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Dr. Poltorak’s scientific vision was influenced by his post-doctoral training with Bruce Beutler, which led to identification of TLR4 as the receptor for bacterial lipopolysaccharide (LPS), the work that had been recognized in the 2011 Nobel Prize awarded to Dr. Beutler. Since being published in 1998, identification of TLR4 as the receptor for LPS had been cited more than 8,000 times and has made a breakthrough that was anticipated for more than 30 years thus showing advantages of forward genetic analysis where all other approaches failed. 20 years after this discovery, the LPS-induced cytotoxicity is being investigated by Dr. Poltorak’s graduate students who contributed as the first authors to all of the papers from the lab including this year publication in Science. Another paper has just been accepted in Nature Communications and has been taken via submission process during difficult COVID times. The Poltorak’s lab executes the genetic approach with particular emphasis on the forward genetic analysis using genetically divergent wild-derived mice. Because of their evolutionary divergence, these mice exhibit high level of polymorphism when compared with the classical inbreds.