Ernest Arenas was born on 13 June 1962 in Lleida, Spain. Ernest studied medicine at the University of Lleida, earning a medical degree in 1986, after which he switched to graduate studies with Jordi Alberch at the University of Barcelona. During his PhD, he discovered that tachykinins regulate cholinergic neurotransmission in the striatum. He defended his thesis in 1991. At that time, the field of molecular biology was emerging and enabling new types of research in neuroscience.

Credit: Ulf Sirborn

Ernest was captivated by the new molecular biology technologies and the recent discovery of the neurotrophic factors neurotrophin-3 and neurotrophin-4 by Håkan Persson at the Department of Molecular Neurobiology in the Karolinska Institutet in Sweden in the early 1990s. Soon after his PhD, Ernest joined Persson’s research group as a postdoctoral fellow. However, in 1993, shortly after Ernest’s arrival at the Department of Molecular Neurobiology, Håkan Persson unexpectedly passed away owing to a cardiac condition. Recognizing Ernest’s remarkable potential, the department’s leadership entrusted him to continue his post-doctoral research, which in 1994 and 1995 led to the discovery of the neuroprotective properties of neurotrophic factors such as GDNF and neurotrophin-3 in the adult brain.

In 1996, Ernest was appointed Assistant Professor. He envisioned a laboratory founded on the pillars of collaboration and trust, where ideas flourished in an atmosphere of shared purpose. In practice this meant sharing offices and lab spaces, resources, and, most importantly, ideas with colleagues while encouraging interactions and pooling expertise across neighboring research groups. His vision, shared with Patrik Ernfors, Carlos Ibáñez and Madis Metsis, laid the groundwork for what would become the current Division of Molecular Neurobiology at the Karolinska Institutet. Ernest cultivated a thriving research environment that is now home to over a hundred dedicated scientists and consistently produces research of the highest quality.

As a newly appointed research group leader in 1996, Ernest faced some challenges. Resources were limited, science was tough, funding was scarce, and the future was uncertain. In the early days, Ernest found himself crammed into a small office with eight colleagues at the Berzelius laboratory at Karolinska Institutet. At least he was fortunate enough to have his own desk, unlike most of the others. As the days turned into late afternoons and evenings, members of the laboratory started dropping off, leaving him still working away behind his desk, immersed in reading, drafting grant proposals and writing manuscripts well into the quiet hours of the night.

Ernest became Associate Professor in1997 and then Professor of Stem Cell Neurobiology in 2002. He remained at the Division of Molecular Neurobiology at MBB throughout his scientific career. Although his career may appear to have been a seamless ascent, it was a path marked by numerous trials and challenges. Right from the start of his career, Ernest knew what he wanted to accomplish. He wanted to find a cure for Parkinson’s disease. He developed groundbreaking research on the development of midbrain dopaminergic neurons. He leveraged these insights along with progress in the field to develop methods to reprogram human stem cells for cell replacement therapy for transplantation in Parkinson’s disease. In 1999, Ernest pioneered the quest for transcription factor-induced dopamine neuron production in vitro by demonstrating that NURR1 bestows competence on neural stem cells to respond to inductive factors derived from the ventral midbrain. This discovery led Ernest into the race to identify molecules that could induce the generation of dopaminergic neurons. However, these molecules were extremely labile, which made it difficult to purify and identify them.

A breakthrough came when Ernest discovered that glial cells are a source of Wnt signaling. He subsequently deciphered the roles of various Wnts and found that they regulate different developmental processes during the formation of midbrain dopaminergic neurons. Whilst these studies identified new factors to be considered in stem cell protocols for transplantation, key pieces of the puzzle were still missing. Next, Ernest focused on using various tissue fractionations, liquid chromatography and mass spectrometry to analyze the developing ventral midbrain. He identified the ligands for Liver X receptors (LXRs) and showed that they promote midbrain dopaminergic neurogenesis, adding another piece to the puzzle. This discovery contributed to improving the generation of human embryonic stem cell-derived dopaminergic neurons that can be used as a cell replacement strategy for the treatment of PD.

In his relentless pursuit of strategies for cell replacement therapy, in recent years Ernest leveraged the emerging single-cell genomics technologies, and his studies resulted in a deeper understanding of the heterogeneity of midbrain dopamine neurons and their developmental trajectories and regulatory factors, as well as unparalleled insights into the quality of human pluripotent stem cell-derived neurons gained by benchmarking these to bona fide dopaminergic neurons. His contributions to our understanding of midbrain dopamine neuron generation in vitro and in vivo will no doubt continue to guide future studies aimed at producing unlimited cellular material for neuronal replacement in Parkinson’s disease.

Ernest was deeply engaged in his research community. He mentored and championed young scientists. Many of his mentees went on to take leadership positions in academia and industry. He undertook several international academic commissions of trust, including the organization of several scientific meetings and conferences, and institutional advisory roles. At Karolinska Institutet, he was co-director of strategic research in stem cell research and regenerative medicine, head of the MBB department, and a member of the Nobel Assembly, among other roles throughout the years.

Ernest shared his life’s journey, both personal and professional, with his beloved wife, Carmen Salto, who was an essential part of his laboratory from the start. Together, they were deeply devoted to raising their two daughters, Clara and Julia. His family and work were the core of his happiness, always taking precedence over all else in his life. If his daughters called and wanted to visit, all other plans were set aside, no matter the circumstances. Despite the challenges of living with a kidney transplant and the enduring effects of immunosuppression, Ernest’s brilliance, generosity, warmth, caring personality, positive attitude, and boundless enthusiasm for science never faltered. He will remain a role model for all of us who were fortunate enough to cross his path.