A personal reflection upon navigating into a senior academic role

There are 22,795 University professors in the UK, where 6,340 are women and only 40 are Black women, whilst Asian women are a few more in number. This clearly demonstrates the uncommon narrative of the under-representation of Black minority ethnic (BME) academics in higher education (HE) which has been written about in detail. In contrast, it is rare to read reports on initiatives to successfully navigate senior academic posts. In this article, I will describe two initiatives that I have developed and organized to successfully navigate senior BME academic posts, which have impacted my journey. The first initiative was to understand why postdoctoral researchers were “post-docing” for years, having not been successful in making the transition to lecturers. What was hindering the transition? I was one of them, and some of my female peers as well, who incidentally left HE. I was determined not to leave. I again thought about how to tackle it. It is a known fact that hearing successful BME people experiences and journeys and also understanding how they navigated HE can be powerful. In addition, empowering oneself with additional skills including mentoring, networking, applying for positions, not excluding ourselves due to the lack of confidence, and finally, the importance of having a work–life balance is important as health is wealth. I used this to put together the BME Early Career Researcher (ECR) conference—How to Stay in Academia. After 6 years, it is still going strong. In this article, I will share the impact made over the years which will include testimonies and promotions, including my recent promotion to an associate professor. The second initiative was to understand the barriers and challenges of senior lecturers being promoted to readers and professors. Having successfully transitioned to a lecturer, being overlooked for promotion was now an issue. The project was conducted in 2016/17 at KCL as part of the action plans that needed to be delivered having been a recipient of the Bronze Race Equality Charter Mark. I was provided with a cohort of 51 names of BME staff from different disciplines and was directed to see how I would engage them to hear their experiences. My first concern was that the staff would have engaged in previous initiatives with little or no benefits to them; however, this did not deter me. I thought of the best approach which commenced with a phone interview and then followed up with a focus group, ending with an informal conversation with the Principal of the University. Within 6 months, a BME male was promoted to professor. After a year, both genders were promoted to associate professors (readers) and professors, and to date, I am aware of at least 10 promotions. In both examples, I will demonstrate the support from our allies, some of whom are senior leaders that have openly supported us in our journey. This article will demonstrate a slight shift in the narrative, but a lot more needs to be done, and I am convinced the time is right to start pushing for more. This special issue is an example

In vitro osteoinductive potential of porous monetite for bone tissue engineering

Tissue engineering–based bone grafts are emerging as a viable alternative treatment modality to repair and regenerate tissues damaged as a result of disease or injury. The choice of the biomaterial component is a critical determinant of the success of the graft or scaffold; essentially, it must induce and allow native tissue integration, and most importantly mimic the hierarchical structure of the native bone. Calcium phosphate bioceramics are widely used in orthopaedics and dentistry applications due to their similarity to bone mineral and their ability to induce a favourable biological response. One such material is monetite, which is biocompatible, osteoconductive and has the ability to be resorbed under physiological conditions. The osteoinductive properties of monetite in vivo are known; however, little is known of the direct effect on osteoinduction of human mesenchymal stem cells in vitro. In this study, we evaluated the potential of monetite to induce and sustain human mesenchymal stem cells towards osteogenic differentiation. Human mesenchymal stem cells were seeded on the monetite scaffold in the absence of differentiating factors for up to 28 days. The gene expression profile of bone-specific markers in cells on monetite scaffold was compared to the control material hydroxyapatite. At day 14, we observed a marked increase in alkaline phosphatase, osteocalcin and osteonectin expressions. This study provides evidence of a suitable material that has potential properties to be used as a tissue engineering scaffold

A novel function for the U2AF 65 splicing factor in promoting pre-mRNA 3 '-end processing

Splicing and 3′-end processing (including cleavage and polyadenylation) of vertebrate pre-mRNAs are tightly coupled events that contribute to the extensive molecular network that coordinates gene expression. Sequences within the terminal intron of genes are essential to stimulate pre-mRNA 3′-end processing, although the factors mediating this effect are unknown. Here, we show that the pyrimidine tract of the last splice acceptor site of the human β-globin gene is necessary to stimulate mRNA 3′-end formation in vivo and binds the U2AF 65 splicing factor. Naturally occurring β-thalassaemia-causing mutations within the pyrimidine tract reduces both U2AF 65 binding and 3′-end cleavage efficiency. Significantly, a fusion protein containing U2AF 65, when tethered upstream of a cleavage/polyadenylation site, increases 3′-end cleavage efficiency in vitro and in vivo. Therefore, we propose that U2AF 65 promotes 3′-end processing, which contributes to 3′-terminal exon definition

Macroporous monetite scaffold for bone tissue engineering

Three dimensional scaffolds based on ceramics, polymers and or composites in combination with mesenchymal stem cells can be utilized to engineer tissues such as bone and cartilage [1]. One of the main limitations of 3D constructs is the mass transfer involved during in vitro culture which results in limited cell growth within the 3D construct. The production of clinically relevant hybrids of the scaffold is also limited by the supply of oxygen and transport of nutrients within the 3D scaffold. Bioreactors that permit the perfusion of medium through the scaffolds thus diminish the mass transfer limitations and in addition mechanical forces are exerted due to fluid flow. In this study a macroporous monetite (CaHPO4) scaffold was produced and characterized, which was then set up in a bioreactor under fluid flow conditions to ascertain the effect of the dynamic conditions in guiding mesenchymal stem cells towards osteogenic lineage

p16/p53 expression and telomerase activity in immortalized human dental pulp cells

INTRODUCTION: Residing within human dental pulp are cells of an ectomesenchymal origin that have the potential to differentiate into odontoblast-like cells. These cells have a limited growth potential owing to the effects of cell senescence. This study examines the effects of immortalizing odontoblast-like cells on cell proliferation and mineralization by comparing transformed dental pulp stem cells (tDPSCs) and non-transformed dental pulp stem cells (nDPSCs). RESULTS: With the exogenous expression of hTERT, tDPSCs maintained a continued expression of odontogenic markers for cell proliferation and mineralization (ALP, COL-1, DMP-1, DSPP, OCN and OPN), as did nDPSCs. Oncoprotein expression was seen in both groups except for a noted absence of p16 in the tDPSCs. nDPSCs also showed lower levels of total ALP and DNA activity in comparison to tDPSCs when assayed, as well as low telomerase activity readings. METHODS: Using a retroviral vector, exogenous human telomerase reverse transcriptase (hTERT) was expressed in tDPSCs. Both cell groups were cultured, and their telomerase activities were determined using a telomerase quantification assay. Also examined, were the expression of genes involved in proliferation and mineralization, such as human alkaline phosphatase (ALP), β-actin, collagen I (col-1), core binding factor (cbfa)-1, dentin matrix protein (DMP-1), dentin sialophosphoprotein (DSPP), GAPDH, hTERT, osteocalcin (OCN), osteopontin (OPN) as well as oncoproteins involved in senescence (p16, p21 and p53) using RT-PCR. DNA and alkaline phosphate activity was also assayed in both cell groups. CONCLUSION: These results indicate maintenance of odontoblast-like differentiation characteristics after retroviral transformation with hTERT and suggest a possible link with a reduced p16 expression

Laryngeal abductor muscle reinnervation in a pig model

OBJECTIVE: To develop a large animal model for studies of laryngeal abductor reinnervation. MATERIAL AND METHODS: Six minipigs underwent unilateral anastomosis of the phrenic nerve-abductor branch of the recurrent laryngeal nerve (RLN). Polyhydroxybutyrate (PHB) conduits were used for repair. At each of 30, 60 and 120 days, 2 animals underwent video laryngeal endoscopy (VLE) and were then killed. VLE was also performed in the 120-day pair at 60 days. Nerve-conduit-nerve-muscle samples were fixed for light and immunofluorescence (pan-neurofilaments, S-100) microscopy. Laryngeal muscles were harvested (myosin heavy chain analysis). RESULTS: VLE showed recovery of abductor function in 1 animal at 60 days and in 1 at 120 days. Haematoxylin-eosin staining demonstrated a complex inflammatory response. Eosinophil recruitment was observed. Stepwise regeneration and reorganization of the distal nerve between 30 and 120 days was observed with pan-NF staining. The mean minimum diameter in the reinnervated posterior crico-arytenoids tended to increase for up to 120 days. CONCLUSIONS: Anastomosis of the phrenic nerve-abductor branch of the RLN with a PHB conduit in a pig can result in functional and histological recovery within 2-4 months and appears to at least sustain abductor muscle fibre morphology. Recovery occurs despite a complex inflammatory response, which may be an essential part of healing rather than inhibitory

Detection of beta-catenin mutations in paraffin-embedded sporadic desmoid-type fibromatosis by mutation-specific restriction enzyme digestion (MSRED): An ancillary diagnostic tool

Desmoid-type fibromatosis is a locally aggressive deep soft tissue tumor. Some cases are associated with adenosis polyposis coli germline mutations whereas others harbor somatic P-catenin point mutations mainly in exon 3, codons 41 and 45. These mutations result in stabilization of P-catenin, and activation of the Writ signaling pathway. The aim of this study was to determine the specificity and sensitivity of these 3 most common P-catenin mutations in the diagnosis of desmoid-type fibromatosis using paraffin-embedded material. The results were compared with nuclear expression of P-catenin. Mutation-specific restriction enzyme digestion methodology was employed to detect the 3 mutations. One hundred and thirty-three cases were analyzed, including 76 desinoid-type, and 18 superficial fibromatosis, in addition to a further 39 fibromatosis mimics. A restriction site was present for analysis of the codon 41 mutation. Mismatch primers were designed for the codon 45 mutations. Mutations were detected in 66 cases (87%) of 76 desmoid-type fibromatosis (71 extra-abdominal). Of these, 34 (45%) were in codon 45 (TCT > TTT), 27 (35%) in codon 41 (ACC > GCC), and 5 (7%) in codon 45 (TCT > CCT). No mutations were detected in the other lesions studied. All desmoid-type fibromatosis cases and 72% of the mimics teste

Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors

Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation of oncogenes to the tumorigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs). Recently, new technologies for whole-genome DNAm (methylome) analysis have been developed, enabling unbiased analysis of cancer methylomes. By using MeDIP-seq, we report a sequencing-based comparative methylome analysis of malignant peripheral nerve sheath tumors (MPNSTs), benign neurofibromas, and normal Schwann cells. Analysis of these methylomes revealed a complex landscape of DNAm alterations. In contrast to what has been reported for other tumor types, no significant global hypomethylation was observed in MPNSTs using methylome analysis by MeDIP-seq. However, a highly significant (P < 10−100) directional difference in DNAm was found in satellite repeats, suggesting these repeats to be the main target for hypomethylation in MPNSTs. Comparative analysis of the MPNST and Schwann cell methylomes identified 101,466 cancer-associated differentially methylated regions (cDMRs). Analysis showed these cDMRs to be significantly enriched for two satellite repeat types (SATR1 and ARLα) and suggests an association between aberrant DNAm of these sequences and transition from healthy cells to malignant disease. Significant enrichment of hypermethylated cDMRs in CGI shores (P < 10−60), non–CGI-associated promoters (P < 10−4) and hypomethylated cDMRs in SINE repeats (P < 10−100) was also identified. Integration of DNAm and gene expression data showed that the expression pattern of genes associated with CGI shore cDMRs was able to discriminate between disease phenotypes. This study establishes MeDIP-seq as an effective method to analyze cancer methylomes

Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study

A variety of analyses, including fluorescence in situ hybridization (FISH), quantitative PCR (qPCR) and array CGH (aCGH), have been performed on a series of chordomas from 181 patients. Twelve of 181 (7%) tumours displayed amplification of the T locus and an additional two cases showed focal amplification; 70/181 (39%) tumours were polysomic for chromosome 6, and 8/181 (4.5%) primary tumours showed a minor allelic gain of T as assessed by FISH. No germline alteration of the T locus was identified in non-neoplastic tissue from 40 patients. Copy number gain of T was seen in a similar percentage of sacrococcygeal, mobile spine and base of skull tumours. Knockdown of T in the cell line, U-CH1, which showed polysomy of chromosome 6 involving 6q27, resulted in a marked decrease in cell proliferation and morphological features consistent with a senescence-like phenotype. The U-CH1 cell line was validated as representing chordoma by the generation of xenografts, which showed typical chordoma morphology and immunohistochemistry in the NOD/SCID/interleukin 2 receptor [IL2r]gamma(null) mouse model. In conclusion, chromosomal aberrations resulting in gain of the T locus are common in sporadic chordomas and expression of this gene is critical for proliferation of chordoma cells in vitro. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd