Shanique Martin

All Publications

• Factors associated with early childhood stunted growth in a 2012-2015 birth cohort monitored in the rural Msambweni area of coastal Kenya: a cross-sectional study. BMC pediatrics Martin, S., Mutuku, F., Sessions, J., Lee, J., Mukoko, D., Malhotra, I., King, C. H., LaBeaud, A. D. 2020; 20 (1): 208

  Abstract

  BACKGROUND: Chronic malnutrition, often measured as stunted growth, is an understudied global health problem. Though poor nutritional intake has been linked to stunted growth, there is evidence suggesting environmental exposures may have a significant role in its occurrence. Here, we characterize the non-nutritional prenatal and postnatal factors that contribute to early childhood stunted growth in rural coastal Kenya.METHODS: Overall, 232 women and 244 children from a 2012-2015 maternal-child cohort in Msambweni, Kenya were included. Women were tested for parasitic infections during the prenatal period and at the time of delivery. Children were tested for parasitic infections and assessed for stunted growth using height-for-age Z-scores (HAZ) at 6-month intervals after birth. Socioeconomic status (SES) was evaluated using both a simplified water, asset, maternal education, and income (WAMI) index and a principal component analysis (PCA) asset score. Multivariate logistic regression analysis was used to determine the relative influence of prenatal and postnatal factors on the occurrence of stunted growth.RESULTS: Of the 244 children (ages 6-37months), 60 (25%) were stunted at the study endpoint. 179 mothers (77%) had at least one parasitic infection during pregnancy and 94 children (38%) had at least one parasitic infection during the study period. There was no significant association between maternal parasitic infection and child stunted growth (p=1.00). SES as determined using the WAMI index was not associated with HAZ in linear regression analysis (p=0.307), however, the PCA asset score was (p=0.048). Multivariate logistic regression analysis identified low birth weight (AOR: 3.24, 95% CI: [1.38, 7.57]) and child parasitic infectious disease burden (AOR: 1.41, 95% CI: [1.05, 1.95]) as independent predictors of stunted growth, though no significant association was identified with PCA asset score (AOR: 0.98, 95% CI: [0.88, 1.10]).CONCLUSIONS: Stunted growth remains highly prevalent in rural Kenya, with low birth weight and child parasitic infectious disease burden demonstrated to be significantly associated with this indicator of chronic malnutrition. These results emphasize the multifaceted nature of stunted growth and the need to address both the prenatal and postnatal environmental factors that contribute to this problem.

  View details for DOI 10.1186/s12887-020-02110-z

  View details for PubMedID 32398049

• An Evaluation of the Utility of the Breast Reconstruction Risk Assessment Score Risk Model in Prepectoral Tissue Expander Breast Reconstruction. Annals of plastic surgery Martin, S., Turner, E., Nguyen, A., Thornton, B., Nazerali, R. S. 2020

  Abstract

  INTRODUCTION: Individualized postsurgical risk assessment models provide surgeons and patients with information that is vital to the surgical decision-making process. One such tool, the Breast Reconstruction Risk Assessment (BRA) score, uses a limited selection of patient-specific factors to predict 30-day postsurgical risk of surgical site infection, seroma, dehiscence, reoperation and explantation associated with immediate submuscular tissue expander breast reconstruction. This model's performance in prepectoral tissue expander reconstruction has not been previously reported. Here, we evaluate the performance of the BRA score model in a population of patients who underwent immediate prepectoral tissue expander breast reconstruction.MATERIALS AND METHODS: A retrospective chart review was conducted of prepectoral breast reconstructions performed in 2 institutions between January 2017 and December 2018. Complications occurring within 30 days postoperatively were documented and compared with the BRA score predicted risk for each patient.RESULTS: Overall 247 patients (average age, 49.2 years) were included in the study. The mean BRA score predicted 30-day risk of a complication was 13.0% (7.5-41.5%). The observed rate of 30-day postoperative complications was 31.2% (77 patients), though only 36 (14.6%) patients had complications included in the model. The remaining patients experienced skin necrosis or hematoma as their only early complication. The 30-day BRA score model demonstrated good fit for the overall occurrence of any of the BRA score predicted complications (Hosmer-Lemeshow 0.7167), though the model discrimination was poor (C statistic <0.60). Notably, half of the 30-day postsurgical complications observed in this study were due to skin necrosis, a complication not currently included in the 30-day BRA score model.CONCLUSIONS: Our results indicate that the current 30-day BRA score model may have poor predictive value in prepectoral breast reconstruction. The most common early complication observed, skin necrosis, is not currently included in the model, suggesting that caution should be applied when using this risk predictive calculator as an adjunct to patient evaluation and counseling.

  View details for DOI 10.1097/SAP.0000000000002320

  View details for PubMedID 32187065

• Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition. The American journal of tropical medicine and hygiene Kao, J. n., Mutuku, F. n., Martin, S. n., Lee, J. n., Muinde, J. n., Mukoko, D. n., Malhotra, I. n., King, C. H., LaBeaud, A. D. 2019

  Abstract

  Anemia is known to impact a child's growth and development, but not all anemias are caused by iron deficiency, and the CDC and WHO have emphasized investigating other contributors to anemia. This cross-sectional sub-study of a 2012-2016 maternal-child cohort in coastal Kenya evaluated 244 children and found 185 (76%) to have been anemic on at least one time point since birth. At the time of assessment in 2016, evaluation included a complete blood count, nutritional assessment, and testing for parasitic infections, focusing on the primary outcome of anemia, defined as hemoglobin (Hb) < 11 g/dL. The average age at assessment was 20.5 ± 7 months. Ninety-five percent had a lifetime average Hb in the anemic range. Adjusting for age and gender, prior or current malaria infection (prior: Hb β = -0.99, 95% CI: -1.49 to -0.49, P = 0.01), or having any current infection with hookworm, Trichuris, Strongyloides, Ascaris, and/or malaria (β = -0.84, 95% CI: -1.36 to -0.33, P = 0.01) was associated with decreased current Hb. Nutritional evaluation revealed that children with a declining Hb ate fewer vitamin-A-rich vegetables per week (P = 0.01) or eggs (P = 0.01), drank more milk (P = 0.07), and ate more bread (P = 0.01), and were more likely to live in a household that experienced food shortage (P = 0.05). The high prevalence of anemia, polyparasitism, and dietary insufficiency among children in rural coastal Kenya suggests that remedial interventions will need to address both diet and parasitic infections to effectively combat this significant health threat.

  View details for PubMedID 31074407

• Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Kao, J., Mutuku, F., Martin, S., Lee, J., Mwandi, J., Mukoko, D., Malhotra, I., King, C. H., LaBeaud, A. 2019; 101 (1): 242–52

  View details for DOI 10.4269/ajtmh.17-0688

  View details for Web of Science ID 000476680300039

• Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance CANCER DISCOVERY Jeong, Y., Hoang, N. T., Lovejoy, A., Stehr, H., Newman, A. M., Gentles, A. J., Kong, W., Diana Truong, D., Martin, S., Chaudhuri, A., Heiser, D., Zhou, L., Say, C., Carter, J. N., Hiniker, S. M., Loo, B. W., West, R. B., Beachy, P., Alizadeh, A. A., Diehn, M. 2017; 7 (1): 86-101

  Abstract

  Lung squamous cell carcinoma (LSCC) pathogenesis remains incompletely understood, and biomarkers predicting treatment response remain lacking. Here, we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histologic and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in patients with non-small lung cancer (NSCLC) and could be noninvasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs.We developed an LSCC mouse model involving Trp53 and Keap1, which are frequently mutated in human LSCCs. In this model, ABSCs are the cell of origin of these tumors. KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy patients. Our findings are of potential clinical relevance and could lead to personalized treatment strategies for tumors with KEAP1/NRF2 mutations. Cancer Discov; 7(1); 86-101. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1.

  View details for DOI 10.1158/2159-8290.CD-16-0127

  View details for Web of Science ID 000396017700024

  View details for PubMedCentralID PMC5222718

• CONTRIBUTING FACTORS FOR ANEMIA IN YOUNG CHILDREN IN COASTAL KENYA Kao, J., Mutuku, F., Martin, S., Lee, J., Muinde, J., Mukoko, D., Malhotra, I., King, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 210

  View details for Web of Science ID 000423215203041

• THE PREVALENCE AND CONTRIBUTING FACTORS OF EARLY CHILDHOOD STUNTING IN RURAL COASTAL KENYA Martin, S., Mutuku, F., Kao, J., Lee, J., Mukoko, D., Malhotra, I., King, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 71

  View details for Web of Science ID 000423215202229

• Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance. Cancer discovery Jeong, Y., Hoang, N. T., Lovejoy, A., Stehr, H., Newman, A. M., Gentles, A. J., Kong, W., Truong, D., Martin, S., Chaudhuri, A., Heiser, D., Zhou, L., Say, C., Carter, J. N., Hiniker, S. M., Loo, B. W., West, R. B., Beachy, P., Alizadeh, A. A., Diehn, M. 2016

  Abstract

  Lung squamous cell carcinoma (LSCC) pathogenesis remains incompletely understood, and biomarkers predicting treatment response remain lacking. Here, we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histologic and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in patients with non-small lung cancer (NSCLC) and could be noninvasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs.We developed an LSCC mouse model involving Trp53 and Keap1, which are frequently mutated in human LSCCs. In this model, ABSCs are the cell of origin of these tumors. KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy patients. Our findings are of potential clinical relevance and could lead to personalized treatment strategies for tumors with KEAP1/NRF2 mutations. Cancer Discov; 7(1); 86-101. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1.

  View details for PubMedID 27663899

• Identification and genetic manipulation of human and mouse oesophageal stem cells. Gut Jeong, Y., Rhee, H., Martin, S., Klass, D., Lin, Y., Nguyen, L. X., Feng, W., Diehn, M. 2016; 65 (7): 1077-1086

  Abstract

  Human oesophageal stem cell research is hampered by the lack of an optimal assay system to study self-renewal and differentiation. We aimed to identify and characterise human and mouse oesophageal stem/progenitor cells by establishing 3-dimensional organotypic sphere culture systems for both species.Primary oesophageal epithelial cells were freshly isolated and fluorescence-activated cell sorting (FACS)-sorted from human and mouse oesophagus and 3-dimensional organotypic sphere culture systems were developed. The self-renewing potential and differentiation status of novel subpopulations were assessed by sphere-forming ability, cell cycle analysis, immunostaining, qPCR and RNA-Seq.Primary human and mouse oesophageal epithelial cells clonally formed esophagospheres consisting of stratified squamous epithelium. Sphere-forming cells could self-renew and form esophagospheres for over 43 passages in vitro and generated stratified squamous epithelium when transplanted under the kidney capsule of immunodeficient mice. Sphere-forming cells were 10-15-fold enriched among human CD49f(hi)CD24(low) cells and murine CD49f(+)CD24(low)CD71(low) cells compared with the most differentiated cells. Genetic elimination of p63 in mouse and human oesophageal cells dramatically decreased esophagosphere formation and basal gene expression while increasing suprabasal gene expression.We developed clonogenic and organotypic culture systems for the quantitative analyses of human and mouse oesophageal stem/progenitor cells and identified novel cell surface marker combinations that enrich for these cells. Using this system, we demonstrate that elimination of p63 inhibits self-renewal of human oesophageal stem/progenitor cells. We anticipate that these esophagosphere culture systems will facilitate studies of oesophageal stem cell biology and may prove useful for ex vivo expansion of human oesophageal stem cells.

  View details for DOI 10.1136/gutjnl-2014-308491

  View details for PubMedID 25897018

• Identification and genetic manipulation of human and mouse oesophageal stem cells GUT Jeong, Y., Rhee, H., Martin, S., Klass, D., Lin, Y., Le Xuan Truong Nguyen, L. X., Feng, W., Diehn, M. 2016; 65 (7): 1077-1086

  Abstract

  Human oesophageal stem cell research is hampered by the lack of an optimal assay system to study self-renewal and differentiation. We aimed to identify and characterise human and mouse oesophageal stem/progenitor cells by establishing 3-dimensional organotypic sphere culture systems for both species.Primary oesophageal epithelial cells were freshly isolated and fluorescence-activated cell sorting (FACS)-sorted from human and mouse oesophagus and 3-dimensional organotypic sphere culture systems were developed. The self-renewing potential and differentiation status of novel subpopulations were assessed by sphere-forming ability, cell cycle analysis, immunostaining, qPCR and RNA-Seq.Primary human and mouse oesophageal epithelial cells clonally formed esophagospheres consisting of stratified squamous epithelium. Sphere-forming cells could self-renew and form esophagospheres for over 43 passages in vitro and generated stratified squamous epithelium when transplanted under the kidney capsule of immunodeficient mice. Sphere-forming cells were 10-15-fold enriched among human CD49f(hi)CD24(low) cells and murine CD49f(+)CD24(low)CD71(low) cells compared with the most differentiated cells. Genetic elimination of p63 in mouse and human oesophageal cells dramatically decreased esophagosphere formation and basal gene expression while increasing suprabasal gene expression.We developed clonogenic and organotypic culture systems for the quantitative analyses of human and mouse oesophageal stem/progenitor cells and identified novel cell surface marker combinations that enrich for these cells. Using this system, we demonstrate that elimination of p63 inhibits self-renewal of human oesophageal stem/progenitor cells. We anticipate that these esophagosphere culture systems will facilitate studies of oesophageal stem cell biology and may prove useful for ex vivo expansion of human oesophageal stem cells.

  View details for DOI 10.1136/gutjnl-2014-308491

  View details for Web of Science ID 000377170200005

• Inhibition of Mouse Breast Tumor-Initiating Cells by Calcitriol and Dietary Vitamin D MOLECULAR CANCER THERAPEUTICS Jeong, Y., Swami, S., Krishnan, A. V., Williams, J. D., Martin, S., Horst, R. L., Albertelli, M. A., Feldman, B. J., Feldman, D., Diehn, M. 2015; 14 (8): 1951-1961

  Abstract

  The anticancer actions of vitamin D and its hormonally active form, calcitriol, have been extensively documented in clinical and preclinical studies. However, the mechanisms underlying these actions have not been completely elucidated. Here, we examined the effect of dietary vitamin D and calcitriol on mouse breast tumor-initiating cells (TICs, also known as cancer stem cells). We focused on MMTV-Wnt1 mammary tumors, for which markers for isolating TICs have previously been validated. We confirmed that these tumors expressed functional vitamin D receptors and estrogen receptors (ER) and exhibited calcitriol-induced molecular responses including ER downregulation. Following orthotopic implantation of MMTV-Wnt1 mammary tumor cells into mice, calcitriol injections or a vitamin D-supplemented diet caused a striking delay in tumor appearance and growth, whereas a vitamin D-deficient diet accelerated tumor appearance and growth. Calcitriol inhibited TIC tumor spheroid formation in a dose-dependent manner in primary cultures and inhibited TIC self-renewal in secondary passages. A combination of calcitriol and ionizing radiation inhibited spheroid formation more than either treatment alone. Further, calcitriol significantly decreased TIC frequency as evaluated by in vivo limiting dilution analyses. Calcitriol inhibition of TIC spheroid formation could be overcome by the overexpression of β-catenin, suggesting that the inhibition of Wnt/β-catenin pathway is an important mechanism mediating the TIC inhibitory activity of calcitriol in this tumor model. Our findings indicate that vitamin D compounds target breast TICs reducing tumor-initiating activity. Our data also suggest that combining vitamin D compounds with standard therapies may enhance anticancer activity and improve therapeutic outcomes.

  View details for DOI 10.1158/1535-7163.MCT-15-0066

  View details for Web of Science ID 000359324600018

  View details for PubMedID 25934710

  View details for PubMedCentralID PMC4549392