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Exosomes: A Clinical Compendium [Pehme köide]

Edited by , Edited by (Former Director, Laboratory for Integrative Neuroscience, Center for Brain and Cognition, Department of Psychology, University of California, San Diego, La Jolla, CA, USA-), Edited by , Edited by (President and Founder, Medimark Corporation, Del Mar, CA, USA)
  • Formaat: Paperback / softback, 548 pages, kõrgus x laius: 229x152 mm, kaal: 810 g
  • Ilmumisaeg: 15-Oct-2019
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0128160535
  • ISBN-13: 9780128160534
Teised raamatud teemal:
  • Formaat: Paperback / softback, 548 pages, kõrgus x laius: 229x152 mm, kaal: 810 g
  • Ilmumisaeg: 15-Oct-2019
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0128160535
  • ISBN-13: 9780128160534
Teised raamatud teemal:

Exosomes: A Clinical Compendium is a comprehensive and authoritative account of exosomes in the context of biomarkers, diagnostics, and therapeutics across a wide spectrum of medical disciplines, as well as their role in cell-cell communication. It is intended to serve as a reference source for clinicians, physicians, and research scientists who wish to gain insight into the most recent advances in this rapidly growing field.

The exosome revolution may well be the greatest advance in physiology and medicine since antibiotics. The discovery of their epigenetic role in intercellular signaling in virtually all tissues is a major breakthrough in our understanding of how cells function.

  • Provides readers with a broad and timely overview of exosomes in health and disease, closing with a thought-provoking chapter on transgenerational inheritance, Darwin and Lamarck.
  • Summarizes the most recent laboratory and clinical findings on exosomes across numerous medical disciplines, thereby offering readers a broad-ranging and solid foundation for prospective investigative efforts
  • Twenty-one chapters authored by a global team of peer-acknowledged experts, each representing a key medical disciplineProvides readers with a broad and timely overview of exosomes in health and disease, closing
Contributors xvii
Editor biography xxi
Preface xxiii
Acknowledgments xxv
Special acknowledgment xxvii
1 Exosome basic mechanisms
Alice Conigliaro
Chiara Corrado
Simona Fontana
Riccardo Alessandro
1 Exosomes biogenesis and release
1(1)
2 Endosomal sorting complex request for transport (ESCRT) and its role in exosome biogenesis
2(2)
3 ESCRT-independent mechanism of exosomes biogenesis
4(2)
4 MVBs transport to the membrane and exosomes release
6(1)
5 Basal composition and cargo
7(5)
6 Mechanisms of action
12(11)
6.1 Exosome mechanism of action
12(5)
References
17(4)
Further reading
21(2)
2 Methods for exosome isolation and characterization
Mi Zhou
Sarah R. Weber
Yuanjun Zhao
Han Chen
Jeffrey M. Sundstrom
1 Introduction
23(1)
2 Methods for exosome isolation
24(4)
2.1 Differential centrifugation
24(1)
2.2 Filtration and ultracentrifugation
24(1)
2.3 Density gradient centrifugation
25(1)
2.4 Precipitation
25(1)
2.5 Immunoaffinity capture-based isolation
26(1)
2.6 Summary of methods for exosome isolation
27(1)
3 Methods for exosome characterization
28(5)
3.1 Ultrastructural analysis
28(1)
3.2 NTA
29(1)
3.3 AF4
30(1)
3.4 RPS
31(1)
3.5 Flow cytometry
32(1)
3.6 ExoView characterization platform
32(1)
3.7 In vivo exosome tracking
32(1)
4 Exosome cargo
33(2)
4.1 Exosomal proteins
33(1)
4.2 Exosomal microRNA (miRNA; miR)
34(1)
5 Summary
35(4)
References
35(4)
3 Exosomes, microvesicles, and their friends in solid tumors
Denis Corbeil
Aurelio Lorico
1 Introduction
39(2)
2 Cellular uptake of (cancer) cell-derived EVs
41(5)
2.1 Positioning role of early and late endosomes in nuclear transfer of extracellular information
44(1)
2.2 VOR protein complex
45(1)
3 EVs and cancer microenvironment
46(9)
3.1 Role of EVs in metastasis
46(5)
3.2 Cancer cell-derived EVs and inhibition of the anti-cancer immune response
51(1)
3.3 EVs, angiogenesis, endothelial cells, and platelets
52(1)
3.4 EVs and cancer drug resistance
53(2)
4 Environmental clues and carcinogenicity of anticancer drugs---Impact on EVs
55(1)
4.1 Air pollutants
55(1)
4.2 Carcinogenic potential of anticancer drugs and treatments
56(1)
5 Clinical applications of EVs
56(10)
5.1 Liquid biopsy: Cancer cell-derived EV-associated proteins and nucleic acids as biomarkers
57(3)
5.2 EV-based anti-cancer strategies
60(6)
6 EV-based clinical cancer therapy studies
66(1)
7 Conclusion and perspective
67(14)
Acknowledgments
67(1)
References
67(14)
4 Hematologic malignancies: The exosome contribution in tumor progression
Stefania Raimondo
Laura Saieva
Riccardo Alessandro
1 Introduction: Hematologic malignancies and the tumor microenvironment
81(1)
2 Physiological regulation and pathological alterations of hematopoiesis by extracellular vesicles
82(2)
3 Endothelial remodeling by extracellular vesicles
84(1)
4 Extracellular vesicles reprogram the bone marrow stromal cells
85(1)
5 Extracellular vesicles alter bone homeostasis
86(2)
6 Extracellular vesicles regulate immune cell functions
88(5)
6.1 Exosomes and NK cells
90(1)
6.2 Exosomes and CD8+cytotoxic lymphocytes
91(1)
6.3 Exosomes and MDSC
91(1)
6.4 Exosomes and Treg
92(1)
6.5 Exosomes and monocytes
92(1)
6.6 Exosomes and B cells
93(1)
7 Extracellular vesicles mediate drug resistance
93(1)
8 Clinical relevance of exosome for disease diagnosis and drug therapy monitoring
94(1)
9 Conclusions
95(6)
Acknowledgment
95(1)
Conflict of interests
95(1)
References
96(5)
5 Physiological and pathological functions of prostasomes: From basic research to clinical application
Fumihiko Urabe
Nobuyoshi Kosaka
Koji Asano
Shin Egawa
Takahiro Ochiya
1 Introduction
101(1)
2 Prostasomes derived from normal prostatic epithelial cells
102(2)
3 Physiological contribution of prostasomes
104(3)
3.1 Sperm motility and prostasomes
104(1)
3.2 Immunosuppressive activity of prostasomes
105(1)
3.3 Antioxidant capacity of prostasomes
105(1)
3.4 Antibacterial activity of prostasomes
106(1)
3.5 Capacitation and acrosome reaction and prostasomes
106(1)
4 Prostasomes derived from prostate cancer
107(2)
5 Pathological contribution of prostasomes in prostate cancer
109(1)
6 Clinical application of prostasomes for prostate cancer treatment
110(6)
6.1 Strategy for prostate cancer treatment targeting prostasomes
110(2)
6.2 Prostasome-associated prostate cancer biomarker
112(4)
7 Conclusion
116(7)
Acknowledgments
116(1)
Conflict of interest
117(1)
References
117(6)
6 The function and therapeutic use of exosomes in bacterial infections
Yong Cheng
Jeffery S. Schorey
1 Introduction
123(2)
2 Extracellular vesicles
125(1)
3 Exosomes
125(2)
3.1 Exosomes biogenesis
126(1)
4 Extracellular vesicles, pathogens and infectious diseases
127(1)
5 Composition and function of exosomes and EVs during mycobacterial infections
128(4)
5.1 M.tb infection and characterization of exosome and EV cargo
130(1)
5.2 Modulating of the adaptive immune response by EVs during a mycobacterial infection
131(1)
6 Composition and function of exosomes and EVs during other bacterial infections
132(3)
7 EVs as vaccines against bacterial infections
135(1)
8 EVs as a drug delivery system
136(2)
9 Exosomes as a source of diagnostic biomarkers for infectious diseases
138(1)
10 Summary
139(8)
References
140(7)
7 Emerging therapeutic roles of exosomes in HIV-1 infection
Siew-Wai Pang
Sin-Yeang Teow
1 Introduction
147(1)
2 Exosomes and HIV-1: The chicken or egg?
148(1)
3 Exosomes as double-edged sword in HIV-1
149(3)
4 Exosomes and autophagy
152(1)
5 Exosomes as biomarkers for HIV-1
153(3)
6 Therapeutic potential of targeting exosomes
156(6)
6.1 Targeting viral proteins
156(3)
6.2 Targeting viral RNAs
159(3)
7 Lessons from the past
162(6)
7.1 Understanding exosomal pathway in revising therapeutic strategy against viruses
162(1)
7.2 Advancement of technologies in exosome detection and characterization
163(2)
7.3 Key challenges of clinical application of exosomes
165(2)
7.4 Enhancement of exosomal therapeutic efficacy
167(1)
7.5 Future perspectives
168(1)
8 Concluding remarks
168(11)
References
169(10)
8 Extracellular vesicles in parasitic disease
Patricia Xander
Andre Cronemberger-Andrade
Ana Claudia Torrecilhas
1 Extracellular vesicles and parasite
179(1)
2 Leishmania
180(3)
3 Trypanosoma cruzi
183(3)
4 Trypanosoma brucei
186(1)
5 Plasmodium
187(2)
6 Toxoplasma gondii
189(1)
7 Ciardia duodenalis
190(1)
8 Concluding remarks
191(8)
References
193(6)
9 Exosomes as intercellular communication messengers for cardiovascular and cerebrovascular diseases
Antonia Teona Deftu
Beatrice Mihaela Radu
Dragos Cretoiu
Alexandru Florian Deftu
Sanda Maria Cretoiu
Junjie Xiao
1 Introduction
199(1)
2 Exosomes biogenesis and release
200(5)
2.1 Cardiomyocytes-derived exosomes
201(1)
2.2 Endothelial cell-derived exosomes
202(1)
2.3 Mesenchymal stem/stromal cells derived exosomes
202(1)
2.4 Platelet-derived exosomes
203(1)
2.5 Leukocyte-derived exosomes
203(1)
2.6 Erythrocytes-derived exosomes
204(1)
2.7 Vascular smooth muscle cells derived exosomes
204(1)
2.8 Brain cells derived exosomes
205(1)
3 Exosomes characterization and methods of study and analysis
205(3)
3.1 Exosomes size
205(1)
3.2 Exosomes separation
206(1)
3.3 Exosomes analysis
207(1)
4 Exosomes and coronary artery disease
208(1)
4.1 Exosomes as biomarkers in coronary artery disease
208(1)
4.2 Exosomes in the recovery after coronary artery disease
209(1)
5 Exosomes in myocardial ischemia and infarction
209(3)
5.1 Exosomes as biomarkers in myocardial ischemia/infarction
209(1)
5.2 Exosomes in the recovery after myocardial ischemia/infarction
210(2)
6 Exosomes in heart failure
212(5)
6.1 Exosomes as biomarkers in heart failure
212(4)
6.2 Exosomes in the recovery after heart failure
216(1)
7 Exosome in cardiac hypertrophy
217(1)
7.1 Exosomes as biomarkers in cardiac hypertrophy
217(1)
7.2 Exosomes in the recovery after cardiac hypertrophy
218(1)
8 Exosome in cardiac arrhythmia
218(1)
8.1 Exosomes as biomarkers in arrhythmia
218(1)
8.2 Exosomes in the recovery after arrhythmia
219(1)
9 Exosome in cerebrovascular diseases
219(4)
9.1 Exosomes as biomarkers in cerebrovascular diseases
219(2)
9.2 Exosomes as cargo in the brain
221(1)
9.3 Exosomes in the treatment of cerebrovascular diseases
222(1)
10 Concluding observations
223(16)
Acknowledgements
224(1)
Competing financial interests
224(1)
References
224(15)
10 Exosomes in cutaneous biology and dermatologic disease
Jeffrey D. McBride
Divya Aickara
Evangelos Badiavas
1 Keratinocytes, the major cells of the upper skin, secrete exosomes that modulate pigment production by melanocytes
239(3)
2 Keratinocyte and immune system exosomes modulate fibroblast expression of proteins that modify the extracellular matrix
242(1)
3 Keratinocyte exosomes modulate the immune system
243(1)
4 The dermis fibroblasts, specifically the dermal papilla cells, secrete exosomes that stimulate hair follicle growth phase, known as the anagen phase
244(1)
5 Disorders of fibrosis have dysregulated expression of fibroblasts exosomes
245(1)
6 Mast cell exosomes, containing phospholipase activity, stimulate Langerhans cell presentation of lipid antigens to T cells
245(2)
7 Exosomes in the fluid of bullous pemphigoid patients potentiates pathogenic inflammation
247(1)
8 Skin repair
247(4)
8.1 Stem cell exosomes stimulate skin repair
247(4)
9 Intercellular adhesion molecules associated with exosomes, such as desmogleins, secreted from malignant cells can modulate the extracellular environment to promote tumor progression
251(1)
10 Exosomes are critical in the pathogenesis of malignant melanoma
251(1)
11 Exosomes in the circulation signal presence of metastatic squamous cell carcinomas, especially in recessive dystrophic epidermolysis bullosa patients
252(1)
12 Exosomes in circulation of patients with melanoma signal metastases and worsened prognosis
253(1)
13 Conclusion
254(3)
References
254(3)
11 Exosomes in nephrology
Robert W. Hunter
James W. Dear
Matthew A. Bailey
1 Introduction
257(1)
1.1 Aim
257(1)
1.2 Exosomes in the kidney and urinary tract: Special considerations
257(1)
1.3 A word on nomenclature
258(1)
2 Urinary exosomes
258(4)
2.1 Isolation methods
258(2)
2.2 Cellular origin and molecular cargo of urinary exosomes
260(1)
2.3 Uptake of EVs by kidney cells
260(2)
3 Urinary exosomes as biomarkers
262(5)
3.1 Two broad approaches to biomarker research
262(1)
3.2 Mechanistic biomarkers reporting on renal tubular function
263(2)
3.3 Biomarkers of renal disease
265(2)
4 Functional role of exosomes in the kidney and urinary tract
267(6)
4.1 Exosome signalling regulating tubulointerstitial cells
267(6)
4.2 Exosome-mediated interactions with urinary pathogens
273(1)
5 Potential for exosome-based therapies
273(1)
6 Conclusions
274(11)
References
276(9)
12 Extracellular vesicles in neurodegenerative disorders
Imre Mager
Eduard Willms
Scott Bonner
Andrew F. Hill
Matthew J.A. Wood
1 Introduction
285(3)
2 EV-mediated healthy CNS maintenance
288(1)
3 EVs in neurodegenerative diseases
289(9)
3.1 Alzheimer's disease
289(2)
3.2 Parkinson's disease
291(1)
3.3 Multiple sclerosis
292(3)
3.4 Amyotrophic lateral sclerosis
295(1)
3.5 Prion diseases (transmissible spongiform encephalopathies)
296(2)
4 Summary and conclusions
298(9)
References
298(9)
13 Extracellular vesicles in fibrotic diseases: New applications for fibrosis diagnosis and treatment
Tsukasa Kadota
Nobuyoshi Kosaka
Yu Fujita
Jun Araya
Kazuyoshi Kuwano
Takahiro Ochiya
1 Introduction
307(1)
2 Mechanisms of fibrosis
308(1)
3 The involvement of EVs in pathogenesis of organ fibrosis
309(5)
3.1 EVs and hepatic fibrosis
309(3)
3.2 EVs and pulmonary fibrosis
312(1)
3.3 EVs and cardiac fibrosis and hypertrophy
313(1)
4 The involvement of EVs in fibrotic disease diagnosis
314(2)
4.1 EV-based biomarker in liver fibrosis
314(1)
4.2 EV-based biomarkers in pulmonary fibrosis
315(1)
4.3 Current limitations of EVs analysis in disease diagnosis
316(1)
5 EVs as new applications for fibrosis treatment
316(3)
5.1 Reversibility of organ fibrosis
316(1)
5.2 The roles of EVs as new applications for fibrosis treatment
317(1)
5.3 Mesenchymal stem cell-derived EVs
317(1)
5.4 Body fluid-derived EVs
318(1)
5.5 Current limitations of EV-based therapy
319(1)
6 Conclusions and perspectives
319(6)
Acknowledgements
319(1)
References
319(6)
14 Mechanisms of exosome-mediated immune cell crosstalk in inflammation and disease
Todd W. Costantini
Raul Coimbra
Brian P. Eliceiri
1 Transfer of exosomes during immune cell-interactions participate in the inflammatory response
325(2)
2 Relevance of exosome biogenesis and secretion pathways in health and disease
327(1)
3 Mechanisms of exosome release in vivo in disease
328(1)
4 Exosomes and immune checkpoint inhibition in oncology
329(1)
5 Exosomes in trauma and ischemia/reperfusion injury
329(2)
6 Exosomes and inflammatory bowel disease
331(1)
7 Exosomes and wound healing
331(1)
8 Exosomes and diabetes
332(1)
9 Potential for species-specific mechanisms of exosome release
333(1)
10 Exosomes and technology-driven advances
333(1)
11 Conclusion
334(9)
References
335(8)
15 Exosomes in metabolic syndrome
Soazig Le Lay
Ramaroson Andriantsitohaina
M. Carmen Martinez
1 Introduction
343(1)
2 Different components of MetS
344(2)
2.1 Obesity
344(1)
2.2 Dyslipidemia
345(1)
2.3 Arterial hypertension
345(1)
2.4 IR and diabetes
345(1)
3 EVs: Biomarkers of MetS components
346(2)
3.1 Obesity
346(1)
3.2 Dyslipidemia
347(1)
3.3 Hypertension
347(1)
3.4 IR and type 2 diabetes mellitus (T2DM)
348(1)
3.5 All MetS components gathered
348(1)
4 EVs: Bioeffectors of the MetS
348(4)
4.1 Exosomes and metabolic complications of obesity: A role for fat-derived exosomes?
348(2)
4.2 Exosomes as promoters of endothelial dysfunction
350(1)
4.3 Role of exosomes in blood pressure regulation
351(1)
4.4 Exosomes as vectors promoting lipid disorders
352(1)
5 Exosomes as a new mode of communication between hosts and microbiota
352(1)
6 Conclusion
353(4)
Acknowledgments
353(1)
References
353(4)
16 Potential role of exosomes in reproductive medicine and pregnancy
Soumyalekshmi Nair
Carlos Salomon
1 Introduction
357(1)
2 Extracellular vesicles: Their diversity, biogenesis and secretion
358(3)
2.1 Exosomes: Intercellular interactions and functions
358(3)
3 The origin and functions of exosomes in pregnancy
361(10)
3.1 Exosomes from placenta
361(3)
3.2 Detection and isolation of placental exosomes
364(1)
3.3 Bio-distribution of placental exosomes and their effect on target cells
365(6)
4 Exosomes in complications of pregnancy
371(3)
4.1 Gestational diabetes mellitus (CDM)
371(1)
4.2 Pre-eclampsia (PE)
372(1)
4.3 Preterm birth
373(1)
5 Conclusions
374(11)
Acknowledgments
374(1)
References
375(10)
17 Exosomes in respiratory disease
Shamila D. Alipoor
Esmaeil Mortaz
1 Exosome in lung microenvironment and pathogenesis
385(2)
2 The roles of exosomes derived from the effector immune cells and structural cells in lung microenvironment
387(3)
3 Exosomes in lung diseases
390(12)
3.1 Asthma
390(3)
3.2 Lung cancer
393(5)
3.3 Tuberculosis
398(1)
3.4 COPD
399(2)
3.5 Sarcoidosis
401(1)
3.6 Other respiratory diseases
401(1)
4 Clinical applications of exosomes in respiratory diseases: Clinical trials and future perspectives
402(13)
References
405(10)
18 Exosomes in retinal diseases
Sarah R. Weber
Mi Zhou
Yuanjun Zhao
Jeffrey M. Sundstrom
1 Introduction
415(2)
2 General disease mechanisms
417(8)
2.1 Oxidative stress
417(1)
2.2 ER stress
418(2)
2.3 Inflammation and immune responses
420(2)
2.4 Retinal and choroidal angiogenesis
422(2)
2.5 Cancer
424(1)
3 Exosome-based therapeutic approaches
425(1)
4 Conclusions
425(8)
References
426(7)
19 MSC-exosomes in regenerative medicine
Yueyuan Zhou
Nobuyoshi Kosaka
Zhongdang Xiao
Takahiro Ochiya
1 Introduction
433(1)
2 Exosomes derived from mesenchymal stromal cells
434(1)
3 Application of MSC-EVs in regenerative medicine
435(9)
3.1 Neurological regeneration
436(1)
3.2 Cardiovascular regeneration
437(2)
3.3 Hepatic regeneration
439(1)
3.4 Renal regeneration
440(1)
3.5 Skeletal, chondral, and muscular regeneration
441(1)
3.6 Cutaneous regeneration
442(2)
4 Exosomal modification in regenerative medicine
444(7)
4.1 Engineering the exosomal surface
444(1)
4.2 Engineering effective exosome contents
445(6)
5 Clinical application of MSC-exosomes in regenerative medicine
451(1)
6 Limitations and challenges
451(3)
7 Conclusion and perspectives
454(13)
Competing interests
455(1)
References
455(12)
20 The potential of exosomes as theragnostics in various clinical situations
Ju-Seop Kang
1 Exosomes as biomarkers of diseases and therapeutic or vaccine candidates for infections
467(6)
2 Extracellular vesicles (EVs) as a drug delivery system
473(14)
References
480(7)
21 Exosomes, gemmules, pangenesis and Darwin
Denis Noble
1 Introduction
487(1)
2 The Darwinist view
487(5)
2.1 The origin of species
487(2)
2.2 Trees of life
489(2)
2.3 The inheritance of acquired characteristics
491(1)
3 The neo-Darwinist (modern synthesis) view
492(5)
3.1 Early experiments to test inheritance of acquired characteristics
492(2)
3.2 Randomness of mutations
494(1)
3.3 Is the Weismann barrier now "embodied by the Central dogma of molecular biology"?
494(1)
3.4 Shifting definition of a gene
495(2)
4 The new trends view
497(1)
5 Modern work on trans-generational role of exosomes and microRNAs
498(5)
Acknowledgements
499(1)
References
499(4)
Index 503
Lawrence R. Edelstein, Ph.D. is a neuroscientist and pharmaceutical industry consultant with research interests in multisensory convergence/integration (claustrum) and intercellular communication (exosomes, telocytes). His interest in exosomes was fueled by a theme issue he guest-edited with John Smythies and Denis Noble entitled Epigenetic information-processing mechanisms in the brain” (2014; https://royalsocietypublishing.org/toc/rstb/369/1652). That undertaking proved to be the impetus for a series of peer-reviewed articles in which he and his colleagues theorized as to the whys and wherefores of the multifunctional roles played by seemingly omnipresent and phyla-agnostic exosomes. In addition, Dr. Edelstein is co-editor (along with John Smythies and Vilayanur S. Ramachandran, M.B.B.S., Ph.D., Hon. F.R.C.P.) of the book Claustrum - Structural, Functional and Clinical Neuroscience (2014; www.elsevier.com/books/the-claustrum/smythies/978-0-12-404566-8). John Raymond Smythies, M.B. B.Chir., M.D., F.R.C.P., F.R.C. Psych. (1922-2019) was the Director of the Integrative Neuroscience Program in the Department of Psychology at the University of California San Diego. As a pre-eminent neuropsychiatrist and neuroscientist he made significant contributions to both these disciplines. Together with Humphry Osmond he developed the first biochemical theory of schizophrenia - the transmethylation hypothesis. This has recently come back into focus following the finding that DNA methylation is abnormal in schizophrenia. He made extensive contributions to knowledge in a number of fields including the neuropharmacology of psychedelic drugs; the functional neuroanatomy of synapses with particular regard to the role of synaptic plasticity, endocytosis and redox factors; the role in the brain of orthoquinone metabolites of catecholamines; and, in particular, theories of brain-consciousness relations. More recently he developed foundational hypotheses and theories specific to the function of exosomes, telocytes and the claustrum, and on epigenetic processes in information processing in the brain. Professor Smythies served as President of the International Society of Psychoneuroendocrinology from 1970-1974, Consultant to the World Health Organization from 1963-1968, and Editor of the International Review of Neurobiology from 1958-1991. He was elected a member of the Athenaeum in 1968. He held the positions of Professor Emeritus and the Charles Byron Ireland Professor of Psychiatric Research at the University of Alabama Medical Center at Birmingham, Visiting Scholar at the Center for Brain and Cognition, University of California San Diego, and Senior Research Fellow at the Institute of Neurology, University College London. He published over 240 scientific papers and sixteen books. https://en.wikipedia.org/wiki/John_Raymond_Smythies Peter J. Quesenberry, M.D., is the Paul Calabresi Professor of Oncology at The Warren Alpert Medical School of Brown University. He received his medical degree from the University of Virginia, completed residency at University Hospital and Boston City Hospital in Boston, MA, and completed a Hematology/Oncology Fellowship at St. Elizabeth's Hospital.

Professor Quesenberry is a leading investigator in stem cell biology and extracellular vesicle research. He was President of the International Society of Hematology, editor of the journal Experimental Hematology from 1990-1998 and the leukocyte editor for the Year Book of Hematology from 1987-1998. More recently he is a co-editor-in-chief for the Journal of Extracellular Vesicles. Denis Noble, C.B.E., Ph.D., F.R.S. is a British biologist who held the Burdon Sanderson Chair of Cardiovascular Physiology at the University of Oxford from 1984 to 2004 and was appointed Professor Emeritus and co-Director of Computational Physiology. He is one of the pioneers of systems biology.

Professor Noble developed the first viable mathematical model of the working heart in 1960 using his discovery, with his supervisor Otto Hutter, of two of the main cardiac potassium ion channels. These discoveries were published in Nature (1960) and The Journal of Physiology (1962). The work was later developed with Dick Tsien, Dario DiFrancesco, Don Hilgemann and others to become the canonical models on which more than 100 cardiac cell models are based today.

He was elected President of the International Union of Physiological Sciences (IUPS) at its Congress in Kyoto in 2009 and was re-elected for a second term at the 2013 Congress in Birmingham, UK.

He is the author of the first popular book on systems biology, The Music of Life, and his most recent lectures concern the implications for evolutionary biology.

Professor Noble has published more than 500 papers and 11 books. https://en.wikipedia.org/wiki/Denis_Noble