PhD positions

OPEN POSITION:

Prof. Julia Esser-von Bieren
Department of Immunobiology
Université de Lausanne (UNIL)
Chemin des Boveresses 155
CH-1066 Epalinges

Our research interests:

Our group studies innate effector mechanisms of allergy, asthma and helminth infection. The team is particularly interested in uncovering the roles of eicosanoid lipid mediators and macrophages in type 2 immune responses in asthma, nasal polyposis and helminth infection. A particular focus is the identification and characterization of helminth molecules that regulate type 2 inflammatory diseases. As a second major aim, the team studies innate memory responses as a mechanism of chronic airway diseases. Ultimately, our team’s research is aimed at contributing to new therapeutic strategies to treat chronic airway inflammation.

Recent publications:

1. Hartung F and Esser-von Bieren J (2022). Trained immunity in type 2 immune responses. Mucosal Immunol, Review, in press
2. Lechner A, Henkel FDR, Hartung F, Bohnacker S, Angioni C., Schreiber Y., Alessandrini F., Haimerl P., Ge Y., Thomas D., Kabat A., Pearce E.J., Ohnmacht C., Murray P.J., Chaker A.M., Schmidt-Weber C.B., Esser-von Bieren J (2022). Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma. J Allergy Clin Immunol., S0091-6749(21)02741-X
3. Bohnacker S, Hartung F, Henkel, FDR, Quaranta A, Kolmert J, Priller A, Ud-Dean M, Giglberger J, Kugler LM, Pechtold L, Yazici S, Lechner A, Erber J, Protzer U, Lingor P, Knolle P, Chaker AM, Schmidt-Weber CB, Wheelock CE, Esser-von Bieren J (2022). Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages. Mucosal Immunol., 15(3):515-524.
4. Henkel FDR, Esser-von Bieren J. (2022) Not just "leuko" after all: Epithelial leukotriene production in type 2 immunity, Sci Immunol., 7(67):eabn4876., Review
5. Haimerl P, Bernhard U, Schindela S, Henkel FDR, Lechner A, Zissler UM, Pastor X, Thomas D, Cécil A, Ge Y, Haid M, Prehn C, Tokarz J, Heinig M, Adamski J, Schmidt-Weber CB, Chaker AM, Esser-von Bieren J (2021). Inflammatory macrophage memory in NSAID-exacerbated respiratory disease. J Allergy Clin Immunol., 147(2):587-599.
6. de Los Reyes Jiménez M, Lechner A, Alessandrini F, Schindela S, Trompette A, Haimerl P, Thomas D, Haslbeck M, Henkel FDR, Prazeres da Costa C, Feige MJ, Chaker AM, Dehne N, Brüne B, Nüsing R, Nockher WA, Ohnmacht C, Marsland BJ, Harris NL, Schmidt-Weber CB, Esser-von Bieren J (2020). An anti-inflammatory eicosanoid switch mediates the suppression of type-2 inflammation by helminth larval products. Science Translational Medicine, 12(540)

PhD projects:

Background: We have recently uncovered an inflammatory metabolic and epigenetic reprogramming of macrophages in patients suffering from asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Our results show that this “trained type 2 immunity” program is distinct from classical trained immunity in bacterial or fungal infections.

However, the functions, longevity and mechanisms of “trained type 2 immunity” programs remain poorly defined. In the proposed PhD projects we aim to establish an unprecedented functional and mechanistic framework of innate memory responses in type 2 immunity.

In project 1, we aim to define roles of leukotrienes in trained type 2 immunity: The functions of leukotrienes, which are key inflammatory mediators of asthma, in type 2 specific reprogramming of resident and recruited macrophages will be studied using adoptive transfer experiments or conditional knock-out mice. The crosstalk of leukotriene source and target cells in training of macrophage progenitors will be visualized by novel bone marrow imaging methods.

In project 2, we aim to define the stability and functions of innate memory responses in distinct settings of type 2 immunity: The impact of type 2 training induced by allergens or helminth molecules on type 2 inflammation or anti-helminth host defense will be studied in vivo, e.g. by using adoptive transfer experiments. The stability and longevity of trained cells in the tissue (lung or gut) will be defined by ATAC-Seq, RNA-Seq and metabolomics.

PhD student profile:

• Interest in immune regulation, innate immunity and inflammation

• Interest in work with genetically modified animal models

• Interest in work with patient material and collaboration with clinicians

• Strong background in immunology and molecular biology

• Curious, driven by the need to understand, and goal-oriented

• Good team spirit

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Prof. Monika Hegi
Laboratory of Brain Tumor Biology and Genetics
Neuroscience Research Center and Neurosurgery
Lausanne University Hospital and University of Lausanne (CHUV-UNIL)
Chemin des Boveresses 155
CH-1066 Epalinges

Our research interests:

Our laboratory is at the interface of clinical and basic brain tumor research, with a particular interest to harness epigenetic changes in low and high-grade glioma for new treatment options. Notably, we have established and implemented the promoter methylation status of the DNA repair gene MGMT as the first predictive marker in glioblastoma. Failures of single agent treatments invoke the development of combination therapies for which we use a systems biology approach followed by investigation of respective molecular mechanisms in vitro and in vivo models. Eventually we aim at translating the findings into clinical trials for glioma patients.

Recent publications (in the field of the proposed project):

1. Tancredi A, Gusyatiner O, Bady P, Buri MC, Lomazzi R, Chiesi D, Messerer M, Hegi ME. BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression. Cell Death Dis, 13(12):1037, 2022, doi: 10.1038/s41419-022-05497-y, PMID: 36513631
2. Gusyatiner O, Bady P, Pham MDT, Lei Y, Park J, Daniel RT, Delorenzi M, Hegi ME. BET inhibitors repress expression of Interferon-stimulated genes and synergize with HDAC inhibitors in glioblastoma. Neuro Oncol, 23(10), 1680-1692, 2021. doi: 10.1093/neuonc/noab115, PMID 33987681
3. Kurscheid S, Bady P, Sciuscio D, Samarzija I, Shay T, Vassallo I, van Criekinge W, Daniel RT, van den Bent MJ, Marosi C, Weller M, Mason WP, Domany E, Stupp R, Delorenzi M, Hegi ME. Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma. Genome Biol, 16:16, 2015. PMID: 25622821
4. Gusyatiner O, Hegi ME. Glioma epigenetics: From subclassification to novel treatment options Semin Cancer Biol 51, 50-58, 2018 doi:10.1016/j.semcancer.2017.11.010 PMID: 29170066
5. Bady P, Marosi C, Weller M, Grønberg BH, Schultz H, Taphoorn MJB, Gijtenbeek JMM, van den Bent MJ, von Deimling A, Stupp R, Malmström A, Hegi ME. DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients. Acta Neuropathol Commun, 10(1):39, 2022 doi: 10.1186/s40478-022-01344-5, PMID :35331339
6. Hegi ME, Genbrugge E, Gorlia T, Stupp R, Gilbert MR, Chinot O, Nabors LB, Jones G, Van Criekinge W, Straub J, Weller M. MGMT Promoter methylation cutoff with safety margin for selecting glioblastoma patients into trials omitting temozolomide. A pooled analysis of four clinical trials. Clin Cancer Res 25(6), 1809-1816, 2019 doi: 10.1158/1078-0432.CCR-18-3181 PMID 30514777
7. Cudalbu C, Bady P, Lai M, Xin L, Gusyatiner O, Hamou M-F, Lepore M, Brouland JP, Daniel RT, Hottinger AF, Hegi, ME Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice. Acta Neuropathol Commun, 9 (1) 133, 2021 doi: 10.1186/s40478-021-01232-4, PMID: 34348785

PhD project:

Background: Tumor related epigenetic changes have been associated with aberrant gene expression patterns that affect cancer-relevant pathways. Certain gene expression signatures have been found aberrantly expressed in a subset of glioblastoma. By associating differential gene expression with changes in histone modifications and/or transcription factor binding, we seek to shed light on the epigenetic mechanisms by which these expression signatures are deregulated and how they could be harnessed for novel treatments.

In the project, we aim at identifying druggable pathway vulnerabilities in glioblastoma that are induced by epigenetic drugs: We have obtained differential gene expression profiles of glioblastoma derived spheres, disturbed with an epigenetic drug. This revealed effects on cancer relevant pathways with potentially druggable vulnerabilities that require validation and mechanistic follow-up.The mechanistic underpinnings will be studied in in vitro models using multi-omic approaches to gain insights into regulatory changes of gene expression (RNA-seq) and chromatin structure (ChIP-seq, capture HiC). The potential clinical relevance of the findings will be tested in mouse glioma xenografts.

PhD student profile:

• Interest in genetic and epigenetic deregulation of cancer

• Interest in bioinformatics

• Interest to work with patient material, cell culture, and mouse brain tumor xenograft models

• Strong background cancer biology and molecular biology

• Curious, open to new ideas, and ready to make a difference

• Team player