- Vanderbilt article highlighting JCI paper.
- Ray PI on Vanderbilt Trans-Institutional Program Award.
- Materials & Methods Blog post, "Why Study That".
Independent Lab (Blind Lab members underlined):
21. Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function.
Seacrist CD, Kuenze G, Hoffmann RM, Moeller BE, Burke JE, Meiler J, Blind RD.
First structure of a full-length monomeric nuclear receptor, LRH-1, which is an important target for Diabetes & NASH. The structure unifies unexplained mutations and human polymorphisms that affect LRH-1 function, providing new therapeutic strategies for Type 2 Diabetes, NAFLD and NASH.
20. Structural analyses of inositol phosphate second messengers bound to signaling effector proteins.
Used the protein structure database (PDB) to identify structural motifs common to proteins known to interact with inositide signaling molecules.
19. Human islets expressing HNF1A variant have defective β cell transcriptional regulatory networks.
Haliyur R, Tong X, Sanyoura M, Shrestha S, Lindner J, Saunders DC, Aramandla R, Poffenberger G, Redick SD, Bottino R, Prasad N, Levy SE, Blind RD, Harlan DM, Philipson LH, Stein RW, Brissova M, Powers AC.
Defines the molecular basis of clinically-relevant pathological human mutations in the nuclear receptor HNF1A.
18. Signaling through non-membrane nuclear phosphoinositide binding proteins in human health and disease.
Bryant JM, Blind RD.
17. Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity.
Seacrist CD, Blind RD.
Crystal structure and functional analyses of human IPMK, an important target in glioblastoma, showing how IPMK disordered domains auto-inhibit its own kinase activity. The data reveal new ways IPMK is regulated and introduce new inhibitor strategies.
16. Nuclear phosphoinositide regulation of chromatin.
Hamann BL, Blind RD.
15. Phospholipid regulation of the nuclear receptor superfamily.
Crowder MK, Seacrist CD, Blind RD.
14. Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism.
Malabanan MM, Blind RD.
Postdoc and PhD:
13. Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket.
*Sablin EP, *Blind RD, Uthayaruban R, Chiu HJ, Deacon AM, Das D, Ingraham HA, Fletterick RJ.
First structure of the nuclear receptor LRH-1 bound to an endogenous mammalian ligand.
12. The signaling phospholipid PIP3 creates a new interaction surface on the nuclear receptor SF-1.
Blind RD, Sablin EP, Kuchenbecker KM, Chiu HJ, Deacon AM, Das D, Fletterick RJ, Ingraham HA.
Used structural biology to show the nuclear receptor SF-1 does not change shape dependent on the PIP3 headgroup, thus this transcription factor is likely regulated through a mechanism distinct from other nuclear receptors.
11. Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes.
10. Direct modification and activation of a nuclear receptor-PIP2 complex by the inositol lipid kinase IPMK.
Blind RD, Suzawa M, Ingraham HA.
(Featured on Cover) - This paper showed signaling enzymes (IPMK and PTEN) can remodel a second-messenger signaling molecule (the PIP2 lipid) while that second messenger is bound to a protein effector (the nuclear receptor SF-1). This paper was the first to show:
1) Nuclear lipid signaling enzymes act directly on non-membrane nuclear phosphoinositides,
2) A specific function for nuclear phosphoinositides,
3) A mechanism nuclear phosphoinositides use to modulate gene expression,
4) Signaling enzymes can modify second messengers bound to an effector protein,
5) Signaling enzymes can operate with unique enzyme kinetics on second messengers bound bound to effector proteins.
10a. Science Signaling Podcast: 19 June 2012.
Ingraham HA, Blind RD, VanHook AM.
Science Signaling 2012 Jun; 5(229): pc13 [DOI: 10.1126/scisignal.2003287]: Podcast
9. Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy.
Blind RD, Pineda-Torra I, Xu Y, Xu HE, Garabedian MJ.
Shows nuclear receptor ligands can induce receptor recruitment to promoters, but fail to activate transcription. SAR to induce this dominant-negative activity could decrease side effects of nuclear receptor partial agonists.
8. Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2).
Whitby RJ, Stec J, Blind RD, Dixon S, Leesnitzer LM, Orband-Miller LA, Williams SP, Willson TM, Xu R, Zuercher WJ, Cai F, Ingraham HA.
Developed novel chemical antagonists of SF-1 and LRH-1 phospholipid binding.
7. Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25.
Mullaney BC, Blind RD, Lemieux GA, Perez CL, Elle IC, Faergeman NJ, Van Gilst MR, Ingraham HA, Ashrafi K.
Functionally and biochemically links NR5A with phospholipid metabolism in worms.
6. Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.
*Lin BC, *Suzawa M, *Blind RD, Tobias SC, Bulun SE, Scanlan TS, Ingraham HA.
Shows estrogen activation of a plasma membrane receptor (GPR30) induces intracellular production of PIP3, which activates a nuclear receptor (NR5A1, SF-1). This represents one of the clearest examples of GPCR-nuclear receptor cross-talk.
5. Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands.
*Sablin EP, *Blind RD, Krylova IN, Ingraham JG, Cai F, Williams JD, Fletterick RJ, Ingraham HA.
First crystal structure of an NR5A nuclear receptor bound to an endogenous mammalian phospholipid.
4. Applying innovative educational principles when classes grow and resources are limited: Biochemistry experiences at Muhimbili University of Allied Health Sciences.
Omer S, Hickson G, Taché S, Blind R, Masters S, Loeser H, Souza K, Mkony C, Debas H, O'Sullivan P.
3. Glucocorticoid receptor phosphorylation differentially affects target gene expression.
*Chen W, *Dang T, *Blind RD, Wang Z, Cavasotto CN, Hittelman AB, Rogatsky I, Logan SK, Garabedian MJ.
2. Differential recruitment of glucocorticoid receptor phospho-isoforms to glucocorticoid-induced genes.
Blind RD, Garabedian MJ.
1. Stabilization of the unliganded glucocorticoid receptor by TSG101.
Ismaili N, Blind R, Garabedian MJ.