Research in our laboratory is focused on Hox genes and transcriptome analysis in the developing, adult, and aged mammalian central nervous system (CNS) to explore the genetic regulation of de novo myelination and remyelination. Myelin insulates the long processes extending from nerve cells (i.e. axons), protecting nerve cells and ensuring fast, efficient nerve impulses. Proper myelination of axons is critical for coordinated movement and cognitive functions (such as memory) although the efficiency of remyelination declines with age. This age-related impairment of remyelination is relevant to cognitive impairments accompanying several neurological disorders, including multiple sclerosis, Alzheimer's disease and dementia, and Parkinson's disease and Huntington’s disease. We are pursuing an integrated study of gene networks that influence myelin stability and repair in the aging brain. Our research lays the groundwork for developing therapeutic approaches to reverse CNS damage caused by several age-related neurodegenerative diseases.

A second important focus of our group is on the role of Hox genes in development, in particular investigating the genetic and epigenetic regulation of craniofacial development.

Research is funded by the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), and the Multiple Sclerosis Society of Canada.

ADDRESS
Neuroscience Research Cluster, GD10
Health Sciences Building
University of Saskatchewan
107 Wiggins Road
Saskatoon, SK S7N 5E5

Dr. Adil Nazarali has been with the University of Saskatchewan since July 1995. He previously worked with Nobel Laureate, Dr. Marshall Nirenberg, at the National Institutes of Health (United States) cloning murine Hox genes. Dr. Nazarali teaches in the areas of Developmental Biology, Pharmaceutical Biotechnology and Toxicology.

Multiple Sclerosis (MS) Disease Modifying Therapy: A Reference Guide for Health Care Professionals

RECENT PUBLICATIONS

  • Lorenz R, Grant E, Muyindike W, Maling S, Card C, Henry C, Nazarali AJ. Caregivers' Attitudes towards HIV Testing and Disclosure of HIV Status to At-Risk Children in Rural Uganda. PLoS One. 2016 Feb 16;11(2):e0148950. Link
  • Hu Y, An Y, Fang N, Li Y, Jin H, Nazarali A, Ji S. The Optimization of Soluble PTEN Expression in Escherichia coli. Open Biochem J. 2015 Aug 21;9:42-8. Link
  • Sadat SM, Saeidnia S, Nazarali AJ, Haddadi A. Nano-pharmaceutical formulations for targeted drug delivery against HER2 in breast cancer. Curr Cancer Drug Targets. 2015;15(1):71-86. Review.
  • Carlson RJ, Doucette JR, Knox K, Nazarali AJ. Pharmacogenomics of interferon-β in multiple sclerosis: what has been accomplished and how can we ensure future progress? Cytokine Growth Factor Rev. 2015 Apr;26(2):249-61.
  • Carlson RJ, Doucette JR, Nazarali AJ. Current developments in pharmacogenomics of multiple sclerosis. Cell Mol Neurobiol. 2014 Nov;34(8):1081-5.
  • Smith TM, Lozanoff S, Iyyanar PP, Nazarali AJ. Molecular signaling along the anterior-posterior axis of early palate development. Front Physiol. 2013 Jan 7;3:488. Link
  • Helal M, Das U, Bandy B, Islam A, Nazarali AJ, Dimmock JR. Mitochondrial dysfunction contributes to the cytotoxicity of some 3,5-bis(benzylidene)-4-piperidone derivatives in colon HCT-116 cells. Bioorg Med Chem Lett. 2013 Feb 15;23(4):1075-8.
  • Wei Z, Gabriel GG, Rui L, Cao X, Pennington PR, Chlan-Fourney J, Nazarali AJ, Baker GB and Mousseau DD. Monoamine oxidase-A physically interacts with presenilin-1 (M146V) in the mouse cortex. J. Alzheimer's Disease 28: 403-422.
  • Ji S, Doucette JR and Nazarali AJ, 2011. Sirt2 is a novel in vivo downstream target of Nkx2.2 and enhances oligodendroglial cell differentiation   Journal of Molecular Cell Biology, 0: 1–9. Link
  • Nazarali AJ, 2011. Marshall Nirenberg 1927-2010. Cellular and Molecular Neurobiology 6:805-807. 
  • Nazarali AJ and Talman WT, 2011. Special Issue on A Tribute to Marshall Nirenberg. Introduction. Cellular and Molecular Neurobiology, 6:803. 
  • Wang Y, Zhang Y, He J, Zhang H, Xiao L, Nazarali A, Zhang Z, Zhang D, Tan Q, Kong J and Li XM, 2011. Hyperforin promotes mitochondrial function and development of oligodendrocytes. Journal of Neurochemistry.  Link
  • Wang JM, Doucette JR and Nazarali AJ, 2011. Conditional Tet-regulated over-expression of Hoxa2 in CG4 cells increases their proliferation and delays their differentiation into oligodendrocyte-like cells expressing myelin basic protein, Cellular and Molecular Neurobiology, 6:875-886. 
  • Elsabahy M, Nazarali A and Foldvari M, 2011. Non-viral nucleic acid delivery: key challenges and future directions Current Drug Delivery 8: 235-244. 
  • Brown, GD and Nazarali, AJ, 2010. Matrix metalloproteinase-25 has a functional role in mouse secondary palate development and is a downstream target of TGF-b3. BMC Developmental Biology 10:93-101. Link  HIGHLY ACCESSED
  • Doucette, JR, Jiao R and Nazarali, 2010. Age-related and cuprizone-induced changes in myelin and transcription factor gene expression and in oligodendrocyte cell densities in the rostral corpus callosum of mice. Cellular and Molecular Neurobiology, 30:607-629. 
  • Zhang B, Wang X and  Nazarali AJ, 2010. Ascorbic acid reverses valproic acid induced inhibition of Hoxa2 and maintains glutathione homeostasis in mouse embryos in culture. Cellular and Molecular Neurobiology, 30:137-148.

Dr. Kendra L. Furber, Research Associate

Kendra joined our lab in September 2013. She holds a BSc in Physiology and BA in Psychology from the University of Saskatchewan. Kendra completed a PhD in neuroscience at the Hotchkiss Brain Institute, University of Calgary investigating lipids and proteins involved in regulated cell secretion. Kendra currently holds an endMS Postdoctoral Fellowship from the Multiple Sclerosis Society of Canada. Her research focuses on cellular and molecular mechanisms underlying myelin degeneration during aging. This work will provide a better understanding of how to prevent myelin damage and promote its repair.

Dennis Okori Okello, Technician

Dennis joined our lab from Kampala, Uganda in September 2012 to pursue graduate studies in Pharmacy. He graduated with a Master's degree in Pharmacy from the University of Saskatchewan in October 2015. His thesis explored the expression profile of Six2 and its role in cell proliferation during early mouse secondary palate development. He has since continued to work in the lab as a technician. Dennis also holds a Bachelor of Pharmacy degree from Uganda.

    

Current Graduate Students

Ran Bi, PhD candidate

  • The Epigenetic Regulation of Hoxa2 Gene Expression

Ran came to our lab from Jiangsu, China in September 2009. She completed her undergraduate degree in China with a major in Marine Pharmacy. In her undergraduate studies Ran took part in the preparation of Anti Human Tumor Necrosis Factor-α Single-Chain variable fragment and analyzed monosaccharide compositions in polysaccharides by high performance liquid chromatography. Ran is currently working on her PhD investigating epigenetic regulation, specifically non-coding RNA and DNA methylation of Hoxa2 gene expression.
   

Paul Pown Raj Iyyanar, PhD candidate

  • Role of Hoxa2 in the osteogenesis of the developing palate

Paul joined our lab as a graduate student in September 2011. He has an MSc in Biotechnology from University of Madras, Chennai, India.  Paul is a PhD candidate and works on characterizing the cellular and molecular mechanisms governing osteogenesis during normal and cleft palate development.

Merlin Thangaraj, PhD candidate

  • Role of Sirt2 gene in myelination and EAE mouse model of multiple sclerosis.

Merlin joined us in September 2011 to pursue her PhD. She received her Masters in zoology (specializing in biotechnology) from Lady Doak College, India. Merlin completed the National Eligibility Test conducted by CSIR –UGC for Lectureship in India and worked as a lecturer. Later she worked as a research scholar in the field of Immunology and Molecular biology. At present Merlin is investigating the role of Sirtuin2 in myelination during development and in the disease severity of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Merlin has received the prestigious University of Saskatchewan International Dean’s Scholarship and currently holds an endMS Doctoral Studentship from the Multiple Sclerosis Society of Canada.

Glaiza Tan, PhD candidate

  • Role of dietary fatty acids in demyelination and remyelination in the central nervous system

Glaiza completed her BSc in Molecular Biology and Biotechnology in 2008, studying neurotoxins of venomous snails and their phylogeny. She then completed her MSc degree in Molecular Medicine, investigating the non-structural proteins of Hepatitis C virus. In 2011, Glaiza worked as a Boston University research scholar with various projects involving the Dual endothelin-1/VEGFsp receptor (DEspR) and its role in cancer, stroke, and cardiovascular diseases. Glaiza joined the lab in September 2015 as a PhD student securing the prestigious University of Saskatchewan Dean’s Scholarship to investigate the role of fatty acids in animal models of multiple sclerosis.​

Former Trainees

  • Rick Lorenz, M.Sc., Caregivers' attitudes towards HIV testing and disclosure of HIV status to at-risk children in rural Uganda
  • Dennis Okello, M.Sc., Six2 exhibits a temporal-spatial expression profile in the developing mouse palate and impacts cell proliferation during murine palatogenesis.
  • Jotham Gan, M.Sc., The Role of QK-5 in CG4 Oligodendrocyte Differentiation
  • Muath Helal, M.Sc. (co-supervised with Dr. J. Dimmock), Investigation of molecular mechanisms of cytotoxic 1,5-diaryl-3-oxo-1,4-pentadienes.
  • Xia Wang, Ph.D., Mechanism of Valproic Acid-induced Dysmorphogenesis via Oxidative Stress and Epigenetic Modifications at the Hoxa2 Gene Promoter
  • Monica Wang, M.Sc., Conditional Regulation of Hoxa2 Gene Expression System in CG-4 Cells
  • Xia Wang, M.Sc., Hoxa2 Gene Function in Palate Development Using a Retroviral Gene Delivery System
  • Danette Rutledge, Ph.D. (co-supervised with JR Doucette), The Role of Hoxa2 in Oligodendrocyte Development
  • Graham Brown, M.Sc., Determination of the Role and Regulation of Matrix Metalloproteinase-25 During Mouse Secondary Palate Formation
  • Tara Smith, Ph.D., The Role of Hoxa2 and characterization of its new downstream targets in murine palatogenesis
  • Rubin Jiao, M.Sc., The Effect of Aging on Myelinating Gene Expression and Oligodendrocyte Cell Densities
  • Jayaum Booth, M.Sc., In Vitro Characterization of Hoxd1 Homeodomain Protein Binding Kinetics to a Region of the Myelin Oligodentrocyte Glycoprotein Promoter
  • Wei Zhang, M.Sc., Temporal and Spatial Expression of Hoxa2 Gene in the Developing Mouse Palate and the Effects of Valproic Acid on Hoxa2 Expression during Murine Palatogenesis
  • Zeynep Akin, Ph.D., Isolation and cloning of in vivo downstream target genes of Hoxa2
  • Louise Wolf, Ph.D., Hoxa2, Hoxd1 and Pax6 in the Developing Murine Brain and Neural Retina
  • Zhengling Hao, M.Sc., Cellular Localization of Hoxa2 Protein During Mouse Development

 POST-DOCTORAL FELLOWS

  • Dr. Shaoping Ji
  • Dr. Ramanan Puthucode
  • Dr. Praveen Kumar