DAVENPORT, ATHENA S.

Assistant Professor
Genetics,Genomics&Informatics

Office: 419 TRANSLATIONAL RESEARCH BUILDING
71 SOUTH MANASSAS
MEMPHIS TN 38163
Tel: (901) 448-3085
astarlar@uthsc.edu

Education

  • Ph.D., University of Arkansas for Medical Sciences, Biochemistry and Molecular Biology
  • M.S., University of Louisiana at Monroe, Biology
  • B.S., University of Louisiana at Monroe, Biology

My Current CV

Research Description

Project #1. Establishment of The STAR Study: A Population-Based Study of Breast Cancer in Memphis:

The Sistas Taking A Stand for Breast Cancer Research (STAR) Study is an ongoing population-based molecular epidemiology study to understand the molecular and environmental causes of breast cancer disparities in African American (AA) women, with an initial focus on AA women in the Memphis community.  Breast cancer mortality rates among AA women in Memphis is one of the highest in the nation. It is unclear whether genetic factors alone or in combination with socioeconomic factors and unhealthy behaviors (i.e. obesity, smoking, alcohol consumption, etc.) contribute to the higher breast cancer mortality disparity gap observed in AA women as compared to non-Hispanic white women in Memphis.  Through community partnerships and a collaboration with the West Cancer Clinic, our laboratory is developing a retrospective cohort consisting of saliva and biological specimens and general health information from women of African ancestry from Memphis to study regional-specific breast cancer. 

 

Project #2. Investigation of the Microbiome and Mucosal Immune System in Breast Cancer: 

African American (AA) women are more likely to die from breast cancer than non-Hispanic white women. Obesity is associated with increased breast cancer risk and deaths in AA women. Obesity promotes breast inflammation which is caused by infectious agents that can cause breast cancer. The breast also consists of a mucosal immune system that provides a complex mechanical barrier and an inherent defense against pathogens. Growing evidence shows that an imbalance in the microbiome due to inflammation may give rise to cancer development.  However, there is a lack of data on the role of the microbiome in breast cancer in AA women. We hypothesize that distinct microbial signatures exists in the breast and these signatures differ between normal and breast cancer tissues by race. In this study, we will assess microbial signatures in normal, benign, and malignant breast tissues samples from AA and non-Hispanic white women and evaluate the role of the microbiome on immune response using microarray and immunohistochemistry.  This study will provide preliminary evidence of a breast microbiome in AA women and supports further investigation to identify a microbial risk signature for breast cancer and potential microbial-based prevention therapies.

 

Project #3. Investigation of MiR-29 Restoration Therapy in A) Triple Negative Breast Cancer Chemoresistance (TNBC) and B) Sickle Cell Disease:

A.      MiR-29 in TNBC: TNBC is the most aggressive form of breast cancer that accounts for ~ 20% of breast cancers in the United States. Since there are no targeted therapies to treat TNBC, systemic chemotherapy is the standard treatment. Doxorubicin (DOX), alone or in combination with other FDA-approved drugs, is commonly used for the treatment of TNBC. However, DOX resistance remains a major challenge in clinical oncology. We previously showed that miR-29 is down-regulated in breast cancers including TNBC and restoration of miR-29 in breast cancer cells inhibited cell proliferation, decreased DNMT3A and DNMT3B messenger RNA (mRNA), and decreased promoter methylation status of several tumor-suppressor genes.  More recently, reduced expression of miR-29 was found to promote epithelial-to mesenchymal transition, a key feature of TNBC chemoresistance, and induce DOX resistance in TNBC cells via targeting TGF-β1 signaling pathway. A major focus of our research is to establish a collection of DOX resistant TNBC cells to evaluate the effectiveness of miR-29 supplementation in reversing DOX resistance in TNBC. To date, a major obstacle in miRNA supplement therapy is lack of robust non-viral delivery methods for cellular and in vivo delivery, which require an efficient and flexible delivery system. In collaboration with Dr. Murali Yallapu, we will also investigate the delivery of miR-29 using his unique nanogel particle formulation in a preclinical xenograft mouse model of DOX resistant TNBC. These efforts will eventually lead to the development of effective and safe methods to treat TNBC.

B.      MiR-29 in Sickle cell disease (SCD) - SCD affects 2 million people of African ancestry worldwide. Therapeutic interventions aimed at reactivating fetal hemoglobin (HbF) is an effective approach for improving survival and ameliorating SCD symptoms. Hydroxyurea is the only FDA-approved drug with proven efficacy for inducing HbF in a subset of SCD patients; however, many patients refuse this option due to concerns about chemotherapy use. Decitabine, a DNA methyltransferase inhibitor drug, has also shown promising results in clinical treatment by inducing HbF and total hemoglobin levels in patients with SCD, but like hydroxyurea, decitabine is also cytotoxic. There is an unmet need to develop non-toxic targeted therapeutics to induce HbF. We found that miR-29 functions as a DNA methyltransferase inhibitor and miR-29 supplementation increases the percentage of HbF positive cells in normal adult erythroid progenitors that initially expressed low or no HbF and decreased expression of the de novo DNA methyltransferase enzymes and the γ-globin repressor protein MYB. We hypothesize that miR-29b mediates γ-globin gene induction through reversible epigenetic DNA modifications in SCD patients.  Through a collaboration with Dr. Patricia Adams-Graves at the UTHSC Diggs-Kraus Sickle Cell Clinic we will evaluate the effect of miR-29 on γ-globin expression, γ-globin promoter methylation and HbF induction from blood isolated from SCD patients. This study will provide preliminary evidence of the role of miR-29b in HbF induction and supports further investigation to expand treatment options for SCD.

Research Keywords

 breast cancer genetics, cancer health disparities, epigenetics, community outreach

Research Interest/Specialty

Molecular epidemiology of breast cancer disparities, breast cancer risk assessment and pharmacogenetics

- Community outreach 

- MicroRNA supplementation therapy in triple negative breast cancer and sickle cell disease

Publications

  1. Vidal, G, Bursac, Z, Miranda-Carboni, G, White-Means, S, Starlard-Davenport, A. Racial disparities in survival outcomes by breast tumor subtype among African American women in Memphis, Tennessee. Cancer Med, 6 (7), 1776-1786, 2017.
  2. Starlard-Davenport, A, Orloff, MS, Dhakal, I, Penney, RB, Kadlubar, SA. Genotypic and allelic variability in CYP19A1 among populations of African and European ancestry. PLoS One, 10 (2), e0117347, 2015.
  3. Allman, R, Dite, GS, Hopper, JL, Gordon, O, Starlard-Davenport, A, Chlebowski, R, Kooperberg, C. SNPs and breast cancer risk prediction for African American and Hispanic women. Breast Cancer Res Treat, 154 (3), 583-9, 2015.
  4. Edavana, VK, Penney, RB, Yao-Borengasser, A, Starlard-Davenport, A, Dhakal, IB, Kadlubar, S. Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples. Int J Cancer Res Mol Mech, 1 (3), 2015.
  5. Vineetha K Edavana, Rosalind B Penney, Aiwei Yao-Borengasser , Athena Starlard-Davenport, Ishwori Dhakal, and Susan Kadlubar. Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples. Int J Cancer Res Mol Mech, 3 (1), 2015.
  6. Greer, AK, Dates, CR, Starlard-Davenport, A, Edavana, VK, Bratton, SM, Dhakal, IB, Finel, M, Kadlubar, SA, Radominska-Pandya, A. A potential role for human UDP-glucuronosyltransferase 1A4 promoter single nucleotide polymorphisms in the pharmacogenomics of tamoxifen and its derivatives. Drug Metab Dispos, 42 (9), 1392-400, 2014.
  7. Athena Starlard-Davenport, Mohammed S. Orloff, Beverly Lyn-Cook, and Susan Kadlubar. MicroRNAs: Potential Therapeutic Targets for Breast Cancer. Epigenetic Diagnosis and Therapy, 1 (1), 60-71, 2014.
  8. Nancy Greer-Williams, Kimberly Enoch, Brandon Booth, Athena Starlard-Davenport, Gloria E. Sarto, Thomas Kieber-Emmons. Rural African American women and breast cancer: Social determinants of health shape ability to conceptualize health in the Arkansas Delta. Journal of Rural and Community Development, 9 (2), 51-66, 2014.
  9. Starlard-Davenport, A, Glover-Collins, K, Mahkoul, I, Hutchins, L, Westbrook, K, Korourian, S, Enoch, K, Preston, M, Jackson, SN, Klimberg, VS, Henry-Tillman, R. Race is not a factor in overall survival in patients with triple negative breast cancer: a retrospective review. Springerplus, 2, 516, 2013.
  10. Starlard-Davenport, A, Kutanzi, K, Tryndyak, V, Word, B, Lyn-Cook, B. Restoration of the methylation status of hypermethylated gene promoters by microRNA-29b in human breast cancer: A novel epigenetic therapeutic approach. J Carcinog, 12, 15, 2013.
  11. Athena Starlard-Davenport, Beverly Word, Beverly Lyn-Cook. Characterization of UDP-glucuronosyltransferase 1 (UGT1A1) promoter polymorphisms and gene expression on ethnicity, stage of disease, and menopausal status in breast cancer. Drug Metabolism and Toxicology, 2012.
  12. Starlard-Davenport, A, Tryndyak, V, Kosyk, O, Ross, SR, Rusyn, I, Beland, FA, Pogribny, IP. Dietary methyl deficiency, microRNA expression and susceptibility to liver carcinogenesis. J Nutrigenet Nutrigenomics, 3 (4-6), 259-66, 2011.
  13. Lyn-Cook, LE, Tareke, E, Word, B, Starlard-Davenport, A, Lyn-Cook, BD, Hammons, GJ. Food contaminant acrylamide increases expression of Cox-2 and nitric oxide synthase in breast epithelial cells. Toxicol Ind Health, 27 (1), 11-8, 2011.
  14. Shpyleva, SI, Tryndyak, VP, Kovalchuk, O, Starlard-Davenport, A, Chekhun, VF, Beland, FA, Pogribny, IP. Role of ferritin alterations in human breast cancer cells. Breast Cancer Res Treat, 126 (1), 63-71, 2011.
  15. Pogribny, IP, Starlard-Davenport, A, Tryndyak, VP, Han, T, Ross, SA, Rusyn, I, Beland, FA. Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice. Lab Invest, 90 (10), 1437-46, 2010.
  16. Starlard-Davenport, A, Lyn-Cook, B, Beland, FA, Pogribny, IP. The role of UDP-glucuronosyltransferases and drug transporters in breast cancer drug resistance. Exp Oncol, 32 (3), 172-80, 2010.
  17. Starlard-Davenport, A, Tryndyak, V, Kosyk, O, Ross, SR, Rusyn, I, Beland, FA, Pogribny, IP. Dietary methyl deficiency, microRNA expression and susceptibility to liver carcinogenesis. World Rev Nutr Diet, 101, 123-30, 2010.
  18. Starlard-Davenport, A, Tryndyak, VP, James, SR, Karpf, AR, Latendresse, JR, Beland, FA, Pogribny, IP. Mechanisms of epigenetic silencing of the Rassf1a gene during estrogen-induced breast carcinogenesis in ACI rats. Carcinogenesis, 31 (3), 376-81, 2010.
  19. Starlard-Davenport, A, Lyn-Cook, B, Radominska-Pandya, A. Identification of UDP-glucuronosyltransferase 1A10 in non-malignant and malignant human breast tissues. Steroids, 73 (6), 611-20, 2008.
  20. Xiao, Y, Word, B, Starlard-Davenport, A, Haefele, A, Lyn-Cook, BD, Hammons, G. Age and gender affect DNMT3a and DNMT3b expression in human liver. Cell Biol Toxicol, 24 (3), 265-72, 2008.
  21. Starlard-Davenport, A, Lyn-Cook, B, Radominska-Pandya, A. Novel identification of UDP-glucuronosyltransferase 1A10 as an estrogen-regulated target gene. Steroids, 73 (1), 139-47, 2008.
  22. Starlard-Davenport, A, Xiong, Y, Bratton, S, Gallus-Zawada, A, Finel, M, Radominska-Pandya, A. Phenylalanine(90) and phenylalanine(93) are crucial amino acids within the estrogen binding site of the human UDP-glucuronosyltransferase 1A10. Steroids, 72 (1), 85-94, 2007.