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   Barbara
    

Barbara Hales, Ph.D.

Professor

McGill University

Pharmacology and Therapeutics

McIntyre Building, room 110

3655 Promenade Sir William Osler

Montreal, QC

H3G 1Y6

Phone: 514-398-3610

Fax: 514-398-7120

Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Website: http://www.medicine.mcgill.ca/pharma/haleslab/

 

Field of research:  

Developmental and Reproductive Toxicology

Resume of recent results:

Birth defects occur in 2-4% of the children in North America, yet the causes of most of these malformations remain unknown. The overall goal of our research is to elucidate the mechanisms(s) underlying the developmental toxicity of environmental chemicals and drugs. We use a combination of in vivo, in vitro, and molecular approaches to elucidate the effects of model teratogens on signaling pathways that play important roles in normal development. In collaboration with Bernard Robaire, we are exploring the consequences of paternal exposure to anticancer agents on male germ cell integrity and on epigenetic programming in early embryos. Finally, we are working with teams of researcher to evaluate the impact of exposure to “green” replacement plasticizers on the developing and adult testis and to determine the effects of chronic exposure to the environmentally relevant mixture of brominated flame retardants found in North American house dust on reproduction and development.

Lab Members: 

Name

Position

Email address

Nazem El Husseini

PhD Student

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Ghalib Bardai

PhD Student

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Han Yan

PhD student

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Publications (Selected recent publications):

 

  1. Delbès G, Hales BF, Robaire B. Toxicants and human sperm chromatin integrity. Mol Hum Reprod. 2010 16:14-22.
  2. O'Flaherty C, Hales BF, Chan P, Robaire B. Impact of chemotherapeutics and advanced testicular cancer or Hodgkin lymphoma on sperm deoxyribonucleic acid integrity. Fertil Steril. 2010 94:1374-9.
  3. Delbès G, Vaisheva F, Luu T, Marcon L, Hales BF, Robaire B. Reversibility of the Effects of the Chemotherapeutic Regimen for Non-Hodgkin Lymphoma, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone, on the Male Rat Reproductive System and Progeny Outcome. Reprod Toxicol. 2010 29:332-28.
  4. Grenier L, Robaire B, Hales BF. Paternal Exposure To Cyclophosphamide Affects The Progression of Sperm Chromatin Decondensation And Activates A DNA Damage Response In The Pre-Pronuclear Rat Zygote. Biol Reprod. 2010 83:195-204.
  5. Marcon L, Zhang X, Hales BF, Nagano MC, Robaire B. Development of a Short-term Fluorescence-based Assay to Assess the Toxicity of Anticancer Drugs on Rat Stem/Progenitor Spermatogonia in vitro. Biol Reprod. 2010 83: 228–37.
  6. Schlisser AE, Yan J, Hales BF. Teratogen-Induced Oxidative Stress Targets Glyceraldehyde-3-Phosphate Dehydrogenase in the Organogenesis Stage Mouse Embryo. Toxicol Sci.2010 118: 686-95.
  7. Marcon L, Zhang X, Hales BF, Robaire B, Nagano MC. Effects of Chemotherapeutic Agents for Testicular Cancer on Rat Spermatogonial Stem/Progenitor Cells. J Androl. 2011 32:432-43.
  8. Hales BF, Grenier L, Lalancette C, Robaire B. Epigenetic Programming: From Gametes to Blastocyst. Birth Defects Res A Clin Mol Teratol. 2011 91:652-65.
  9. Bardai GK, Hales BF, Sunahara GI. The Developmental Toxicity of Glyceryl Trinitrate in Quail Embryos. Birth Defects Res A Clin Mol Teratol. 2011 91:230-40.
  10. Grenier L, Robaire B, Hales BF. Paternal Cyclophosphamide Exposure Induces The Formation Of Functional Micronuclei During The First Zygotic Division. PLOS One. 2011. 6:e27600.
  11. O’Flaherty CM, Chan PT, Hales BF, Robaire B. Sperm chromatin structure components are differentially repaired in cancer survivors. J Androl. 2012 33:629-636.
  12. Ernest SR, Wade MG, Lalancette C, Ma YQ, Berger RG, Robaire B, Hales BF. Effects of Chronic Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants on the Reproductive and Thyroid System in Adult Male Rats. Toxicol Sci. 2012 127:496-507.
  13. Maselli J, Hales BF, Chan P, Robaire B. Exposure to Bleomycin, Etoposide, and Cis-platinum Alters Rat Sperm Chromatin Integrity and Sperm Head Protein Profile. Biol Reprod. 2012 86:166, 1-10.
  14. Grenier L, Robaire B, Hales BF. The Activation of DNA Damage Detection and Repair Responses in Cleavage Stage Rat Embryos by a Damaged Paternal Genome. Toxicol Sci. 2012 127:555-566.
  15. Paradis FH, Huang C, Hales BF. The Murine Limb Bud In Culture As An In Vitro Teratogenicity Test System. Methods Mol Biol. 2012 889:197-213.
  16. Huang C, Hales BF. Effects of the Exposure to a DNA Damaging Agent on the Hypoxia Inducible Factors in Organogenesis Stage Mouse Limbs. PLoS One. 2012 7(12):e51937. doi: 10.1371/journal.pone.0051937.
  17. Paradis FH, Hales BF. Exposure to Valproic Acid Inhibits Chondrogenesis and Osteogenesis in Mid-Organogenesis Mouse Limbs. Toxicol Sci. 2013 131(1):234-241.
  18. Delbes DG, Chan D, Hales BF, Trasler J, Robaire B. Selective Induction Of Glutathione S-Transferases In Round Spermatids From The Brown-Norway Rat By The Chemotherapeutic Regimen For Testicular Cancer. Reprod Toxicol. 2013 36:24-32.
  19. Banh S, Hales BF. Hydroxyurea Exposure Triggers Tissue Specific Activation of p38 Mitogen-Activated Protein Kinase Signaling and the DNA Damage Response in Organogenesis Stage Mouse Embryos. Toxicol Sci. 2013 133(2):298-308.
  20. Bardai GK, Hales BF, Sunahara GI. Glyceryl trinitrate metabolism in the quail embryo by the glutathione S-transferases leads to a perturbation in redox status and embryotoxicity. Comp Biochem Physiol B. 2013 165(3):153-164.
  21. Schlisser A, Hales BF. Deprenyl Enhances the Teratogenicity of Hydroxyurea in Organogenesis Stage Mouse Embryos. Toxicol Sci. 2013 134(2):391-399.
  22. Maselli J, Hales BF, Chan P, Robaire B. The Effects of Chemotherapy with Bleomycin, Etoposide, and Cis-Platinum (BEP) on Rat Sperm Chromatin Remodeling, Fecundity and Testicular Gene Expression in the Progeny. Biol Reprod. 2013. 89(4):85. doi: 10.1095/biolreprod.113.110759.
  23. Kichine E, Di Falco M, Hales BF, Robaire B, Chan P. Analysis of the Sperm Head Protein Profiles in Fertile Men: Consistency Across Time in the Levels of Expression of Heat Shock Proteins and Peroxiredoxins. PLoS One. 2013 8(10):e77471. doi: 10.1371/journal.pone.0077471.
  24. Liu M, Hales BF, Robaire B. Effects of four chemotherapeutic agents, bleomycin, etoposide, cisplatin, and cyclophosphamide, on DNA damage and telomeres in a mouse spermatogonial cell line. Biol Reprod. 201490(4):72.
  25. Berger RG, Lefèvre PL, Ernest SR, Wade MG, Ma YQ, Rawn DF, Gaertner DW, Robaire B, Hales BF. Exposure to an environmentally relevant mixture of brominated flame retardants affects fetal development in Sprague-Dawley rats. Toxicology. 2014 320:56-66.
  26. Dayan C, Hales BF. Effects of ethylene glycol monomethyl ether and its metabolite, 2-methoxyacetic acid, on organogenesis stage mouse limbs in vitro. Birth Defects Res B Dev Reprod Toxicol. 2014 101(3):254-61.
  27. Poon S, Wade MG, Aleksa K, Rawn T, Carnevale A, Gaertner DW, Sadler A, Breton F, Koren G, Ernest S, Lalancette C, Robaire B, Hales BF, Goodyer CG. Hair as a Biomarker of Exposure to Polybrominated Diphenyl Ethers (PBDEs). Environ Sci Technol. 2014. (In Press).
  28. Bigaeva E, Paradis FH, Moquin A, Hales BF, Maysinger D. Assessment of the developmental toxicity of nanoparticles in an ex-vivo 3D model, the murine limb bud culture system. Nanotoxicology. 2015 9:780-791.
  29. Paradis FH, Hales BF. Valproic Acid Induces the Hyperacetylation of P53, the Expression of P53 Target Genes and Markers of the Intrinsic Apoptotic Pathway in Mid-Organogenesis Murine Limbs. Birth Defects Res B Dev 2015 104(5):177-183. doi: 10.1002/bdrb.21149.
  30. Paradis FH, Hales BF. The Effects of Class-Specific Histone Deacetylase Inhibitors on the Development of Limbs During Organogenesis. Toxicol Sci. 2015 148(1):220-228. doi: 10.1093/toxsci/kfv174.
  31. Liu M, Maselli J, Hales BF, Robaire B. The Effects of Chemotherapy with Bleomycin, Etoposide, and Cis-Platinum (BEP) on Telomeres in Rat Male Germ Cells. Andrology. 2015 Oct 7. doi: 10.1111/andr.12102.
  32. Lefèvre PLC, Berger RG, Ernest SR, Gaertner DW, Rawn DFK, Wade MG, Robaire B, Hales BF. Exposure of Female Rats to an Environmentally-Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis. Biol Reprod. In press. pii: biolreprod.115.134452.

 

Books or book chapters

  1. Hales B, Robaire B. Can spermatozoa be targets for drugs? If so, what are the consequences of such drug exposures? Is there a need for pre-conception counseling for men? In: Robaire B, Chan P, eds. Handbook of Andrology, 2nd ed. The American Society of Andrology. Lawrence, Kansas, 2010.
  2. Hales BF, Robaire B. The Male Germ Cell as a Target for Toxicants. In: McQueen CA, ed. Comprehensive Toxicology, 2nd ed. Vol. 11. Oxford: Elsevier, 2010. p.115-29. Reproductive and Endocrine Toxicology. Richburg JH, Hoyer PB, eds.
  3. Hales B, Scialli A, Tassinari M, editors. Teratology Primer, 2nd ed. Teratology Society, 2010
  4. Robaire B, Hales BF. What are the possible consequences of pre-conception germ cell exposures on pregnancy outcome? In: Hales B, Scialli A, Tassinari M, eds. Teratology Primer, 2nd ed. Teratology Society. 2010. p. 6-8.
  5. Hales BF. Can in vitro methods contribute to the identification of teratogenic exposures? In: Hales B, Scialli A, Tassinari M, eds. Teratology Primer, 2nd ed. Teratology Society. 2010. p. 40-2.
  6. Hales BF, Robaire B. Paternally-Mediated Effects On Development. In: Developmental and Reproductive Toxicology, a practical approach. (R.D. Hood, ed., 3rd edition) Informa Healthcare, New York, NY, 2012. pp. 76-92.
  7. Hales BF, Robaire B. The Male Germ Cell as a Target for Toxicants. In: Reference Module in Biomedical Sciences. Elsevier. 17-Oct-2014 doi:10.1016/B978-0-12-801238-3.02138-3.

 

Awards :

  • James McGill Professor, 2011-2018
  • Society of Toxicology of Canada Award of Distinction, 2008                 
  • Faculty Honour List for Educational Excellence, 2002
  • Medical Research Council Scholar (1981-86)