
Ray Blind, Ph.D.
- Assistant Professor of Medicine
- Assistant Professor of Pharmacology
- Assistant Professor of Biochemistry
Phone
2213 Garland Avenue
8405 MRB4
Nashville, TN 37232
Ray Blind, Ph.D.
- Assistant Professor of Medicine
- Assistant Professor of Pharmacology
- Assistant Professor of Biochemistry
615-936-1037
ray.blind@vumc.org
2213 Garland Avenue
8405 MRB4
Nashville, TN 37232
Research Program
Departments/Affiliations
Profile
In the tissues originating all these tumors, the nuclear receptors SF-1 and LRH-1 mediate genetic programs that are essential determinants of development, differentiation and adult physiology. Despite this importance, little is known about how these transcription factors are turned on and off.
At the molecular level, these proteins bind phosphoinositides (PIPs), small signaling lipids essential in PTEN-dependent cancers. We recently uncovered a novel mechanism that these lipids and their signaling enzymes use to regulate SF-1 and LRH-1 gene expression. This mechanism now links dysregulation of these pathways to the cancers mentioned above.
Our central hypothesis is that lipids bound to nuclear proteins are directly remodeled by lipid signaling enzymes, namely the PI3-kinase inositol polyphosphate multikinase (IPMK) and the PTEN lipid phosphatase. This hypothesis is a clear departure from the standard dogma that PI3-kinases and PTEN only act on phosphoinositides within cellular membrane systems.
Education
- Ph.D., Biomedical Sciences/Molecular Pharmacology, New York University, New York, New York
Research Emphasis
We use genomics, structural biology and chemical genetics to discover new ways gene expression is regulated. We use this mechanistic information to develop new and unique drug screening platforms, focused on cancer, diabetes & liver diseases. I have joint appointments in both the Pharmacology and Biochemistry Departments, I lead a section of the FOCUS class for 1st year PhD students, and I am an active member of many Vanderbilt Institutes and Centers throughout the University & Medical Center communities.
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Keywords: transcription, lipids, inositol phosphates, phospholipids, nuclear signaling, crystallography, integrated structural biology, SAXS, HDACs and epigenetics, biophysics, chromatin marks, histone acetylation, mechanistic biochemistry, enzymology, chemical biology, IRACDA, teaching. .............................................................................................
Research Description
Genome Regulation by 2nd Messengers
Publications
- Bryant JM, Malabanan MM, Vanderloop BH, Nichols CM, Haratipour Z, Poon KT, Sherrod SD, McLean JA, Blind RD. The acyl chains of phosphoinositide PIP3 alter the structure and function of nuclear receptor steroidogenic factor-1. J Lipid Res [print-electronic]. 2021; 62: 100081. PMID: 33933440, PMCID: PMC8178125, PII: S0022-2275(21)00063-8, DOI: 10.1016/j.jlr.2021.100081, ISSN: 1539-7262.
- Seacrist CD, Kuenze G, Hoffmann RM, Moeller BE, Burke JE, Meiler J, Blind RD. Integrated Structural Modeling of Full-Length LRH-1 Reveals Inter-domain Interactions Contribute to Receptor Structure and Function. Structure [print-electronic]. 2020 Jul 7/7/2020; 28(7): 830-846.e9. PMID: 32433991, PMCID: PMC7347456, PII: S0969-2126(20)30166-0, DOI: 10.1016/j.str.2020.04.020, ISSN: 1878-4186.
- Blind RD. Structural analyses of inositol phosphate second messengers bound to signaling effector proteins. Adv Biol Regul [print-electronic]. 2020 Jan; 75: 100667. PMID: 31648945, PMCID: PMC7056587, PII: S2212-4926(19)30088-0, DOI: 10.1016/j.jbior.2019.100667, ISSN: 2212-4934.
- Bryant JM, Blind RD. Signaling through non-membrane nuclear phosphoinositide binding proteins in human health and disease. J. Lipid Res [print-electronic]. 2019 Feb; 60(2): 299-311. PMID: 30201631, PMCID: PMC6358298, PII: jlr.R088518, DOI: 10.1194/jlr.R088518, ISSN: 1539-7262.
- 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. Human islets expressing HNF1A variant have defective ß cell transcriptional regulatory networks. J. Clin. Invest [print-electronic]. 2019 Jan 1/2/2019; 129(1): 246-51. PMID: 30507613, PMCID: PMC6307934, PII: 121994, DOI: 10.1172/JCI121994, ISSN: 1558-8238.
- Seacrist CD, Blind RD. Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity. Sci Rep. 2018 Nov 11/12/2018; 8(1): 16672. PMID: 30420721, PMCID: PMC6232094, PII: 10.1038/s41598-018-34941-3, DOI: 10.1038/s41598-018-34941-3, ISSN: 2045-2322.
- Hamann BL, Blind RD. Nuclear phosphoinositide regulation of chromatin. J. Cell. Physiol [print-electronic]. 2018 Jan; 233(1): 107-23. PMID: 28256711, DOI: 10.1002/jcp.25886, ISSN: 1097-4652.
- Crowder MK, Seacrist CD, Blind RD. Phospholipid regulation of the nuclear receptor superfamily. Adv Biol Regul [print-electronic]. 2016 Oct 10/29/2016; PMID: 27838257, PII: S2212-4926(16)30046-X, DOI: 10.1016/j.jbior.2016.10.006, ISSN: 2212-4934.
- Malabanan MM, Blind RD. Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism. Biochem. Soc. Trans. 2016 Feb; 44(1): 279-85. PMID: 26862216, PII: BST20150225, DOI: 10.1042/BST20150225, ISSN: 1470-8752.
- Sablin EP, Blind RD, Uthayaruban R, Chiu HJ, Deacon AM, Das D, Ingraham HA, Fletterick RJ. Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket. J. Struct. Biol [print-electronic]. 2015 Dec; 192(3): 342-8. PMID: 26416531, PMCID: PMC4651778, PII: S1047-8477(15)30067-8, DOI: 10.1016/j.jsb.2015.09.012, ISSN: 1095-8657.