^{Name: Satyabrata Kar}

^{Our laboratory works on two complementary research projects. The first project is designed to address the interactions between beta-amyloid (Ab) peptides and central cholinergic neurons and their relevance to Alzheimer’s disease (AD) pathology. The second program is aimed to study the role of insulin-like growth factors (IGFs) in normal brain cholinergic functions and their implications in AD pathology. The overall objective of these two projects is to establish the cause of the preferential vulnerability of the forebrain cholinergic neurons in AD and to determine how these neurons could be protected.}

^{A: Ab-related peptides and central cholinergic neurons in AD pathology}

^{Alzheimer’s disease (AD), the most common type of senile dementia, is a progressive neurodegenerative disorder. The neuropathological features associated with the disease include selective loss of neurons, abnormal extracellular deposits of b-amyloid (Ab) protein in neuritic plaques and the intracellular accumulation of a filamentous structure referred to as neurofibrillary tangles. Among vulnerable neuronal populations, basal forebrain neurons which provide major cholinergic inputs to the hippocampus and neocortex, areas associated with learning and memory processing, are most severely affected in AD brains. Several lines of experimental approaches indicate that Ab accumulation in the brain may initiate and/or contribute to the process of neuronal loss and thereby development of AD pathogenesis. However, the underlying mechanisms by which Ab-related peptides can induce rather selective neurodegeneration in the AD brain remains unclear. Using a variety of in vitro and in vivo approaches we are currently addressing the physiological role of Ab-related peptides in normal brain and their implications in the degeneration of the basal forebrain cholinergic neurons in AD brains.}

^{B: IGFs in normal brain and their possible implication in AD pathology}

^{Insulin-like growth factors (IGFs) are pleiotropic polypeptides with structural and functional homologies to the hormone insulin. These trophic factors are selectively localized in various brain regions and are considered to play an important role during development by regulating neuronal growth and differentiation. Evidence further suggests that in the adult nervous system these growth factors participate in the maintenance of normal as well as activity-dependent functioning of the brain. The biological responses of IGFs are mediated by interactions with specific receptors i.e., IGF-I and IGF-II, that are differentially regulated during development and following lesion-induced brain injury. We are currently addressing the role of these growth factors in regulation of normal brain functions and their possible involvement in AD pathology.}

^{Our Lab is located at the Room 106 Centre for Prions and Protein Folding Diseases, Environmental Engineering Building, University of Alberta in Edmonton, Alberta}

^{Contact S. Kar}

^{Tel:   (780) 492-9357  (780) 492-9357}

^{Fax: (780) 492-9352}

^{Email: skar@ualberta.ca}

Centre for Prions and Protein Folding Disease (CPPFD)
University of Alberta

Academic Positions

• ^{2009 - present}

^{· Professor}

^{Canada Research Chair (Tier-II)}

^{AHFMR Senior Scholar
Departments of Medicine and Psychiatry, University of Alberta}

• ^{2003 - 2009}

^{· Associate Professor}

^{Canada Research Chair (Tier-II)}

^{AHFMR Senior Scholar
Departments of Medicine and Psychiatry, University of Alberta}

^{· 1997 - 2003}

^{· Assistant Professor}

^{FRSQ Chercheur-Boursier Senior
FRSQ Chercheur-Boursier/Fraser, Monat & McPherson Scholarship}

^{Departments of Psychiatry, Neurology and Neurosurgery, McGill University}

Research Training

• ^{1995 - 1996}
• ^{Research Associate
  Douglas Hospital Research Centre
  McGill University, Montreal}
  
• ^{1990 - 1995}
• ^{Postdoctoral training with Prof. Remi Quirion, PhD
  Douglas Hospital Research Centre, Department of Psychiatry
  McGill University, Montreal}
  
• ^{1986 - 1990}
• ^{PhD in Neurology with Prof. J. M. Polak, DSc, MD
  Hammersmith Hospital, Royal Postgraduate Medical School
  University of London, England}

Selected Publications - Click HERE

Scholarships and Awards

^{· 2008 - 2013}

^{o Canada Research Chair Tier-II}

^{· 2004 - 2010}

^{o AHFMR Senior Scholar}

^{· 2007}

^{o “Basic Science Publication Award” by Dept. of Medicine, Univ. of Alberta}

^{· 2003 - 2008}

^{o Canada Research Chair Tier-II}

^{· 2002}

^{o "Young Investigator Award" by Canadian College of Neuropsychopharmacology}

^{· 2002 - 2006}

^{o Chercheur-Boursier Senior from Fonds de la Recherche en Sante du Quebec (FRSQ)}

^{· 2001 - 2002}

^{o Fraser, Monat and McPherson Scholarship}

^{· 1998 - 2001}

^{o Chercheur-Boursier Junior-II from Fonds de la Recherche en Sante du Quebec (FRSQ)}

^{· 1996 - 1998}

^{o Chercheur-Boursier Junior-I from Fonds de la Recherche en Sante du Quebec (FRSQ)}

^{· 1992 - 1993}

^{o Postdoctoral Fellowship from Fonds de la Recherche en Sante du Quebec (FRSQ)}

^{· 1986 - 1989}

^{o Commonwealth Scholarship for PhD at Hammersmith Hospital, University of London, U.K.}

Teaching

^{· Course Co-Coordinator}

^{o "Neurobiology of Normal Aging and Neurodegenerative Disease" - Neuro-410}

^{· Teaching in Courses}

^{o Neuro-410, Pharmacol-412, Psychiatry-511, Neurology Residents}

^{· Topics}

^{o Brain neurotransmitters and modulators}

^{o Neurobiology of normal aging}

^{o Neurorestoration}

^{o Neurobiology of Alzheimer’s disease}

Current Graduate Students / Postdocs

Ms. A. Amritraj, MSc · Graduate Student (09/2004 - ) · Project o Regulation of central cholinergic and glutamatergic functions by insulin-like growth factor-II receptor. · Contact o Tel:  (780) 492-9297 o Email:  amritraj@ualberta.ca	^Ms. M. Maulik, MSc · Graduate Student (05/2007 - ) · Project o Role of beta-amyloid peptides in the regulation of central cholinergic function · Contact o Tel:  (780) 492-9297 o Email:  madhuka@gmail.com
Mr. B. Ghoshal, MSc · Graduate Student (09/2009 - ) · Project o Role of cholesterol in Alzheimer's disease pathology · Contact o Tel:  (780) 492-9297 o   (780) 492-4222 o Email:  ghoshal@ualberta.ca

Past Graduate Students /Postdocs

Postdoctoral Fellows

^{· Dr. M. Song - postdoctoral fellow 2005 - 2008}

^{· Dr. Z. Wei - postdoctoral fellow  2004 - 2006}

^{· Dr. E. Vaucher - postdoctoral fellow  1998 - 2000}

Ph.D. Students

^{· Ms. C. Hawkes - Ph. D. awarded in 2005      (2000 - 2005)}

^{· Mr. W.H. Zheng - Ph. D. awarded in 2002    (1998 - 2002)}

M. Sc. Students

^{· Ms A. Kodam - M. Sc. (2006 - 2009)}

^{· Ms D. Kabogo - M. Sc. awarded in 2006    (2004 - 2006)}

^{· Ms. S. Jafferali - M. Sc. awarded in 2000     (1997 - 2000)}

Click HERE for Graduate Student and Postdoctoral positions available

^{Selected Recent Publications}

^{28. A. Amritraj, K. Peake, A. Kodam, C. Salio, A. Merighi, J. Vance and S. Kar (2009) Increased activity and altered subcellular distribution of lysosomal enzymes determine neuronal vulnerability Niemann-Pick type C1 deficient mice. Am. J. Pathol. (in press)}

^{27. D. Kabogo, G. Rauw, G. Baker and S. Kar (2009) b-amyloid-related peptides potentiate potassium-evoked glutamate release from adult rat hippocampal slices. Neurobiol. Aging (in press)}

^{26. A. Amritraj, C. Hawkes, A.L. Phinney, H.T. Mount, C.D. Scott, D. Westaway and S. Kar (2009) Altered levels and distribution of IGF-II/M6P receptor and lysosomal enzymes in mutant APP and APP+PS1 transgenic mouse brains. Neurobiol. Aging 30:54-70.}

^{25. Z. Wei, M.S. Song, D. MacTavish, J.H. Jhamandas and S. Kar (2008) Involvement of calpain and caspase in b-amyloid-induced cell death in rat primary septal cultured neurons. Neuropharmacology 54: 721-733.}

^{24. A. Kodam, V. Vetrivel, G. Thinakaran and S. Kar (2008) Cellular distribution of g-secretase subunit nicastrin in the developing and adult rat brains. Neurobiol. Aging 29: 724-738.}

^{23. L. Saavedra, A. Mohamed A, V. Ma, S. Kar and E. Posse de Chaves (2007) Internalization of b-amyloid peptide by primary neurons in the absence of APOE. J. Biol. Chem. 282: 35722-35732.}   

^{22. C. Hawkes, A. Amritraj, R.G. MacDonald, J.H. Jhamandas and S. Kar (2007) Heterotrimeric G proteins and the single transmembrane domain IGF-II/M6P receptor: functional interaction and relevance to cell signaling. Mol. Neurobiol. 35: 329-345.} 

^{21. C. Hawkes, D. Kabogo, A. Amritraj and S. Kar (2006) Up-regulation of cation-independent mannose 6-phosphate receptor and endosomal-lysosomal markers in surviving neurons following 192 IgG-saporin administrations into the adult rat brain. Am. J. Pathol. 169: 1140-1154.}

^{20. C. Hawkes, J.H. Jhamandas, K. Harris, J. Fu, R.G. MacDonald and S. Kar (2006) Single transmembrane IGF-II/M6P receptor regulates central cholinergic function by activating a G protein-sensitive, protein kinase C-dependent pathway. J. Neuroscience 26: 585-596.}

^{19. S. Kar, J. Poirier, J. Geuvara, D. Dea, C. Hawkes, Y. Robitaille and R. Quirion (2006) Cellular distribution of insulin-like growth factor-II/mannose-6-phosphate receptor in normal human brain and its alteration in Alzheimer’s disease pathology. Neurobiol. Aging  27: 199-210.}

^{18. T. Li, C. Hawkes, H.Y. Qureshi, D. Han, S. Kar and H.K. Paudel (2006) Cross-talk between cyclin-dependent protein kinase 5 and glycogen synthase kinase-3b in the brain. Biochemistry 45: 3134-3145.}

^{17. P. Boksa, Y. Zhang, A. Amritraj and S. Kar (2006) Birth insults involving hypoxia produce long-term increases in hippocampal [125I]IGF-I and [125I]IGF-II receptor binding in the rat. Neuroscience 139: 451-462.}

^{16. C. Hawkes, J. Jhamandas and S. Kar (2005) Selective loss of basal forebrain cholinergic neurons by 192 IgG-saporin is associated with decreased phosphorylation of Ser9glycogen synthase kinase-3b. J. Neurochem. 95: 263-272.}

^{15. J.H. Jhamandas, M. Wei, K. Harris, D. MacTavish and S. Kar (2005) Fucoidan inhibits cellular and neurotoxic effects of b-amyloid (Ab) in rat cholinergic basal forebrain neurons. Eur. J. Neurosci. 21: 2649-2659.}

^{14. S. Kar, S.P.M. Slowikowski, D. Westaway and H.T.J. Mount (2004) Beta-amyloid peptide and central cholinergic neurons: functional interrelationships and possible implications in Alzheimer’s disease pathology. J. Psychiat. Neurosci. 29: 427-441.}

^{13. C. Hawkes and S. Kar (2004) The insulin-like growth factor-II/mannose-6-phosphate receptor: structure, distribution and function in the central nervous system. Brain Res. Rev. 44: 117-140.}

^{12. C. Hawkes and S. Kar (2003) Insulin-like growth factor-II/Mannose-6-phosphate receptor: widespread distribution in neurons of the central nervous system including those expressing cholinergic phenotype. J. Comp. Neurol. 458: 113-127.}

^{11. S. Kar (2002) Role of amyloid b peptides in the regulation of central cholinergic function and its relevance to Alzheimer’s disease pathology. Drug Dev. Res. 56: 248-263.}

^{10. W.-H. Zheng, S. Bastianetto, F. Mennicken, W. Ma and S. Kar (2002) Amyloid b peptide induces tau phosphorylation and neuronal degeneration in rat primary septal cultured neurons. Neuroscience, 115: 201-211.}

^{9. D. Seto, W.-H. Zheng, A. McNicoll, B. Collier, R. Quirion and S. Kar (2002) Involvement of GABA in insulin-like growth factor-I mediated inhibition of acetylcholine release from rat hippocampal formation. Neuroscience, 115: 603-612.}

^{8. E. Vaucher, P. Fluit, M.A. Chishti, D. Westaway, H.T.J. Mount and S. Kar (2002) Alteration in working memory but not cholinergic receptor binding sites in transgenic mice expressing human presenilin 1 transgenes. Exp. Neurol. 175: 398-406.}

^{7. C. Hawkes and S. Kar (2002) Insulin-like growth factor-II/Mannose-6-phosphate receptor in the spinal cord and dorsal root ganglia of the adult rat. Eur. J. Neurosci. 15: 33-39.}

^{6. W.-H. Zheng, S. Kar and R. Quirion (2002) Insulin-like growth factor-1-induced phosphorylation of transcription factor FKHRL1 is mediated by phosphatidylinositol 3-kinase/Akt kinase and role of this pathway in insulin-like growth factor-1-induced survival of cultured hippocampal neurons. Mol. Pharmacol. 62: 225-233.}

^{5. E. Vaucher, N. Amount, Rowe W., D. Pearson, J. Poirier and S. Kar (2001) Amyloid b peptide levels and its effects on hippocampal acetylcholine release in aged, cognitively-impaired and -unimpaired rats. J. Chem. Neuroanat. 21: 323-329.}

^{4. P.W. Marinelli, C. Gianoulakis and S. Kar (2000) Effects of voluntary alcohol drinking on [125I]insulin-like growth factor-I, [125I]insulin-like growth factor-II and [125I]insulin receptor binding sites in the mouse hippocampus and cerebellum. Neuroscience, 98: 687-695.}

^{3. S. Jafferali, Y. Dumont, S. Sotty, Y. Robitaille, R. Quirion and S. Kar (2000) Insulin-like growth factor-I and its receptor in the frontal cortex, hippocampus and cerebellum of normal human and Alzheimer’s disease brains. Synapse, 38: 450-459.} 

^{2. W.-H. Zheng, S. Kar and R. Quirion (2000) Insulin-like growth factor 1-induced phosphorylation of the Forkhead family of transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells. J. Biol. Chem. 275: 39152-39158.}

^{1. W.-H. Zheng, S. Kar and R. Quirion (2000) Stimulation of protein kinase C modulates insulin-like growth factor-I (IGF-I) induced Akt activation in PC12 cells. J. Biol. Chem. 275: 13377-13385.}

Current Operating Grants

• Canadian Institutes of Health Research (CIHR)
  
• Natural Sciences and Engineering Council of Canada (NSERC)
  

Establishment Grants

• Alberta Heritage Foundation of Medical Research (AHFMR)
  
• Canadian Foundation for Innovation (CFI)

• ^{Immediate openings for Postdoctoral Fellows with experience in molecular biology (gene cloning, neuronal transfection and routine techniques such as RT-PCR, Northern blotting, RNAse protection assay).  Competitive salaries offered}
• ^{Potential graduate students are always welcome to contact for a possible position in our lab.}

^{Contact S. Kar}

^{Tel:   (780) 492-9357  (780) 492-9357}

^{Fax: (780) 492-9352}

^{Email: skar@ualberta.ca}