Fred Schaufele, PhD
Professor Emeritus
Ob/Gyn, Reproductive Sciences
School of Medicine

In the nuclear receptor field, our studies on androgen and estrogen receptors have been oriented towards understanding their basic mechanisms of action and their roles as central regulators of the growth, respectively, of the majority of breast tumors and almost all prostate tumors. This led to the development of high throughput, highly quantitative capabilities for rapidly identifying agents that up- or down-regulate receptor activity. We currently are incorporating that experience into a research program designed to identify new classes of pharmaceuticals for the treatment of advanced prostate cancer. The growth of those tumors is strongly driven by abnormal activation of the androgen receptor. Most of those tumors initially respond to currently available androgen receptor-targeted drugs. But the tumors change over time in ways in which the drugs no longer are effective and, when a patient becomes resistant to all available drugs, the tumor unfortunately becomes lethal. Most tumors that develop such drug ‘resistance’ still rely on androgen receptors for their growth. Our research program is oriented towards creating a new class of drugs that blocks a specific variant of the androgen receptor that arises during the development of treatment resistance but that lacks the binding sites for currently available drugs. The aim of these studies is to prolong the success of prostate cancer treatment, hopefully indefinitely.

• Insulin resistance induced by hyperinsulinemia coincides with a persistent alteration at the insulin receptor tyrosine kinase domain.
  PloS one 2014 Catalano KJ, Maddux BA, Szary J, Youngren JF, Goldfine ID, Schaufele F
• Maximizing the quantitative accuracy and reproducibility of Förster resonance energy transfer measurement for screening by high throughput widefield microscopy.
  Methods (San Diego, Calif.) 2013 Schaufele F
• A versatile, bar-coded nuclear marker/reporter for live cell fluorescent and multiplexed high content imaging.
  PloS one 2013 Krylova I, Kumar RR, Kofoed EM, Schaufele F
• FRET analysis of androgen receptor structure and biochemistry in living cells.
  Methods in molecular biology (Clifton, N.J.) 2011 Schaufele F
• Structure, affinity, and availability of estrogen receptor complexes in the cellular environment.
  The Journal of biological chemistry 2009 Kofoed EM, Guerbadot M, Schaufele F
• Drug and cell type-specific regulation of genes with different classes of estrogen receptor beta-selective agonists.
  PloS one 2009 Paruthiyil S, Cvoro A, Zhao X, Wu Z, Sui Y, Staub RE, Baggett S, Herber CB, Griffin C, Tagliaferri M, Harris HA, Cohen I, Bjeldanes LF, Speed TP, Schaufele F, Leitman DC
• Dimerization between aequorea fluorescent proteins does not affect interaction between tagged estrogen receptors in living cells.
  Journal of biomedical optics 2008 Kofoed EM, Guerbadot M, Schaufele F
• Fluorescent protein tools for studying protein dynamics in living cells: a review.
  Journal of biomedical optics 2008 Day RN, Schaufele F
• A palmitoylation cycle dynamically regulates partitioning of the GABA-synthesizing enzyme GAD65 between ER-Golgi and post-Golgi membranes.
  Journal of cell science 2008 Kanaani J, Patterson G, Schaufele F, Lippincott-Schwartz J, Baekkeskov S
• Functional sequestration of transcription factor activity by repetitive DNA.
  The Journal of biological chemistry 2007 Liu X, Wu B, Szary J, Kofoed EM, Schaufele F
• Selective activation of estrogen receptor-beta transcriptional pathways by an herbal extract.
  Endocrinology 2006 Cvoro A, Paruthiyil S, Jones JO, Tzagarakis-Foster C, Clegg NJ, Tatomer D, Medina RT, Tagliaferri M, Schaufele F, Scanlan TS, Diamond MI, Cohen I, Leitman DC
• Ligand-selective interdomain conformations of estrogen receptor-alpha.
  Molecular endocrinology (Baltimore, Md.) 2006 Padron A, Li L, Kofoed EM, Schaufele F
• Analysis of in vivo conformation: full-length estrogen receptor-alpha dimers bound by estradiol, tamoxifen, raloxifene or ICI 182780.
  The FASEB Journal 2006 Adrian Padron, Li Li, Fred Schaufele
• Functional sequestration of transcription factors by junk DNA.
  The FASEB Journal 2006 Xiaowei Liu, Bo Wu, Jaroslaw Szary, Fred Schaufele
• Molecular imaging of biochemical structure and interactions in live cells, tissues and animals.
  The FASEB Journal 2006 Fred Schaufele, Adrian Padron, Martin Guerbadot
• Pericentromeric concentration of transcription factors by junk DNA.
  The FASEB Journal 2006 Jaroslaw Szary, Xiaowei Liu, Fred Schaufele
• The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions.
  Proceedings of the National Academy of Sciences of the United States of America 2005 Schaufele F, Carbonell X, Guerbadot M, Borngraeber S, Chapman MS, Ma AA, Miner JN, Diamond MI
• Imaging molecular interactions in living cells.
  Molecular endocrinology (Baltimore, Md.) 2005 Day RN, Schaufele F
• 4 FRET Imaging in the Wide-Field Microscope.
  Molecular Imaging 2005 Fred Schaufele, Ignacio Demarco, Richard N. Day
• Phosphorylation of C/EBPalpha inhibits granulopoiesis.
  Molecular and cellular biology 2004 Ross SE, Radomska HS, Wu B, Zhang P, Winnay JN, Bajnok L, Wright WS, Schaufele F, Tenen DG, MacDougald OA
• A PIT-1 homeodomain mutant blocks the intranuclear recruitment of the CCAAT/enhancer binding protein alpha required for prolactin gene transcription.
  Molecular endocrinology (Baltimore, Md.) 2003 Enwright JF, Kawecki-Crook MA, Voss TC, Schaufele F, Day RN
• Conformation of CCAAT/enhancer-binding protein alpha dimers varies with intranuclear location in living cells.
  The Journal of biological chemistry 2003 Schaufele F, Wang X, Liu X, Day RN
• Imaging the localized protein interactions between Pit-1 and the CCAAT/enhancer binding protein alpha in the living pituitary cell nucleus.
  Molecular endocrinology (Baltimore, Md.) 2002 Day RN, Voss TC, Enwright JF, Booker CF, Periasamy A, Schaufele F
• Cellular Imaging Technologies for Discovering Improved Breast Cancer Therapies.
  2002 Fred J. Schaufele
• CCAAT/enhancer binding protein alpha uses distinct domains to prolong pituitary cells in the growth 1 and DNA synthesis phases of the cell cycle.
  BMC cell biology 2002 Liu W, Enwright JF, Hyun W, Day RN, Schaufele F
• Ligand-selective interactions of ER detected in living cells by fluorescence resonance energy transfer.
  Molecular endocrinology (Baltimore, Md.) 2002 Weatherman RV, Chang CY, Clegg NJ, Carroll DC, Day RN, Baxter JD, McDonnell DP, Scanlan TS, Schaufele F
• CCAAT/Enhancer Binding Protein   Assembles Essential Cooperating Factors in Common Subnuclear Domains.
  Endocrinology 2001 F. Schaufele
• Fluorescence resonance energy transfer microscopy of localized protein interactions in the living cell nucleus.
  Methods (San Diego, Calif.) 2001 Day RN, Periasamy A, Schaufele F
• Growth factors signal to steroid receptors through mitogen-activated protein kinase regulation of p160 coactivator activity.
  The Journal of biological chemistry 2001 Lopez GN, Turck CW, Schaufele F, Stallcup MR, Kushner PJ
• Functional interaction of NF-Y and Sp1 is required for type a natriuretic peptide receptor gene transcription.
  The Journal of biological chemistry 2001 Liang F, Schaufele F, Gardner DG
• Shedding light on molecular timing.
  Nature biotechnology 2001 Schaufele F
• Temporally distinct and ligand-specific recruitment of nuclear receptor-interacting peptides and cofactors to subnuclear domains containing the estrogen receptor.
  Molecular endocrinology (Baltimore, Md.) 2000 Schaufele F, Chang CY, Liu W, Baxter JD, Nordeen SK, Wan Y, Day RN, McDonnell DP
• Regulation of estrogen receptor activation of the prolactin enhancer/promoter by antagonistic activation function-2-interacting proteins.
  Molecular endocrinology (Baltimore, Md.) 1999 Schaufele F
• Sp1 dependence of natriuretic peptide receptor A gene transcription in rat aortic smooth muscle cells.
  Endocrinology 1999 Liang F, Schaufele F, Gardner DG
• Mechanisms of thyroid hormone action: insights from X-ray crystallographic and functional studies.
  Recent progress in hormone research 1998 Ribeiro RC, Apriletti JW, Wagner RL, West BL, Feng W, Huber R, Kushner PJ, Nilsson S, Scanlan T, Fletterick RJ, Schaufele F, Baxter JD
• Activities in Pit-1 determine whether receptor interacting protein 140 activates or inhibits Pit-1/nuclear receptor transcriptional synergy.
  Molecular endocrinology (Baltimore, Md.) 1997 Chuang FM, West BL, Baxter JD, Schaufele F
• CCAAT/enhancer-binding protein alpha activation of the rat growth hormone promoter in pituitary progenitor GHFT1-5 cells.
  The Journal of biological chemistry 1996 Schaufele F
• An activation function in Pit-1 required selectively for synergistic transcription.
  The Journal of biological chemistry 1996 Chang W, Zhou W, Theill LE, Baxter JD, Schaufele F
• The c-Jun delta-domain inhibits neuroendocrine promoter activity in a DNA sequence- and pituitary-specific manner.
  The Journal of biological chemistry 1996 Farrow KN, Manning N, Schaufele F, Gutierrez-Hartmann A
• The molecular biology of thyroid hormone action.
  Annals of the New York Academy of Sciences 1995 Ribeiro RC, Apriletti JW, West BL, Wagner RL, Fletterick RJ, Schaufele F, Baxter JD
• Eukaryotic regulatory elements lurking in plasmid DNA: the activator protein-1 site in pUC.
  Molecular endocrinology (Baltimore, Md.) 1994 Kushner PJ, Baxter JD, Duncan KG, Lopez GN, Schaufele F, Uht RM, Webb P, West BL
• Distance-dependent interactions between basal, cyclic AMP, and thyroid hormone response elements in the rat growth hormone promoter.
  The Journal of biological chemistry 1993 Tansey WP, Schaufele F, Heslewood M, Handford C, Reudelhuber TL, Catanzaro DF
• Positive and Negative Modulation of Jun Action by Thyroid Hormone Receptor at a Unique AP1 Site.
  Molecular and Cellular Biology 1993 Gabriela Lopez, Fred Schaufele, Paul Webb, Jeffrey M. Holloway, John D. Baxter, Peter J. Kushner
• Positive and negative modulation of Jun action by thyroid hormone receptor at a unique AP1 site.
  Molecular and Cellular Biology 1993 G Lopez, F Schaufele, P Webb, J M Holloway, J D Baxter, P J Kushner
• Positive and negative modulation of Jun action by thyroid hormone receptor at a unique AP1 site.
  Molecular and cellular biology 1993 Lopez G, Schaufele F, Webb P, Holloway JM, Baxter JD, Kushner PJ
• Synergistic activation of the rat growth hormone promoter by Pit-1 and the thyroid hormone receptor.
  Endocrinology 1992 F. Schaufele
• Synergistic activation of the rat growth hormone promoter by Pit-1 and the thyroid hormone receptor.
  Molecular endocrinology (Baltimore, Md.) 1992 Schaufele F, West BL, Baxter JD
• Diagonal Gel Mobility-Shift Assays for the Resolution of Multi-Subunit Complexes Binding to Regulatory Elements of Specific Genes.
  A Laboratory Guide to In Vitro Studies of Protein-DNA Interactions 1991 Fred Schaufele, Brian L. West, Jean-Pierre Jost, Tim Reudelhuber
• Overlapping Pit-1 and Sp1 binding sites are both essential to full rat growth hormone gene promoter activity despite mutually exclusive Pit-1 and Sp1 binding.
  The Journal of biological chemistry 1990 Schaufele F, West BL, Reudelhuber TL
• Somatotroph- and lactotroph-specific interactions with the homeobox protein binding sites in the rat growth hormone gene promoter.
  Nucleic acids research 1990 Schaufele F, West BL, Reudelhuber T
• Resolution by diagonal gel mobility shift assays of multisubunit complexes binding to a functionally important element of the rat growth hormone gene promoter.
  The Journal of biological chemistry 1990 Schaufele F, Cassill JA, West BL, Reudelhuber T
• Conserved terminal hairpin sequences of histone mRNA precursors are not involved in duplex formation with the U7 RNA but act as a target site for a distinct processing factor.
  Proceedings of the National Academy of Sciences of the United States of America 1989 Vasserot AP, Schaufele FJ, Birnstiel ML
• Functional analysis of the sea urchin U7 small nuclear RNA.
  Molecular and cellular biology 1988 Gilmartin GM, Schaufele F, Schaffner G, Birnstiel ML
• The inability of the Psammechinus miliaris H3 RNA to be processed in the Xenopus oocyte is associated with sequences distinct from those highly conserved amongst sea urchin histone RNAs.
  Nucleic acids research 1987 Schaufele F, Birnstiel ML
• Compensatory mutations suggest that base-pairing with a small nuclear RNA is required to form the 3' end of H3 messenger RNA.
  Nature 1986 Schaufele F, Gilmartin GM, Bannwarth W, Birnstiel ML