Thomas A. Rando | |
---|---|
Born | 1957 [1] |
Academic background | |
Alma mater | Harvard College Harvard Medical School |
Academic work | |
Discipline | Neurology,stem cell biology,biology of aging,regenerative medicine,tissue engineering |
Institutions | Stanford University School of Medicine |
Thomas A. Rando is an American stem cell biologist and neurologist,best known for his research on basic mechanisms of stem cell biology and the biology of aging. He is the Director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and a professor of Neurology and Molecular,Cell and Developmental Biology at the University of California,Los Angeles. [2] Prior to joining the UCLA faculty,he served as Professor of Neurology and Neurological Sciences at Stanford University School of Medicine,where he was also founding director of the Glenn Center for the Biology of Aging. [3] His additional roles while at Stanford included co-founder and deputy director of the Stanford Center on Longevity,founding director of Stanford's Muscular Dystrophy Association Clinic,and Chief of Neurology at the VA Palo Alto Health Care System. [4] [5] [6]
Rando was born in Brooklyn,New York, [1] and grew up in Maine. [7] He earned a bachelor's degree from Harvard College in biochemistry in 1979,and an MD from Harvard Medical School and PhD in cell and developmental biology from Harvard University in 1987. [6] [7] [8] He interned at Massachusetts General Hospital and completed his residency in neurology at the University of California,San Francisco. [9] He joined Stanford's Department of Molecular Pharmacology as a research fellow in 1991,and joined Stanford's medical school faculty in 1995. [8] He relocated to Los Angeles to join the UCLA faculty in 2021. [10] Rando is also a founder of Fountain Therapeutics. [11]
Rando’s research on stem cells has addressed how stem cells in tissues throughout the body maintain their potency to participate in tissue homeostasis and tissue repair throughout the life of an organism. [12] [13] [14] Through these studies,his laboratory has explored the basic mechanisms by which stem cells maintain a dormant,or “quiescent”state,when not engage in generation of new tissue. [15] [16] [17] They have demonstrated how the depth of stem cell quiescence influences the potency of those cells to participate in tissue repair and regeneration. [18] These findings have led to advances in studies of stem cell therapeutics in the broader field of regenerative medicine. [19]
In 2005,Rando’s laboratory was the first to use the technique of heterochronic parabiosis to explore the effects of the systemic circulation on stem cell function. [20] [21] [22] Rando’s group has pioneered studies of the epigenetics of stem cell aging,exploring the role of “epigenetic rejuvenation”as an explanation for the paradigm-shifting findings of heterochronic parabiosis. [23] [24] These studies have revealed how exercise itself can lead to rejuvenation of aged stem cells. [25] Their studies focus on physiologic,pharmacologic,genetic,and dietary interventions to reverse cellular aging and to produce therapies for aging-related diseases. [26] [27] [28]
Rando's research interests also include muscular dystrophies,tissue engineering,and regenerative rehabilitation. [14] [29] [30] [31] [32]
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected,the degree of weakness,how fast they worsen,and when symptoms begin. Some types are also associated with problems in other organs.
Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates and/or a decrease in fecundity with increasing age,at least in the later part of an organism's life cycle. However,the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats,the existence of species having negligible senescence,and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.
The G0 phase describes a cellular state outside of the replicative cell cycle. Classically,cells were thought to enter G0 primarily due to environmental factors,like nutrient deprivation,that limited the resources necessary for proliferation. Thus it was thought of as a resting phase. G0 is now known to take different forms and occur for multiple reasons. For example,most adult neuronal cells,among the most metabolically active cells in the body,are fully differentiated and reside in a terminal G0 phase. Neurons reside in this state,not because of stochastic or limited nutrient supply,but as a part of their developmental program.
Dystrophin is a rod-shaped cytoplasmic protein,and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins,such as α-dystrobrevin,syncoilin,synemin,sarcoglycan,dystroglycan,and sarcospan,colocalize with dystrophin at the costamere. It has a molecular weight of 427 kDa
Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four,with rapid progression. Initially,muscle loss occurs in the thighs and pelvis,extending to the arms,which can lead to difficulties in standing up. By the age of 12,most individuals with Duchenne muscular dystrophy are unable to walk. Affected muscles may appear larger due to an increase in fat content,and scoliosis is common. Some individuals may experience intellectual disability,and females carrying a single copy of the mutated gene may show mild symptoms.
Regenerative medicine deals with the "process of replacing,engineering or regenerating human or animal cells,tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.
Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy,a group of heritable diseases that cause degeneration of muscle and progressive weakness. Per the name,FSHD tends to sequentially weaken the muscles of the face,those that position the scapula,and those overlying the humerus bone of the upper arm. These areas can be spared,and muscles of other areas usually are affected,especially those of the chest,abdomen,spine,and shin. Almost any skeletal muscle can be affected in advanced disease. Abnormally positioned,termed 'winged',scapulas are common,as is the inability to lift the foot,known as foot drop. The two sides of the body are often affected unequally. Weakness typically manifests at ages 15–30 years. FSHD can also cause hearing loss and blood vessel abnormalities at the back of the eye.
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.
Rejuvenation is a medical discipline focused on the practical reversal of the aging process.
A neuromuscular disease is any disease affecting the peripheral nervous system (PNS),the neuromuscular junctions,or skeletal muscles,all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur.
Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli,such as cytokines,ultraviolet irradiation,heat shock,and osmotic shock,and are involved in cell differentiation,apoptosis and autophagy. Persistent activation of the p38 MAPK pathway in muscle satellite cells due to ageing,impairs muscle regeneration.
A mesoangioblast is a type of progenitor cell that is associated with vasculature walls. Mesoangioblasts exhibit many similarities to pericytes,which are found in the small vessels. Mesoangioblasts are multipotent stem cells with the potential to progress down the endothelial or mesodermal lineages. Mesoangioblasts express the critical marker of angiopoietic progenitors,KDR (FLK1). Because of these properties,mesoangioblasts are a precursor of skeletal,smooth,and cardiac muscle cells along with endothelial cells. Research has suggested their application for stem cell therapies for muscular dystrophy and cardiovascular disease.
Sarcospan is a protein that in humans is encoded by the SSPN gene.
Laminin subunit alpha-2 is a protein that in humans is encoded by the LAMA2 gene.
Collagen VI (ColVI) is a type of collagen primarily associated with the extracellular matrix of skeletal muscle. ColVI maintains regularity in muscle function and stabilizes the cell membrane. It is synthesized by a complex,multistep pathway that leads to the formation of a unique network of linked microfilaments located in the extracellular matrix (ECM). ColVI plays a vital role in numerous cell types,including chondrocytes,neurons,myocytes,fibroblasts,and cardiomyocytes. ColVI molecules are made up of three alpha chains:α1(VI),α2(VI),and α3(VI). It is encoded by 6 genes:COL6A1,COL6A2,COL6A3,COL6A4,COL6A5,and COL6A6. The chain lengths of α1(VI) and α2(VI) are about 1,000 amino acids. The chain length of α3(VI) is roughly a third larger than those of α1(VI) and α2(VI),and it consists of several spliced variants within the range of 2,500 to 3,100 amino acids.
Helen Blau is a cell biologist and stem cell researcher famous for her work on muscle diseases,regeneration and aging. She is the Donald E. and Delia B. Baxter Foundation Professor and the Director of the Baxter Laboratory for Stem Cell Biology at Stanford University. Blau is known for overturning the prevailing view that once a cell assumes a certain specialty in the body —or differentiated state —such as a skin or liver cell,it cannot be changed. Her research established that the fate of mammalian cells can be altered. Her finding that specialized cells can be triggered to turn on genetic programs characteristic of other differentiated states provided early evidence that mammalian cellular reprogramming was possible and opened the door to the use of reprogramming in stem cell biology. Her work set the stage for the development of induced pluripotent stem cells and associated stem cell therapies.
Amy J. Wagers is the Forst Family Professor of Stem Cell and Regenerative Biology at Harvard University and Harvard Medical School,an investigator in islet cell and regenerative biology at the Joslin Diabetes Center,and principal faculty of the Harvard Stem Cell Institute. She is co-chair of the Department of Stem Cells and Regenerative Biology at Harvard Medical School.
Muscle tissue engineering is a subset of the general field of tissue engineering,which studies the combined use of cells and scaffolds to design therapeutic tissue implants. Within the clinical setting,muscle tissue engineering involves the culturing of cells from the patient's own body or from a donor,development of muscle tissue with or without the use of scaffolds,then the insertion of functional muscle tissue into the patient's body. Ideally,this implantation results in full regeneration of function and aesthetic within the patient's body. Outside the clinical setting,muscle tissue engineering is involved in drug screening,hybrid mechanical muscle actuators,robotic devices,and the development of engineered meat as a new food source.
Young blood transfusion refers to transfusing blood specifically from a young person into an older one with the intention of creating a health benefit. The efficacy and safety of young blood transfusions for anti-aging purposes remain a subject of debate in the scientific community,with limited clinical evidence in humans. There are also concerns of harm. While some preclinical studies on animals suggest potential benefits,there is a lack of robust clinical evidence to support its use in humans. The U.S. Food and Drug Administration,in 2019,cautioned "consumers against receiving young donor plasma infusions" stating that they are an "unproven treatment".
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