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Журнал микробиологии, эпидемиологии и иммунобиологии

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Alexander V. Bocharov

Alexander V. Bocharov, MD, PhD (Medicine), Staff scientist, Department of Laboratory Chemistry, Clinical Center, National Insitutes of Health, Bethesda, USA

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The Scopus h-index — 20

 

Research interests

Research interests are connected with the study of Class B scavenger receptors (SR-B) such as SR-BI, SR-BII and CD36 in PAMP/DAMP recognition and host defense. He also studies mechanisms of SR-BI and SR-BII function in regard of both host defense and lipid metabolism associated with development infectious diseases, AKD and inflammatory associated diseases such as CKD and atherosclerosis.

Main scientific achievements

A.V. Bocharov and colleagues were the first to show that SR-B function in sensing of PAMPs such as LPS, LTA, bacterial HSPs such as Gro EL and bacteria mediating downstream signaling leading MAPK activation and cytokine secretion. By utilizing synthetic amphipathic helical peptides, SR-B antagonists, they successfully reduced inflammatory responses and improved survival in CLP induced sepsis in mice, reduced ALI associated inflammation and improved CKD outcome.

Area of Research Expertise

Cell and tissue culture; ligand-receptor interaction; scavenger receptors class B (SR-BI, SR-BII, CD36); lipoprotein and cholesterol metabolism; Pathogen Associated Molecular Pattern compounds (PAMP) such as cytosolic and bacterial cell wall components such as LPS, LTA and chaperonin 60 (Gro-EL), Damage Associated Molecular Pattern compounds (DAMP) and their role in development and progression of pulmonary infections and sepsis (PAMPs and DAMPs) as well as sterile, DAMP related inflammation and tissue damage in artherogenesis acute kidney damage and chronic kidney disease.

Future directions for projects based on his research

Since SR-BI/II and CD36 targeting proved as promising treatment approach for pulmonary sterile infection, CKD as well as sepsis, he suggests following sequence of experimental research to produce pharmaceutically relevant products blocking these receptor and specifically reducing inflammation:

First step is to identify potent inhibitors of PAMPs and DAMPs induced SR-B-dependent inflammatory response among small molecules and peptides:

  1. Pepscan analysis (JPT Innovative Peptide Solutions, GmbH) to map the specific epitopes for known SR-BI/BII/CD36 ligands (SAA, LPS, etc.) in order to synthesize corresponding short-sequence ligand-binding peptides derived from these receptors;
  2. Scan an existing small molecule libraries to identify the most effective inhibitors blocking binding SR-B ligands to short-sequence ligand-binding peptides.
  3. Assess ability of the best small inhibitors to block PAMP (LPS, LTA and GroEL) induced cytokine secretion in HEK 293 cells overexpressing SR-BI, SR-BII and CD36;

The second step is to assess best small inhibitors in mouse models of CLP-induced sepsis, ALI (acute lung injury) and CKD.