Registration for a live webinar on 'Innovative Vaccines and Viral Pathogenesis: Insights from Recent Monkeypox Research' is now open.
See webinar detailsWe noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
- Introduction to Protein Structure and Function
-
1. Nature’s strategies in the regulation of enzyme activity by modifiers
- Prof. Antonio Baici
- Creation of Protein Variability by Manipulation of Genes
-
3. Perspectives on biological catalysis
- Prof. Stephen Benkovic
-
4. Fundamentals and principles for engineering proteolytic activity
- Prof. Charles Craik
- Metabolic Diseases Caused by Genetic Mutation
-
5. Modifications of pyruvate handling in health and disease
- Prof. Mary Sugden
-
6. Mitochondrial fatty acid oxidation deficiencies
- Prof. Niels Gregersen
-
7. Inborn errors of ketone body metabolism
- Prof. Toshiyuki Fukao
-
8. Cathepsin K in bone and joint diseases
- Prof. Dieter Bromme
-
9. Fabry disease: alfa-galactosidase A deficiency and enzyme replacement therapy
- Prof. David Warnock
-
10. Acid beta-glucosidase/glucocerebrosidase (GCase)
- Prof. Gregory Grabowski
-
11. GM2 gangliosidosis future treatments 1
- Prof. Brian Mark
-
12. GM2 gangliosidosis future treatments 2
- Prof. Brian Mark
-
13. The neuronal ceroid lipofuscinoses
- Prof. Sandra Hofmann
- Disorders of Blood Coagulation
-
14. Advances in fibrinolysis
- Dr. Paul Kim
-
16. Structure of thrombin, a Janus-headed proteinase
- Prof. Wolfram Bode
-
18. Fibrinogen and factor XIII
- Prof. John Weisel
-
19. Factor VIII and haemophilia A
- Dr. Geoffrey Kemball-Cook
-
20. Factor IX
- Prof. Bruce Furie
-
21. The biology and pathobiology of von Willebrand factor
- Prof. David Lillicrap
-
22. Thrombotic thrombocytopenic purpura
- Prof. J. Evan Sadler
-
23. Fibrinolysis
- Prof. Edward Tuddenham
- Other Molecular and Metabolic Disorders
-
24. Glucose-6-phosphate dehydrogenase deficiency
- Dr. Jane Leopold
-
25. Cytochrome b5 reductase deficiency and hereditary methemoglobinemia
- Dr. Scott Reading
-
26. Sickle cell disease
- Prof. Martin H. Steinberg
-
27. Pyruvate kinase deficiency
- Prof. Alberto Zanella
-
28. Heritable disorders of collagen
- Dr. Heather Yeowell
-
29. Duchenne muscular dystrophy
- Prof. Jeff Chamberlain
- Archived Lectures *These may not cover the latest advances in the field
-
30. Protein crystallography
- Prof. Michael James
-
31. Regulation of blood coagulation by the serpin, antithrombin
- Prof. Steve Olson
-
32. Rhodopsin and retinitis pigmentosa
- Dr. Shalesh Kaushal
-
33. The physiology and pathology of coagulation factor XI
- Dr. David Gailani
-
34. Cytochrome b5 reductase deficiency and hereditary methemoglobinemia
- Prof. Josef Prchal
-
35. Metachromatic leukodystrophy
- Prof. Volkmar Gieselmann
-
36. Serpins and serpinopathies
- Dr. James Whisstock
-
38. Pleiotropic and epistatic genes in sickle cell anaemia
- Prof. Ronald Nagel
-
39. Genetic disorders of carbonic anhydrases II and IV
- Prof. William Sly
-
40. GM2 gangliosidoses
- Prof. Don Mahuran
-
41. Kinetic analysis of protein activity
- Prof. Antonio Baici
Printable Handouts
Navigable Slide Index
- Introduction
- Galen discovered blood travels in arteries and veins
- Reasons to think about vascular disease
- The inert vessel wall...
- Quiescent vs. active epithelial layer
- Questions
- Outline
- Coagulation pathway
- Discovery of protein C (PC)
- Protein C (PC)
- Structure of PC
- Extrahepatic sites of PC synthesis
- Major players: TM, PF4, EPCR, thrombin, PC
- Thrombomodulin (TM) and protein C activation
- APC promotes fibrinolysis
- PC activation and clearance of APC
- Physiologic importance of PC (1)
- Physiologic importance of PC (2)
- Resistance to APC: factor VLeiden
- Factor VLeiden
- Benefits of factor VLeiden
- The PC-TM system and inflammation (1)
- The PC-TM system and inflammation (2)
- Anti-inflammatory properties of APC
- Anti-inflammatory properties of APC-EPCR
- Vasculoprotective properties of APC-EPCR
- Therapeutic importance of APC
- APC versus PC
- Thrombomodulin and the TAFI
- TM and role of C-type lectin-like domains
- Deletion of the lectin-like domain of TM
- Increased sensitivity of TMLed/Led mice to LPS
- Higher serum cytokines in TMLed/Led mice
- Increased PMN accumulation in TMLed/Led lungs
- More myocardial infracts after ischemia-reperfusion
- Increased PMN adhesion to TMLed/Led ECs
- ICAM, VCAM and pERK1/2 endothelial cells
- Soluble thrombomodulin (sTM)
- TMLec155 suppresses leukocyte adhesion
- TMLec155 suppresses activation of ERK1/2
- Co-ordinate action of TM and APC-EPCR
- HMGB1 - high mobility group box 1
- N-terminal domain of TM: inhibitor of HMGB1
- Summary of role of TM in inflammation
- Role of TM in cancer
- Regulation of TM
- Regulation of EPCR
- TM and proteinase activated receptors
- TM mutations and disease
- PC-TM system in development
- PC-TM mechanism - in feto-maternal interface
- Pulling it together...
- Local response to injury
- Protection of adjacent tissue
- Future directions
- Therapeutics of PC/APC
- Therapeutics of EPCR
- Therapeutics of thrombomodulin
- Diagnostic insights
- Potential impact
- We need to do more research
Topics Covered
- Protein C and thrombomodulin
- Mechanisms of action in coagulation and inflammation
- Diagnostic and therapeutic insights
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Conway, E. (2020, August 12). The protein c-thrombomodulin mechanism: regulating multiple biological systems [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 31, 2024, from https://doi.org/10.69645/SWUG6888.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Edward Conway has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
The protein c-thrombomodulin mechanism: regulating multiple biological systems
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:00
The Protein C-Thrombomodulin Mechanism
regulating multiple biological systems.
0:08
Almost 2000 years ago, Claudius Galen, the
Greek physician to gladiators and related
to the emperor of Rome, recognized that
blood travels through arteries and veins.
This was the start to a long journey
to understanding vascular disease.
0:23
In spite of hundreds of years of progress
in understanding the vascular system,
diseases, directly or indirectly related
to its dysfunction continue to be common.
In North America and Europe alone,
pulmonary emboli cause over 100,000
deaths per year, heart disease and
strokes in excess of 1 and a half million.
Infections and cancer, both of which
rely on the vasculature to invade and
disseminate, combine to be the major
killers in the world each year,
as well as a key source of morbidity.
0:55
From our current level of knowledge,
it's remarkable to consider that until
only 40 to 50 years ago, the vascular
endothelium was viewed as being inert,
sort of like a pipe,
the purpose being only to carry blood.
1:10
Since that time the vascular endothelium
has literally been brought to life.
Endothelial cells express all kinds
of proteins on their surface,
secrete cytokines and chemokines, transmit
signals into the underlying tissue and
closely interact with bloodborne proteins,
cells and invading organisms.
At its healthiest we view the endothelial
layer as being quiescent.
In this situation, the endothelial
cell surface may be considered smooth,
protecting against blood
clot formation and
accumulation of white blood cells that
may otherwise promote inflammation.
In response to injury, the endothelial
cell surface becomes activated,
the cells become permeable to proteins and
cells.
They become more sticky, so
that leukocytes adhere to their surface so
that they can invade underlying
tissue to fight infection.
They promote platelet activation and
clot formation and attempts
to restrict the wound to prevent bleeding
and ultimately to promote healing.
Since the state of activation of
the endothelium is dynamically changing in
response to a myriad of
stimuli of varying severity,
forces exist to allow the organism
to respond quickly and
at the right place and to an appropriate
extent to fight infections,
inflammatory stimuli or
wounds and to prevent disease.
Hide