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Rhett A. Kovall, PhD


Molecular & Cellular Biosciences | College of Medicine

  • Post Doc: Columbia University
  • Ph.D.: University of Oregon, Institute of Molecular Biology (Structural Biology & Biochemistry)
  • B.A.: University of Colorado (Biochemistry)
Contact Information
Research Interests

My research interests involve understanding at the molecular level how transcription is regulated in the Notch signaling pathway. The Notch pathway is a highly conserved cell-to-cell signaling mechanism in metazoans that is essential for embryonic development and tissue homeostasis. Aberrant Notch signaling underlies the pathogenesis of many human diseases, including congenital defects, cardiovascular disease, and cancer. Notch signaling ultimately results in changes in gene expression, which is regulated...

Peer Reviewed Publications

Giaimo, Benedetto Daniele; Gagliani, Ellen K; Kovall, Rhett A; Borggrefe, Tilman 2021. Transcription Factor RBPJ as a Molecular Switch in Regulating the Notch Response. Advances in experimental medicine and biology, 1287 , 9-30

Hassett, Daniel J; Kovall, Rhett A; Schurr, Michael J; Kotagiri, Nalinikanth; Kumari, Harshita; Satish, Latha 2021. The Bactericidal Tandem Drug, AB569: How to Eradicate Antibiotic-Resistant Biofilm Pseudomonas aeruginosa in Multiple Disease Settings Including Cystic Fibrosis, Burns/Wounds and Urinary Tract Infections. Frontiers in microbiology, 12 , 639362

Kobia, Francis M; Preusse, Kristina; Dai, Quanhui; Weaver, Nicholas; Hass, Matthew R; Chaturvedi, Praneet; Stein, Sarah J; Pear, Warren S; Yuan, Zhenyu; Kovall, Rhett A; Kuang, Yi; Eafergen, Natanel; Sprinzak, David; Gebelein, Brian; Brunskill, Eric W; Kopan, Raphael 2020. Notch dimerization and gene dosage are important for normal heart development, intestinal stem cell maintenance, and splenic marginal zone B-cell homeostasis during mite infestation. PLoS biology, 18 10, e3000850

Kuang, Yi; Golan, Ohad; Preusse, Kristina; Cain, Brittany; Christensen, Collin J; Salomone, Joseph; Campbell, Ian; Okwubido-Williams, FearGod V; Hass, Matthew R; Yuan, Zhenyu; Eafergan, Nathanel; Moberg, Kenneth H; Kovall, Rhett A; Kopan, Raphael; Sprinzak, David; Gebelein, Brian 2020. Enhancer architecture sensitizes cell specific responses to Notch gene dose via a bind and discard mechanism. eLife, 9 ,

Hall, Daniel P; Kovall, Rhett A 2019. Structurally conserved binding motifs of transcriptional regulators to notch nuclear effector CSL. Experimental biology and medicine (Maywood, N.J.), 244 17, 1520-1529

Thompson, Thomas B; Kovall, Rhett A 2019. Structural biology: Gaining atomic level insight into the biological function of macromolecules. Experimental biology and medicine (Maywood, N.J.), 244 17, 1507-1509

Yuan, Zhenyu; VanderWielen, Bradley D; Giaimo, Benedetto Daniele; Pan, Leiling; Collins, Courtney E; Turkiewicz, Aleksandra; Hein, Kerstin; Oswald, Franz; Borggrefe, Tilman; Kovall, Rhett A 2019. Structural and Functional Studies of the RBPJ-SHARP Complex Reveal a Conserved Corepressor Binding Site. Cell reports, 26 4, 845-854.e6

Zhang, Xinghao; McGrath, Patrick S; Salomone, Joseph; Rahal, Mohamed; McCauley, Heather A; Schweitzer, Jamie; Kovall, Rhett; Gebelein, Brian; Wells, James M 2019. A Comprehensive Structure-Function Study of Neurogenin3 Disease-Causing Alleles during Human Pancreas and Intestinal Organoid Development. Developmental cell, 50 3, 367-380.e7

Gomez-Lamarca, Maria J; Falo-Sanjuan, Julia; Stojnic, Robert; Abdul Rehman, Sohaib; Muresan, Leila; Jones, Matthew L; Pillidge, Zoe; Cerda-Moya, Gustavo; Yuan, Zhenyu; Baloul, Sarah; Valenti, Phillippe; Bystricky, Kerstin; Payre, Francois; O'Holleran, Kevin; Kovall, Rhett; Bray, Sarah J 2018. Activation of the Notch Signaling Pathway In Vivo Elicits Changes in CSL Nuclear Dynamics. Developmental cell, 44 5, 611-623.e7

Miesfeld, Joel B; Moon, Myung-Soon; Riesenberg, Amy N; Contreras, Ashley N; Kovall, Rhett A; Brown, Nadean L 2018. Rbpj direct regulation of Atoh7 transcription in the embryonic mouse retina. Scientific reports, 8 1, 10195

Oswald, Franz; Kovall, Rhett A 2018. CSL-Associated Corepressor and Coactivator Complexes. Advances in experimental medicine and biology, 1066 , 279-295

Kovall, Rhett A; Gebelein, Brian; Sprinzak, David; Kopan, Raphael 2017. The Canonical Notch Signaling Pathway: Structural and Biochemical Insights into Shape, Sugar, and Force. Developmental cell, 41 3, 228-241

Nagel, Anja C; Auer, Jasmin S; Schulz, Adriana; Pfannstiel, Jens; Yuan, Zhenyu; Collins, Courtney E; Kovall, Rhett A; Preiss, Anette 2017. Phosphorylation of Suppressor of Hairless impedes its DNA-binding activity. Scientific reports, 7 1, 11820

Tabaja, Nassif; Yuan, Zhenyu; Oswald, Franz; Kovall, Rhett A 2017. Structure-function analysis of RBPJ-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes. The Journal of biological chemistry, ,

Xu, Tao; Park, Sung-Soo; Giaimo, Benedetto Daniele; Hall, Daniel; Ferrante, Francesca; Ho, Diana M; Hori, Kazuya; Anhezini, Lucas; Ertl, Iris; Bartkuhn, Marek; Zhang, Honglai; Milon, Eléna; Ha, Kimberly; Conlon, Kevin P; Kuick, Rork; Govindarajoo, Brandon; Zhang, Yang; Sun, Yuqing; Dou, Yali; Basrur, Venkatesha; Elenitoba-Johnson, Kojo Sj; Nesvizhskii, Alexey I; Ceron, Julian; Lee, Cheng-Yu; Borggrefe, Tilman; Kovall, Rhett A; Rual, Jean-François 2017. RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1. The EMBO journal, 36 21, 3232-3249

Oswald, Franz; Rodriguez, Patrick; Giaimo, Benedetto Daniele; Antonello, Zeus A; Mira, Laura; Mittler, Gerhard; Thiel, Verena N; Collins, Kelly J; Tabaja, Nassif; Cizelsky, Wiebke; Rothe, Melanie; Kühl, Susanne J; Kühl, Michael; Ferrante, Francesca; Hein, Kerstin; Kovall, Rhett A; Dominguez, Maria; Borggrefe, Tilman 2016. A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes. Nucleic acids research, 44 10, 4703-20

Yuan, Zhenyu; Praxenthaler, Heiko; Tabaja, Nassif; Torella, Rubben; Preiss, Anette; Maier, Dieter; Kovall, Rhett A 2016. Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster. PLoS biology, 14 7, e1002509

Contreras, Ashley N; Yuan, Zhenyu; Kovall, Rhett A 2015. Thermodynamic binding analysis of Notch transcription complexes from D. melanogaster. Protein science : a publication of the Protein Society, ,

Collins, Kelly J; Yuan, Zhenyu; Kovall, Rhett A 2014. Structure and function of the CSL-KyoT2 corepressor complex: a negative regulator of notch signaling. Structure (London, England : 1993), 22 1, 70-81

Su, Shengchang; Panmanee, Warunya; Wilson, Jeffrey J; Mahtani, Harry K; Li, Qian; Vanderwielen, Bradley D; Makris, Thomas M; Rogers, Melanie; McDaniel, Cameron; Lipscomb, John D; Irvin, Randall T; Schurr, Michael J; Lancaster, Jack R; Kovall, Rhett A; Hassett, Daniel J 2014. Catalase (KatA) plays a role in protection against anaerobic nitric oxide in Pseudomonas aeruginosa. PloS one, 9 3, e91813

Torella, Rubben; Li, Jinghua; Kinrade, Eddie; Cerda-Moya, Gustavo; Contreras, Ashley N; Foy, Robert; Stojnic, Robert; Glen, Robert C; Kovall, Rhett A; Adryan, Boris; Bray, Sarah J 2014. A combination of computational and experimental approaches identifies DNA sequence constraints associated with target site binding specificity of the transcription factor CSL. Nucleic acids research, 42 16, 10550-63

Greenwald, Iva; Kovall, Rhett 2013. Notch signaling: genetics and structure. WormBook : the online review of C. elegans biology, , 1-28

Kovall, Rhett A 2012. In notch, one ANK repeat is not like the other. Structure (London, England : 1993), 20 2, 202-4

Yuan, Zhenyu; Friedmann, David R; Vanderwielen, Bradley D; Collins, Kelly J; Kovall, Rhett A 2012. Characterization of CSL (CBF-1, Su(H), Lag-1) Mutants Reveals Differences in Signaling Mediated by Notch1 and Notch2. The Journal of biological chemistry, 287 42, 34904-16

Bahassi, El Mustapha; Yin, Moying; Robbins, Susan B; Li, Ya-Qin; Conrady, Deborah G; Yuan, Zhenyu; Kovall, Rhett A; Herr, Andrew B; Stambrook, Peter J 2011. A human cancer-predisposing polymorphism in Cdc25A is embryonic lethal in the mouse and promotes ASK-1 mediated apoptosis. Cell division, 6 1, 4

Kurth, Patricia; Preiss, Anette; Kovall, Rhett A; Maier, Dieter 2011. Molecular analysis of the notch repressor-complex in Drosophila: characterization of potential hairless binding sites on suppressor of hairless. PloS one, 6 11, e27986

Maier, Dieter; Kurth, Patricia; Schulz, Adriana; Russell, Andrew; Yuan, Zhenyu; Gruber, Kim; Kovall, Rhett A; Preiss, Anette 2011. Structural and functional analysis of the repressor complex in the Notch signaling pathway of Drosophila melanogaster. Molecular biology of the cell, 22 17, 3242-52

VanderWielen, Bradley D; Yuan, Zhenyu; Friedmann, David R; Kovall, Rhett A 2011. Transcriptional repression in the Notch pathway: thermodynamic characterization of CSL-MINT (Msx2-interacting nuclear target protein) complexes. The Journal of biological chemistry, 286 17, 14892-902

Conrady, Deborah G; Flagler, Michael J; Friedmann, David R; Vander Wielen, Bradley D; Kovall, Rhett A; Weiss, Alison A; Herr, Andrew B 2010. Molecular basis of differential B-pentamer stability of Shiga toxins 1 and 2. PloS one, 5 12, e15153

Friedmann, David R; Kovall, Rhett A 2010. Thermodynamic and structural insights into CSL-DNA complexes. Protein science : a publication of the Protein Society, 19 1, 34-46

Kovall, Rhett A; Blacklow, Stephen C 2010. Mechanistic insights into Notch receptor signaling from structural and biochemical studies. Current topics in developmental biology, 92 , 31-71

Friedmann, David R; Wilson, Jeffrey J; Kovall, Rhett A 2008. RAM-induced allostery facilitates assembly of a notch pathway active transcription complex. The Journal of biological chemistry, 283 21, 14781-91

Kovall, R A 2008. More complicated than it looks: assembly of Notch pathway transcription complexes. Oncogene, 27 38, 5099-109

Kovall, Rhett A 2007. Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex. Current opinion in structural biology, 17 1, 117-27

Wilson, Jeffrey J; Kovall, Rhett A 2006. Crystal structure of the CSL-Notch-Mastermind ternary complex bound to DNA. Cell, 124 5, 985-96

Kovall, Rhett A; Hendrickson, Wayne A 2004. Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. The EMBO journal, 23 17, 3441-51

Min, K Christopher; Kovall, Rhett A; Hendrickson, Wayne A 2003. Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency. Proceedings of the National Academy of Sciences of the United States of America, 100 25, 14713-8

Kovall, R A; Matthews, B W 1999. Type II restriction endonucleases: structural, functional and evolutionary relationships. Current opinion in chemical biology, 3 5, 578-83

Kovall, R A; Matthews, B W 1998. Structural, functional, and evolutionary relationships between lambda-exonuclease and the type II restriction endonucleases. Proceedings of the National Academy of Sciences of the United States of America, 95 14, 7893-7

Kovall, R; Matthews, B W 1997. Toroidal structure of lambda-exonuclease. Science (New York, N.Y.), 277 5333, 1824-7

Rhett Kovall and Brian W. Matthews 1997. Toroidal Structure of Lambda-Exonuclease Science, 277 5333, 1824-1827

Landor, Sebastian K J; Santio, Niina M; Eccleshall, William B; Paramonov, Valeriy M; Gagliani, Ellen K; Hall, Daniel; Jin, Shao-Bo; Dahlström, Käthe M; Salminen, Tiina A; Rivero-Müller, Adolfo; Lendahl, Urban; Kovall, Rhett A; Koskinen, Päivi J; Sahlgren, Cecilia . PIM-induced phosphorylation of Notch3 promotes breast cancer tumorigenicity in a CSL-independent fashion. The Journal of biological chemistry, 296 , 100593