Lorenz Studer | |
---|---|
Born | Solothurn, Switzerland | March 5, 1966
Nationality | Swiss |
Alma mater | University of Fribourg (1987) University of Bern (1991, 1994) |
Known for | Stem cell Parkinson's disease research |
Awards | MacArthur Fellowship (2015) Annemarie Opprecht Parkinson Award (2012) Louise and Allston Boyer Young Investigator in Basic Research, MSKCC (2005) |
Scientific career | |
Fields | Developmental biology Stem cells Neuroscience Parkinson's disease |
Institutions | Memorial Sloan Kettering Cancer Center Sloan Kettering Institute Weill Cornell Medical College (Affiliated) |
Lorenz Studer (born March 5, 1966)[ citation needed ] is a Swiss biologist. He is the founder and director of the Center for Stem Cell Biology at Memorial-Sloan Kettering Cancer Center in New York City. He is a developmental biologist and neuroscientist who is pioneering the generation of midbrain dopamine neurons for transplantation and clinical applications. [1] His expertise in cell engineering spans a wide range of cells/tissues within the nervous system geared toward disease modeling and exploring cell replacement therapy. Currently, he is a member of the Developmental Biology Program and Department of Neurosurgery at Memorial Sloan-Kettering Cancer Center and a professor of Neuroscience at Weill Cornell Medical College in New York City, NY. [2]
In 2015, he was named a recipient of the MacArthur Fellowship (also known as the "Genius Grant") for his innovative work on stem cell and Parkinson's disease research. [3]
Implementation of Studer's cell replacement therapy clinical trial which utilizes dopamine neurons generated from human embryonic/pluripotent stem cells for Parkinson's disease would be the first of its kind. The clinical trial which already has begun recruiting patients, is expected to receive the FDA's study permission by the end of 2020, with an anticipated start date in 2021. [4]
Most recently, Studer was awarded an $8.95 million grant from the Aligning Science Across Parkinson's (ASAP) Initiative, in partnership with the Michael J. Fox Foundation. [5] Memorial Sloan Kettering Cancer Center, where Studer works, was designated as the lead grant recipient among the five that will be sharing the overall award.
In 1998, while at the lab of Ronald D. McKay at the National Institutes of Health in Bethesda, Maryland, he developed techniques that facilitate the generation of dopamine cells, the primary cell type affected in Parkinson's disease in vitro from dividing precursor cells. He successfully demonstrated that upon transplantation, these newly developed dopaminergic neurons can improve clinical symptoms in Parkinsonian rat models. [6]
Over the years, he has developed a variety of novel cell engineering strategies for developing specific neural cell types in culture. Most notably, he has devised protocols for the transition (or "differentiation") of human pluripotent stem cells into neural and neural crest tissues and for the generation of functional dopaminergic neurons in large-scale quantities. In long-term studies, Studer demonstrated that these cells are non-tumorigenic, can integrate into the host brain and may serve as functional replacements for the substantia nigra dopamine neurons which die in Parkinson's disease. [7]
Current research efforts also include directing the fate and age of human pluripotent stem cells, and using pluripotent stem cells as valuable tools for modeling human diseases such as Familial Dysautonomia, Hirschsprung's disease, neurodevelopmental disorders such as autism, melanocyte-related diseases, as well as mechanisms of aging. On aging research, he has also been among the first to manipulate cellular age in pluripotent-derived lineages.
Other major contributions include the directed differentiation of nuclear transfer embryonic stem cells and parthenogenetic stem cells into specific neuron types. His lab was also the first to demonstrate "therapeutic cloning" in a mouse model of a central nervous system disorder.
Overall, Studer's decades long investigation into neurological diseases such as Parkinson's disease and clinical applications of stem cells has helped advance the field of cell replacement therapy. He currently also leads a multidisciplinary consortium to pursue the application of human stem cell-derived dopamine neurons for the treatment of Parkinson's disease.
Studer, a native of Switzerland, graduated from medical school in 1991 and earned his neuroscience doctoral degree in 1994 at the University of Bern. There, he worked with Christian Spenger, culminating in the first clinical trial of fetal tissue transplantation for Parkinson's disease in Switzerland in 1995. The following year, he joined Ronald McKay's lab at the National Institute of Health (NIH) to investigate how neural cells could be isolated, cultured, and differentiated to produce neurons with the aim of restoring brain function in Parkinson's disease mouse models. [8]
In 2000, Studer moved to New York City where he embarked on his own research program at Memorial-Sloan Kettering Cancer Center (MSKCC) with a focus on exploring stem cells and brain repair. He also established the Sloan-Kettering Center for Stem Cell Biology and has been involved in a number of stem cell research committees and initiatives including the Tri-Institutional Stem Cell Initiative, (a collaboration between Memorial-Sloan Kettering Cancer Center, Rockefeller University, and Weill-Cornell Medical College), Michael J. Fox Foundation for Parkinson's disease research, and the New York Stem Cell Foundation.
In 2016, Studer became a scientific cofounder of BlueRock Therapeutics, a biotech company to develop induced pluripotent stem cell (iPSC) therapies for degenerative conditions like Parkinson's disease and heart failure. Its launch was the product of a joint venture between Versant Ventures and Bayer AG, with a $225 million investment – one of the largest-ever series A financings for a biotech company. [9] In 2019, BlueRock was acquired by Bayer AG, in a transaction valued at up to $1 billion. [10]
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.
Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (embryoblast) using immunosurgery results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage have the same moral considerations as embryos in the post-implantation stage of development.
Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinson's disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases.
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.
Neuroepithelial cells, or neuroectodermal cells, form the wall of the closed neural tube in early embryonic development. The neuroepithelial cells span the thickness of the tube's wall, connecting with the pial surface and with the ventricular or lumenal surface. They are joined at the lumen of the tube by junctional complexes, where they form a pseudostratified layer of epithelium called neuroepithelium.
Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution.
An amniotic epithelial cell is a form of stem cell extracted from the lining of the inner membrane of the placenta. Amniotic epithelial cells start to develop around 8 days post fertilization. These cells are known to have some of the same markers as embryonic stem cells, more specifically, Oct-4 and nanog. These transcription factors are the basis of the pluripotency of stem cells. Amniotic epithelial cells have the ability to develop into any of the three germ layers: endoderm, mesoderm, and ectoderm. They can develop into several organ tissues specific to these germ layers including heart, brain, and liver. The pluripotency of the human amniotic epithelial cells makes them useful in treating and fighting diseases and disorders of the nervous system as well as other tissues of the human body. Artificial heart valves and working tracheas, as well as muscle, fat, bone, heart, neural and liver cells have all been engineered using amniotic stem cells. Tissues obtained from amniotic cell lines show promise for patients with congenital diseases or malformations of the heart, liver, lungs, kidneys, and cerebral tissue.
The nuclear receptor 4A2 (NR4A2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the NR4A2 gene. NR4A2 is a member of the nuclear receptor family of intracellular transcription factors.
Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.
Gene therapy in Parkinson's disease consists of the creation of new cells that produce a specific neurotransmitter (dopamine), protect the neural system, or the modification of genes that are related to the disease. Then these cells are transplanted to a patient with the disease. There are different kinds of treatments that focus on reducing the symptoms of the disease but currently there is no cure.
Translational neuroscience is the field of study which applies neuroscience research to translate or develop into clinical applications and novel therapies for nervous system disorders. The field encompasses areas such as deep brain stimulation, brain machine interfaces, neurorehabilitation and the development of devices for the sensory nervous system such as the use of auditory implants, retinal implants, and electronic skins.
A neuronal lineage marker is an endogenous tag that is expressed in different cells along neurogenesis and differentiated cells such as neurons. It allows detection and identification of cells by using different techniques. A neuronal lineage marker can be either DNA, mRNA or RNA expressed in a cell of interest. It can also be a protein tag, as a partial protein, a protein or an epitope that discriminates between different cell types or different states of a common cell. An ideal marker is specific to a given cell type in normal conditions and/or during injury. Cell markers are very valuable tools for examining the function of cells in normal conditions as well as during disease. The discovery of various proteins specific to certain cells led to the production of cell-type-specific antibodies that have been used to identify cells.
Marcel R.M. van den Brink is a Dutch oncologist and researcher known for his research in hematopoietic stem cell transplantation for cancer patients.
Directed differentiation is a bioengineering methodology at the interface of stem cell biology, developmental biology and tissue engineering. It is essentially harnessing the potential of stem cells by constraining their differentiation in vitro toward a specific cell type or tissue of interest. Stem cells are by definition pluripotent, able to differentiate into several cell types such as neurons, cardiomyocytes, hepatocytes, etc. Efficient directed differentiation requires a detailed understanding of the lineage and cell fate decision, often provided by developmental biology.
Jeanne Frances Loring is an American stem cell biologist, developmental neurobiologist, and geneticist. She is the founding Director of the Center for Regenerative Medicine and emeritus professor at the Scripps Research Institute in La Jolla, California. She has founded two biotechnology companies, Arcos BioScience (1999) and Aspen Neuroscience (2018)
Viviane Tabar is an American neurosurgeon, the Chair of the Department of Neurosurgery at Memorial Sloan Kettering Cancer Center in New York since 2017.
Cell-based therapies for Parkinson's disease include various investigational procedures which transplant specific populations of cells into the brains of people with Parkinson's disease. The investigation of cell transplantation therapies followed the discovery that the death of dopaminergic neurons in the substantia nigra pars compacta resulted in the motor symptoms of the disease. Thus, cell transplantation has focused on various dopamine producing cells throughout the body.
Anders Björklund is a Swedish neuroscientist and pioneer in the study of cell- and gene-based reparative and neuroprotective mechanisms in the brain. He has spent his academic career at Lund University in Sweden, as professor since 1983 and as senior professor at the Wallenberg Neuroscience Center since his formal retirement in 2012.
Foetal brain cell graft is a surgical procedure that can be used as a regenerative treatment for various neurological conditions, but was mainly explored and used specifically for treating Parkinson's disease (PD). A standardised procedure is followed: the cells are usually obtained from a 7–8 weeks old foetus and the collected cells undergo testing to examine whether they are free from infectious agents and safe for transplantation. It is found that this procedure results in an overall improvement in motor functions and a reduction in reliance on medication for PD patients.