University of Pittsburgh Department of Cell Biology
  • Research

    Dr. Mallampalli's research in the area of pulmonary molecular and cell biology as it relates to acute lung injury (ALI) and the mechanisms of sepsis. He is an internationally recognized investigator in the area of lipid metabolism and ubiquitin-mediated proteolysis as it relates to inflammation and injury. His work discovered a new model of innate immunity that led to the synthesis of a first-in-class genus of ubiquitin E3 ligase (F box) inhibitors that modulate proteolysis thereby inhibiting inflammation in preclinical models of ALI and multi-organ failure. This work is rapidly moving through the FDA milestone pipeline for eventual therapeutic application in clinical trials for subjects with respiratory illness. A second, more untapped area of interest is based on the laboratory's discovery that the mitochondrial-specific lipid, cardiolipin, is a unique cellular damage signal and important mediator of pneumonia. His lab uncovered a new paradigm for pneumonia. Pneumonia patients had increased levels of a toxin, cardiolipin, which reproduces this disorder when given to mice. From clues in a rare disease, he uncovered that a pump normally removes cardiolipin from lung fluid but is degraded in pneumonia. This work is ongoing and could lead to non-antibiotic therapies in this illness.

  • Publications

    1. Agassandian M., Chen, B.B., Schuster, C.C., and Mallampalli, R.K. 14-3-3ζ escorts CCTalpha for calcium-activated nuclear import in a calcium-dependent manner. FASEB J. 24:1271-83, 2010.
    2. Butler, P. and Mallampalli, R.K. Cross-talk between remodeling and de novo pathways maintains phospholipid balance through ubiquitination J. Biol. Chem. 26;285:6246-58, 2010
    3. Chen, B.B. and Mallampalli, R.K. Masking of a nuclear signal motif by monoubiquitination leads to mislocalization and degradation of the regulatory enzyme, CCTa. Mol. Cell. Biol. 29:3062-3075, 2009.
    4. Ryan, A.J., Chen, B.B., Vennalaganti P. R., Henderson F. L., Tephly, L.A., Carter, A.B. and Mallampalli, R.K. 15d-PGJ2 impairs phosphatidylcholine synthesis by inducing nuclear accumulation of thiol-modified cytidylyltransferase. J. Biol. Chem. 283, 24628-24640, 2008.
    5. Mallampalli, R.K., Salome, R.G., Bowen, S.L., and Chappell, D.A.: Very low density lipoproteins stimulate surfactant lipid synthesis in vitro. J. Clin. Invest., 99:2020-2029, 1997

     

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