Elucidation of Chemical Signaling Among Antibiotic Producing Bacteria
Duration: 09/2012 - 08/2014
Funding Agency: BTI research grant, UMN
Principal Investigator: Christine Salomon, PhD

Novel Antivirals Targeting the RNase H Activity of HIV Reverse Transcriptase
Grant Number: 1R01AI100890-01A1
Duration: 07/01/2012—06/30/2017
Funding Agency: NIH/NIAID
Type: Multiple PI R01
Principal Investigator(s): Michael A. Parniak, PhD; Stefan Sarafianos, PhD; Zhengqiang Wang, PhD
Total UMN Award: $1,122,840

Meropenem Prodrugs for XDR-TB
Grant Number: R21 A1090147
Duration: 07/01/2012–06/31/2014
Funding Agency: NIH/NIAID
Principal Investigator: Rory P. Remmel, PhD
Subcontracted to: Courtney Aldrich, PhD
Total direct costs for the Aldrich lab subcontract: $13,800

Understanding the Hidden Language of Antibiotic Production
Duration: 07/2012 - 06/2013
Funding Agency: OVPR Grant in Aid, UMN
Principal Investigator: Christine Salomon, PhD

A Fluorescence Displacement Assay for BioA: An Enzyme Involved in Biotin Biosynthesis
Grant Number: R03 MH096537
Duration: 1/01/2012–12/31/2013
Funding Agency: NIH/NIMH
Principal Investigator: Courtney Aldrich, PhD
Total direct costs: $50,000

Novel Natural Product Modulators of Zebrafish Limb Regeneration
Duration: 01/2012 - 12/2013
Funding Agency: AHC Cancer Center Seed Grant, UMN
Investigator(s): Anindya Bagchi, PhD (PI); Christine Salomon, PhD (Co-PI); Yasuhiko Kawakami, PhD (Co-PI)

Interspecies Signaling Interactions and Pathogen Suppression Among Soilborne Streptomyces
Duration: 03/2011 - 02/2014
Funding Agency: United States Department of Agriculture (USDA)
Investigator(s): Christine Salomon, PhD (PI); Linda L. Kinkel, PhD (Co-PI)

Design of Antituberculosis Agents that Target Biotin Metabolism
Grant number: R01 A1091790
Duration: 12/01/2010–1/30/2015
Funding Agency: NIH/NIAID
Principal Investigators: Dirk Schnappinger, PhD; Courtney Aldrich, PhD
Total Direct Costs for the Aldrich Labs: $930,000

Structures of Peptide Synthetases and Related Enzymes - R01 GM068440 (Gulick)
Grant Number: R01 GM068440
Duration: 7/01/10–6/30/2014
Funding Agency: NIH/NIGMS
Principal Investigator: Andrew Gulick, PhD
Subcontracted to: Courtney Aldrich, PhD
Total direct costs for the Aldrich lab subcontract: $92,000

Extreme Microbes of Minnesota-Geomicrobiology in the Soudan Iron Mine
Duration: 07/2010 - 06/2013
Funding Agency: Legislative-Citizen Commission on Minnesota Resources (LCCMR)
Investigator(s): Jeff Gralnick, PhD (PI); Christine Salomon, PhD (Co-PI)

Design of Antituberculosis Agents that Target Siderophore Biosynthesis
Grant Number: R01 AI070219-4
Duration: 3/01/2010–2/28/2014
Funding Agency: NIH/NIAID
Principal Investigator: Courtney Aldrich, PhD
Total Direct Costs: $900,000

A Fluorescence Polarization Assay for Fatty Acid Adenylating Enzymes
Grant Number: R21 NS066415
Duration: 6/01/2009–5/31/2011; 2/01/2012–1/30/2013 (supplement)
Funding Agency: NIH/NINDS
Principal Investigator: Courtney Aldrich, PhD
Total direct costs: $125,000

A Novel Zebrafish Screen for Discovery of Natural Compounds that Enhance Limb Regeneration
Duration: 07/2010 - 07/2011
Funding Agency: AHC Seed Grant, UMN
Investigator(s): Anindya Bagchi, PhD (PI); Christine Salomon, PhD (Co-PI); Yasuhiko Kawakami, PhD (Co-PI)

A Novel Synergistic Approach for the Treatment of Medical Biofilms
Duration: 07/2010 - 07/2011
Funding Agency: AHC Seed Grant, UMN
Principal Investigator: Christine Salomon, PhD

FadD Inhibitors as Chemotherapeutic Agents for Multidrug Resistant Tuberculosis
Duration: 10/01/2009–9/30/2011
Funding Source: GLRCE (Greater Lakes Regional Center for Biodefense and Emerging Infectious Diseases)
Type of Grant: Development Project-5
Principal Investigator: Courtney Aldrich, PhD
Total Direct Costs: $250,000

Biorational Development of Plant Disease Biocontrol
Duration: 01/2009 - 06/2010
Funding Agency: University of Minnesota (Healthy Foods, Healthy Lives Institute)
Principal Investigator(s): Christine Salomon, PhD; Linda L. Kinkel, PhD

New Drugs for Treatment of Latent Tuberculosis Infections
Duration: 11/01/2008–8/31/2010
Funding Agency: Bill & Melinda Gates Foundation & Wellcome Trust
Principal Investigator: Douglas B. Young, PhD
Subcontracted to: Courtney Aldrich, PhD
Total direct costs for the Aldrich lab were: $272,000

Design of Antituberculosis Agents that Target Siderophore Biosynthesis
Grant Number: R01 AI070219
Duration: 7/01/2006–7/01/2009
Funding Agency: NIH/NIAID
Principal Investigator: Courtney Aldrich, PhD
Total direct costs: $600,000

Thioesterase Inhibitors of Mycolic Acid Biosynthesis as Antitubercular Agents
Grant Number: R21 A1072136-02
Duration: 8/1/2007–7/31/2009
Funding Agency: NIH/NIAID
Principal Investigator: Courtney Aldrich, PhD
Total direct costs were: $275,000

Novel Selective Inhibitors of IMPDH Type II Against CML
Grant Number: DoD CM043020
Year of Completion: 2004
Funding Agency: Department of Defense
Principal Investigator: Krzysztof W. Pankiewicz

Cyanide is a rapid acting toxin that inhibits cellular respiration, rapidly shutting down many of the fundamental biochemical processes the body needs to survive by preventing the body from using oxygen. Symptoms of acute cyanide poisoning include headache, vertigo, lack of motor coordination, weak pulse, abnormal heartbeat, vomiting, stupor, convulsions, coma, and even death. When released in an enclosed area, cyanide can be particularly deadly and impact a victim very quickly. Survivors of cyanide poisoning are also at risk of short-term memory loss and development of a Parkinson's-like syndrome. A fast-acting antidote to cyanide poisoning has the potential to save the lives of those who are exposed to the toxin, including firefighters, industrial workers, and victims of terrorist attack. In severe cyanide poisonings, rapid intervention is the key.
Recently the researchers from the University of Minnesota Center for Drug Design and the Minneapolis Veterans Affairs Medical Center have discovered a fast acting antidote based on mechanisms used by the body to detoxify small amounts of cyanide that occur naturally in pitted fruits, some grasses, and other foods. The new antidote takes advantage of this natural detoxification pathway by converting cyanide to non-toxic thiocyanate. Independently, the team at UCSD has also discovered another rapidly acting antidote that works by sequestering cyanide. The resulting complex is then safely removed from the body in urine.
At the University of California Irvine (UCI), the team has developed an effective and fast method for assessing cyanide toxicity. Using this non-invasive optical method, the team at UCI can rapidly access the effects of cyanide and efficacy of novel antidotes. In addition, the team at UCI has developed a new formulations and administration methods that provide for faster and easier delivery of antidotes to victims of cyanide poisoning.
This project is a collaboration between researchers from the Center for Drug Design, University of Minnesota, the Minneapolis Veterans Affairs (VA) Medical Center (MN, USA), The University of California San Diego (UCSD), and the University of California Irvine. When combined in animal models, the Minnesota and UCSD antidotes work synergistically against cyanide poisoning and are being developed as combination therapy by the above teams. The resulting antidote works prophylactically to prevent or limit toxicity associated from exposure to cyanide. Our antidotes are faster acting and are safer than existing antidotes.
Sponsored by NIH grant: 1U54NS063718-01

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