The Striker Lab is interested in optimizing therapy against human viruses and bacteria. Anti-infectives are life giving miracle drugs but the principles of molecular medicine and molecular microbiology are just now being used to tailor therapy against pathogens to give sufficient anti-infective potency while minimizing side effects and the selection of resistance. Often clinical decisions are based on the response of the “average pathogen” in the “average patient” without regards to the specific genetic background of either the pathogen, or patient, or both, which can now be characterized with increasing precision. Examples of how the genetic lineage of the pathogen might be unique include the naturally occurring genotype 2b/1a strain Hepatitis C (HCV) strain we discovered similar to the 2k/1b St Petersburg strain that is spreading in Eastern Europe, as well as a cyclophilin inhibitor resistant strain selected in a HCV infected liver transplant patient by the immunosuppressant cyclosporine. The human genetic background is also important for antiHepatitis C treatment as we have reported some of the shortest HCV in patients that are homozygous for Interferon lambda 4, and tailored therapy based on this polymorphism.
Clinical Virology: We are currently working on maximizing effectiveness of direct-acting antivirals in young patients who are technically past the acute stage but still have low viral loads, and in incarcerated patients. Approximately 1 in 3 of the ~ 6 million HCV infected patients in the US have spent some time in the criminal justice system. There is a unique public health opportunity to cure HCV in patients and prevent further morbidity and mortality as well as spread of the virus by treating patients in the incarceration system, but currently therapy is far too expensive and regimens have to many side effects to capitalize on this opportunity. The W. S. Middleton VA where I also work also is now a site of the Million Veteran Program, MVP, and Rob Striker is the site PI. We are keen to partner with other MVP sites to gather data about how human genetic variation can be used to tailor HIV and HCV therapy.
Novel Antibiotics: We are repurposing human kinase inhibitor like molecules to target bacterial kinases, specifically the Penicillin Binding Protein And Serine/Threonine kinase Associated (often referred to as PASTA Kinases) that many drug resistant positive bacteria have include Methicillin Resistant Staphylococcus Aureus (MRSA), mycobacterium (including tuberculosis) and Nocardia. While these kinases share many features with human kinases, they can be successfully and selectively targeted and when combined with cell wall active beta lactam antibiotics they alter the physiology of bacteria to turn MRSA back into MSSA (Methicillin Sensitive). We are developing a comprehensive pharmacologic understanding of this so that it can be applied clinically using the many kinase inhibitors that industry and academia have placed in the public domain.
Improve the scientific basis and use of anti-infectives and tailor therapy to minimize patient specific exposure to anti-infectives
Honors & Awards
- The Hartwell Foundation, Individual Biomedical Award “Novel Antibiotic for MRSA”
- Burroughs Welcome Career Award Interviewee, 2001
- HHMI Physician Postdoctoral Research Fellowship, 1998
- Pensinger DA, Schnauzer A, Bolden K, Aliota MT, Ansari IH, Knight B, Reniere ML, Striker R, and Sauer JD (2014). Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to β-lactam Antibiotics. in press in Antimicrobial Agents and Chemotherapy.
- Striker R, Mehle A (2014). Inhibitors of peptidyl proline isomerases as antivirals in hepatitis C and other viruses. PLoS Pathology. 2014 Nov 6;10(11):e1004428. PMCID: PMC4223064
- Bhattacharya D, Ansari IH, Hamatake R, Walker J, Kazmierski WM, and Striker R (2014). Pharmacological disruption of hepatitis C NS5A protein intra- and intermolecular conformations. J Gen Virol. 95(Pt 2):363-372.
- Ansari, I. Allen, T. Barin, B. Stock PG, and Striker R. (2013) Phenotypic analysis of NS5A variant from liver transplant patient with increased cyclosporine susceptibility. Virology. 436(2):268-73. PMID: 23290631
- Carlson A. Gregorich, Z. and Striker, R (2013).Telaprevir to Boceprevir switch highlight slack of crossreactivity.Clin Infect Dis. 56:552-4. PMID: 23166191. Policy exempt – Not resulting from NIH funding.