Laboratory of Molecular Cell Biology

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About Our Lab

The research in our lab is focused on the analysis of homeobox (Hox) genes in the developing mammalian embryo primarily in the eye, palate and myelinating glia of the central nervous system. We are exploring the genetic regulation of myelination, remyelination in normal and aged models as well as looking at epigenetic factors in drug-induced teratogenicity and changes in gene expression. We are also studying the genetic regulation of palatal abnormalities such as cleft palate.

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

ADDRESS:
Room 215-110 Science Place
Thorvaldson Building
University of Saskatchewan
S7N 5C9

About Our Lab Intro Image

Dr. Adil J. Nazarali

Dr. Adil J. Nazarali

Dr. 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.

phone: 306-966-6334
e-mail: adil.nazarali@usask.ca

Multiple Sclerosis (MS) Disease Modifying Therapy
A Reference Guide for Health Care Professionals 
(Click to open PDF)

RECENT PUBLICATIONS:

  1. Helal M, Das U,  B. 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. Medicinal Chem. Lett. (in press)
  2. 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.
  3. 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.
  4. Nazarali AJ, 2011. Marshall Nirenberg 1927-2010. Cellular and Molecular Neurobiology 6:805-807. 
  5. Nazarali AJ and Talman WT, 2011. Special Issue on A Tribute to Marshall Nirenberg. Introduction. Cellular and Molecular Neurobiology, 6:803. 
  6. 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, doi: 10.1111/j.1471-4159.2011.07433. 
  7. 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. 
  8. Elsabahy M, Nazarali A and Foldvari M, 2011. Non-viral nucleic acid delivery: key challenges and future directions Current Drug Delivery 8: 235-244. 
  9. 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. 
  10. 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. 
  11. 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. 
  12. Smith TM, Wang X, Zhang B, Kulyk W and Nazarali AJ, 2009.  Hoxa2 plays a direct role in murine palate development. Developmental Dynamics, 238: 2364-2373. 
  13. Ji L, Nazarali AJ and Paterson PG, 2008.  Protein-Energy Malnutrition Increases Activation of Transcription Factor, Nuclear Factor Kappa B, in Gerbil Hippocampus Following Global Ischemia. Journal of Nutritional Biochemistry, 19: 770-777. 
  14. Nicolay DJ, Doucette JR and Nazarali AJ, 2007.  Transcriptional Control of Oligodendrogenesis, GLIA, 55: 1287-1299. 
  15. Booth J, Nicolay DJ, Doucette JR and Nazarali AJ, 2007.  Hoxd1 is Expressed by Oligodendroglial Cells and Binds to a Region of the Human Myelin Oligodendrocyte Glycoprotein Promoter In Vitro. Cellular and Molecular Neurobiology, 27: 641-650. 
  16. Nazarali AJ, Zhang B and Wang X, 2007.  Effect of Valproic Acid on Glutathione Homeostasis in Mouse Whole Embryo Cultures. Proceedings of SECOTOX, 1:61-66. 
  17. Wang X, Zhang W and Nazarali AJ, 2007.  Toxic Effects of Valproic Acid on Mouse Palatal Development In Vitro, Proceedings of SECOTOX, 1: 139-144. 
  18. Nicolay DJ, Doucette JR and Nazarali AJ, 2006.  Transcriptional Regulation of Neurogenesis in the Olfactory Epithelium, Cellular and Molecular Neurobiology, 26: 803-821. 
  19. Akin Z and Nazarali AJ, 2005.  Hox Genes and their Candidate Downstream Targets in the Developing Central Nervous System, Cellular and Molecular Neurobiology, 25: 697-741. 
  20. Nicolay D, Doucette JR and Nazarali AJ, 2004.  Early stages of Oligodendrocyte Development in the Embryonic Murine Spinal Cord proceed normally in the absence of Hoxa2 GLIA: 48: 14-26. 
  21. Nicolay D, Doucette JR and Nazarali AJ, 2004.  Hoxb4 in Oligodendrogenesis, Cellular and Molecular Neurobiology, 24: 357-366.
  22. Anderson PL, Doucette JR and Nazarli AJ, 2003. A Novel Method of Eliminating Non-neuronal Proliferating Cells from Cultures of Mouse Dorsal Root Ganglia, Cellular and Molecular Neurobiology, 23: 205-210.

Our Staff

Photo of LaRhonda Sobchishin

LaRhonda Sobchishin, Senior Research Technician

Phone:306-966-6357
e-maillkd447@mail.usask.ca


LaRhonda Graduated with distinction from the Biotechnology Program at SIAST Kelsey campus in Saskatoon and has since been active in the research community in Saskatoon. LaRhonda joined our lab in 2004 and has since become a valued member of our Lab family. LaRhonda's main research focus is the development of new in-vitro models for studying early murine myelination in neonatally leathal transgenic mouse lines. If we can understand the normal process of myelination, perhaps we can better devise strategies for fighting diseases such as Multiple Sclerosis. LaRhonda is also developing methods for culturing adult brain tissue as an in-vitro model for drug screening and experimental treatments. The ability to take these experiments ex-vivo will greatly reduce many experimental factors such as time and costs of housing for in-vivo treatments. LaRhonda also manages the lab and trains new lab members.

Graduate Studies

CURRENT GRADUATE STUDENTS:

Photo of Ran Bi  

Ran Bi

Project: The Epigenetic Regulation of Hoxa2 Gene Expression by miRNA

Ran came to our lab from Jiangsu, China in September 2009. She completed her undergraduate degree in China in 2009 with a major in Marine Pharmacy. In her undergraduate studies she 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 M.Sc looking at the Epigenetic Regulation of Hoxa2 Gene Expression by miRNA.

     
Joatham Gan  

Jotham Gan

Project: The Role of QK-5 in CG4 Oligodendrocyte Proliferation and Differentiation

Jotham received his B.Sc. (Honors) from the University of Saskatchewan working on cloning the heat shock protein in Zebra fish he joined our lab in September 2008 to pursue his M.Sc. looking at the role of Quaking gene in oligodendrocyte development.

        
Muath Helal

Muath Helal

Thesis Title: Effects of Valproic acid on mitochondrial function and embryo development

Muath earned a degree in Pharmacy in 2007 and later came to the University of Saskatchewan to gain his Masters studying  the design and testing of new agents for cancer therapy.  Muath joined our lab in 2012 to pursue his Ph.D. Currently he is studying the effect of valproic acid on embryo development and mitochondrial function. 

     
Paul Iyyanar

Paul Iyyanar

Thesis Title: The role of proteases in TGF-β/BMP signaling pathway for secondary palate fusion and development.

Paul joined our lab as a graduate student in September 2011. After completing Masters in Biotechnology, Paul worked for two years as a Junior Research Fellow in protein separation and mass spectrometry. His Masters thesis was on genetic analysis using Mitochondrial and Y- Chromosome markers to study the ancestry of on an ethnic population in Tamil Nadu, India.  

        
Dennis Okello

Dennis Okello

Thesis title: The role of Six2 in palatogenesis

Dennis came to our lab from Kampala, Uganda in September 2012. Dennis has a BSc in pharmacy and is currently pursuing his M.Sc. investigating the role of Six2 gene in normal and abnormal palate development, ossification and fusion.

        
Merlin Thangaraj

Merlin Thangaraj

Thesis Title:  Role of Sirt2 in myelinogenesis, cholesterol biosynthesis and aging

Merlin joined us in September 2011 to pursue her PhD. Her Masters dissertation was on anti-hepatotoxic effect of Citrus Limon on hepatotoxicity. She completed the National Eligibility Test conducted by CSIR –UGC for Lectureship. Later she worked as a research scholar in the field of Immunology and Molecular biology. At present she is investigating the role of Sirtuin2 in myelination and the aging brain.

        
Xia Wang  

Xia Wang

Project: Mechanism of Valproic Acid-induced Dysmorphogenesis via Oxidative Stress and Epigenetic Modifications at the Hoxa2 Gene Promoter

Upon finishing her M.Sc. with Dr.Nazarali, Xia started a PhD in May 2006. Xia is looking at VPA-induced teratogeneicity in mouse whole embryo culture in vitro through VPA induced oxidative stress, and is investigating the underlying mechanisms of VPA associated epigenetic regulation at one developmental gene (Hoxa2 gene).

     

FORMER GRADUATE STUDENTS:

Monica Wang

Thesis Title: Molecular Cloning and Expression Analysis of Homeobox (Hox) Genes in CG4 Oligodendroglial Cells

Monica graduated from Sun-Yat-Sen University with a B.Sc and joined our lab in 2003. Monica looked at the effects of upregulation of the Hoxa2 gene in an oligodendroglial cell line (CG4). After finishing her M.Sc., Monica worked at VIDO in Saskatoon, she is now working as a research assistant at a biotech company in Edmonton.

 

Danette Rutledge

Thesis title: The Role of Hoxa2 in Oligodendrocyte Development

Danette graduated with a Bachelor of Pharmacy from the University of Saskatchewan and went on to pursue a PhD with Dr.Nazarali. Danette looked at the role of Hoxa2 in the development of oligodendrocyte cells (myelinating glia in the central nervous system). After finishing her PhD, Danette moved to the Cleveland Clinic to continue her research in the area of oligodendrocyte development.

 

Graham Brown

Project: The Role and Regulation of Matrix Metalloproteinase-25 in Mouse Secondary Palate Development

Graham received a B.Sc. (Honors) from the University of Regina. His honors project involved working on thyroid hormone receptors in lamprey. Graham joined our lab in August 2006 to look at the role of matrix metalloproteinase-25 in the development of the murine secondary palate. Graham successfully defended his M.Sc. thesis in July 2009 and has moved on to the University of Connecticut to pursue his PhD.

 

Tara Smith

Project: The Role of Hoxa2 and Characterization of its New Downstream Targets in Murine Palatogenesis

Tara received a B.Sc. (Honors) from the University of Regina in 2004. Her honors project involved cloning the thyroid hormone binding protein Transthyretin in the sea lamprey. Tara joined our lab in September 2004 where she looked at the role of Hoxa2 in the development of the murine palate. Tara successfully defended her PhD thesis in September 2009 and has moved on to a post doctoral fellowship at Freedom Pharma in Saskatoon.

 

Rubin Jiao

Project: The Effect of Aging on Oligodendrocyte Remyelination

Rubin came to our lab from China in 2005. He will be defending his masters thesis late 2009 and then hopes to pursue a PhD.