Nathan Ng

All Publications

• 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: 104627

  View details for DOI 10.1101/524835

• 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: 100979

  Abstract

  Organismal aging involves the progressive decline in organ function and increased susceptibility to age-associated diseases. This has been associated with the aging of stem cell populations within the body that decreases the capacity of stem cells to self-renew, differentiate, and regenerate damaged tissues and organs. This review aims to explore how aging is associated with the dysregulation of stem cell-derived extracellular vesicles (SCEVs) and their corresponding miRNA cargo (SCEV-miRNAs), which are short non-coding RNAs involved in post-transcriptional regulation of target genes. Recent evidence has suggested that in aging stem cells, SCEV-miRNAs may play a vital role regulating various processes that contribute to aging: cellular senescence, stem cell exhaustion, telomere length, and circadian rhythm. Hence, further clarifying the age-dependent molecular mechanisms through which SCEV-miRNAs exert their downstream effects may inform a greater understanding of the biology of aging, elucidate their role in stem cell function, and identify important targets for future regenerative therapies. Additionally, current studies evaluating therapeutic role of SCEVs and SCEV-miRNAs in treating several age-associated diseases are also discussed.

  View details for DOI 10.1016/j.arr.2019.100979

• 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): 3435–50

  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

• 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 (*authors contributed equally)

  View details for DOI 10.1016/j.scr.2017.12.003

• 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 (*authors contributed equally)

  View details for DOI 10.1016/j.jneumeth.2017.07.019

• 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