Biology subjects

Oguche, S.

Publications and source records attributed to Oguche, S..

3 recordsLinked to original sources

bioRxiv2023

Computational design of Matrix Metalloprotenaise-9 (MMP-9) resistant to auto-cleavage

Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that remodels the extracellular matrix and has been implicated as a major driver in cancer metastasis. Hence, there is a high demand for MMP-9 inhibitors for therapeutic purposes. For such drug design efforts, large amounts of MMP-9 are required. Yet, the catalytic domain of MMP-9 (MMP-9Cat) is an intrinsically unstable enzyme that tends to auto-cleave within minutes, making it difficult to use in drug design experiments and other biophysical studies. We set our goal to design MMP-9Cat variant that is active but stable to autocleavage. For this purpose, we first identified potential autocleavage sites on MMP-9Cat using mass spectroscopy and then eliminated the autocleavage site by predicting mutations that minimize autocleavage potential without reducing enzyme stability. Four computationally designed MMP-9Cat variants were experimentally constructed and evaluated for auto-cleavage and enzyme activity. Our best variant, Des2, with 2 mutations, was as active as the wild-type enzyme but did not exhibit auto-cleavage after seven days of incubation at 37{degrees}C. This MMP-9Cat variant, with an identical to MMP- 9Cat WT active site, is an ideal candidate for drug design experiments targeting MMP-9 and enzyme crystallization experiments. The developed strategy for MMP-9CAT stabilization could be applied to redesign of other proteases to improve their stability for various biotechnological applications.

biochemistry↗

bioRxiv2021

Mapping cellular subpopulations within triple negative breast cancer tumors provides a tool for cancer sensitization to radiotherapy

Triple negative breast cancer (TNBC) is an aggressive type of cancer that is known to be resistant to radiotherapy (RT). Evidence is accumulating that is indicative of the plasticity of TNBC, where one cancer subtype switches to another in response to various treatments, including RT. In this study we aim to overcome tumor resistance by designing TNBC-sensitizing targeted therapies that exploit the plasticity occurring due to radiation exposure. Using single cell analysis of molecular changes occurring in irradiated TNBC tumors, we identified two initially undetected distinct subpopulations, represented by overexpressed Her2 and cMet, expanding post-RT and persisting in surviving tumors. Using murine cancer models and patient-derived TNBC tumors, we showed that only simultaneous targeting of Her2 and cMet was successful in sensitizing TNBC to RT and preventing its regrowth. The strategy presented herein holds the potential to be broadly applicable in clinical use. HighlightsO_LISensitization of TNBC to radiotherapy (RT) is a clinically unmet need C_LIO_LISingle cell strategy creates a precise map of subpopulations expanding post-RT C_LIO_LIEvolution of intra-tumor heterogeneity is turned into a therapeutic advantage C_LIO_LISimultaneous targeting of expanding subpopulations sensitizes TNBC to radiotherapy C_LI

cancer biology↗

bioRxiv2018

Evaluation of the capacity of Pediatricians in Nigeria to conduct of research: A nationwide Survey.

BackgroundQuality health care service delivery to children and adolescents is enhanced by continuous research into the health challenges of this subpopulation led by paediatricians with tremendous capacity to investigate and proffer solutions to the myriads of childhood illnesses. Understanding the health issues therefore is the foundation for implementation of viable interventions that assure optimum service delivery. In view of this background, the Paediatric Association of Nigeria (PAN) directed that research into childrens health challenges in Nigeria should be brought to the front burner in the country. Pursuant to this laudable goal this study was conceived to evaluate the research capacity and capability of paediatricians in Nigeria and the institutions they represent. In view of above needs, this study aimed at evaluating the research capacities and challenges among paediatricians.\n\nMethodsThe survey used a cross-sectional nationwide design to enroll paediatricians into the study. The study was a combination of both online and face-to-face survey using questionnaire developed from Research Capacity Assessment Framework. Information on previous research work, challenges encountered, existing capacity and utilization of research outcome were obtained. The SPSS version 20 was used for data entry and analysis. For qualitative variables, similar responses were grouped under thematic heading.\n\nResultsThe response rates for online (via email survey, group-administered in a conference and individual face-to-face (at workshops) were 32 (3.2%), 75 (13.6%) and 15 (60%) respectively. The majority, 87(85.5%) of the participants had conducted prevalence studies, compared to 9 (8.8%) that had done experimental studies. Those who have ever received grant funding for their studies were 21 (19.4%), while the proportion whose research outcome had informed policy update and practice were policy 20 (18.2%). More than 55% of the participants had challenges on some of the seven aspects of research: research topic, proposal, funding, fieldwork, analysis, utilizing findings and collaboration. Less than 40% of the participants had received training on some of the tested 14 research capacity areas except for the area of ethics where 78 (70.9%) reported having received training. For 51 (46.4%) this ethics training included the Good Clinical Practice Guidelines.\n\nConclusionNigerian Academic Paediatricians need to be stimulated to develop interest in research by building their presently low research capacity if future paediatric practice is to be driven significantly by evidence.

scientific communication and education↗