Tuchoiski_Janusz

Janusz Tucholski, Ph.D.
Assistant Professor, Department of Psychiatry and Behavioral Neurobiology

Areas of Focus: Project #1:  Schizophrenia, glutamate receptors, assembly and trafficking, N-glycosylation; and Project #2:  Tissue transglutaminase, retinoic acid, neuroblastoma, neuronal death and survival



Publications

Contact Information
CIRC 593
(205) 934-2144
Email:  This email address is being protected from spambots. You need JavaScript enabled to view it.


RESEARCH DESCRIPTION

Project no 1. Biochemistry and molecular biology of schizophrenia

     Schizophrenia is a disabling brain disorder that typically has its symptomatic onset in early adulthood and persists, in most cases, throughout life.  Schizophrenia is a complex disease that engages multiple domains of human brain resulting in range of cognitive and behavioral abnormalities. Accumulating evidence suggests that disturbances in cognition, including deficits in working memory may represent the core feature of schizophrenia. Converging evidence from neuroimaging, neurocognitive, gene expression analysis, neuropathological and biochemical studies strongly suggests that defective cortical studies strongly suggests that defective cortical glutamatergic neurotransmission may initiate a neuropathological cascade leading to deterioration of subcortical and cortical dopaminergic neurotransmission and cortical hypofrontality observed in schizophrenia patients. The goal of our research is understanding biochemical and molecular processes that produce abnormalities in glutamate neurotransmission observed in schizophrenia. Particularly, we are interested in the assembly and processing of ionotropic glutamate AMPA and NMDA receptors in the endoplasmic reticulum, their subsequent trafficking the plasma membrane, stability at the membrane and recycling cortex synapses in  schizophrenia.

Project 2. Role of tissue transglutaminase (TG2) in neuronal cells

     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. In cell culture, TG2 appears to be an essential element of differentiation of neuronal-like cells, such neuroblastoma (NB) into neuronal-like morphology in response to all-trans retinoic acid (ATRA).

     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. 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 Huntington's disease (HD) or Alzheimer's disease (AD).

BIOGRAPHY

     Dr. Janusz Tucholski  received his M.S. degree from the University of Gdañsk, Gdañsk, Poland in Biology in 1988.  He went on to receive his Ph.D. degree from University of Gdañsk, Gdañsk, Poland with Honors in Biological Sciences in 1996. Dr. Tucholski completed postdoctoral fellowships in Neurobiology at Barrow Neurological Institute, Phoenix, AZ in 1996-97;  Pathology, School of Medicine, Wayne State University, Detroit, MI in 1997-98; and Psychiatry and Behavioral Neurobiology, UAB, Birmingham, AL in 1998-2002. He joined the UAB faculty in 2003 as a Research Instructor in Psychiatry and Behavioral Neurobiology.