Linda-Gail Bekker: Mentorship is critical for anyone in STEM.

Linda-Gail Bekker is a professor, chief executive officer of the Desmond Tutu HIV Foundation, and director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. Her research interests include HIV treatment and prevention and tuberculosis, and she is active in developing community projects to promote education and research. We talked to Linda-Gail about her career, the importance of mentorship, and how rewarding it is to collaborate, mentor, and uplift other scientists.

Irene Salinas: The joy of continuous growth and learning.

Irene Salinas is a professor in the Department of Biology, University of New Mexico. Her lab uses multiple animal models to study nasal immunity and neuroimmune interactions in the olfactory-central nervous system axis in response to microorganisms. We recently spoke with Irene about her current work, her diversity, equity, and inclusion (DEI) work, and how her leadership style has changed over the years.

Xiaoyu Hu: Let the data guide you.

Xiaoyu Hu is a professor and director of the Institute for Immunology at Tsinghua University. Her lab is interested in understanding the molecular mechanisms underlying the transcriptional, translational, and metabolic mechanisms of the key cell types involved in host defense and inflammatory responses: macrophages and intestinal epithelial cells (IECs). We recently spoke with Xiaoyu about her current work, the benefits of a multidisciplinary team, and how being part of journal editorial boards brings her intellectual stimulation and inspiration for her own lab.

Rita Colwell: Use your voice to bring about positive change.

Rita Colwell is a Distinguished University Professor at the University of Maryland at College Park and at Johns Hopkins University Bloomberg School of Public Health, senior advisor and chairman emeritus at Canon US Life Sciences, Inc., founder and chairman of CosmosID, Inc., and president of the Rosalind Franklin Society. She has authored or co-authored 20 books and more than 800 scientific publications, and throughout her career has focused on improving health outcomes across the world and highlighting the impacts of infectious diseases in drinking/bathing water. We recently spoke to Rita about her career and her thoughts about the future for women in science.

Yukiko Gotoh: I am fascinated by the beauty of science.

Yukiko Gotoh is a professor in the Department of Pharmaceutical Sciences at the University of Tokyo. Her lab studies the mechanisms that underlie the regulation of neural stem/progenitor cell fate during brain development and homeostasis. They are particularly interested in the underlying genetic and epigenetic mechanisms that control cell fate and neuronal maturation, as well as the relevance of neural stem/progenitor cell dysregulation in neurodevelopmental disorders. We recently spoke to Yukiko about her current work, the joys of teamwork, and her passion for helping other scientists in Japan.

Distinct mesenchymal cell states mediate prostate cancer progression.

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin's role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.

Jen Gommerman: Leadership is not a one-way street.

Jen Gommerman is a Canada Research Chair in Tissue Specific Immunity, and a professor and newly appointed chair for the Department of Immunology at the University of Toronto. Her lab is interested in the underlying mechanisms of immune dysregulation in autoimmune diseases such as MS, mucosal immunology, and the role of TNF family members in immune cell biology. We spoke to Jen about the importance of authenticity and openness in leadership, and her goals as she begins her tenure as department chair of Immunology.

Nina Cabezas Wallscheid: Enjoying the freedom to decide my research path.

Nina Cabezas Wallscheid is a group leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. Taking a multidisciplinary approach, her lab investigates the mechanisms by which metabolites regulate the epigenetic and metabolic state of hematopoietic stem cell fate in young and upon aging, with the aim to identify therapeutic strategies for nutritional and hematological diseases. We spoke to Nina recently to learn more about her long-term interest in cell regulation, the joys of being a group leader, and the adventures she goes on while outside of the lab.

María Mittelbrunn: Science feeds my curiosity every day.

María Mittelbrunn leads the Immunometabolism and Inflammation Laboratory at the Severo Ochoa Molecular Biology Center. Her lab takes a multidisciplinary approach to explore immunometabolism as a therapeutic target in the treatment of chronic inflammation and aging. We recently spoke to María about the joy of discussing results with your team and how this can influence future projects, and optimism about the future of research.

The Identification of CELSR3 and Other Potential Cell Surface Targets in Neuroendocrine Prostate Cancer.

Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a significant subset of patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine prostate cancer (NEPC)]. On the basis of RNA sequencing (RNA-seq) data from a clinical cohort of tissue from benign prostate, locally advanced prostate cancer, metastatic castration-resistant prostate cancer and NEPC, we developed a multi-step bioinformatics pipeline to identify NEPC-specific, overexpressed gene transcripts that encode cell surface proteins. This included the identification of known NEPC surface protein CEACAM5 as well as other potentially targetable proteins (e.g., HMMR and CESLR3). We further showed that cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) knockdown results in reduced NEPC tumor cell proliferation and migration in vitro. We provide in vivo data including laser capture microdissection followed by RNA-seq data supporting a causal role of CELSR3 in the development and/or maintenance of the phenotype associated with NEPC. Finally, we provide initial data that suggests CELSR3 is a target for T-cell redirection therapeutics. Further work is now needed to fully evaluate the utility of targeting CELSR3 with T-cell redirection or other similar therapeutics as a potential new strategy for patients with NEPC. Significance: The development of effective treatment for patients with NEPC remains an unmet clinical need. We have identified specific surface proteins, including CELSR3, that may serve as novel biomarkers or therapeutic targets for NEPC.

Golnaz Vahedi: My environment enables me to achieve impossible goals.

Golnaz Vahedi is an associate professor of genetics at the Perelman School of Medicine, University of Pennsylvania. Golnaz runs a multidisciplinary lab that uses cutting-edge computational and experimental approaches to understand the molecular mechanisms by which genomic information in immune cells is interpreted in normal development and during immune-mediated diseases. We talked about her diverse scientific background, the benefits of integrating molecular biology and immunology, and the importance of staying positive in academia.

Michelle Linterman: We are always learning.

Michelle Linterman is a group leader at the Babraham Institute, Cambridge, UK. The research focus of her lab is to understand the fundamental biology of the germinal center response after immunization and infection and how this changes with age. We caught up with Michelle to talk about how her interest in germinal center biology started, the benefits of team science, and her collaboration between the Malaghan Institute of Medical Research, New Zealand, and Churchill College, Cambridge.

Ruth Scherz-Shouval: Together we can ask big questions.

Ruth Scherz-Shouval is an Assistant Professor in the Department of Biomolecular Sciences at the Weizmann Institute of Science, Israel. Her lab is interested in the tumor microenvironment, how stress responses can shape the tumor microenvironment, and also how different cells within the tumor microenvironment interact. We talked about how her interest in science began at an early age, the impact of having strong female role models, and ways to encourage collaboration and create an engaging and welcoming lab environment.

Distinct mesenchymal cell states mediate prostate cancer progression.

Alterations in tumor stroma influence prostate cancer progression and metastatic potential. However, the molecular underpinnings of this stromal-epithelial crosstalk are largely unknown. Here, we compare mesenchymal cells from four genetically engineered mouse models (GEMMs) of prostate cancer representing different stages of the disease to their wild-type (WT) counterparts by single-cell RNA sequencing (scRNA-seq) and, ultimately, to human tumors with comparable genotypes. We identified 8 transcriptionally and functionally distinct stromal populations responsible for common and GEMM-specific transcriptional programs. We show that stromal responses are conserved in mouse models and human prostate cancers with the same genomic alterations. We noted striking similarities between the transcriptional profiles of the stroma of murine models of advanced disease and those of of human prostate cancer bone metastases. These profiles were then used to build a robust gene signature that can predict metastatic progression in prostate cancer patients with localized disease and is also associated with progression-free survival independent of Gleason score. Taken together, this offers new evidence that stromal microenvironment mediates prostate cancer progression, further identifying tissue-based biomarkers and potential therapeutic targets of aggressive and metastatic disease.

Soyon Hong: My role is to empower.

Soyon Hong is a group leader at the UK Dementia Research Institute at UCL. Her lab is interested in investigating how multiple cell types work together to maintain brain function, and how these interactions are affected and altered in neurodegenerative disease states such as Alzheimer's disease. Here, Soyon talks about how she got interested in science, what she's currently working on, and the importance of good mentorship throughout your academic career.

Kate Schroder: Gender equality in STEM.

Kate Schroder is a professor and director of the Centre for Inflammation and Disease Research at the Institute for Molecular Bioscience (IMB), University of Queensland, Australia. Her lab, the IMB Inflammasome Laboratory, is interested in the mechanisms that underlie inflammasome activity and inhibition, regulators of inflammasome-dependent inflammation, and caspase activation. We recently got the opportunity to speak with Kate about gender equality in science, technology, engineering, and mathematics (STEM). We covered steps her institute is taking to improve gender equality in the workplace, advice for female early career researchers (ECRs), and how something as simple as a robot vacuum cleaner can make a huge difference to a person's life.

Sara Suliman: Science is better when it's shared.

Sara Suliman is an assistant professor in the Department of Experimental Medicine at the University of California, San Francisco (UCSF). Her lab uses multiple approaches to identify candidate tuberculosis (TB) risk pathways and to determine their role in TB progression. I caught up with Sara to talk about how she got interested in science, what she's currently working on, and what she thinks about the future of academic science.