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Andrew Bradford, PhD


Associate Professor, Division of Reproductive Sciences

Education:

PhD (1987) University of Newcastle upon Tyne

Contact:

Mail Stop 8309, RC2, Room 3007
Phone: (303) 724 3507
Fax:     (303) 724 3512
Andrew.Bradford@ucdenver.edu

Polotsky Lab
Santoro Lab

Research Interests:

My research interests focus on hormone/growth factor signaling and cancer. Specifically, our laboratory is studying the role of selective protein kinase C (PKC) isoforms in the modulation of cell growth and death in endometrial cancer. Endometrial cancer is the most common invasive gynecological malignancy in the United States. Although the annual incidence of endometrial cancer has remained relatively constant over the past decade, statistics indicate a dramatic increase in mortality, suggesting a higher prevalence of tumors, which are refractory to treatment. Thus, there is an urgent need to identify prognostic markers in endometrial cancer and to develop agents that have greater efficacy and biological specificity in the treatment of gynecological malignancies.

Recent studies from our laboratory and others suggest that members of the protein kinase C (PKC) family play critical roles in the pathogenesis of endometrial tumors, regulating both proliferation and programmed cell death (apoptosis), Moreover, PKC isozyme expression patterns may reflect the invasive or metastatic potential of endometrial cancers. Using endometrial cancer cell lines and specific adenoviral constructs, we have investigated the role of specific PKCs in etoposide-induced cell cycle arrest and apoptosis. Our results suggest that PKCα and δ exert opposing influences on proliferation and apoptosis in endometrial tumors. PKCα appears to promote proliferation and survival of endometrial cancer cells, whereas PKCδ is pro-apoptotic. Thus, PKCs are clearly important factors in the formation and progression of endometrial tumors. However, little is known regarding the molecular mechanisms underlying PKC modulation of proliferation and apoptosis in the endometrium, particularly with respect to the possible differential role of specific PKC isoforms. We postulate that specific transcriptional, mitogenic and/or apoptotic responses to PKC and isoforms may result in a more aggressive, chemotherapy-resistant endometrial tumor phenotype. Further study of PKCs in the endometrium may identify novel diagnostic/ prognostic indicators and provide new potential targets for therapeutic intervention.

We are also investigating the role of growth factor signaling and Ets transcription factors in the pathogenesis of uterine fibroids or leiomyomata.

Publications:
Al-Safi ZA, Liu H, Carlson NE, Chosich J, Harris M, Bradford AP, Robledo C, Eckel RH, Polotsky AJ. Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women. J Clin Endocrinol Metab. 2016Jan;101(1):324-33. doi: 10.1210/jc.2015-2913. Epub 2015 Nov 2. PubMed PMID:  26523525.

Al-Safi ZA, Liu H, Carlson NE, Chosich J, Lesh J, Robledo C, Bradford AP, Gee NA, Phang T, Santoro N, Kohrt W, Polotsky AJ. Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women. J Clin Endocrinol Metab. 2015 Nov;100(11):4372-81. doi: 10.1210/jc.2015-1946. Epub 2015 Oct 1. PubMed PMID: 26425884.

Noshchenko A, Hoffecker L, Lindley EM, Burger EL, Cain CM, Patel VV, Bradford AP. Predictors of spine deformity progression in adolescent idiopathic scoliosis: A systematic review with meta-analysis. World J Orthop. 2015 Aug 18;6(7):537-58. doi: 10.5312/wjo.v6.i7.537. eCollection 2015 Aug 18. PubMed PMID: 26301183; PubMed Central PMCID: PMC4539477.

Bradford AP, Jones K, Kechris K, Chosich J, Montague M, Warren WC, May MC, Al-Safi Z, Kuokkanen S, Appt SE, Polotsky AJ. Joint MiRNA/mRNA expression profiling reveals changes consistent with development of dysfunctional corpus luteum after weight gain. PLoS One. 2015 Aug 10;10(8):e0135163. doi:10.1371/journal.pone.0135163. eCollection 2015. PubMed PMID: 26258540; PubMed Central PMCID: PMC4530955.

Kitamura H, Ozono E, Iwanaga R, Bradford AP, Okuno J, Shimizu E, Kurayoshi K, Kugawa K, Toh H, Ohtani K. Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts. Genes Cells. 2015 Sep;20(9):739-57. doi: 10.1111/gtc.12268. Epub 2015 Jul 23. PubMed PMID:26201719.

Merhi Z, Polotsky AJ, Bradford AP, Buyuk E, Chosich J, Phang T, Jindal S, Santoro N. Adiposity Alters Genes Important in Inflammation and Cell Cycle Division in Human Cumulus Granulosa Cell. Reprod Sci. 2015 Oct;22(10):1220-8. doi: 10.1177/1933719115572484. Epub 2015 Feb 11. PubMed PMID: 25676576.

Wooding KM, Hankin JA, Johnson CA, Chosich JD, Baek SW, Bradford AP, Murphy RC, Santoro N. Measurement of estradiol, estrone, and testosterone in postmenopausal human serum by isotope dilution liquid chromatography tandem mass spectrometry without derivatization. Steroids. 2015 Apr;96:89-94. doi:10.1016/j.steroids.2015.01.007. Epub 2015 Jan 21. PubMed PMID: 25617740; PubMed Central PMCID: PMC4366052.

Kurayoshi K, Ozono E, Iwanaga R, Bradford AP, Komori H, Ohtani K. Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs. Biochem Biophys Res Commun. 2014 Jul 18;450(1):240-6. doi:10.1016/j.bbrc.2014.05.102. Epub 2014 Jun 2. PubMed PMID: 24893334.

Roth LW, Bradshaw-Pierce EL, Allshouse AA, Lesh J, Chosich J, Bradford AP, Polotsky AJ, Santoro N. Evidence of GnRH antagonist escape in obese women. J Clin Endocrinol Metab. 2014 May;99(5):E871-5. doi: 10.1210/jc.2013-3598. Epub 2014 Mar 20. PubMed PMID: 24650013; PubMed Central PMCID: PMC4010706.

Roth LW, Allshouse AA, Bradshaw-Pierce EL, Lesh J, Chosich J, Kohrt W, Bradford AP, Polotsky AJ, Santoro N. Luteal phase dynamics of follicle-stimulating and luteinizing hormones in obese and normal weight women. Clin Endocrinol (Oxf). 2014 Sep;81(3):418-25. doi: 10.1111/cen.12441. Epub 2014
Mar 20. PubMed PMID: 24576183; PubMed Central PMCID: PMC4115008.

Dai D, Bradford AP, Prossnitz ER. Endometrial cancer: molecular and cellular basis of tumor development, novel biomarkers and therapeutic agents, and innovative research approaches. Obstet Gynecol Int. 2014;2014:710405. doi:10.1155/2014/710405. Epub 2014 Jan 16. PubMed PMID: 24550988; PubMed Central  PMCID: PMC3914482.

Ross LA, Polotsky AJ, Kucherov A, Bradford AP, Lesh J, Chosich J, Gee N, Santoro N. Profound reduction of ovarian estrogen by aromatase inhibition in obese women. Obesity (Silver Spring). 2014 Jun;22(6):1464-9. doi:10.1002/oby.20713. Epub 2014 Feb 18. PubMed PMID: 24482405; PubMed Central PMCID: PMC4037337.

Wooding KM, Barkley RM, Hankin JA, Johnson CA, Bradford AP, Santoro N, Murphy RC. Mechanism of formation of the major estradiol product ions following collisional activation of the molecular anion in a tandem quadrupole mass spectrometer. J Am Soc Mass Spectrom. 2013 Oct;24(10):1451-5. doi:
10.1007/s13361-013-0705-y. Epub 2013 Aug 18. PubMed PMID: 23955001; PubMed Central PMCID: PMC3786604.

Thorne AM, Jackson TA, Willis VC, Bradford AP. Protein Kinase C α Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells. Obstet Gynecol Int. 2013;2013:537479. doi: 10.1155/2013/537479. Epub 2013 Jun 17. PubMed PMID: 23843797; PubMed Central PMCID: PMC3703424.

Kundu MC, May MC, Chosich J, Bradford AP, Lasley B, Gee N, Santoro N, Appt SE, Polotsky AJ. Assessment of luteal function in the vervet monkey as a means to develop a model for obesity-related reproductive phenotype. Syst Biol Reprod Med. 2013 Apr;59(2):74-81. doi: 10.3109/19396368.2012.752547. Epub 2013 Jan 2. PubMed PMID: 23278149; PubMed Central PMCID: PMC4349572.
 
Iwanaga R, Wang CA, Micalizzi DS, Harrell JC, Jedlicka P, Sartorius CA, Kabos P, Farabaugh SM, Bradford AP, Ford HL. Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways. Breast Cancer Res. 2012 Jul 5;14(4):R100. doi:10.1186/bcr3219. PubMed PMID: 22765220; PubMed Central PMCID: PMC3680936.

Korch C, Spillman MA, Jackson TA, Jacobsen BM, Murphy SK, Lessey BA, Jordan VC, Bradford AP. DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination. Gynecol Oncol. 2012 Oct;127(1):241-8. doi: 10.1016/j.ygyno.2012.06.017. Epub 2012 Jun 16. PubMed PMID: 22710073; PubMed Central PMCID: PMC3432677.

Georgieva B, Milev I, Minkov I, Dimitrova I, Bradford AP, Baev V. Characterization of the uterine leiomyoma microRNAome by deep sequencing. Genomics. 2012 May;99(5):275-81. doi: 10.1016/j.ygeno.2012.03.003. Epub 2012 Mar 16. PubMed PMID: 22446413.