HHS Recovery Act Recipient Reporting Readiness Tool

Step 4. Review and Copy the Grant Awards Data

TAGGS provides some – but not all – of the data needed for the Recipient Report. Recipients are responsible for directly collecting and reporting all required data to FederalReporting.gov. Data that HHS does not currently collect are highlighted in yellow. Do not copy this highlighted information. Please enter the appropriate data for your organization in these required fields. For assistance with entering these data please contact FederalReporting.gov.

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Prime Recipient Report

Award Detail for: STRUCTURAL STUDIES OF AIDS-RESPONSIVE DRUGS
Recipient Name:HAUPTMAN-WOODWARD MEDICAL RESEARCH INSTITUTE, INC
DUNS Number: 074025479
700 Ellicott St
Buffalo, NY 14203-1102

Reporting Information

Award Type*: Grant

Award Number*: 3R01GM051670-14S2

Final Report*: Recipient responsible for this data

Award Recipient Information

Recipient DUNS Number*: 074025479

Recipient Account Number: Recipient responsible for this data

Recipient Congressional District*: 28

Award Information

Funding Agency Code*: 7529

Awarding Agency Code*:7529

Award Date*: 02-24-2010

Amount of Award*: $ 269,251

Program Source (TAS)*: 750852

CFDA Number*: 93.701

Sub Account Number for Program Source (TAS)*: Recipient responsible for this data

Total Number of Sub Awards to Individuals*: Recipient responsible for this data

Total Amount of Sub Awards to Individuals*: Recipient responsible for this data

Total Number of Payments to Vendors less than $25,000/award*: Recipient responsible for this data

Total Amount of Payments to Vendors less than $25,000/award*: Recipient responsible for this data

Total Number of Sub Awards less than $25,000/award*: Recipient responsible for this data

Total Amount of Sub Awards less than $25,000/award*: Recipient responsible for this data

Award Description* Pathogens such as Pneumocystis (P), Toxoplasma gondii (Tg)and Mycobacterium avium (Ma) are major causes of opportunistic infection and mortality in immunocompromised patients, particularly those with AIDS. Pneumocystis organisms represent a large group of species of atypical fungi with universal distribution,each with specificity for a specific mammalian host. Pneumocystis jirovecii (pj) is the causative agent of Pneumocystis pneumonia(PcP), one of the most frequent and severe opportunistic infections in immunocompromised patients. Current treatment for PcP combines sulfamethoxazole with trimethoprim, targeting folate biosynthesis. Up to 50% of AIDS patients do not tolerate this treatment long term. Recent studies also show that mutations accumulate over time in the target enzymes, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), potentially giving rise to drug resistance. These findings underscore the crucial need to develop more effective treatments. A major goal of this project is to structurally and biochemically characterize pjDHFR and its variants in order to design effective inhibitors that have potential as therapeutic agents for the treatment of PcP. Two specific aims are proposed to test the hypothesis that efficacy of antifolate use in combating infections from opportunistic pathogens is the result of specific enzyme-inhibitor interactions with the target DHFR. Specific aim one focuses on cloning, expression, purification and crystallization of pjDHFR in complex with selected enzyme inhibitors. A baculovirusexpression system has been developed to produce soluble, stable enzyme and initial biochemical assays reveal nanomolar inhibitionagainst pjDHFR by a novel antifolate. Structural characterization of this pjDHFR inhibitor complex is underway. Molecular modelingtools will be used for in silico screening of small molecule libraries to define novel scaffolds for synthesis and testing. Computational methods such as 3D QSAR will be used to predict the efficacy of known antifolates for binding to pjDHFR. These data will be used to guide synthesis of novel inhibitors. Th e focus of the second specific aim is to carry out site-directed mutagenesis studies on DHFR to determine the role of specific residues in modulatingpjDHFR inhibitorpotency and in conferring drug-resistance as observed in AIDS patient isolates. Application of novel proteomic tools and homology modeling techniques will be used to determine residues that are critical to enzyme fold and function. These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors.

Project Information

Project Name or Project/Program Title*: STRUCTURAL STUDIES OF AIDS-RESPONSIVE DRUGS

Project Status*: Recipient responsible for this data

Total Federal Amount of ARRA Funds Received/Invoiced*: Recipient responsible for this data

Number of Jobs*: Recipient responsible for this data

Description of Jobs Created*: Recipient responsible for this data

Quarterly Activities/Project Description*: Recipient responsible for this data

Activity Code (NAICS or NTEE-NPC)*: Recipient responsible for this data

Total Federal Amount of ARRA Expenditure* (Enter the cumulative total amount of Recovery Funds received that were expended to projects or activities. Refer to the Data Model for details on how to calculate this amount.): Recipient responsible for this data

Total Federal ARRA Infrastructure Expenditure Recipient responsible for this data

Infrastructure Contact Name: Recipient responsible for this data

Infrastructure Contact Email: Recipient responsible for this data

Infrastructure Contact Phone: Recipient responsible for this data

Infrastructure Contact Phone Ext: Recipient responsible for this data

Infrastructure Contact Street Address 1: 700 Ellicott St

Infrastructure Contact Street Address 2: 0

Infrastructure Contact Street Address 3: Recipient responsible for this data

Infrastructure City: Buffalo

Infrastructure State: NY

Infrastructure ZIP Code+4: 14203-1102

Infrastructure Purpose and Rationale (If applicable, enter an explanation about how the infrastructure investment will contribute to one or more purposes of the Recovery Act. Refer to the Data Model for details on what to report. 4000 characters or less.): Recipient responsible for this data

Primary Place of Performance

Street Address 1: MEDICAL RESEARCH INSTITUTE700 EILLICOTT STREET

Street Address 2: BUFFALO

City*: BUFFALO

State*: NY

ZIP Code+4*: 14203

Congressional District*: 28

Country*: US

Recipient Highly Compensated Officers

Prime Recipient Indication of Reporting Applicability*: Recipient responsible for this data

1. Officer Name and Compensation: Recipient responsible for this data
2. Officer Name and Compensation: Recipient responsible for this data
3. Officer Name and Compensation: Recipient responsible for this data
4. Officer Name and Compensation: Recipient responsible for this data
5. Officer Name and Compensation: Recipient responsible for this data

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