The research projects of PhD students participating in the Cell Migration program deal with questions related to

A) cell migration in immunosurveillance and inflammation
B) cell migration in tumorigenesis and metastasis
C) the influence of soluble Factors in cell migration.

A) Cell migration in immunosurveillance and inflammation

Mounting a specific immune response requires the timely interaction of various immune cell types within secondary lymphoid organs. Studies on the regulation and function of homing receptors in T lymphocytes and on how these receptors orchestrate cell positioning and interactions with other immune cells in secondary lymphoid tissues are central to our understanding of immune responses. Several PhD projects are dedicated to study immune cell migration into peripheral organs with a strong focus on the central nervous system (CNS) in the context of immunosurveillance and inflammation in experimental autoimmune encephalomyelitis (EAE), as a model for multiple sclerosis, in particular studies on the cellular and molecular cues guiding T cell subsets across the epithelial blood-cerebrospinal fluid barrier (BCSFB) and the multistep T cell interactions with the inflamed blood-brain barrier (BBB) during EAE as well as detailed analysis of the phenotype, function and chemokine receptor expression in autoreactive T cells in MS patients.

Completed PhD thesis within this frame

Mariana Castro Dias (October 2019, Group Britta Engelhardt, TKI)
The role of the brain-barrier tight junctions in neuroinflammation
Best Thesis of the Graduate School for Cellular and Biomedical Sciences, University of Bern, 2019

Luca Marchetti (December 2019, Group Britta Engelhardt, TKI)
Combining live cell imaging and RNA-seq analysis to unveil cellular and molecular mechanisms directing T-cell migration across the blood-brain barrier

Miguel Palomino (30th October 2019, Group Santiago F. González, IRB Bellinzona)
Role of Innate Immunity in the Protection against Influenza Infection

Flavian Thelen, Graduation March 28, 2018 (Group Stein TKI)
Tissue resident memory T cell surveillance of exocrine gland is guided by three dimensional macrophage scaffold

Miguel Palomino Segura, Graduation October 30, 2018 (Group Santiago F. González, IRB Bellinzona)
Role of Innate Immunity in the Protection against Influenza Infection

Karthik Sathiyanadan; Graduation January 30, 2014 (Group Engelhardt TKI)
In vivo analysis of the multistep-recruitment of different leukocyte subpopulations across the blood-brain-barrier: molecular cues beyond

Michael Abadier; Graduation September 12, 2014 (Group Lyck TKI)
Cell surface levels of endothelial ICAM-1 decide on transcellular or paracellular T cell diapedesis across the blood-brain barrier.

Markus Ackerknecht; Graduation December 10, 2014 (Group Stein TKI)
In vivo analysis of motility-inducing factors governing CD4+ T cell migration and activation.

Neda Haghayegh; Graduation November 20, 2015 (Group Engelhardt TKI)
Involvement of ICAM-1 and ICAM-2 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE)

Ivana Lazarevic; Graduation November 20, 2015 (Group Engelhardt TKI)
T cell trafficking across the blood cerebrospinal fluid barrier.

Aleksandra Ozga; Graduation December 15, 2015 (Group Stein TKI)
The Impact of pMHC Affinity on Differentiation and Expansion of CD8+ T Cells.

Stephanie Uster, Graduation March 2, 2016 (Groups Engelhardt TKI & Seitz Inselspital Bern)
Effects of anti-TNFα therapy on the distribution of osteoclast precursors in a murine antigen induced arthritis model.

Wypych Thomasz; Graduation March 21, 2016 (Group Sallusto IRB)
The role of B cells as antigen presenting cells in a mouse model of asthma.

Xenia Ficht, Graduation January 22, 2018 (Group Stein TKI) 
Mechanisms underlying tissue-resident memory T cell surveillance of non-lymphoid tissues

Yağmur Farsakoğlu, Graduation January 26, 2018 (Group Santiago F. González, IRB Bellinzona)
Role of Innate Immune Cells in Response to Influenza Vaccination

B) Cell migration in tumorigenesis and metastasis

Malignant cell transformation is the result of the accumulation of multiple genetic and epigenetic cell-autonomous events leading to uncontrolled cell proliferation and survival. Transformed cells, however, require support from the surrounding normal tissue (i.e. the tumor microenvironment) in order to progress to life-threatening invasive and metastatic cancers. The tumor microenvironment is mainly composed of cancer-associated fibroblasts, angiogenic blood and lymphatic endothelial cells, immune, inflammatory and bone marrow-derived cells (BMDC) and newly deposited or modified extracellular matrix. Cell migration is key to many events of cancer progression. Tumor cells acquire migratory and invasive capacities during transformation and migration is necessary for metastatic spreading; angiogenic endothelial cells migrate toward the growing tumors, and immune, inflammatory and BMD-cells migrate to primary tumors and metastatic sites. These PhD projects address important aspects of cancer research involving cell migration.

Completed PhD thesis within this frame

Christoph Wyss; Graduation February 2, 2016 (Group Rüegg UNIFR)
Mechanisms of migration of brain metastatic cells across the blood-brain barrier

Marina Treines-Fertig, Graduation July 11, 2016 (Group Bourquin UNIFR/UNIGE)
Immunotherapy of gastric cancer: Enhancing T cell recruitment into tumor.

Thibaud Spinetti; Graduation March 31, 2017 (Group Bourquin UNIFR/UNIGE)
The role of TLR-mediated activation of myeloid-derived suppressor cells (MDSC) on their ability to migrate into tumors.

C) Role of chemokine receptors and soluble factors in cell migration

Cell migration is fundamental to immunosurveillance and inflammation but also to tumor invasion and metastatic dissemination. Chemokines and their receptors play a central role in positioning both immune and tumor cells within the organism. Chemokines are endogenous molecules that control the migration of circulating cells by making them move across the vascular wall and along surface-bound chemokine gradients to their destination. In the immune system, this is relevant to the recirculation of lymphocytes through lymphatic tissues as well as to the recruitment of leukocytes to tissues during acute or chronic inflammation. In cancer, in addition to migration, chemokines also promote tumor cell proliferation and survival.
These PhD projects address the roles of chemotactic factors and their cognate receptors in myeloid, lymphoid and tumor cell migration:

Completed PhD thesis within this frame

Rafet Ameti (July 2019, Group Marcus Thelen, IRB Bellinzona)
Role of ACKR3 in leukocyte migration and the microarchitecture of mouse spleen

Sabrina Casella (August 2019, Group Macrus Thelen, IRB Bellinzona)
The biochemistry of ACKR3 and its role in diffuse large B cell lymphoma

Barbara Jakobs (December 2019, Group Daniel Legler, Biotechnology Institute Thurgau)
Engineering of Nanobodies for the Human Chemokine Receptor CCR7

Egle Radici; Graduation May 25, 2018 (Group Thelen IRB)
Functional expression of the scavenger ACKR3 on B Lymphocytes of Secondary Lymphoid Organs

Viola Puddinu; Graduation December 13, 2016 (Group Thelen IRB)
Role of the Atypical Chemokine Receptor 3 in Diffuse Large B Cell Lymphoma

Lorenzo Spagnuolo; Graduation January 2017 (Group Bourquin UNIFR/UNIGE)
Enhancing T cell recruitment into tumors through synergy between soluble mediators