Back to Main

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

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Psychiatry   Psychiatry Chair Office Assistant Professor Center  Center for Aging  Center for Aging Assistant Professor Center  General Clinical Research Center  Comprehensive Neuroscience Center Assistant Professor

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 Parkinson’s disease (PD), Huntington’s disease (HD) or Alzheimer’s 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   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   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  First Prev   1 2 of  2  Next Last

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

© 2008 University of Alabama at Birmingham. All rights reserved. DisclaimerAbout this SiteGraphic Design Created by UAB Web Communications.
Calendar Designed by Medical Education Information Services. To report problems with the site, email us at meis@uab.edu. Last Revision: February 15, 2012.
The UAB School of Medicine Mailing Address: 1530 3rd Avenue South, FOT 1203, Birmingham AL 35294-3412