Research Projects
Introduction
The primary focus of our lab is to discover new potential drugs to treat infectious diseases. We specialize in medicinal chemistry, synthetic organic chemistry, and drug discovery and partner with collaborators whose expertise is in disease biology and pharmacology. Current projects of particular focus in the lab include anti-parasitics (Cryptosporidium), anti-virals (Hepatitis B virus), anti-fungals (Cryptococcus neoformans), anti-bacterials (Mycobacterium tuberculosis), and rare diseases (facioscapulohumeral muscular dystrophy, FSHD).
The primary focus of our lab is to discover new potential drugs to treat infectious diseases. We specialize in medicinal chemistry, synthetic organic chemistry, and drug discovery and partner with collaborators whose expertise is in disease biology and pharmacology. Current projects of particular focus in the lab include anti-parasitics (Cryptosporidium), anti-virals (Hepatitis B virus), anti-fungals (Cryptococcus neoformans), anti-bacterials (Mycobacterium tuberculosis), and rare diseases (facioscapulohumeral muscular dystrophy, FSHD).
Cryptosporidiosis
Cryptosporidiosis is a major health issue in the developing world for which there is only one approved drug, nitazoxanide. However, nitazoxanide is not effective in young children or immunocompromised patients. We are collaborating with the Huston and Griggs labs to identify new drugs to treat this disease.
Collaborators: Chris Huston (Univ. of Vermont) and Fran Sverdrup (SLU)
Current funding: NIH R01 AI143951, NIH R33 AI14118
Cryptosporidiosis is a major health issue in the developing world for which there is only one approved drug, nitazoxanide. However, nitazoxanide is not effective in young children or immunocompromised patients. We are collaborating with the Huston and Griggs labs to identify new drugs to treat this disease.
Collaborators: Chris Huston (Univ. of Vermont) and Fran Sverdrup (SLU)
Current funding: NIH R01 AI143951, NIH R33 AI14118
Malaria
We have been systematically optimizing phenotypic antimalarial screening hits as potential new drugs. We have shown some of these compounds to inhibit aspartic proteases (plasmepsins II, IV and X). Our most promising compounds are active in mouse models of malaria. We are also working on inhibitors of the MEP pathway.
Collaborators: Micky Tortorella and Xiaoping Chen (Guangzhou Institutes for Biomedicine and Health, Chinese Academy of Science), Dan Goldberg (Washington University) and Audrey Odom (Children's Hospital of Philadelphia), Cindy Dowd (George Washington University)
Current Funding: NIH R01 AI123433
We have been systematically optimizing phenotypic antimalarial screening hits as potential new drugs. We have shown some of these compounds to inhibit aspartic proteases (plasmepsins II, IV and X). Our most promising compounds are active in mouse models of malaria. We are also working on inhibitors of the MEP pathway.
Collaborators: Micky Tortorella and Xiaoping Chen (Guangzhou Institutes for Biomedicine and Health, Chinese Academy of Science), Dan Goldberg (Washington University) and Audrey Odom (Children's Hospital of Philadelphia), Cindy Dowd (George Washington University)
Current Funding: NIH R01 AI123433
Tuberculosis
We have identified a novel class of compounds that potently and selectively kill Mycobacterium tuberculosis (Mtb). These compounds appear to be working through a novel mechanism of action which suggests they have the potential for treating drug resistant Mtb. We are also working on target-based drug discovery project seeking to develop inhibitors of the hydrolase domain of RelMtb.
Collaborators: Christina Stallings (Washington University), Dave Griggs (SLU)
Recently completed funding: NIH R33 AI111696
We have identified a novel class of compounds that potently and selectively kill Mycobacterium tuberculosis (Mtb). These compounds appear to be working through a novel mechanism of action which suggests they have the potential for treating drug resistant Mtb. We are also working on target-based drug discovery project seeking to develop inhibitors of the hydrolase domain of RelMtb.
Collaborators: Christina Stallings (Washington University), Dave Griggs (SLU)
Recently completed funding: NIH R33 AI111696
Cryptococcal Meningitis
Cryptococcus neoformans is an opportunistic fungus that kills over half a million people every year, primarily those infected with HIV in Africa. We are working to develop inexpensive and more effective drugs that can be utilized in resource poor regions of the world.
Collaborators: Damian Krysan (Univ. of Iowa) and Maureen Donlin (SLU)
Current Funding: NIH R21 AI164578 (with Krysan)
Cryptococcus neoformans is an opportunistic fungus that kills over half a million people every year, primarily those infected with HIV in Africa. We are working to develop inexpensive and more effective drugs that can be utilized in resource poor regions of the world.
Collaborators: Damian Krysan (Univ. of Iowa) and Maureen Donlin (SLU)
Current Funding: NIH R21 AI164578 (with Krysan)
Hepatitis B Virus
We are optimizing multiple classes of inhibitors of hepatitis B virus (HBV) that target RNAseH.
Collaborators: John Tavis (SLU), Ryan Murelli (City Univ. of New York), Grigoris Zoidis (Univ. of Athens)
Current & completed funding: NIH R21 AI124672, R01 AI12266, R01 AI150610
We are optimizing multiple classes of inhibitors of hepatitis B virus (HBV) that target RNAseH.
Collaborators: John Tavis (SLU), Ryan Murelli (City Univ. of New York), Grigoris Zoidis (Univ. of Athens)
Current & completed funding: NIH R21 AI124672, R01 AI12266, R01 AI150610
Herpes Simplex Virus
We are optimizing multiple classes of potential drugs for herpes simplex virus (HSV).
Collaborators: Lynda Morrison (SLU)
Completed funding: NIH R21 AI135311
We are optimizing multiple classes of potential drugs for herpes simplex virus (HSV).
Collaborators: Lynda Morrison (SLU)
Completed funding: NIH R21 AI135311
FSHD Muscular Dystrophy
We are collaborating on a research project to discover and develop a drug therapy to prevent the loss of muscle in facioscapulohumeral muscular dystrophy (FSHD) patients. The muscle loss experienced by FSHD patients is thought to be due to sporadic expression of the developmental DUX4 gene which is normally silenced. We are optimizing compounds that repress the expression of DUX4 and its downstream targets as a potential treatment for FSHD.
Collaborators: Fran Sverdrup (SLU)
Completed funding: Ultragenyx Pharmaceuticals
We are collaborating on a research project to discover and develop a drug therapy to prevent the loss of muscle in facioscapulohumeral muscular dystrophy (FSHD) patients. The muscle loss experienced by FSHD patients is thought to be due to sporadic expression of the developmental DUX4 gene which is normally silenced. We are optimizing compounds that repress the expression of DUX4 and its downstream targets as a potential treatment for FSHD.
Collaborators: Fran Sverdrup (SLU)
Completed funding: Ultragenyx Pharmaceuticals
