Abstract
COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.
COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.
Main Text
Metastatic Plasticity
Karuna Ganesh
Memorial Sloan Kettering Cancer Center
Why does metastasis cause 90% of cancer death? As an oncologist, I must frequently explain to patients that their metastatic cancer is lethal, while similar cancers that have not yet spread to distant organs can often be completely cured. The difference lies in the ability of metastatic stem cells to dynamically alter their gene expression programs to adapt to the stresses of growing and resisting therapy far from their normal tissue niche. To understand metastatic plasticity, my lab generates patient-derived organoid models of advanced gastrointestinal cancers. We integrate transcriptomic and epigenetic profiling of patient samples with lineage tracing and mechanistic studies in human organoids and mouse models. In this way, we are defining the plasticity, cell fate trajectories, and selection of metastatic stem cells, their relationship with normal regenerative progenitors, and their therapeutic vulnerabilities. Our ultimate goal is to improve outcomes for patients with metastatic cancers.
Just 6 months after starting my lab, COVID-19 posed a double whammy for physician-scientists. We share with other scientists the pressures of shutting down experiments, providing support to trainees, and the loss of networking opportunities. Simultaneously, we have undertaken increased clinical responsibilities, sometimes at the pandemic frontlines. However, the vaccines emerging on the horizon are an inspiring testament to the power of science. Forged in this pandemic fire, my young lab emerges resilient, collaborative, and passionate to see our ideas turn into new insights.
Vascular Repair and Regeneration
Jatin Patel
Queensland University of Technology (QUT), Australia
During my training I became very interested in how a functioning vascular network rapidly develops in the human placenta during trimesters of gestation and became intrigued by the placental stem cell populations that drive this process. My postdoctoral work focused on defining the biology of resident vascular stem cells in the placenta but also expanded into adult tissues and the role these cells play in vessel repair and regeneration in homeostasis and disease, such as wound healing or cancer. This work was leveraged by using multiple transgenic in vivo models and single-cell transcriptomics and bioinformatics. I am now establishing my lab within the Cancer and Aging Research Program at QUT. We have two developing paths: (1) assessing vascular stem cell function and fate choice in the development and progression of atherosclerosis, and (2) developing a cellular therapy using fetal vascular stem cells isolated from the placenta to treat ischemic disease. The excitement of starting my new position was soon overshadowed by the global pandemic, which not only affected work but also created some chaos with online schooling for the kids. However, there was tremendous solidarity and support among colleagues that helped with the transition. We are now back to work with our environment almost back to normal, including having local face-to-face conferences. 2020 has provided many key learning experiences but most importantly the need to rapidly adapt in competitive research environments.
Building Better Disease Models
Valeria V. Orlova
Leiden University Medical Center, the Netherlands
Trained as a vascular biologist, I have been fascinated by endothelial cells since my graduate and postdoc study at the Experimental Immunology Branch at the National Institutes of Health (NIH). Endothelial cells play an integral role in many diseases beyond cardiovascular diseases, including neurodegenerative conditions, vascular dementia, autoimmune diseases, and many others.
In my lab, we are interested in creating realistic disease models by recreating local tissue microenvironments in engineered microphysiological systems or organ-on-chips. Integrating hiPSC-derived vascular cells with tissue-specific cells, such as cardiomyocytes and brain cells, allows us to study how the addition of tissue-specific cells affects endothelial cells and, in turn, how endothelial cells affect tissue-specific cells in these synthetic constructs. The COVID-19 pandemic has demonstrated the importance of endothelial cells, as many clinical complications in severe patients result from endothelial cell dysfunction. Therefore, in vitro models would help us to unravel endothelial cell dysfunction in COVID-19 and other diseases and facilitate the generation of cells that closely resemble vasculature in native organs, and help us to understand the early stages of vasculature development in humans. I envision that this approach would teach us about many diseases and improve our understanding of tissue and organ regenerative strategies where proper vascularization is the key.
Getting to the Heart of the Matter
Casey Gifford
Stanford University School of Medicine
When I started my postdoc, I met the mother of three children that suffer from congenital heart disease (CHD). She was eager to involve her family in research because she wanted answers regarding the disease’s cause that physicians could not provide. Even though CHD is the most common birth defect, we often cannot ascertain the genetic cause. Research in my lab is focused on the possibility that complex, multigenic mechanisms underlie some unexplained CHD cases. We are revisiting this longstanding hypothesis with novel experimental and computational tools to define the genetic interactions involved in heart development, hopefully allowing us to pinpoint the combinations of genes that cause disease when collectively mutated. Ultimately, our goal is to make personalized medicine a reality for CHD patients and their families.
My lab opened in November 2020. I planned to spend the intervening time between the end of my postdoc and the start of my lab performing foundational experiments so I could hit the ground running, as well as traveling to conferences to recruit (I’m hiring!). But given the limitations caused by the pandemic, I pivoted to writing grants, establishing collaborations, and thinking more deeply about the experimental avenues I plan to pursue. Recently, I’ve turned my focus away from the obstacles that COVID-19 has created and toward the positive impact that simply having time to think about science and connect with my peers has had. I look forward to building a team of motivated scientists that will help me improve outcomes for those affected by CHD.
Oriented Cell Divisions and Adult Organogenesis
Salah Elias
University of Southampton
Oriented cell divisions (OCDs) in polarized epithelia represent a critical mechanism for cell fate decisions, epithelial maintenance, and morphogenesis. Yet their requirement in highly dynamic mammalian epithelial systems such as the mammary gland remains subject to deliberation. In my lab we combine expertise in cell and developmental biology, physics, and mathematics to investigate the mechanisms of OCDs in the adult mammary epithelium and determine how this influences organogenesis. We also aim to understand how imbalance in OCDs can lead to the abnormal cell fate and behavior that contribute to malignant transformation.
COVID-19 has caused major disruptions in our research. As a new PI, closing my lab during the pandemic was heartbreaking. However, despite the uncertain situation, I have been heartened by my lab trainees who have gone the extra mile to support each other and help me run the lab remotely. The pandemic has made us a stronger and more cohesive team. I am also grateful to the leadership and collogues at my department who have been working to make things easier. The COVID-19 pandemic has also brought new opportunities for international collaboration and open science. Virtual conferences have allowed me to meet new peers who helped me launch a forum for new PIs in cell and developmental biology, which has an e-seminar series and offers opportunities for peer support and collaboration (you can find information by following @NewPICellDev on Twitter). The forum has grown into a diverse international network driven by a strong ambition to outlast the pandemic.
One Size Doesn’t Fit All
Andrew Vaughan
University of Pennsylvania
What is the most effective progenitor cell type for organ repair? This is a contentious question in the field of adult tissue stem cell biology and is difficult to answer, as differing severities of injury elicit distinct cellular responses; different cell types, for example, might participate in different modes of repair. My lab’s work in pulmonary stem cell biology is fundamentally informed by this understanding. We’re particularly interested in what happens in the most extreme scenarios because these often correlate with dire clinical conditions, e.g., acute respiratory distress syndrome (ARDS).
One of my lab’s ongoing fascinations is the dysplastic alveolar remodeling that occurs after severe lung injury. We think of this type of repair as “better than nothing,” but ultimately the differentiation state of these cells isn’t particularly amenable to gas exchange and normal lung function. Even so, there’s reason to think these cells possess some plasticity, so we’re pursuing epigenetic reprogramming to promote more appropriate cell fates for normal lung function. This idea frames much of the ongoing work in our lab: to better understand maladaptive/insufficient repair mechanisms in the hopes of learning to instead promote more effective, complete tissue regeneration. COVID-19 has certainly impacted my lab’s momentum, but we feel fortunate to have been able to safely continue much of our work throughout the pandemic, and we believe many of our studies will provide insight into the long-term consequences of COVID-19-induced ARDS.