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SELECTIVE INHIBITORS OF HUMAN HSF2

Award Number: R03MH097538
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2014

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SELECTIVE INHIBITORS OF HUMAN HSF2 - DESCRIPTION (provided by applicant): Recent scientific developments indicate that the molecular chaperone system is actively involved in cancerogenesis, neurodegeneration and cardiovascular disorders. The master regulator of molecular chaperone expression at the level of transcription is the heat shock factor (HSF). The specific aim of the proposed research is to setup and implement the screening system for affecters of human HSF2. Inhibitors (in case of cancer) or activators (in case of neurodegenerative and cardiovascular disorders) of HSF can be used as important future drug leads in pharmacology. The screening system design is based on the utilization of a new yeast strain created by our laboratory, in which the conditional overexpression of human HSF2 under Gal1 promoter creates a slow growth phenotype. Potential compounds increasing the growth rate of the tester strain will be verified and used as leads for new drug development. The initial growth rate of the tester strain will be easily adjusted for screens of different stringencies by the incorporation of glucose in the growth media containing galactose as a major carbon source nutrient. The detection of cell growth restoration will be done by registering a change in the light absorption of the cell culture and, in addition, y registering luminescence using the commercially available BacTiter-Glo" Microbial Cell Viability Assay (Promega). Compound hits will be evaluated over a range of concentrations around the initial screening and the IC50 will be determined. Hits will be verified additionally by measuring change in the mRNA level of a set of reporter heat shock genes using real-time quantitative RT-PCR for non-heat shock and heat shock conditions in the presence of the identified compound and compared to similar samples from untreated cells. The advantage of this approach is that the true in vivo affecters of hHSF2 will be identified and confirmed.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2013 ( Subtotal = $29,175 )
2013	2013	BUTLER UNIVERSITY	4600 SUNSET AVENUE	INDIANAPOLIS	IN	46208	MARION	USA	Trans-NIH Research Support	001	2	6/11/2013	NON-COMPETING CONTINUATION	$2,106
2013	2013	BUTLER UNIVERSITY	4600 SUNSET AVENUE	INDIANAPOLIS	IN	46208	MARION	USA	Trans-NIH Research Support	000	2	4/18/2013	NON-COMPETING CONTINUATION	$27,069
														Subtotal = $29,175

Issue Date FY: 2012 ( Subtotal = $30,011 )
2012	2012	BUTLER UNIVERSITY	4600 SUNSET AVENUE	INDIANAPOLIS	IN	46208	MARION	USA	Trans-NIH Research Support	000	1	4/30/2012	NEW	$30,011
														Subtotal = $30,011

Grand Total All Awards = $59,186

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SELECTIVE INHIBITORS OF HUMAN HSF2

Award Number: R03MH097538

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2014

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