TIFFANY N. SEAGROVES, Ph.D.

Associate Professor
Pathology
Executive Director, Molecular Resource Center (MRC)
Associate Vice Chancellor for Research-Core Laboratories

Office: RM 262 CANCER RESEARCH BUILDING
19 SOUTH MANASSAS
MEMPHIS TN 381033403
Tel: (901) 448-5018
tseagro1@uthsc.edu
http://www.uthsc.edu/Seagroves_Lab/

Education

  • San Diego State University, Food and Drug Law; Marketing, MBA
  • PostDoc, University of California, San Diego, CA, Cell & Cancer Biology
  • Ph.D., Baylor College of Medicine, Houston, TX, Cell & Molecular Biology
  • B.S., University of North Carolina, Chaaapel Hill, NC, Biology

Research description

The long-term goal of the laboratory is to determine how the oxygen-regulated transcription factor HIF-1alpha acts as a positive factor in solid tumor growth and metastasis. We predict that HIF-1 transcriptional activity is required in multiple cells types of the mammary gland (epithelial, endothelial, tumor-associated macrophages) to mediate several steps of tumorigenesis and metastasis. Recently, we have shown that deletion of HIF-1alpha in breast tumor cells inhibits primary tumor growth and metastasis. The impact of HIF-1alpha deletion may be to modulate tumor growth in several ways including reducing glucose uptake and the production of energy by glycolysis, reducing angiogenesis, reducing expression of matrix remodeling enzymes, and/or inhibiting cancer stem cell renewal or tumor-initiating activity. Moreover, hypoxic regions of tumors are notoriously resistant to radiation and chemotherapy, therefore understanding the downstream genes regulated by HIF-1 may be exploited to design targeted therapies. We utilize a variety of transgenic mouse models of breast cancer and genetically modified primary tumor epithelial cell lines that are either wild type or null for HIF-1alpha to investigate these questions.

Research Interest/Specialty

Research Interests: The research in my laboratory is focused on utilizing pre-clinical, syngeneic transgenic mouse models or patient-derived xenograft (PDX) models of metastatic breast cancer (MBC) to understand how genes that impact the tumor microenvironment, particularly the Hypoxia-Inducible Factor (HIF) transcription factors, regulate breast cancer progression and metastasis in vivo. I have over twenty-two years of experience using mouse models, and over 16 years of experience investigating the role of the hypoxic response in breast biology and cancer. Our current areas of research are: 1) To identify novel or understudied HIF-dependent genes that promote metastasis in breast cancer, 2) To identify the mechanisms by which these HIF-dependent genes induce metastasis, 3) To perform pre-clinical screens of inhibitors that block the hypoxic response for treatment of MBC and 4) To validate observations from the study of syngeneic, immunocompetent murine models of MBC using human breast cancer models, including conventional human breast cancer cell lines and more innovative PDX models. 5) To modify PDX models to express reporters, such as luciferase, to track tumor cell growth and metastasis in vivo using bio-imaging.

Education/Mentoring Experience: I am a founding member of the UTHSC Postdoctoral Association (PhDA) on the UTHSC campus, which launched in 2006, and I served as the PhDA faculty representative for over seven years. I also served on the Postdoctoral Advisory Committee (PAC) to the Chancellor for three years. I have directly mentored five postdoctoral trainees and one graduate student, who is now a postdoctoral fellow at the NCI in the laboratory of Dr. Patricia Steeg. I directed the Cancer and Developmental Biology track of the Interdisciplinary Biomedical Sciences (IBS) graduate Ph.D. program at UTHSC/St. Jude from 2010-2016. I have served as Course Director for two courses in the CDB track curriculum, including PATH834 (CDB Track Journal Club) and PATH840 (Special Topics: Science as a Profession), a course I developed to teach writing and laboratory management skills to first-year students. I also have extensive experience mentoring undergraduate students and medical students in my laboratory (19 trainees since 2005). I recently served as a permanent member of the NCI-I review panel (Transition to Independence, K99, Awards panel, 2013-2016). Since 2011, I have mentored nine UTHSC M1 medical students for their full-time summer research experience.

Research keywords

breast cancer, hypoxia, HIF-1alpha, von Hippel-Lindau, tumorigenesis, metastasis, transcription factor, gene expression

Area of teaching/subject

IPBS Program, Organ and Systems Biology, Pathology block leader

Co-Cancer and Developmental Biology Track Head, new IBS program

Publications

  1. Lillo, MA, Nichols, C, Perry, C, Runke, S, Krutilina, R, Seagroves, TN, Miranda-Carboni, GA, Krum, SA. Methylparaben stimulates tumor initiating cells in ER+ breast cancer models. J Appl Toxicol, 2016.
  2. Sethuraman, A, Brown, M, Seagroves, TN, Wu, ZH, Pfeffer, LM, Fan, M. SMARCE1 regulates metastatic potential of breast cancer cells through the HIF1A/PTK2 pathway. Breast Cancer Res, 18 (1), 81, 2016.
  3. Brooks, DL, Schwab, LP, Krutilina, R, Parke, DN, Sethuraman, A, Hoogewijs, D, Schörg, A, Gotwald, L, Fan, M, Wenger, RH, Seagroves, TN. ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models. Mol Cancer, 15, 26, 2016.
  4. Regan Anderson, TM, Ma, SH, Raj, GV, Cidlowski, JA, Helle, TM, Knutson, TP, Krutilina, RI, Seagroves, TN, Lange, CA. Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. Cancer Res, 76 (6), 1653-63, 2016.
  5. Wilson, R, Urraca, N, Skobowiat, C, Hope, KA, Miravalle, L, Chamberlin, R, Donaldson, M, Seagroves, TN, Reiter, LT. Assessment of the Tumorigenic Potential of Spontaneously Immortalized and hTERT-Immortalized Cultured Dental Pulp Stem Cells. Stem Cells Transl Med, 4 (8), 905-12, 2015.
  6. Sodi, VL, Khaku, S, Krutilina, R, Schwab, LP, Vocadlo, DJ, Seagroves, TN, Reginato, MJ. mTOR/MYC Axis Regulates O-GlcNAc Transferase Expression and O-GlcNAcylation in Breast Cancer. Mol Cancer Res, 13 (5), 923-33, 2015.
  7. Slominski, A, Kim, TK, Brożyna, AA, Janjetovic, Z, Brooks, DL, Schwab, LP, Skobowiat, C, Jóźwicki, W, Seagroves, TN. The role of melanogenesis in regulation of melanoma behavior: melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways. Arch Biochem Biophys, 563, 79-93, 2014.
  8. Chen, J, Wang, J, Schwab, LP, Park, KT, Seagroves, TN, Jennings, LK, Miller, DD, Li, W. Benzimidazole analogs as potent hypoxia inducible factor inhibitors: synthesis, biological evaluation, and profiling drug-like properties. Anticancer Res, 34 (8), 3891-904, 2014.
  9. Paatero, I, Seagroves, TN, Vaparanta, K, Han, W, Jones, FE, Johnson, RS, Elenius, K. Hypoxia-inducible factor-1α induces ErbB4 signaling in the differentiating mammary gland. J Biol Chem, 289 (32), 22459-69, 2014.
  10. Krutilina, R, Sun, W, Sethuraman, A, Brown, M, Seagroves, TN, Pfeffer, LM, Ignatova, T, Fan, M. MicroRNA-18a inhibits hypoxia-inducible factor 1α activity and lung metastasis in basal breast cancers. Breast Cancer Res, 16 (4), R78, 2014.
  11. Ferrer, CM, Lynch, TP, Sodi, VL, Falcone, JN, Schwab, LP, Peacock, DL, Vocadlo, DJ, Seagroves, TN, Reginato, MJ. O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway. Mol Cell, 54 (5), 820-31, 2014.
  12. Regan Anderson, TM, Peacock, DL, Daniel, AR, Hubbard, GK, Lofgren, KA, Girard, BJ, Schörg, A, Hoogewijs, D, Wenger, RH, Seagroves, TN, Lange, CA. Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression. Cancer Res, 73 (18), 5810-20, 2013.
  13. Whelan, KA, Schwab, LP, Karakashev, SV, Franchetti, L, Johannes, GJ, Seagroves, TN, Reginato, MJ. The oncogene HER2/neu (ERBB2) requires the hypoxia-inducible factor HIF-1 for mammary tumor growth and anoikis resistance. J Biol Chem, 288 (22), 15865-77, 2013.
  14. Wang, C, Schwab, LP, Fan, M, Seagroves, TN, Buolamwini, JK. Chemoprevention activity of dipyridamole in the MMTV-PyMT transgenic mouse model of breast cancer. Cancer Prev Res (Phila), 6 (5), 437-47, 2013.
  15. Zbytek, B, Peacock, DL, Seagroves, TN, Slominski, A. Putative role of HIF transcriptional activity in melanocytes and melanoma biology. Dermatoendocrinol, 5 (2), 239-51, 2013.
  16. Hallett, MA, Teng, B, Hasegawa, H, Schwab, LP, Seagroves, TN, Pourmotabbed, T. Anti-matrix metalloproteinase-9 DNAzyme decreases tumor growth in the MMTV-PyMT mouse model of breast cancer. Breast Cancer Res, 15 (1), R12, 2013.
  17. Schwab, LP, Peacock, DL, Majumdar, D, Ingels, JF, Jensen, LC, Smith, KD, Cushing, RC, Seagroves, TN. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res, 14 (1), R6, 2012.
  18. Seagroves, TN, Peacock, DL, Liao, D, Schwab, LP, Krueger, R, Handorf, CR, Haase, VH, Johnson, RS. VHL deletion impairs mammary alveologenesis but is not sufficient for mammary tumorigenesis. Am J Pathol, 176 (5), 2269-82, 2010.
  19. Doronkin, S, Djagaeva, I, Nagle, ME, Reiter, LT, Seagroves, TN. Dose-dependent modulation of HIF-1alpha/sima controls the rate of cell migration and invasion in Drosophila ovary border cells. Oncogene, 29 (8), 1123-34, 2010.
  20. Golipour, A., Myers, D., Seagroves, T., Murphy, D., Evan, G., Donoghue, D.J., Moorehead, R.A., Porter, L.A. Moorehead, R. and L. Porter. The Spy1/RINGO Family Represents a Novel Mechanism Regulating Mammary Growth and Tumorigenesis. Cancer Research, 10 (68), 3591-3600, 2008.
  21. Liao, D, Corle, C, Seagroves, TN, Johnson, RS. Hypoxia-inducible factor-1alpha is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res, 67 (2), 563-72, 2007.
  22. Reiter, LT, Seagroves, TN, Bowers, M, Bier, E. Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase. Hum Mol Genet, 15 (18), 2825-35, 2006.
  23. Seagroves, TN, Hadsell, D, McManaman, J, Palmer, C, Liao, D, McNulty, W, Welm, B, Wagner, KU, Neville, M, Johnson, RS. HIF1alpha is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland. Development, 130 (8), 1713-24, 2003.
  24. Grimm, SL, Seagroves, TN, Kabotyanski, EB, Hovey, RC, Vonderhaar, BK, Lydon, JP, Miyoshi, K, Hennighausen, L, Ormandy, CJ, Lee, AV, Stull, MA, Wood, TL, Rosen, JM. Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development. Mol Endocrinol, 16 (12), 2675-91, 2002.
  25. Cao, Y, Bonizzi, G, Seagroves, TN, Greten, FR, Johnson, R, Schmidt, EV, Karin, M. IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell, 107 (6), 763-75, 2001.
  26. Seagroves, TN, Ryan, HE, Lu, H, Wouters, BG, Knapp, M, Thibault, P, Laderoute, K, Johnson, RS. Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. Mol Cell Biol, 21 (10), 3436-44, 2001.
  27. Seagroves, TN, Lydon, JP, Hovey, RC, Vonderhaar, BK, Rosen, JM. C/EBPbeta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development. Mol Endocrinol, 14 (3), 359-68, 2000.
  28. Seagroves, TN, Krnacik, S, Raught, B, Gay, J, Burgess-Beusse, B, Darlington, GJ, Rosen, JM. C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. Genes Dev, 12 (12), 1917-28, 1998.