2nd CCBIO-VBP Research Meeting, 2024

The INTPART project is an RCN-supported reinforcement of existing collaborations between CCBIO and Boston Children’s Hospital and Harvard Medical School, following Lars A. Akslen’s collaboration with the Folkman lab since 2004 and later with strong support from the subsequent director of VBP Marsha A. Moses as well as from Bruce Zetter, member of the CCBIO SAB since 2013. Activities are set up to foster stronger integration between excellent teaching and research environments in collaboration with international partners. Lars A. Akslen and Marsha A. Moses (Director, VBP) are the INTPART project leaders. Agnete Engelsen was the main coordinator in Bergen for this meeting, with Michael Rogers as the Boston coordinator. INTPART is the funding mechanism of the collaboration, the Research Council of Norway’s program for International Partnerships for Excellent Education, Research and Innovation.

Some of the speakers during the meeting had to compete with thunder and lightning from the shifting Western Norway weather, not unlike the dramatic surroundings at the scientific eruptions meeting on Iceland in 2019. Nevertheless, indoors the atmosphere was much more welcoming, facilitating great sessions and networking.

Speedtalks mapping out common interests

Following the opening remarks by CCBIO Director Lars A. Akslen, the meeting started with all participants presenting themselves and their research in 3-minute speed talks. This was also done at Iceland and proved a great way to introduce the participants to each other and to map out potential common research interests. The Vascular Biology Program at Boston Children’s Hospital takes an interdisciplinary approach to the study of physiological and pathological processes that are dependent, in some way, on adaptations of the vascular system. They examine the biological processes and search for solutions to the studied diseases, the same way CCBIO researchers study the microenvironment of cancers, including the vascular and neural systems, to find new approaches of cutting the tumor off their supporting mechanisms.

Inspirational stories and intriguing research at the VBP

Main speakers included renowned professors as well as junior scientists presenting their current research. Keynote speaker Timothy Hla, professor of surgery and a vascular biologist trained in molecular biology and biochemistry, shared his inspiring career journey. His laboratory has characterized lipid signaling in endothelial cells focusing on the prostanoid pathway and sphingosine 1-phosphate (S1P) signaling. Hla provided an overview of S1P signaling and discussed his team’s recent work on S1P biology focusing on the vascular system, and their recent efforts to target S1P signaling axis therapeutically to enhance vascular endothelial health. The endothelium was also covered by Associate Professor Hong Chen who explained how recruiting neural stem cells to the endothelium could enhance endothelial resilience.

Endometriosis is one of the VBP research fields and characterized by the presence of “metastatic” endometrium, which forms lesions which can be found throughout the body but are most common in the pelvic or abdominal cavity. This is interesting for a cancer researcher, as it shows “tissue metastasis”, but without a tumor. Epithelial cells in these lesions usually exhibit cancer-associated mutations in a single gene. Postdoc Daniëlle Peterse gave a talk about fatty acid synthesis as a potential target to treat endometriosis, using fatty acid metabolism pathway as potential drug target in cell culture- and animal models for endometriosis. Her colleague Victor Fattori explained how nociceptor neuron to macrophage communication via CGRP/RAMP1 signaling is a driver of endometriosis-associated pain and lesion growth. Dr. Michael S. Rogers’ research relates to the role of angiogenesis in disease pathology, including cancer, corneal neovascularization, and endometriosis, and in his talk, he focused on the insulin PI3 kinase signaling pathway in endometriosis, and how reducing this signaling might reduce pain in endometriosis.

Aram Ghalali’s research at Harvard is focused on drug development targeting childhood brain cancer. He explained how neogenin-1 expression is crucial for invasion and dissemination of diffuse intrinsic pontine gliomas and is altered by the K27M mutation. Joseph Ogbede is designing nanoparticle-based therapeutic strategies for overcoming drug resistance in multiple myeloma. He showed how he aimed at overcoming the major problem with development of drug resistance in multiple myeloma (MM) treatment, by restoring sensitivity to pomalidomide-resistant cells through nanoparticle-mediated delivery of CRBN mRNA.

Other Boston scientists included Lufei Sui, who showed how breast cancer stem cell function is driven by a cleavage-independent non-canonical Notch1 pathway via activation of the p53 superfamily, and Joyce Bischoff (standing inn for Annegret Holm), explained how an endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma. In addition, Edward Smith shared his viewpoint as a neurosurgeon, discussing the potential to supplement — or replace — current antiquated, anatomically-based disease classification systems with a molecular taxonomy, and how molecular genetic data is already informing clinical trials and catalyzing the development of targeted therapies.

CCBIO research and methods

From CCBIO, Dana Costea showed how her group used imaging mass cytometry to reveal distinct subpopulations of cancer associated fibroblasts (CAFs) in oral squamous cell carcinoma, to better understand clinical implications of CAF heterogeneity in clinical samples from large OSCC patient cohorts with FFPE tissues available in diagnostic biobanks. Katrin Kleinmanns explained how her team developed and characterized humanized patient-derived xenograft (PDX) models, comprising of a functional human immune system and an orthotopically implanted primary ovarian cancer tumor and evaluated encouraging immunological targets. Lorena Larios Salazar presented work on development of double-functionalized nanodiamonds (NDs) for targeted treatment to prevent oral cancer recurrence. Agnete Engelsen showed how they apply preclinical models and recently established clinical cohorts to explore how phenotypic plasticity interferes with therapeutic efficacy and immune cell-mediated killing in non-small cell lung cancer. 

Erling A. Hoivik gave an overview of how the Bergen Breast Cancer of the Young Research group at CCBIO is tackling the increased tumor aggressiveness seen among young breast cancer patients. They are investigating the somatic mutational landscape of younger woman with breast cancer, and comparing it to older, using publicly available datasets from The Cancer Genome Atlas (TCGA). Rasmus O.C. Humlevik of the same group presented results indicating that young women showed significantly higher expression of immunosuppressive genes, including CTLA4 and PD1. Their studies demonstrate age-related differences in tumor features and clinical outcomes, arguing for age-dependent treatment and follow-up specifically for the younger patients. Heidrun Vethe from the Akslen group explained studies on how nerves emerge in tumors and potential processes of breast cancer-induced neurogenesis, by complementary use of human tumor tissue and experimental cell models. Kenneth Finne from the same group showed how to combine low-resolution and high-resolution proteomics techniques for discovery and targeted approaches. He presented a study on spatial proteomics where micro-dissected breast cancer stromal tissue from human patients were analyzed by mass spectrometry. Carina Strell explained her group’s work on in situ detection of PD1-PDL1 interaction as a functional predictor for response to immune checkpoint inhibition in non-small cell lung cancer. This offers functional insights and can identify patient subsets likely to benefit from immunotherapy and can enhance the predictive accuracy for patient selection in clinical practice.

The program also included a CCBIO alumna. Silje Kjølle is now in the Erler group at the Biotech Research & Innovation Centre (BRIC), University of Copenhagen, working in precision medicine and development of novel therapies for metastatic cancers. She explained how reduced and insufficient oxygen availability is a tumor microenvironmental condition promoting cancer progression, and how BRIC explores the breast cancer hypoxia responses. Data on secreted proteins from low-grade (luminal-like) and high-grade (basal-like) cell lines were presented, using a mass spectrometry-based proteomics approach, showing distinct hypoxia responses for the luminal-like and basal-like breast cancer subtypes.

Although very diverse backgrounds and research fields, the spectrum of methods and results were highly interesting for all participants. 

“The CCBIO-VBP partnership has been very rewarding over the years” says Lars A. Akslen, CCBIO’s director and a long-time collaborator with the Folkman lab. “With a joint interest in the tumor microenvironment and vascular biology in particular, the complementary nature of this network gives promise for the future.”

A conversation on cancer research futures

One session was dedicated to a discussion on the topic Futures of cancer research and cancer care, with a panel consisting of Marta Bertolaso (Rome), Caroline Engen (Bergen), Jiyeon Kang (London) and Roger Strand (Bergen). This was a looking beyond the slides-kind of conversation between the panelists as much as with the rest of the room, offering philosophical, ethical, societal and economic perspectives. Futures in plural was intentional, pointing to the fact that the future can change in a split second, and the trajectory of science is no more determined than anything else in society. Societal developments shape the future of science and technologies, and what we imagine for the future, may or may not be realized. These kinds of discussions have become an important CCBIO tradition, lifting the view from the microscope and to ethical, economic and social aspects of our research.

Important soft skills

As also is tradition in the CCBIO–VBP meetings, the program included so-called “soft skills” sessions, focusing on other parts of a researcher’s path than the actual research. 

Diane Bielenberg from the VBP focused on the power of mentoring in a career development workshop with tips for both mentor and mentee and discussed the role that each play in a productive laboratory environment. This included building your own “board of advisers” to advance your career, and crafting and utilizing an Individual Development Plan as a roadmap to success for both employees and supervisors. Mentoring, not to be confused with supervision, has increasingly been focused in CCBIO since the CCBIO–VBP collaboration, notably in the Masterclass program.

Yves Aubert from UiB’s Division of Research and Innovation explored how researchers can make their work more relevant, how clinicians can respond more effectively to medical needs, and how centers and institutions may establish infrastructure and support systems to promote their research staff and create impactful outputs. He challenged the audience to take their knowledge to create value, to figure out what purpose it could be for society, showing innovation examples from the UiB. Finally, he gave the floor to the participants themselves, discussing ideas with their row neighbors, leading to a very vibrant session. 

Setting sails together

The design theme from this meeting was maritime, inspired by the common US-Norwegian maritime heritage, by the fjords nearby and the imagery of the two research environments navigating the ship together towards excellence in research, education and innovation. As a reflection, the very last session was a 5-hour trip where the CCBIO/VBP crew sailed the 140-year-old and authentically restored wooden ship Mathilde from Hardanger Fartøyvernsenter. With a lot of heave and hoys, the enthusiastic crew set full sails and steered towards the symbolic great unknown, together. 

“Towards the end of the third day, scientists at sea used the opportunity to reflect on the importance and fun of teamwork — and the necessity of navigation — in science and in life. The meeting again proved the power of personal proximity — with a lot of science to discuss,” Lars A. Akslen concludes.