Sean Pepper

Simon Fraser University, Microbiology, Alumnus

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Papers by Sean Pepper

Angiogenesis-Regulating Cytokines: Activities and Interactions

Current Topics in Microbiology and Immunology, 1996

The establishment of a vascular supply is an absolute requirement for the growth of normal and ne... more The establishment of a vascular supply is an absolute requirement for the growth of normal and neoplastic tissues and, as might be expected, the cardiovascular system is the first organ system to develop and to become functional during embryogenesis. It has been known since the beginning of this century (Evans 1909) that, both during development and in postnatal life, all blood vessels begin as simple endothelial-lined capillaries. Although some remain as capillaries, many of these newly formed vessels develop into larger vessels, in part through the addition of a variable number of concentrically disposed smooth muscle cell layers. The heterogeneity and variable complexity of blood vessels thus generated serves to ensure structural and functional diversity in the vascular tree.

Stem cells: current reality & future promise

Invitation to and PowerPoint presentation of the 9th lecture in the UP expert lecture series, del... more

The FitTrack Index as fitness indicator: A pilot study

Health SA Gesondheid, 2016

Background: The FitTrack Index is a web-based programme developed in South Africa and widely used... more Background: The FitTrack Index is a web-based programme developed in South Africa and widely used by athletes to indicate their fitness. A need exists for a self-managed, noninvasive tool to evaluate and categorise health-related fitness in different population groups. The aim of this study was to compare the FitTrack Index with a reliable measure of cardio-respiratory fitness as indicated by maximal oxygen uptake (direct VO 2max). Methods & results: During a 12-week cross-sectional, descriptive pilot study the direct laboratory tested VO 2max indicated a moderate to strong correlation with the FitTrack Index (Spearman's rho ¼ 0.439, p ¼ 0.089 at baseline; Spearman's rho ¼ 0.853, p < 0.001 after 12 weeks). Conclusions: These results suggest that the web-based FitTrack Index may be considered an appropriate tool to evaluate exercise capacity and cardiovascular fitness in healthy individuals following an aerobic training programme.

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Plasminogen Activator Expression in Rat Arterial Smooth Muscle Cells Depends on Their Phenotype and Is Modulated by Cytokines

Circulation Research, 1998

Cultured rat aortic smooth muscle cells (SMCs) exhibit at least 2 phenotypic variants: (1) a spin... more Cultured rat aortic smooth muscle cells (SMCs) exhibit at least 2 phenotypic variants: (1) a spindle-shaped phenotype, obtained from normal adult media, and (2) an epithelioid phenotype, obtained from intimal thickening 15 days after endothelial injury. Both phenotypes can be cloned from each location, with normal media yielding a majority of spindle-shaped clones and intimal thickening yielding a majority of epithelioid clones. These findings suggest that intimal thickening develops essentially from a subpopulation of medial SMCs exhibiting epithelioid features in vitro. Using zymographic and Northern blot analyses, we have studied plasminogen activator (PA) expression by these SMCs. Our results show that epithelioid SMCs, cultured as whole SMC populations or as clones, display higher PA activity than do spindle-shaped SMCs, irrespective of their origin. This is mainly due to differences in the expression of tissue PA and, to a lesser extent, urokinase PA and is accompanied by a decrease in PA inhibitor 1. Tissue PA activity is increased by basic fibroblast growth factor and platelet-derived growth factor-BB, particularly in epithelioid SMCs. Taken together, these results indicate that SMCs are heterogeneous with respect to their proteolytic profile, at least as far as the PA system is concerned. Proteolytic activity of the different SMC populations is modulated by cytokines that play a role in intimal thickening. Our results are in agreement with the suggestion that epithelioid SMCs are mainly responsible for intimal thickening.

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Lymphatic Vessel Density and Vascular Endothelial Growth Factor-C Expression Correlate with Malignant Behavior in Human Pancreatic Endocrine Tumors

Clinical Cancer Research, 2004

Metastatic dissemination of tumor cells to regional lymph nodes is a common early feature of many... more Metastatic dissemination of tumor cells to regional lymph nodes is a common early feature of many human cancers including pancreatic adenocarcinoma. In contrast, lymph node metastasis is more variably observed in pancreatic endocrine tumors. The objective of this study was to assess the lymphatic system of human pancreatic endocrine tumors and correlate this to clinical behavior. Immunohistochemistry was performed using antibodies to two recently identified markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C. As has been reported previously, we observed that in the normal pancreas, islets of Langerhans are devoid of intra-islet lymphatics, but that lymphatics are present in connective tissue in association with ducts and blood vessels. We found that both benign and malignant pancreatic endocrine tumors contain intratumoral lymphatic vessels. Lymphatic vessel density was related to the size of ...

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Design of a Primary Mirror Fine Positioning Mechanism for a Deployable Space Telescope

The TU Delft Deployable Space Telescope proposes to meet increasing demand for high spatio-tempor... more The TU Delft Deployable Space Telescope proposes to meet increasing demand for high spatio-temporal resolution Earth observation imagery by reducing the mass, volume and launch cost of space telescopes by using segmented deployable optics. A 3DOF piston/ tip/ tilt fine positioning mechanism is proposed to actively align the primary mirror segments in orbit. A preliminary thermo-mechanical design of the mechanism was synthesised and its mechanical performance verified with an efficient, low order finite element model. The results showed that the mechanism can support the mirror through launch without a hold down mechanism; has a piston step size of 10 nm; a range of ±4 µm in piston and ±9 µrad in tip/ tilt with accuracies of 0.005±0.780 µm (2σ) in position and 0.000±0.041 µrad (2σ) in rotation. A Monte Carlo ray tracing analysis showed that the active optics could successfully align the mirror segments in all considered deployment scenarios.

Membrane Type-1 Matrix Metalloproteinase Confers Aneuploidy and Tumorigenicity on Mammary Epithelial Cells

Cancer Research, 2006

An elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) is closely associate... more An elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) is closely associated with multiple malignancies. Recently, we discovered that recycled MT1-MMP was trafficked along the tubulin cytoskeleton into the centrosomal compartment and cleaved the integral centrosomal protein pericentrin-2. These events correlated with the induction of chromosome instability and aneuploidy in nonmalignant Madine-Darby canine kidney cells. Accordingly, we hypothesized that MT1-MMP is an oncogene that promotes malignant transformation of normal cells rather than just an enzyme that supports growth of preexisting tumors. To prove our hypothesis, we transfected normal 184B5 human mammary epithelial cells with MT1-MMP (184B5-MT1 cells). MT1-MMP was colocalized with pericentrin in the centrosomal compartment and especially in the midbody of dividing cells. 184B5-MT1 cells acquired the ability to activate MMP-2, to cleave pericentrin, and to invade the Matrigel matrix. 184B5-MT1 cells e...

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Characterization of Novel Clonal Murine Endothelial Cell Lines with an Extended Life Span

In Vitro Cellular & Developmental Biology - Animal, 2000

A murine endothelial cell line was recently established from microvessels that had invaded a subc... more

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Gender and sexual diversity - changing paradigms in an ever-changing world

South African Medical Journal, 2015

Enshrined in the Bill of Rights of South Africa's Constitution [1] are a number of rights that af... more Enshrined in the Bill of Rights of South Africa's Constitution [1] are a number of rights that affirm the democratic values of human dignity, equality and freedom. Section 9(3) states that 'The state may not unfairly discriminate directly or indirectly against anyone on one or more grounds, including race, gender, sex, pregnancy, marital status, ethnic or social origin, colour, sexual orientation, age, disability, religion, conscience, belief, culture, language and birth. ' Despite these rights, which are also embodied in policy and law at the highest levels internationally, lesbian, gay, bisexual, transgender and intersex (LGBTI) people are subjected to discrimination, abuse, violence and even death because they do not fit into the expectations of what certain sectors of society consider to be the 'norm'. In his book A Social Justice Advocate's Handbook: A Guide to Gender, Sam Kellerman [2] defines four elements that together contribute to gender and sexual diversity: 1. Biological sex (which I also refer to as physical sex) 2. Gender identity (which I also refer to as psychological sex) 3. Sexual orientation 4. Gender expression (which is a manifestation of 1, 2 and 3).

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Genomic sovereignty and the African promise: mining the African genome for the benefit of Africa

Journal of Medical Ethics, 2012

Scientific interest in genomics in Africa is on the rise with a number of funding initiatives aim... more Scientific interest in genomics in Africa is on the rise with a number of funding initiatives aimed specifically at supporting research in this area. Genomics research on material of African origin raises a number of important ethical issues. A prominent concern relates to sample export, which is increasingly seen as being problematic by researchers and ethics committees across the continent. The concept of genomic sovereignty proposes that unique patterns of genomic variation can be found in human populations, and that these are commercially, scientifically or symbolically valuable and in need of protection against exploitation. Although it is appealing as a response to increasing concerns regarding sample export, there are a number of important conceptual problems relating to the term. It is not clear, for instance, whether it is appropriate that ownership over human genomic samples should rest with national governments. Furthermore, ethnic groups in Africa are frequently spread across multiple nation states and protection offered in one state may not prevent researchers from accessing the same group elsewhere. Lastly, scientific evidence suggests that the assumption that genomic data is unique for population groups is false-although the frequency with which particular variants are found can differ between groups, such genes or variants per se are not unique to any population group. In this paper, we describe these concerns in detail and argue that the concept of genomic sovereignty alone may not be adequate to protect the genetic resources of people of African descent.

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Modeling and simulation of electromodulation imaging spectrum based on a MEMS-FP array with a high filling-factor

The Fabry-Perot interferometer (FP) can be used as a kind of filter for obtaining spectral inform... more The Fabry-Perot interferometer (FP) can be used as a kind of filter for obtaining spectral information of targets in several wavelength ranges such as in the visible or infrared regions. Micro-electro-mechanical systems (MEMS) are generally micro-structures that integrate micro-sensors for converting incident microbeams into arrayed electronic signals and micro-actuators. The MEMS-FP filter constructed by combining the MEMS and FP functions, can be further integrated into a chip-level imaging spectrometer to achieve spectral imaging operation. In our design, the MEMS-FP filter is also mounted a liquid-crystal microlens array with a high filling-factor. The key micro-bridges of each MEMS-FP unit are modeled and simulated in this paper. We have designed two types of supporting structures and simulated them with the simulation software COMSOL Multiphysics 5.2. The key factors include tuning range, filling-factor, and parallelism of the bridges. After calculating and analyzing, we found...

The stem cell regulatory environment in South Africa: cause for concern

South African Medical Journal, 2009

Every innovation in medicine is met with a mixture of excitement, expectation and a certain degre... more Every innovation in medicine is met with a mixture of excitement, expectation and a certain degree of apprehension. Nowhere is this more apparent than in the field of cell-based therapy, i.e. the application of cells to patients, locally or systemically, for therapeutic purposes. Excitement and expectation are generated by the many preclinical and early clinical studies that continue to reveal the enormous potential of regenerative medicine. The recent successful implantation of a large airway, engineered ex vivo from a donor trachea, into a patient as a replacement for a stenosed left main bronchus (post-tuberculosis), is a case in point. Likewise, reports of dramatic functional improvement in children with cerebral palsy treated with autologous cord-blood stem cells at Duke University warrant our serious consideration. And this is just the beginning. It is believed that cell-based therapy will have a significant positive impact on virtually every organ system in the body, and that...

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Slc7a8 deletion is protective against diet-induced obesity and attenuates lipid accumulation in multiple organs

Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giv... more Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of adipogenesis in human adipose derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. This study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. slc7a8 knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On HFD, both WT and KO (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WT HFD. KOHFD significantly reduced the level of glucose intolerance observed in WTHFD. KOHFD significantly reduced both adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD decr...

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Cancer Stem Cells in Head and Neck Carcinomas: Identification and Possible Therapeutic Implications

Stem Cells: Biology and Engineering

The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attr... more The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse. Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignancy worldwide with the highest incidence occurring in East Asia and eastern and southern Africa. Several cellular subpopulations believed to have CSC properties have been isolated from HNSCCs, but at present, identification and characterization of CSCs remains an experimental challenge with no established or standardized protocols in place to confirm their identity. In this review we discuss current approaches to the study of CSCs with a focus on HNSCCs, particularly in the context of what this might mean from a therapeutic perspective.