TIFFANY N. SEAGROVES, Ph.D.

Associate Professor
Director, Gerwin Small Animal Imaging Center, CRB
Track Head, Cancer and Developmental Biology track, IBS program

Office: Rm 262 Cancer Research Building
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

Understanding the role of transcription factors in normal mammary gland development and in transgenic mouse models of breast cancer, particularly the oxygen-sensitive Hypoxia-Inducible Factor (HIF)-1alpha protein. Our laboratory focuses on primary cell culture, culture of cells on extracellular matrix substrata, DNA/RNA/protein extraction from normal mammary gland or mammary tumors, real-time PCR, immunohistochemistry and adenoviral/lentiviral transduction.

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

Research interest/specialty

Understanding the role of transcription factors in normal mammary gland development and in transgenic mouse models of breast cancer, particularly the oxygen-sensitive Hypoxia-Inducible Factor (HIF)-1alpha protein. Our laboratory focuses on primary cell culture, culture of cells on extracellular matrix substrata, DNA/RNA/protein extraction from normal mammary gland or mammary tumors, real-time PCR, immunohistochemistry and adenoviral/lentiviral transduction.

Research keywords

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

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.

Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.