Niraja Dighe
Singapore General Hospital
TransgeneGenetic enhancementVirologyCarcinogenesisBiology
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Publications 17
#1Zhiyong Poon (SGH: Singapore General Hospital)H-Index: 6
#2Niraja Dighe (SGH: Singapore General Hospital)H-Index: 2
Last. William Yk Hwang (NUS: National University of Singapore)H-Index: 18
view all 9 authors...
The study of myelodysplastic syndromes (MDS) in murine models has now indicated the possible involvement of the bone marrow microenvironment in the generation of dysplastic hematopoietic cells. However, there is scant work on patient samples and the role of hypomethylating agents on the bone marrow stromal cells of MDS patients is unclear. We show that human MDS-MSCs exhibit phenotypic, transcriptomic and epigenetic abnormalities. Stimuli provided by MDS-MSCs impaired the growth and function of ...
13 CitationsSource
#1Sudipto BariH-Index: 9
#2Qixing Zhong (Genome Institute of Singapore)H-Index: 1
Last. William Yk HwangH-Index: 18
view all 11 authors...
: Umbilical cord blood (UCB) transplants in adults have slower hematopoietic recovery compared to bone marrow (BM) or peripheral blood (PB) stem cells mainly due to low number of total nucleated cells and hematopoietic stem and progenitor cells (HSPC). As such in this study, we aimed to perform ex vivo expansion of UCB HSPC from non-enriched mononucleated cells (MNC) using novel azole-based small molecules. Freshly-thawed UCB-MNC were cultured in expansion medium supplemented with small molecule...
6 CitationsSource
#1Niraja Dighe (NUS: National University of Singapore)H-Index: 6
#2Kang Wei Tan (NUS: National University of Singapore)H-Index: 1
Last. Citra Nurfarah Zaini Mattar (NUS: National University of Singapore)H-Index: 14
view all 14 authors...
Major hemoglobinopathies place tremendous strain on global resources. Intrauterine hemopoietic cell transplantation (IUHCT) and gene transfer (IUGT) can potentially reduce perinatal morbidities with greater efficacy than postnatal therapy alone. We performed both procedures in the thalassemic HbbTh3/+ mouse. Intraperitoneal delivery of co-isogenic cells at embryonic days13-14 produced dose-dependent chimerism. High-dose adult bone marrow (BM) cells maintained 0.2–3.1% chimerism over ~24 weeks an...
1 CitationsSource
#1Jerry Chan (NUS: National University of Singapore)H-Index: 32
#2Lay-Geok Tan (NUS: National University of Singapore)H-Index: 5
Last. Citra Nurfarah Zaini Mattar (NUS: National University of Singapore)H-Index: 14
view all 7 authors...
Intrauterine haemopoietic stem cell therapy (IUHSCT) can be considered for treating haemoglobinopathies and certain metabolic diseases in early pregnancy, for the ability to easily escalate cell dose for higher engraftment and to target the pre-immune fetus. The potential therapeutic benefits are currently unrealised due to sub-therapeutic cell engraftment from host cell competition for haemopoietic niches or neutralising immune response.We investigated the strategy of IUHSCT followed by post-na...
#1Niraja Dighe (NUS: National University of Singapore)H-Index: 6
#2Maroun Khoury (MIT: Massachusetts Institute of Technology)H-Index: 4
Last. Jerry Kok Yen Chan (NUS: National University of Singapore)H-Index: 6
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Hematopoietic Stem Cell (HSC) targeted gene transfer is an attractive treatment option for a number of hematopoietic disorders caused by single gene defects. However, extensive methylation of promoter sequences results in silencing of therapeutic gene expression. The choice of an appropriate promoter is therefore crucial for reproducible, stable and long-term transgene expression in clinical gene therapy. Recent studies suggest efficient and stable expression of transgenes from the ubiquitous ch...
14 CitationsSource
#1Ali NowrouziH-Index: 17
#2Wing T. Cheung (Imperial College London)H-Index: 2
Last. Michael Themis (Imperial College London)H-Index: 25
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Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the live...
15 CitationsSource
#1Citra Nurfarah Zaini Mattar (NUS: National University of Singapore)H-Index: 14
#2Amit C. Nathwani (UCL: University College London)H-Index: 41
Last. Jerry Chan (NUS: National University of Singapore)H-Index: 32
view all 20 authors...
Intrauterine gene transfer (IUGT) offers ontological advantages including immune naivete mediating tolerance to the vector and transgenic products, and effecting a cure before development of irreversible pathology. Despite proof-of-principle in rodent models, expression efficacy with a therapeutic transgene has yet to be demonstrated in a preclinical nonhuman primate (NHP) model. We aimed to determine the efficacy of human Factor IX (hFIX) expression after adeno-associated-viral (AAV)-mediated I...
41 CitationsSource
#2Amit C. NathwaniH-Index: 41
Last. Jerry ChanH-Index: 32
view all 15 authors...
#2Niraja DigheH-Index: 6
Last. Jerry ChanH-Index: 32
view all 10 authors...
2 Citations
#2Simon N. Waddington (Imperial College London)H-Index: 40
#3Manfred Schmidt (University of Freiburg)H-Index: 43
Last. Charles Coutelle (Imperial College London)H-Index: 41
view all 17 authors...
Gene therapy by use of integrating vectors carrying therapeutic transgene sequences offers the potential for a permanent cure of genetic diseases due to the ability of these vectors to integrate in a stable manner into the patients’ chromosomes. Since three cases of T-cell leukaemia have been identified after retrovirus gene therapy for X-linked severe combined immune deficiency as being associated with the integrating vector used for gene therapy the need for animal models to test for vector sa...