng, N. N., Figueroa, P., Pham, A. T., O'Dowd, D. K. 2018; 294: 91-101

  Abstract

  Human induced pluripotent stem cell (hiPSC)-derived neuronal cultures are a useful tool for studying the mechanisms of neurological disorders and developing novel therapeutics. While plating hiPSC-derived neuronal progenitors onto glial feeder layers prepared from rodent cortex has been reported to promote functional differentiation of neuronal networks, this has not been examined in detail.Here we describe a method of using cryopreserved cells from primary cultures for generation of mouse astrocyte-enriched, neuron-free feeder layers that grow from 10% to 100% confluence in 1 week.Electrophysiological analysis demonstrated that compared to biochemical substrates alone, astrocyte-enriched feeder layers support more rapid differentiation of hiPSC-derived progenitors into excitable neurons that form spontaneously active networks in culture. There was a positive correlation between the degree of astroglial confluence at the time of progenitor plating and the average frequency of postsynaptic currents 3 weeks after plating. One disadvantage to plating on 100% confluent feeder layers was a high incidence of the astroglial layer with the overlying neurons detaching from the coverslips during transfer to the recording chamber.Prevailing methods using primary glial feeder layers can result in possible contamination with rodent neurons and an unpredictable rate of growth. We provide a reliable method of generating mouse astroglial feeder layers from cryopreserved primary cultures to support differentiation of hiPSC-derived neurons.The ability to make astrocyte-enriched feeder layers of defined confluence from cryopreserved primary cultures will facilitate the use of human stem cell derived neuronal cultures for disease modeling.

  View details for DOI 10.1016/j.jneumeth.2017.07.019

  View details for PubMedCentralID PMC5776056

• Reproducible and efficient generation of functionally active neurons from human iPSCs for preclinical disease modeling. Stem Cell Research ‡Xie, Y., ‡Schutte, R. J., ‡Ng, N. N., Ess, K. C., Schwartz, P. H., O'Dowd, D. K. 2018; 26: 84-94

  Abstract

  The use of human induced pluripotent stem cell (hiPSC)-derived neuronal cultures to study the mechanisms of neurological disorders is often limited by low efficiency and high variability in differentiation of functional neurons. Here we compare the functional properties of neurons in cultures prepared with two hiPSC differentiation protocols, both plated on astroglial feeder layers. Using a protocol with an expandable intermediate stage, only a small percentage of cells with neuronal morphology were excitable by 21-23days in culture. In contrast, a direct differentiation strategy of the same hiPSC line produced cultures in which the majority of neurons fired action potentials as early as 4-5days. By 35-38days over 80% of the neurons fired repetitively and many fired spontaneously. Spontaneous post-synaptic currents were observed in ~40% of the neurons at 4-5days and in ~80% by 21-23days. The majority (75%) received both glutamatergic and GABAergic spontaneous postsynaptic currents. The rate and degree of maturation of excitability and synaptic activity was similar between multiple independent platings from a single hiPSC line, and between two different control hiPSC lines. Cultures of rapidly functional neurons will facilitate identification of cellular mechanisms underlying genetically defined neurological disorders and development of novel therapeutics.

  View details for DOI 10.1016/j.scr.2017.12.003

  View details for PubMedCentralID PMC5899925

• Research Associates Program: Expanding clinical research productivity with undergraduate students. SAGE Open Medicine Hoonpongsimanont, W., Sahota, P. K., Ng, N. N., Farooqui, M. J., Chakravarthy, B., Patel, B., Lotfipour, S. 2017; 5: 1-7

  View details for DOI 10.1177/2050312117730245