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Jeanne Frances Loring (born May 4, 1950) 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)
Loring was born on May 4, 1950, in Tucson, Arizona, to William and Elizabeth Loring. She has one sister, Anne Loring, who is an attorney. Her father had a Ph.D. in geology, and his job as a uranium and copper prospector required that the family move frequently. Loring grew up in mining towns in Arizona, Colorado, Utah, New Mexico, and Wyoming. Bill Loring was an intellectual, and at home, he filled in the gaps of her small-town education. In 1968, Loring was selected for a National Merit Scholarship, which allowed her to attend the University of Washington in Seattle, where she completed a bachelor of science degree, magna cum laude, in molecular biology in 1972 [1] and was elected to Phi Beta Kappa.
Loring began her graduate studies as a National Science Foundation Research Fellow [2] in the newly established Institute for Molecular Biology at the University of Oregon in Eugene, where she became interested in stem cell development through her research on neural crest cells. [3] [4] She earned her Ph.D. in 1979 and began work as a visiting assistant professor at the University of California Davis.
After completing her doctoral work, Loring spent five years studying and lecturing on embryology and neurobiology at UC Davis before moving to the biotechnology industry. As Staff Scientist at Hana Biologics (1987-1989), Loring's work included development of cell therapy for Parkinson's disease. She then began to focus on the intersection of genomics with stem cells as a Senior Scientist at GenPharm International [5] (1989–1995), Senior Research Fellow at Molecular Dynamics (1995–1997), and Senior Director at Incyte Genomics (1997–2001). At GenPharm, Loring worked on gene editing in mouse embryonic stem cells, and created mouse models for human disease. She was the first to produce a transgenic mouse harboring a large human genomic sequence cloned in a yeast artificial chromosome (YAC) that retained regulatory elements of the human genes. [6] [7] At Incyte Genomics, she discovered the value of combining knowledge of genomics and bioinformatics with knowledge of stem cell biology. Loring founded Arcos Bioscience in 1997 in part to work on human embryonic stem cells and derived nine of the human embryonic stem cell preparations that were approved for federal funding by President George W. Bush in 2001. [8] [9] [10]
The Wisconsin Alumni Foundation (WARF) was issued a patent in 2001 that covered all human embryonic stem cells, and because of high patent licensing fees, Arcos decided to merge with another small company, Cythera, [11] which then merged with another stem cell company, Bresagen. [12] After another merger with Novocell, the company became Viacyte, [13] which was acquired by Vertex in 2022 [14] for its experience in development of stem cell-derived therapies for Type 1 Diabetes. The initiation in 2003 of federal funding for human embryonic stem cells made Dr. Loring eligible to receive National Institutes of Health funding, and she was awarded a grant to provide the first West coast training course for hESC research. [15] Loring moved to academia, becoming the founding co-director of the Stem Cell Center at the Burnham Institute (now called the Sanford Burnham Prebys Medical Discovery Institute).
In 2006, Dr. Loring initiated a challenge of the WARF patents on hESCs [16] with Dan Ravicher, who founded the Public Patent Foundation and John Simpson from Consumer Watchdog. In response, the US Patent Office rejected the patents, leading WARF to narrow its claims; the PTO reversed its ruling and allowed the modified patent. The modification meant that WARF's patent now covered only embryo-derived stem cells, and excluded iPSCs, an important victory for the stem cell field. In 2014, the Supreme Court declined to take up the case (https://www.kpbs.org/news/science-technology/2015/02/25/san-diego-scientists-stem-cell-patent-challenge-st,) and the primary patent expired in 2015.
In 2007, Loring was recruited to The Scripps Research Institute, where she was the founding director of the Center for Regenerative Medicine and Professor in the Department of Molecular Medicine. [17] In 2019, she moved her lab and research projects to Aspen Neuroscience, a biotechnology company she founded in 2018 with her postdoctoral fellow, Andres Bratt-Leal. [18] Aspen was founded to bring forward translational research to clinical utility. [19] She was Chief Scientific Officer at Aspen, [20] and remains at Scripps as a professor emerita. [21] She was also an adjunct professor in human genetics at Sanford Burnham Prebys Institute, and remains an Adjunct Professor in the School of Public Health at San Diego State University, and Research Fellow at the Zoological Society of San Diego.
Her research is currently focused on human pluripotent stem cells, a remarkable cell type made by reprogramming adult cells to an embryonic state, making them capable of developing into all of the cell types in the body. She has published over 200 peer-reviewed scientific articles, which have been cited more than 16,000 times. [22] She holds 5 issued patents on transgenic methods, Alzheimer disease, and stem cells. [23]
Loring is an advocate for patient education and against stem cell tourism, and has frequently spoken out on these subjects [24] including commentaries in ethics journals with bioethicist Mary Devereaux. [25] [26] She has also commented on the ethics of stem cell research in articles with ethicist Jonathan Moreno [27] and pro-life advocate Christine Scheller. [28] She often guest blogs on the stem cell blog, The Niche, describing her experiences, such as attending an FDA public meeting on Huntington's disease and Parkinson's disease. [29] For her outspoken support of patients and advocacy of stem cell research she was awarded the Stem Cell Person of the Year award in 2015 [30] and received the Stem Cell Action Advocacy Award in 2015 from the Genetics Policy Institute, which hosts the World Stem Cell Summit, [31] and won a Stem Cell Pioneer award from Xconomy in 2019. [32]
Genomics and epigenetics
A major theme of the research that Loring oversees is focused on the study of genomics and epigenetics of pluripotent stem cells, with the goal of ensuring their effectiveness and safety for cell therapy. Loring oversaw the development of PluriTest, an animal-free, molecular test of pluripotency that uses gene expression profiling to predict pluripotency of novel cell lines. [33] The patent on PluriTest is licensed for microarrays to ThermoFisher and was assigned to Aspen Neuroscience in 2019. [34] She has also done analysis of genomic integrity of cells in culture, and a comparative analysis the mutational loads of different reprogramming methods. [35]
Parkinson's disease cell replacement therapy
Symptoms of Parkinson's disease are caused by the death of dopamine neurons in a part of the brain called the substantia nigra. Aspen Neuroscience is developing a dopamine neuron replacement therapy for Parkinson's disease. [36] The project was launched in 2012 by funding by the patient advocacy group Summit For Stem Cell. [37] The goal of the project is to produce autologous (patient-specific) dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) for use as a cell replacement therapy. The approach of using autologous cells ensures that they will not be rejected after transplantation. The project is notable for the high level of community involvement, including fundraisers, lab tours, and community education. [38]
Multiple sclerosis therapy development
Another project in Dr. Loring's lab is development based therapy for multiple sclerosis. In a collaboration with Tom Lane, a notable MS researcher, a type of human neural precursor cell derived from pluripotent stem cells restored motor function in a mouse model of MS. [39] [40] The transplanted cells do not permanently engraft within the mouse but the recovery process continues for several months before stabilizing. The goal of this research is to identify the mechanism by which the human cells induced recovery from paralysis in the mouse. This knowledge is to be used to develop a novel evidence-based therapy for MS.
Autism
Fragile X syndrome is a genetic form of autism, and Loring's laboratory is using iPSCs derived from Fragile X patients to understand the causes of the disease. The goal of this research is to understand how autism affects brain development. Because the project uses iPSCs that are developed into the neurons affected in autism, the work has the potential to lead to identification of drugs to treat Fragile X and autism. [41]
The Stem Cell Zoo
Loring and her postdoctoral fellow, Inbar Friedrich Ben-Nun, were the first to report the generation of induced pluripotent stem cells from endangered species. [42] IPSCs were generated from a primate, the drill Mandrillus leucophaeus and the nearly extinct northern white rhinoceros, Ceratotherium simum cottoni. There are only two northern white rhinos left in the world (2022), and the hope is that the iPSCs can be differentiated into sperm and egg cells to generate new animals. "If everything falls into place and everything works, there is a way to generate new animals," said Loring in an interview with Nature News. [43] The project is a collaboration with The Frozen Zoo at the San Diego Zoo Institute for Conservation Research, which has collected and frozen samples from thousands of animals, including twelve northern white rhinos, in The Frozen Zoo. "It's really brilliant in retrospect that when animals die, you can freeze some of their cells and they'll last forever," said Loring. [44] In December 2015, an expert meeting was convened in Vienna, Austria, "Conservation by cellular technologies" where a plan was devised to rescue the northern white rhino [45] and their paper was published detailing this plan. [46] The story of her involvement in this project was published in a special Nature Outlook edition in 2021.
Stem Cells in Space
Dr. Loring is involved in a project to study the effects of microgravity on neurons on the International Space Station (ISS). Supported by the National Stem Cell Foundation and in collaboration with the New York Stem Cell Foundation, the team has sent neural-glial organoids to the ISS on four missions: SpaceX CRS-18, CRS-19, CRS-24, and CRS-25. The neurons survived and thrived for 30 days on the ISS. Early analysis suggests that there are unexpected changes caused by microgravity. On CRS-25, Loring's own iPSC-derived neurons were sent to the ISS and returned in September 2022. The team is analyzing the data from these missions.
Loring has received many awards, including a Rosalind Franklin Society Science Award (2022), American Physiological Society Solomon Berson Distinguished Lectureship (2022), the 2019 Xconomy Stem Cell Pioneer award, the 2015 Stem Cell Action Advocacy Award, [47] the 2015 Stem Cell Person of the Year, [48] a Millipore Foundation Stem Cell Research Award, [49] an Esther O'Keefe Foundation Award for Stem Cell Research, The Burnham Institute for Medical Research Leadership Award and the Marie and Jimmy Mayer Award for Melanoma Research. [50] She was a National Merit Scholar (1968) and was awarded a National Science Foundation Predoctoral Fellowship. She is a member of Phi Beta Kappa, and was inducted as an American Institute for Medical and Biological Engineering (AIMBE) Fellow in 2021. In 2017, she was invited to join an international group of researchers working toward development of cell replacement therapies for Parkinson's disease, called G-Force PD. [51]
Loring lives in Del Mar, California (2022) and is married to her lifelong partner and fellow scientist David L. Barker, former Chief Scientific Officer of the genomics biotechnology company Illumina, Inc (ILMN), founder of Singular Genomics (OMIC), and chair of the BOD of BioNano Genomics (BNGO). Dr. Barker received the Director Lifetime Achievement Award in 2022 from the Corporate Directors Forum. Loring and Barker enjoy traveling and often travel to wherever in the world has the best viewing of total solar eclipses, [52] including Libya, Zambia, Aruba, Easter Island, Bolivia, Russia, Turkey, Indonesia, the US, and Australia. Loring has experienced 17 eclipses. [53] Fourteen were total, in which the moon completely eclipsed the sun for up to 5 minutes, and 3 were annular, in which the moon covered all but the edges of the sun. She has logged a total time in the darkness of the totally eclipsed sun of more than 45 minutes. [54]
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.
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.
A stem cell line is a group of stem cells that is cultured in vitro and can be propagated indefinitely. Stem cell lines are derived from either animal or human tissues and come from one of three sources: embryonic stem cells, adult stem cells, or induced stem cells. They are commonly used in research and regenerative medicine.
The stem cell controversy concerns the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, and thus are minimally, if at all, controversial. Many less controversial sources of acquiring stem cells include using cells from the umbilical cord, breast milk, and bone marrow, which are not pluripotent.
In biology and medicine, stem cell genomics is the analysis of the genomes of stem cells. Currently, this field is rapidly expanding due to the dramatic decrease in the cost of sequencing genomes. The study of stem cell genomics has wide reaching implications in the study of stem cell biology and possible therapeutic usages of stem cells.
Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes, collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."
Gladstone Institutes is an independent, non-profit biomedical research organization whose focus is to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as heart failure, HIV/AIDS and Alzheimer's disease. Its researchers study these diseases using techniques of basic and translational science. Another focus at Gladstone is building on the development of induced pluripotent stem cell technology by one of its investigators, 2012 Nobel Laureate Shinya Yamanaka, to improve drug discovery, personalized medicine and tissue regeneration.
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.
Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.
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.
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.
Lorenz Studer 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. 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.
Sergiu P. Pașca is a Romanian-American scientist and physician at Stanford University in California. He is known for creating and developing stem cell-based models of the human brain and applying organoids and assembloids to gain insights into neuropsychiatric disease.
Viviane Tabar is an American neurosurgeon, the Chair of the Department of Neurosurgery at Memorial Sloan Kettering Cancer Center in New York since 2017.
Kristin K. Baldwin is an American scientist who is a professor at the Department of Genetics and Development at Columbia University. Her research focuses on using reprogrammed and induced pluripotent stem cells to identify mechanisms and therapies related to human genetic risk for neurologic and cardiovascular disease. Her lab also studies how disease and aging affect the genome; they have used cloning to produce the first complete genome sequence of a single neuron and helped assess the effect of aging on induced pluripotent stem cells that may be used for cell therapies. They also design bespoke neuronal cells in a dish to understand brain function and disease. Baldwin's earlier work included being the first to clone a mouse from a neuron and being one of three groups to first produce an entire mouse from a skin cell by generating induced pluripotent stem cells. epigenetic changes of the genome and the brain.
Christine L. Mummery (1953) is an appointed professor of Developmental Biology at Leiden University and the head of the Department of Anatomy and Embryology at Leiden University Medical Center in the Netherlands.
The European Bank for induced pluripotent Stem Cells (EBiSC) is a non-profit induced pluripotent stem cell (iPSC) biorepository and service provider with central facilities in Germany and the United Kingdom.
Experimental models of Alzheimer's disease are organism or cellular models used in research to investigate biological questions about Alzheimer's disease as well as develop and test novel therapeutic treatments. Alzheimer's disease is a progressive neurodegenerative disorder associated with aging, which occurs both sporadically or due to familial passed mutations in genes associated with Alzheimer's pathology. Common symptoms associated with Alzheimer's disease include: memory loss, confusion, and mood changes.
Valentina Fossati is an Italian stem cell biologist. She is a Senior Research Investigator at the New York Stem Cell Foundation. Her research is focused on developing human stem cell-based models to study the role of glia in neurodegeneration and neuroinflammation.
Richard Carl Elciario Dolmetsch is a Colombian-American neuroscientist, Stanford University professor and biotechnology entrepreneur. He is known for his research on calcium signaling in neurons and lymphocytes, and for his work in neuropsychiatric disease. He was an early developer of human stem cell models for studying diseases of the brain and heart, both in his laboratory at Stanford University and at the Allen Institute for Brain Science. As the Global Head of Neuroscience at Novartis, he helped create a drug pipeline for neuropsychiatric diseases, introduced human stem cell models as tools for drug discovery in neuroscience and contributed to the development of several treatments for brain disorders that are now in the clinic including Aimovig (Erenumab) for migraine and Kesimpta (Ofatumumab) for multiple sclerosis. Dolmetsch was also involved in early successes in gene therapy, including two approved therapies – Zolgensma and Hemgenix. Dolmetsch is currently the President of Tempero Bio, a biotech company seeking to cure substance use disorders, and an Adjunct Professor in Neurobiology at Stanford University.
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