Dr. Lucie Jeannotte is a regular researcher at the CHU Research Centre of Québec- Université Laval, Oncology Axis, and Professor in the Department of Molecular Biology, Medical Biochemistry and Pathology of the Faculty of Medicine at Université Laval. She is also a regular researcher at the Centre for Cancer Research at Université Laval. Her research aims at understanding the molecular mechanisms involved in the formation of the mammalian embryo with a specific interest for Hox genes. Hox genes encode transcriptional factors that play key roles in the developmental hierarchy leading to pattern formation of the embryo. Loss of Hox gene function in mice results in numerous malformations of skeleton and organs, among others, that can impair survival. The developmental origin of several diseases, including cancers, reveals how important it is to understand the mechanisms that control embryogenesis.

Function of the Hoxa5 gene in the formation of the respiratory system

Lung development implies a coordinated regulation of numerous molecules and factors. The team of Dr. Jeannotte has characterized the Hoxa5 mutant mouse line et revealed the critical and unique role of this gene in survival at birth. The loss of Hoxa5 function cause severe defects of the respiratory system that result in death of the mutants at birth. The malformations mimic pediatric congenital diseases, such as tracheal stenosis, lung hypoplasia and congenital diaphragmatic hernia as well as chronic obstructive pulmonary diseases (COPD), a major cause of death in the human population. Hoxa5 mutant mice thus provide a unique animal model to further study these pathologies. Dr. Jeannotte is interested in identifying the targets of HOXA5 transcriptional factor in the respiratory system in order to define the molecular mechanisms perturbed by the Hoxa5 mutation that underlie the phenotypes observed and may lead to future therapies.

Role of YY1 in the pathogenesis of the pleuropulmonary blastoma

The pleuropulmonary blastoma (PPB) is a rare pediatric lung tumor that arises during fetal life. It results from the progression of abnormal lung cysts to an aggressive sarcoma with poor survival. The team of Dr. Jeannotte has produced mutant mice devoid of Yy1 function in lung epithelium. This mutation causes lung cysts as those seen in PPB patients. YY1 is a transcription factor essential for embryo development and survival. YY1 expression is reduced in PPB lung tumors raising the hypothesis that the loss of Yy1 function is important for PPB pathogenesis. To determine the role and mechanisms of action of YY1 in PPB, Dr. Jeannotte aims at identifying  the mechanisms of action of YY1 in lung formation in order to resolve its implication in PPB formation. These studies may reveal novel molecular targets for the design of effective and innovative therapies and better tools for the diagnosis and prognosis of this severe cancer.

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Mitchel K, Bergmann JM, Brent AE, Finkelstein TM, Schindler KA, Holzman MA, Jeannotte L, Mansfield JH

Hoxa5 Activity Across the Lateral Somitic Frontier Regulates Development of the Mouse Sternum

Journal Article

Front Cell Dev Biol, 10 , 2022.

Abstract | Links:

Holzman MA, Ryckman A, Finkelstein TM, Landry-Truchon K, Schindler KA, Bergmann JM, Jeannotte L, Mansfield JH

HOXA5 Participates in Brown Adipose Tissue and Epaxial Skeletal Muscle Patterning and in Brown Adipocyte Differentiation

Journal Article

Front Cell Dev Biol, 9 , 2021.

Abstract | Links:

Landry-Truchon K, Houde N, Lhuillier M, Charron L, Hadchouel A, Delacourt C, Foulkes WD, Galmiche-Rolland L, Jeannotte L

Deletion of Yy1 in mouse lung epithelium unveils molecular mechanisms governing pleuropulmonary blastoma pathogenesis

Journal Article

Dis Model Mech, 13 (12), 2020.

Abstract | Links:

Vagnozzi AN, Garg K, Dewitz C, Moore MT, Cregg JM, Jeannotte L, Zampieri N, Landmesser LT, Philippidou P

Phrenic-specific transcriptional programs shape respiratory motor output

Journal Article

Elife, 9 , 2020.

Abstract | Links:

Landry-Truchon K, Houde N, Boucherat O, Joncas FH, Dasen JS, Philippidou P, Mansfield JH, Jeannotte L

Correction: HOXA5 plays tissue-specific roles in the developing respiratory system (doi: 10.1242/dev.152686)

Journal Article

Development, 146 (18), 2019.

| Links:

Kanagaratham C, Chiwara V, Ho B, Moussette S, Youssef M, Venuto D, Jeannotte L, Bourque G, de Sanctis JB, Radzioch D, Naumova AK

Loss of the zona pellucida-binding protein 2 (Zpbp2) gene in mice impacts airway hypersensitivity and lung lipid metabolism in a sex-dependent fashion

Journal Article

Mamm Genome, 29 (3-4), 2018.

Abstract | Links:

Holzman MA, Bergmann JM, Feldman M, Landry-Truchon K, Jeannotte L, Mansfield JH

HOXA5 protein expression and genetic fate mapping show lineage restriction in the developing musculoskeletal system

Journal Article

Int J Dev Biol, 62 (11-12), 2018.

Abstract | Links:

Gofflot F, Jeannotte L, Rezsohazy R

A scientific journey in the garden of the Hox genes: an interview with Jacqueline Deschamps

Journal Article

Int J Dev Biol, 62 (11-12), 2018.

Abstract | Links:

Gofflot F, Jeannotte L, Rezsohazy R

Four decades of Hox gene investigation and many more to go

Journal Article

Int J Dev Biol, 62 (11-12), 2018.

Abstract | Links:

Clemenceau A, Boucherat O, Landry-Truchon K, Lamontagne M, Biardel S, Joubert P, Gobeil S, Secco B, Laplante M, Morissette M, Obeidat M, Timens W, Jeannotte L, Bossé Y

Lung cancer susceptibility genetic variants modulate HOXB2 expression in the lung

Journal Article

Int J Dev Biol, 62 (11-12), 2018.

Abstract | Links:

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Active projects

  • Deciphering the role of the Yin Yang1 (YY1) transcription factor to understand pleuropulmonary blastoma, from 2020-04-01 to 2025-03-31
  • Understanding how the master transcriptional regulator HOXA5 defines cell fate in the developing embryo, from 2020-04-01 to 2025-03-31
  • Understanding the context-dependent roles of HOXA5 in cell fate and patterning, from 2020-08-01 to 2023-07-31

Recently finished projects

  • Characterization of the role of the Yin Yang1 (YY1) transcription factor in pleuropulmonary blastoma, from 2019-09-01 to 2021-08-31
Data provided by the Université Laval research projects registery