Our laboratory is interested in understanding signal transduction pathways involved in the pathogenesis of cancer with a specific focus on glioblastoma (GBM).

Elucidating the role of inflammation and NF-κB activation in the pathogenesis
of glioma  

Chronic inflammation predisposes to diverse types of human cancer. We are interested in studying how inflammation promotes cancer. The NF-κB family of transcriptional regulators plays a central role in inflammation and may also drive inflammation induced cancer. Our laboratory has found that the receptor interacting protein (RIP, RIP1, RIPK1), an essential component of the NF-κB signaling pathway, is a key node that mediates cross-talk between inflammatory and oncogenic pathways. RIP1 is overexpressed in glioblastoma (GBM) the most common adult brain tumor.  Increased RIP1 expression in GBM confers a worse prognosis. RIP1 also has a central role in activation of cell death pathways and we are interested in the possibility of therapeutically activating the cell death function in vivo. We use cell culture, in vivo mouse models as well as tissue from human cancers to investigate the inflammation cancer interface in glioblastoma and other cancers.

Epidermal growth factor signaling in cancer

The epidermal growth factor receptor is frequently amplified and mutated in human cancer. EGFRvIII is a mutant EGFR found commonly in GBM and is more tumorigenic than the wild type receptor. EGFRwt and EGFRvIII are commonly co-expressed in GBM and we are interested in downstream signal transduction by the two receptors and also interactions between EGFRwt and EGFRvIII.
Increased expression of the EGFR can paradoxically induce a RIP1 dependent growth cell death. We are also interested in exploring potential synthetic lethal interactions between RIP1- NF-κB and EGFR in cancer.

We have recently found that a non-canonical form of EGFR signaling that is triggered in cancer cells exclusively in the absence of ligand and that my mediate resistance to chemotherapy.


Selected Publications

  1. Chakraborty S., Li L, Puliyappadamba VT, Guo G, Hatanpaa KJ, Mickey B, Souza RF, Vo P, Herz J, Chen MR, Boothman DA, Pandita TK, Wang DH, Sen GC, and Habib AA*. Constitutive and ligand-induced EGFR signaling triggers distinct and mutually exclusive downstream signaling networks. Nature Communications 2014 Dec 15;5:5811. doi: 10.1038/ncomms6811


  1. Puliyappadamba VT, Chakraborty S, Chauncey SS, Li L, Hatanpaa KJ, Mickey B, Noorani S, Shu HG, Burma S, Boothman DA, and Habib AA*. Opposing effect of EGFRwt on EGFRvIII mediated NF-kappaB activation with RIP1 as a cell death switch. Cell Reports 4, 764-775. 2013


  1. Li L, Chakraborty S, Yang CR, Hatanpaa KJ, Cipher DJ, Puliyappadamba VT, Rehman A, Jiwani AJ, Mickey B, Madden C, Raisanen J, Burma S, Saha D, Wang Z, Pingle SC, Kesari S, Boothman DA, Habib AA*. An EGFR wild type-EGFRvIII-HB-EGF feed forward loop regulates the activation of EGFRvIII. Oncogene. 2013 Sep 30. doi:10.1038/onc.2013.400. [Epub ahead of print].


  1. Li, L, Puliyappadamba VT, Chakraborty S, Rehman A, Vemireddy V, Saha D, Souza RF, Hatanpaa KJ, Koduru P, Burma S, Boothman DA, and Habib AA*. EGFR wild type antagonizes EGFRvIII-mediated activation of Met in glioblastoma. Oncogene. 2013 Dec 23. doi: 10.1038/onc.2013.534. [Epub ahead of print]


  1. Park S, Zhao D, Hatanpaa KJ, Mickey BE, Saha D, Boothman DA, Story MD, Wong ET, Burma   S,  Georgescu MM, Rangnekar V, Chauncey SS, and *Habib AA. RIP1 activates PI3K-Akt via a dual mechanism involving NF-kappa B mediated inhibition of the mTOR-S6K-IRS1 negative feedback loop and downregulation of PTEN. Cancer Research 69, 4107-4111, 2009


  1. Park S, Hatanpaa KJ, Xie Y, Mickey BE, Madden CJ, Raisanen J, Ramnarain DB, Xiao G, Saha D, Boothman DA, Zhao D, Bachoo RM, Pieper RO, and *Habib AA. The receptor interacting protein (RIP1) inhibits p53 induction through NF-kappa B activation and confers a worse prognosis in glioblastoma. Cancer Research 69, 69: 2809-2816, 2009