Biology and Biochemistry Department
Office: 3009 SERC Bldg
Despite the discovery of nuclear receptors (NRs) more than four decades ago, their regulation or how they elicit their biological effects are still not well understood. The objective of the Frigo Laboratory is to better understand how NRs function in specific disease states, with a focus on cancer. The long-term goal of our research is to develop novel therapies that target these newly identified NR-mediated mechanisms.
Our research involves a multidisciplinary approach that integrates bioinformatics, pharmacology, biochemistry and molecular and cellular biology. Bioinformatics is used as a guide to identify signaling pathways highlighted in particular physiological or pathological states of interest. This approach has the added benefit of being able to combine clinical and experimental data to highlight select pathways that are both important in medical settings and can readily be tested in a scientific research environment. From here, we apply pharmacological, biochemical, and molecular and cellular biology approaches to test hypotheses in various in vitro cellular models. Those concepts that require a more comprehensive understanding are then taken into in vivo mouse models.
Frigo DE, Burow ME, Mitchell KA, Chiang T, and McLachlan JA. DDT and its metabolites alter gene expression in human uterine cell lines through ER-independent mechanisms. Environ Health Perspect 110: 1239-1245, 2002.
Frigo DE, Duong BN, Melnik LI, Schief LS, Collins-Burow BM, Pace DK, McLachlan JA, and Burow ME. Flavonoid Phytochemicals Regulate Activator Protein-1 Signal Transduction Pathways in Endometrial and Kidney Stable Cell Lines. J. Nutr. 132: 1848-1853, 2002.
Weldon, C.B., Parker, A.P. Patten, D., Elliott S., Tang, Y., Frigo, D.E., Dugan, C.M., Coakley, E.L., Butler, N.N., Clayton, J.L., Alam, J., Curiel, T.J., Beckman, B.S., Jaffe, B.M., Burow, M.E. Sensitization of Apoptotically-Resistant Breast Carcinoma Cells to TNF and TRAIL by Inhibition of p38 Mitogen Activated Protein Kinase Signaling. International Journal of Oncology 24: 1473-1480, 2004.
Frigo DE, Tang Y, Beckman BS, Scandurro, AB, Alam J, Burow ME, and McLachlan JA. Mechanism of AP-1-mediated gene expression by select organochlorines through the p38 MAPK pathway. Carcinogenesis 25 (2): 249-261, 2004.
Frigo DE, Vigh KA, Struckhoff AP, Elliott S, Beckman BS, Burow ME, and McLachlan JA. Xenobiotic-Induced TNF-alpha Expression and Apoptosis Through the p38 MAPK Signaling Pathway. Toxicology Letters 155 (2): 227-238, 2005.
Duong BN, Elliott S, Frigo DE, Melnik LI, Vanhoy L, Tomchuck S, Lebeau HP, David O, Beckman BS, Alam J, Bratton MR, McLachlan JA, Burow ME. AKT Regulation of Estrogen Receptor beta Transcriptional Activity in Breast Cancer. Cancer Research 66 (17): 8373-81, 2006.
Frigo DE, Basu A, Nierth-Simpson EN, Weldon CB, Dugan CM, Elliott S, Collins-Burow BM, Salvo VA, Zhu Y, Melnik LI, Lopez GN, Kushner PJ, Curiel TJ, Rowan BG, McLachlan JA, and Burow ME. p38 MAPK Stimulates Estrogen-Mediated Transcription and Proliferation Through the Phosphorylation and Potentiation of the p160 Coactivator GRIP1. Molecular Endocrinology 20: 971-983, 2006.
Sherk AB, Frigo DE, Schnackenberg CG, Bray JD, Laping NJ, Trizna W, Hammond M, Patterson JR, Thompson SK, Kazmin D, Norris JD, and McDonnell DP. Development of a Small Molecule Serum and Glucocorticoid-regulated Kinase 1 Antagonist and its Evaluation as a Prostate Cancer Therapeutic. Cancer Research 68 (18): 1-9, 2008.
Frigo DE and McDonnell DP. Differential Effects of Prostate Cancer Therapeutics on Neuroendocrine Transdifferentiation. Molecular Cancer Therapeutics 7 (3): 659-69, 2008.
Frigo DE*, Bratton MR*, Vigh KA, Fan D, John A. McLachlan JA, and Burow ME. Phosphorylation and potentiation of the transcriptional coactivator p300 by p38 MAPK. Carcinogenesis 30 (1): 106-13, 2009. *denotes co-first authors
Wardell SE, Ilkayeva OR, Wieman HL, Frigo DE, Rathmell JC, Newgard CB, and McDonnell DP. Glucose Metabolism as a Target of Histone Deacetylase Inhibitors. Molecular Endocrinology 23 (3): 388-401, 2009.
Frigo DE, Sherk AB, Wittmann BM, Norris JD, Wang Q, Joseph JD, Toner AP, Brown M, and McDonnell DP. Induction of Krüppel-like Factor 5 Expression by Androgens Results in Increased CXCR4-dependent Migration of Prostate Cancer Cells in vitro. Molecular Endocrinology 23: 1385-1396, 2009.
Frigo DE, Howe MK, Wittmann BM, Brunner AM, Cushman I, Wang Q, Brown M, Means AR and McDonnell DP. CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells. Cancer Research 71: 528-537, 2011.
Bratton MR, Antoon JW, Duong BN, Frigo DE, Tilghman S, Collins-Burow BM, Elliott S, Tang Y, Melnik LI, Lai L, Alam J, Beckman BS, Hill SM, Rowan BG, McLachlan JA and Burow ME. GalphaO Potentiates Estrogen Receptor-alpha Activity via the ERK Signaling Pathway. J Endocrinol 214: 45-54, 2012.
Bratton MR, Frigo DE, Segar HC, McLachlan JA, Wiese TE and Burow ME. The Organochlorine o,p-DDT Plays a Role in Coactivator-Mediated MAPK Crosstalk in MCF-7 Breast Cancer Cells. Environ Health Perspect 120 (9): 1291-6, 2012.
Collins-Burow BM, Antoon JW, Frigo DE, Elliot S, Weldon CB, Boue SM, Beckman BS, Curiel TJ, Alam J, McLachlan JA and Burow ME. Antiestrogen activity of flavonoid phytochemicals mediated via c-jun N-terminal protein kinase pathway: cell-type specific regulation of estrogen receptor alpha. J Steroid Biochem & Mol Biol 132: 186-193, 2012.
Augello MA, Burd CJ, Birbe R, McNair C, Ertel A, Magee MS, Frigo DE, Wilder-Romans K, Shilkrut M, Han S, Jernigan DL, Dean JL, Fatatis A, McDonnell DP, Visakorpi T, Feng FY and Knudsen KE. Convergence of Oncogenic and Hormone Receptor Pathways Promotes Pro-Metastatic Phenotypes. J Clin Invest 123 (1): 493-508, 2013.
Shi Y, Han JJ, Tennakoon JB, Mehta FF, Merchant FA, Burns AR, Howe MK, McDonnell DP and Frigo DE. Androgens Promote Prostate Cancer Cell Growth through Induction of Autophagy. Mol Endocrinol 27 (2): 280-95, 2013. (Cover)
Tennakoon JB, Shi Y, Han JJ, Tsouko E, White MA, Burns AR, Zhang A, Xia X, Ilkayeva OR, Xin L, Ittmann MM, Rick FG, Schally AV and Frigo DE. Androgens Regulate Prostate Cancer Cell Growth via an AMPK-PGC-1alpha-Mediated Metabolic Switch. Oncogene 33(45):5251-61, 2014.
Tsouko E, Khan AS, White MA, Han JJ, Shi Y, Merchant FA, Sharpe MA, Xin L and Frigo DE. Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated mechanism and its role in prostate cancer cell growth. Oncogenesis 3: e103, 2014.
Popovics P*, Frigo DE*, Schally AV and Rick FG. Targeting the 5-AMP-activated protein kinase (AMPK) and related metabolic pathways for the treatment of prostate cancer. Expert Opin Ther Targets, 19(5):617-32, 2015. *Co-first authors
Tsouko E, Wang J, Frigo DE, Aydogdu E, Williams C. miR-200a inhibits migration of triple-negative breast cancer cells through direct repression of the EPHA2 oncogene. Carcinogenesis. 36(9):1051-60, 2015.
Gaur S, Wen Y, Song JH, Mangala LS, Blessing AM, Ivan C, Wu SY, Parikh NU, Varkaris A, Shi Y, Lopez-Berestein G, Frigo DE, Sood AK and Gallick GE. Chitosan Nanoparticle-Mediated Delivery of miRNA-34a Decreases Prostate Tumor Growth in the Bone and its Expression Induces Non-Canonical Autophagy. Oncotarget 6(30):29161-77, 2015.
Shafi AA, Putluri V, Arnold JM, Tsouko E, Maity S, Roberts JM, Coarfa C, Frigo DE, Putluri N, Sreekumar A and Weigel NL. Differential Regulation of Metabolic Pathways by Androgen Receptor (AR) and its Constitutively Active Splice Variant, AR-V7. Oncotarget 6(31):31997-2012, 2015.
Blessing AM, Sathya G, Rajapakshe K, Sung YY, Bollu LR, Shi Y, Cheung E, Coarfa C, Chang JT, McDonnell DP and Frigo DE. Identification of a novel coregulator, SH3YL1, that interacts with the androgen receptor N-terminus. Mol Endocrinol 29(10):1426-39, 2015.
Klionsky DJ, Abdelmohsen K, Abe A, ..Frigo DE, ..Zughaier SM. Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (3rd Edition). Autophagy 12(1):1-222, 2016.
Park JH, Vithayathil S, Kumar S, Sung PL, Dobrolecki LE, Putluri V, Bhat V, Bhowmik S, Gupta V, Arora K, Wu D, Tsouko E, Zhang Y, Maity S, Donti TR, Graham BH, Frigo DE, Coarfa C, Yotnda P, Putluri N, Lewis MT, Sreekumar A, Creighton CJ, Wong LJC and Kaipparettu BA. Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming to the Regulation of Oncogenic Properties in Triple Negative Breast Cancer. Cell Rep 14(9):2154-65, 2016.
Kaushik AK, Shojaie A, Panzitt K, Sonavane R, Venghatakrishnan H, Manikkam M, Zaslavsky A, Putluri V, Vasu VT, Zhang Y, Khan AS, Lloyd S, Szafran AT, Dasgupta S, Bader DA, Stossi F, Li H, Samanta S, Cao X, Tsouko E, Huang S, Frigo DE, Chan L, Edwards D, Kaipparettu BA, Mitsiades N, Weigel NL, Mancini M, McGuire SE, Mehra R, Ittmann MM, Chinnaiyan AM, Putluri N, Palapattu GS, Michailidis G and Sreekumar A. Inhibition of Hexosamine Biosynthetic Pathway Promotes Castration Resistant Prostate Cancer. Nat Commun 7;11612, 2016.
Blessing AM, Rajapakshe K, Bollu LR, Shi Y, White MA, Pham AH, Lin C, Jonsson P, Cortes CJ, Cheung E, La Spada AR, Bast RC Jr, Merchant FA, Cristian Coarfa C and Frigo DE. Transcriptional Regulation of Core Autophagy and Lysosomal Genes by the Androgen Receptor Promotes Prostate Cancer Progression. Autophagy [Epub ahead of print] 2016.
Khan AS and Frigo DE. Regulation, Role and Therapeutic Targeting of AMPK in Prostate Cancer. Nat Rev Urol [Epub ahead of print] 2017.