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Benjamin Spike

Assistant Professor of Oncological Sciences

Stem Cells, Tissue Development, Cellular Plasticity, Cellular Heterogeneity, Transcriptomics, Tumor Microenvironment, Myofibrosis and Extracellular Vesicles

Spike Photo

 

Molecular Biology Program

Education

B.A./B.S./M.S. University of California, San Diego

Ph.D. University of Chicago

Links

Lab Page

PubMed Literature Search

benjamin.spike@hci.utah.edu

 

Research

We study stem cells, development and cancer at the single cell and systems level using a combination of molecular genetic tools, cellular/molecular assays, mouse models, bioinformatics approaches and functional genomics. We are particularly interested in the molecular bases of stem cell stress responses, plasticity and cellular heterogeneity as they are likely to be of critical importance for the development of effective cancer therapies as well as new strategies in tissue engineering, tissue repair and aging.

We are currently investigating the ability of the signaling protein Cripto to promote cellular adaptation and reprogramming under stress in vitro and in vivo.  Cripto, which plays separable roles in TGF-beta and growth-factor-like signaling, may play a critical role in cellular plasticity in both normal and neoplastic settings, and we are now evaluating the therapeutic potential of blocking Cripto activity in mouse models of cancer.

We are also using high resolution, single cell gene expression profiling techniques to identify novel mechanisms in development and cancer, to delineate cellular heterogeneity in these systems and to characterize rare cells types in breast and other tissues, such as normal somatic stem cells or resistant, dormant or metastatic tumor cells.

References

  1. Mirzaei Mehrabad E, Bhaskara A,  Spike BT. Factorization-based Imputation of Expression in Single-cell Transcriptomic Analysis (FIESTA) recovers Gene-Cell-State relationships. bioRxiv 2021.04.29.441691
  2. Kelber JA, Iwanicki M, Kruithof-de Julio M, Spike BT, Martínez-Montemayor MM. Editorial: Mechanisms of microenvironment governed plasticity and progression in solid tumors. Front Cell Dev Biol. 2024 Mar 25;12:1373496.
  3. Balcioglu O, Gates BL, Freeman DW, Hagos BM, Mehrabad EM, Ayala-Talavera D, Spike BT. Mcam stabilizes luminal progenitor breast cancer phenotypes via Ck2 control and Src/Akt/Stat3 attenuation. bioRxiv [Preprint]. 2024 Mar 20:2023.05.10.540211.
  4. Freeman DW, Gates BL, Spendlove MD, Gulbahce HE, Spike BT. CRIPTO promotes extracellular vesicle uptake and activation of cancer associated fibroblasts. bioRxiv [Preprint]. 2024 Apr 2:2024.03.01.583059.
  5. Hughes EP, Syage AR, Mehrabad EM, Lane TE, Spike BT, Tantin D. OCA-B promotes autoimmune demyelination through control of stem-like CD4 +T cells. bioRxiv [Preprint]. 2024 Apr 17:2023.11.29.569210.
  6. Polanco ER, Moustafa TE, Butterfield A, Scherer SD, Cortes-Sanchez E, Bodily T, Spike BT, Welm BE, Bernard PS, Zangle TA. Multiparametric quantitative phase imaging for real-time, single cell, drug screening in breast cancer. Commun Biol. 2022 Aug 8;5(1):794.
  7. Orstad G, Fort G, Parnell TJ, Jones A, Stubben C, Lohman B, Gillis KL, Orellana W, Tariq R, Klingbeil O, Kaestner K, Vakoc CR, Spike BT, Snyder EL. FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma. Dev Cell. 2022 Aug 8;57(15):1866-1882.e10.
  8. Freeman DW, Rodrigues Sousa E, Karkampouna S, Zoni E, Gray PC, Salomon DS, Kruithof-de Julio M, Spike BT. Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal. Int J Mol Sci. 2021 Sep 21;22(18):10164.
  9. Ranjan M, Lee O, Cottone G, Mirzaei Mehrabad E, Spike BT, Zeng Z, Yadav S, Chatterton R, Kim JJ, Clare SE, Khan SA. Progesterone receptor antagonists reverse stem cell expansion and the paracrine effectors of progesterone action in the mouse mammary gland. Breast Cancer Res. 2021 Aug 3;23(1):78.
  10. Balcioglu O, Heinz RE, Freeman DW, Gates BL, Hagos BM, Booker E, Mirzaei Mehrabad E, Diesen HT, Bhakta K, Ranganathan S, Kachi M, Leblanc M, Gray PC, Spike BT. CRIPTO antagonist ALK4L75A-Fc inhibits breast cancer cell plasticity and adaptation to stress. Breast Cancer Res. 2020 Nov 13;22(1):125. doi: 10.1186/s13058-020-01361-z. PMID: 33187540; PMCID: PMC7664111.
  11. Cowman SJ, Fuja DG, Liu XD, Tidwell RSS, Kandula N, Sirohi D, Agarwal AM, Emerson LL, Tripp SR, Mohlman JS, Stonhill M, Garcia G, Conley CJ, Olalde AA, Sargis T, Ramirez-Torres A, Karam JA, Wood CG, Sircar K, Tamboli P, Boucher K, Maughan B, Spike BT, Ho TH, Agarwal N, Jonasch E, Koh MY. Macrophage HIF-1α Is an Independent Prognostic Indicator in Kidney Cancer. Clin Cancer Res. 2020 Sep 15;26(18):4970-4982. doi: 10.1158/1078-0432.CCR-19-3890. Epub 2020 Jun 25.
  12. Ireland AS, Micinski AM, Kastner DW, Guo B, Wait SJ, Spainhower KB, Conley CC, Chen OS, Guthrie MR, Soltero D, Qiao Y, Huang X, Tarapcsák S, Devarakonda S, Chalishazar MD, Gertz J, Moser JC, Marth G, Puri S, Witt BL, Spike BT, Oliver TG. MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate. Cancer Cell. 2020 Jul 13;38(1):60-78.e12.
  13. Jiao X, Li Z, Wang M, Katiyar S, Di Sante G, Farshchian M, South AP, Cocola C, Colombo D, Reinbold R, Zucchi I, Wu K, Tabas I, Spike BT, Pestell RG. Dachshund Depletion Disrupts Mammary Gland Development and Diverts the Composition of the Mammary Gland Progenitor Pool. Stem Cell Reports. 2019 Jan 8;12(1):135-151.
  14. Giraddi RR, Chung CY, Heinz RE, Balcioglu O, Novotny M, Trejo CL, Dravis C, Hagos BM, Mehrabad EM, Rodewald LW, Hwang JY, Fan C, Lasken R, Varley KE, Perou CM, Wahl GM, Spike BT. Single-Cell Transcriptomes Distinguish Stem Cell State Changes and Lineage Specification Programs in Early Mammary Gland Development. Cell Rep. 2018 Aug 7;24(6):1653-1666.e7.
  15. Maya Saison-Ridinger, Kathleen E. DelGiorno, Tejia Zhang, Annabelle Kraus, Randall French, Dawn Jaquish, Crystal Tsui, Galina Erikson, Benjamin T. Spike, Maxim N. Shokhirev, Christopher Liddle, Ruth T. Yu, Michael Downes, Ronald M. Evans, Alan Saghatelian, Andrew M. Lowy, and Geoffrey M. Wahl. Reprogramming pancreatic stellate cells via p53 activation: A putative target for pancreatic cancer therapy. (2017) PLoS One. Dec 6;12(12):e0189051.
  16. Christy L. Trejo, Gidsela Luna, Christopher Dravis, Benjamin T. Spike, and Geoffrey M. Wahl. LGR5 labels but is not essential for stem cellactivity in the embryonic mammary gland. NPJ Breast Cancer 3, Article number: 16 (2017)
  17. Geoffrey M. Wahl and Benjamin T. Spike. Cell state plasticity, stem cells and the generation of intratumoral heterogeneity. NPJ Breast Cancer --Review. npj Breast Cancer 3, Article number: 14 (2017)
  18. Benjamin T. Spike. Breast cancer stem cells and the move toward high resolution stem cell systems. Chapter 5 in Cancer Stem Cells. ed. by H.Liu and J. Lathia. (Elsevier, 2016). ISBN: 978-0-12-803892-5
  19. Benjamin T. Spike. Breast cancer stem cells and the move toward high resolution stem cell systems. Book Chapter: Cancer Stem Cells. ed. by H. Liu and J. Lathia. (Elsevier, 2016).
  20. Christopher Dravis, Benjamin T. Spike, J. Chuck Harrell, Claire Johns, Christy Trejo, E. Michelle Southard-Smith, Charles M. Perou, and Geoffrey M. Wahl. Sox10 regulates stem/progenitor and mesenchymal states in mammary epithelial cells. (2015) Cell Reports. Sep 29;12(12):2035-48.
  21. Adam D. Pfefferle, Benjamin T. Spike, Geoffrey M. Wahl, and Charles M. Perou. Luminal progenitor and fetal mammary stem cell expression features predict breast tumor response to neoadjuvant chemotherapy. (2015) Breast Cancer Res Treat. Jan;149(2):425-37.
  22. Malgorzata Klausinska, Nadia P. Castro, Maria Cristina Rangel, Benjamin T. Spike, Peter C. Gray, Daniel Bertollette, Frank Cuttitta, and David Salomon. The multifaceted role of the embryonic gene Cripto-1 in cancer, stem cells and epithelial-mesenchymal transition. (2014) Seminars in Cancer Biology. Dec;29:51-8. Review.
  23. Genyuan Zhu, Miao Wang, Benjamin T. Spike, Peter C. Gray, Jieli Shen, Sung-Hyung Lee, Si-Yi Chen, and Amy S. Lee. Characterization of mammary gland development in MMTV-Cre mediated GRP94 and GRP78 knockout mouse models. (2014) Scientific Reports Jun 23;4:5390
  24. Benjamin T. Spike*, Jonathan A. Kelber, Evan Booker, Madhuri Kalathur, Rose Rodewald, Julia Lipianskaya, Justin La, Marielle He, Tracy Wright, Richard Klemke, Geoffrey M. Wahl and Peter C. Gray*. Cripto/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo. (*co-corresponding) (2014) Stem Cell Reports. Apr 8;2(4):427-439 (COVER PICTURE)
  25. Adam D. Pfefferle, Jason I. Herschkowitz, Jerry Usary, J. Chuck Harrell, Benjamin T. Spike, Geoffrey M. Wahl, Jeffrey M. Rosen, and Charles M. Perou. Transcriptomic Classification of Genetically Engineered Mouse Models of Breast Carcinoma Identifies Human Subtype Counterparts. (2013) Genome Biology 2013 Nov 12;14(11):R125
  26. Maisam Makarem, Benjamin T. Spike, Christopher Dravis, Nagarajan Kannan, Geoffrey M. Wahl, and Connie J. Eaves. Stem cells and the developing mammary gland. (2013) Journal of Mammary Gland Biology and Neoplasia. Jun;18(2):209-19
  27. Benjamin T. Spike*, Dannielle D. Engle*, Jennifer C. Lin*, Justin La, Samantha K. Cheung and Geoffrey M. Wahl. A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. (2012) Cell Stem Cell Feb 3;10(2):183-97
  28. Benjamin T. Spike and Geoffrey M. Wahl. p53, Stem Cells, and Reprogramming: Tumor Suppression beyond Guarding the Genome. (2011) Genes and Cancer Apr; 2(4):404-19. (COVER PICTURE)
  29. Hideaki Mizuno*, Benjamin T. Spike*, Geoffrey M. Wahl, and Arnold J. Levine. Inactivation of p53 in breast cancers correlates with stem cell transcriptional signatures. (2010) Proc Natl Acad Sci U S A. Dec 28;107(52):22745-50. (*co-equal contribution)
  30. Huiping Liu, James R. Knabb, Benjamin T. Spike and Kay F. Macleod. Elevated Poly-(ADP-Ribose)-Polymerase Activity Sensitizes Retinoblastoma-Deficient Cells to DNA Damage-Induced Necrosis. (2009) Mol Cancer Res. Jul;7(7):1099-109.
  31. Alexandra Dirlam, Benjamin T. Spike, Kay F. Macleod. Deregulated E2f-2 underlies cell cycle and maturation defects in Rb null erythroblasts. (2007) Mol Cell Biol. Dec;27(24):8713-28
  32. Thesis (Ph.D.): Benjamin T. Spike, The Retinoblastoma Tumor Suppressor in Stress Erythropoiesis. (Chicago: University of Chicago Press, Aug. 2007)
  33. Benjamin T. Spike and Kay F. Macleod Effects of Hypoxia on Heterotypic Macrophage Interactions. (2007) Cell Cycle 6(21): 2620-2624
  34. Kristin Tracy, Benjamin C. Dibling, Benjamin T. Spike, James R. Knabb, Paul Schumacker, and Kay F. Macleod. BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. (2007) Mol Cell Biol. 27(17):6229-42.
  35. Benjamin T. Spike, Benjamin C. Dibling, and Kay F. Macleod. Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse. (2007) Blood 110(6):2173-81.
  36. Abhinav Diwan, Andrew G. Koesters, Amy M. Odley, Suvarnamala Pushkaran, Christopher P. Baines, Benjamin T. Spike, Diedre Daria, Anil G. Jegga, Hartmut Geiger, Bruce J. Aronow, Jeffery D. Molkentin, Kay F. Macleod, Theodosia A. Kalfa, and Gerald W. Dorn, II. Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. (2007) Proc Natl Acad Sci U S A. 104(16):6794-9.
  37. Benjamin T. Spike and Kay F. Macleod. The Rb Tumor suppressor in stress responses and hematopoietic homeostasis. (2005) Cell Cycle, 4(1):42-45
  38. Benjamin T. Spike, Alexandra Dirlam, Benjamin C. Dibling, James Marvin, Bart O. Williams, Tyler Jacks and Kay F Macleod. The Rb tumor suppressor is required for stress erythropoiesis. (2004) The EMBO Journal 23(21):4319-29
  39. Huiping Liu, Benjamin Dibling, Benjamin Spike, Alexandra Dirlam and Kay Macleod. New roles for the RB tumor suppressor protein. (2004) Current Opinion in Genetics & Development 14(1):55-64
  40. Anne H. Rowley, Benjamin T. Spike, Carrie A. Mask, Stanford T. Shulman and Susan C. Baker. Oligoclonal IgA response in the vascular wall in acute Kawasaki Disease. (2001) Journal of Immunology 166(2):1334-1343
  41. Nicole Max, Karin Wolf, Benjamin Spike, Eckhard Theil and Ulrich Keilholz. Nested quantitative real time PCR for detection of occult tumor cells. (2001) Recent Results in Cancer Research 158: 25-31
  42. Ulrich Keilholz, Nicole Max, Benjamin Spike and Martina Willhauk. PCR-based detection of malignant cells: Towards molecular staging? Chapter 1. Strategies in Adjuvant Therapy. ed. John M. Kirkwood, (London, 2000; Martin Dunitz Ltd.) pp.1-18.
  43. Thesis (M.S.): Benjamin T. Spike, Characterization of the DNA damage response in embryonic stem cells. (San Diego: University of California, San Diego, 1999)
  44. Mirit I. Aladjem, Benjamin T. Spike, Luo Wei Rodewald, Thomas J. Hope, Martina Klemm, Rudolf Jaenisch and Geoffrey M. Wahl. ES cells do not activate p53-dependent stress responses and undergo p53-independent apoptosis in response to DNA damage. (1998) Current Biology 8: 145-155. (COVER PICTURE)c
Last Updated: 8/12/24