I am an Assistant Professor of Medicine and principal investigator at the Case Cardiovascular Research Institute (CVRI), Case Western Reserve University School of Medicine. My laboratory research goal is to identify and decipher the molecular role of novel transcriptional regulators in the pathogenesis of human chronic, and acute inflammatory disease conditions. My laboratory studies to date have identified several novel transcriptional regulators of macrophage pro- and anti-inflammatory activation.
Currently, my laboratory is actively working to define the molecular functions of two such transcription regulators. Namely, kruppel-like factor 6 (KLF6) and Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 (CITED2). My laboratory studies are first to demonstrate KLF6 promotes pro-inflammatory macrophage activation, while suppressing anti-inflammatory gene expression. Specifically, KLF6 levels are dramatically upregulated in human myeloid cells under chronic or acute inflammatory disease conditions. In addition, my laboratory discovered that KLF6 regulates key inflammatory genes involved in human inflammatory bowel diseases (IBD).
In parallel with these studies, my investigations revealed CITED2 as a potent anti-inflammatory transcriptional regulator. Recent human genomic studies revealed that mutation in CITED2 and KLF6 gene is associated with lipid abnormalities and coronary artery diseases. Therefore, we are currently investigating molecular functions of these genes in macrophage lipid homeostasis and atherogenesis.
- KimG-D, Das R, Goduni L,McClellan S, Hazlett LD, Mahabeleshwar GH. Kruppel-like factor 6 promotes macrophage-mediated inflammation by suppressing B cell leukemia/lymphoma 6 expression. J. Biol. Chem. 2016. 291(40):21271-21282. (PMCID:PMC5076533)
- Goodman WA, O.S., Date D, Di Martino L, De Salvo C, Kim G-D, Chowdhry S, Bamias G, Cominelli F, Pizarro TT, Mahabeleshwar GH. KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation. Mucosal Immunology. 2016:9(5):1250-62. (PMCID:PMC4972715)
- Date D, Das R, NarlaG, Simon DI, Jain MK, and Mahabeleshwar, GH. Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization. J. Biol. Chem. 2014; 289 (15):10318-29. (PMCID:PMC4036156).
- Nayak L, Goduni L, Takami Y, Sharma N, Kapil P, Jain MK, Mahabeleshwar GH. 2013. Kruppel-like factor 2 is a transcriptional regulator of chronic and acute inflammation. American Journal of Pathology 182(5): 1696-704 (PMCID:PMC3644709)