Dysautonomia Foundation Research --
Current Projects 

Tuula Kallunki

Understanding the mechanism of the IKAP-mediated c-Jun N-terminal kinase signaling and its role in cell death and survival  

The aim of this study is to find out how the association of IKAP and JNK is regulated in mammalian cells and what is the actual function of it, which might account for FD.

In our recent study “A novel and specific role for IkB kinase complex-associated protein in cytosolic stress signaling” (Holmberg et al., 2002) we demonstrated that the IkB kinase complex-associated protein (IKAP) is able to regulate stress response via activation of the c-Jun N-terminal kinase (JNK) signaling pathway. In this study we found out that JNK interacts with the carboxy (C)-terminus of IKAP, which was previously shown to confer a mutation that will make IKAP to undergo tissue specific splicing in majority of patients (99%) affected by familial dysautonomia (FD). As a result these patients express IKAP truncated at amino acid 714 (FD-IKAP) in affected tissues (Anderson et al., 2001; Slaugenhaupt et al., 2001). We showed that the truncated IKAP cannot further interact with JNK.

We suggest that impaired JNK signaling might be one of the key elements behind the molecular mechanism of FD. Thus the main objective of this study is to define the molecular mechanism underlying IKAP mediated JNK signaling in order to facilitate development of efficient treatment strategies against FD.

Tuula Kallunki

Tuula Kallunki has been working as a senior scientist at Danish Cancer Society since 1998. Dr. Kallunki earned her M.S. and Ph.D. from the Department of Biochemistry, University of Oulu , Finland after which she had her postdoctoral training at the Department of Pharmacology, University of California , San Diego , USA.