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Faculty Detail    
Name JANUSZ TUCHOLSKI
 
Campus Address CIRC 593A Zip 0017
Phone 205-934-2144
E-mail jtuchol@uab.edu
Other websites
     


Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Neuroscience 

Biographical Sketch 
EDUCATION:
M.Sc. in Biology, 1988, University of Gdansk University of Gdansk, Gdansk, Poland
Ph.D. with Honors in Biological Sciences, 1996, University of Gdansk, Gdansk, Poland
POSTDOCTORAL TRAINING:
1995 Visiting Scientist, Max-Delbrueck-Centrum for Molecular Medicine, Dept. of Protein Chemistry, Berlin, Germany
1996 Visiting Scientist, Biochemistry, Oxford University, Oxford, UK
1996-97 Barrow Neurological Institute, Phoenix
1997-98 Wayne State University, Dept. of Pathology, Detroit
1998-02 UAB, Dept. of Psychiatry and Beh. Neurobiology
ACADEMIC APPOINTMENTS:
2003-05 Instructor, Dept. of Psychiatry and Beh. Neurobiology, UAB
2005- Assistant Professor, Psychiatry and Beh. Neurobiology, UAB
2005- Associate Scientist, Center for Aging, UAB
2006- Member, Comprehensive Neuroscience Center, UAB

Research/Clinical Interest
Title
Cellular and molecular biology of neuroblastoma. Response of neuronal cells and neurons to stress.
Description
Tissue transglutaminase (TG2) is a multifunctional member of transglutaminase family of proteins (TGases), that modifies protein substrates in a calcium-dependent reaction and that can bind and hydrolyze GTP. Tissue TG is a normal constituent of the central and peripheral nervous system, localizing mostly in a cytoplasmic compartment of neurons. Intriguingly, in the developing mouse brain the TG2 protein and TG activity levels are tightly regulated. Nonetheless, TG2 increases coincide with differentiation and maturation of neurons. The exact, if any, contribution of TG2 (other TGases) to these developmental processes remains to be investigated. In culture, TG2 appears to be an essential element of maturation and differentiation of neuronal-like cells, such neuroblastoma (NB), into neuronal-like morphology in response to all-trans retinoic acid (ATRA); NB cells that don't express TG2 protein fail to differentiate. Given that TG2 is a direct target of a RAR-RXR/RARE-dependent signaling pathway, being rapidly transcriptional activated in NB and other neuronal cells, it is likely that TG2 play an important, yet still to be determined role in development and maturation of neurons. A myriad of functions have been postulated for TG2, however, a general consensus emerges that TG2 likely promotes differentiation or/and survival of cells in response to physiological signals (increase in cAMP levels) or to mild stress (e.g. heat shock) or amplifies their demise when cells are subjected to pathological condition (e.g. in brain injury) or to supra- physiological stress (e.g. osmotic stress or excitotoxicity). The first aspect of our research is focused on understanding a possible interplay between TG2, RA-signaling and other cell signaling pathways that are either triggered or regulated by cAMP and calcium in human NB tumor cells, as well as, in cells of neuronal lineage or adult neurons. Indeed, in NB cells and in breast cancer cells, TG2 has been demonstrated to play a critical tumor suppressing role during cell response to histone deacetylase inhibitors (HDACi) treatment that resulted in a substantial inhibition of Myc-driven oncogenesis. The second focus of our research is the role of TG2 and its calcium-induced transamidation (TG) activity in a response of CNS cells to stress, particularly in neurological conditions, such as epilepsy and brain injury and in neurodegenerative conditions, such as Parkinsonís disease (PD), Huntingtonís disease (HD) or Alzheimerís disease (AD). This line of our investigation is, we believe, underscored by the fact that increases in TG2 protein and/or TG activity levels have been well documented in all of these neurodegenerative conditions, as well as in supranuclear pals and in HIV-associated dementia. Furthermore, increases in TG2 protein or TG activity levels have been well documented in a number of animal models of acute CNS damage, including spinal cord injury, traumatic brain injury (TB), ischemia or a primate model of HIV-related pathology.

Selected Publications 
Publication PUBMEDID
Ruan, Q., Tucholski J, Gundemir S, Johnson GV.
The differential effects of R580A mutation on transamidation and GTP activity of rat and human type 2 transglutaminase. International Journal of Clinical and Experimental Medicine. 1(3):248-259;2008.

 
19079660  
Filiano, A.J., Bailey, C.D.C., Tucholski, J., Gundemir, G., Johnson G.V.W. Transglutaminase 2 protects against ischemic insult, interacts with HIF1 beta and attenuates HIF1 signaling. FASEB J. 2008 Mar 28.   18375543  
Tucholski, J., Roth, K.A. Johnson, G. V.W. Tissue transglutaminase overexpression in the brain potentiates excitotoxicity-induced hippocampal damage. Journal of Neurochemistry, 97 (2006)
582-94.
 
16539654  
Bailey, C. D.C., Tucholski, J., Johnson, G. V.W. Transglutaminases in neurodegenerative disorders. Progress in Experimental Tumor Research 38 (2005) 139-57.   15746534  
Milakovic, T., Tucholski, J., McCoy, E., Johnson, G.V.W. Intracellular localization and activity state of tissue transglutaminase differentially impacts cell death. Journal of Biological Chemistry, 279 (10) (2004), 8715-22.   14670969  
Tucholski, J., Johnson, G.V.W. Tissue transglutaminase modulates CREB transcriptional activity through the cAMP pathway. Journal of Biological Chemistry, 278 (29) (2003), 26838-43.  12743114 
Lesort, M., Lee, M., Tucholski, J., Johnson, G.V.W. Cystamine inhibits caspase activity: implication for the treatment of polyglutamine disorder. Journal of Biological Chemistry, 278 (6) (2003), 3825-30.  12458211 
Tucholski, J., Johnson, G.V.W. Tissue transglutaminase differentially modulates apoptosis in a stimuli-dependent manner. Journal of Neurochemistry 81 (2002), 780-91.  12065637  
Watacharasit, P., Tucholski, J., Jope, R.S. Src family kinase involvement in muscarinic receptor-induced tyrosine phosphorylation in differentiated SH-SY5Y cells. Neurochemistry Research 26(7) (2001), 809-16.  11565612 
Chun, W., Lesort, M., Tucholski, J., Faber, P.W., MacDonald, M.E., Ross, C. A., Johnson, G.V.W. Tissue transglutaminase selectively modifies proteins associated with truncated mutant huntingtin in situ. Neurobiology of Disease 8 (3) (2001), 391-404.  11442349 
Chun, W., Lesort, M., Tucholski, J., Ross, C.A., Johnson, G.V.W. Tissue transglutaminase does not contribute to the formation of mutant huntingtin aggregates. Journal of Cell Biology 153 (1) (2001), 25-34.  11285271 
Tucholski, J., Lesort, M., Johnson, G.V.W. Tissue transglutaminase is essential for neurite outgrowth in human neuroblastoma SH-SY5Y cells. Neuroscience 102 (2) (2001), 481-491.  11166134 
Lesort, M., Tucholski, J., Zhang, J., Johnson, G.V.W. Impaired mitochondrial function in increased tissue transglutaminase activity in situ. Journal of Neurochemistry 75 (2000), 1951-61.  11032884 
Tucholski, J., Kuret, J., Johnson, G.V.W. Tau is modified by tissue transglutaminase in situ: possible functional and metabolic effects of polyamination. Journal of Neurochemistry, 73 (1999), 1871-80.  10537045 
Robitaille, K., Daviau, A., Tucholski, J., Johnson, G. V.W., Rancourt, C., Blouin, R. Tissue
transglutaminase triggers oligomerization and activation of dual leucine zipper-bearing kinase to promote apoptosis. Cell Death and Differentiation, 11 (5) (2004), 542-9.
 
14739943  
Tucholski, J. TG2 protects neuroblastoma cells against DNA-damage induced stress, suppresses p53 activation. Amino Acids. In press.    

Keywords
Tissue transglutaminase, cAMP, retinoic acid, neuronal death and survival, neuronal stress, plasticity, mice