Overcoming Diseases by International Collaboration | Shinya Yamanaka, MD, PhD

so i'd like to introduce dr yamanaka as the first speaker of this symposium so i would like to introduce dr yamanakaz briefly so in 2012 yamanaka was awarded the nobel prize in physiology or medicine for his discovery that other somatic cells can be reprogrammed into prepotent cells and in addition he has received many hours and honors including the advert alaska basic medical research award the world flight in medicine the millennium technology award the show prides the killed plate for advanced technology the gliding international award the robot cohort and the merge of demands flights so he is a director of our research institute and today he will talk about the recent progress of ipsa research so shinya can you share your screen thank you very much saito-san for your kind introduction and thank you so much for always helping me uh let me share my slide so i hope you can see my slide i am so happy to have this opportunity finally um i really appreciate your efforts many of you including two of my presidents for president shivastava and president minato and everyone thank you thank you so much for having this as you heard from deepak uh i have been working both in kyoto university and in addition at gladstone institute since 2007 but even before that i have been a gladstone family i was trained as a post doctoral pharaoh almost 25 years ago so this is a picture of myself and my uh mentor dr tom inarity which i believe we took 25 years ago so the main point of this slide is that uh 25 years ago i had a bit more hair that's the main point so i stayed three and a half years at gradstone and this period is really one of the i i i should say probably the best period of my life i had a a great time as a scientist and also we grew up two daughters in san francisco so i really appreciate these beautiful days during this postdoc training i was able to identify one novel gene which i designated not one nabo apovic one target one so as you may know at this time 25 years ago in the early age of gladstone the main focus of the institute was lipid metabolism atherosclerosis so many researchers including dr mele and my boss doctor inaudible they were working on lipid metabolism like april or b april e and very naturally i was working on april b more specifically i was working on mrna editing of april or bmrna just i joined gladstone the enzyme responsible for this mrna 18 was was discovered and designated a public one so to make a long story very short i was able to identify a new target of this rna-18 enzyme and i designated this new target apovic one and i found this apobic one i'm sorry not one and cause a protein very similar to eif 4g eukaryotic translational initiation factor 4g which plays the central role in translation initiation not only in mammals but also in many other species like east and drosophila so from this early result i got very interested in translational initiation and i'm still working on translation initiation and dr uh ichiro tomoda kichiro he will talk a little bit about uh how we are doing about nut one at the same time by trying to understand the function of net one i found that nut one is very important in potency in mouse embryonic stem cells as you know es cells have have two important properties one is the rapid proliferation infinite proliferation and the second important property is pure potency the ability to differentiate into many types of cells and i found that nut one is essential for this second property of es cells free potency without not one esls they can still proliferate but they cannot properly differentiate so this was a totally unexpected uh result uh but thanks to this uh unexpected results result i got very interested in pre-potency and also es cells and this finding led to the identification of ips cells 10 years later so now we have been working on ips cells induced pre-important stem cells there are two major medical applications of ips cells one is regenerative medicine the second is disease modeling and drug discovery because from each patient from their blood to skin cells we can generate ips cells and we can expand ips cells and we can differentiate patient own ips cells into many types of cells like brain neurons heart cells and hepatic cells and so on so let me briefly introduce you how we are doing about these two major medical applications let me start with disease modeling and drug discovery so at the moment in 2021 probably the most important disease for all of us is probably 19. because of that i haven't been able to visit san francisco for the last 12 months so i really miss my friends and colleagues in bay area so as you know or essentially all countries on earth are being affected by starscope 2 nearly identical or virus i shouldn't say the identical virus because we do see genetic mutation is occurring but we are suffering from a very similar virus more than 200 countries but each country like japan and the us each country is taking very different approach very different policy and strategy and as a result we are seeing very different outcome in each country so this graph shows the stringency of of each government against profit 19 provided by oxford university they scored the stringency of each country's policy from zero which means no or no policy at all to 100 which is the stringent policy so as you can see here many u.s and european countries have been taking a very severe policy very strict policy against kobe 19 last march and april or almost 100 and even now it's close to 70 or 80. uh by great contrast japan has been taking a relatively lower milder policy right now we are about 50 but it's been always less than 50. so japan has been taking a milder policy than many other countries including u.s and this graph shows the number of pcr tests per population so once again japan the number of pcl is very very limited compared to other countries including u.s compared to u.s it's only one tenth compared to uk it's only one twentieth so all the pcl test capacity in japan is is very very limited however if you look at the number of deaths for population it's very different so oh japan so far it's only like 50 per million whereas in the states uh it's more than one thousand thirteen hundred per million in uk is sixteen hundred per million so it's a huge difference so if you look at the policy p-cell tests and the outcome death per population among countries we see a huge discrepancy for some reason japan i would say has been in a sense very lucky even with very mild policy and low test capacity our death population has been very limited even within country by the same virus some people are asymptomatic some people shows mild and some people show very severe uh pneumonia so there there are discrepancies even in even within country so there may be there should be multiple reasons behind this these discrepancies but one factor can be a genetic background so in order to study this kind of genetic background of kobe 19 and cyscop2 ips cells is a very good tool because we can make ips cells from uh each of these patients or recoveries who showed asymptomatic mild intermediate or severe pneumonia and of course we can make ips cells from people in u.s and japan and from ips cells we can generate lung organoid and also we can generate cardiomyocytes and we can use these cells in infection study by starscopter and other viruses so in the second part of this of today's program i believe taught mark david dr mark david we talked about we talked about cardiomyocyte study his cardiomyocyte study and dr takayama we'll talk about lung organoid study so we have been collaborating with multiple hospitals reading coping 19 patients in japan so far we have recruited 12 donors who showed either asymptomatic mild intermediate or severe pneumonia and we have collected blood samples from those donors and we have uh established ips cells from five donors and we have almost finished uh initial characterizations of these uh ips cells from copied patients so these cells will be available or to everyone uh very soon so i hope uh this kind of activity will contribute to kobe 19 research so our collaborators uh dr uh goto of kyoto university hospital and uh dr cozy sakai from national institute of infectious diseases they have they have been differentiating ips cells into lung cells including airway epithelial cells as well as lung epithelial cells here i showed the data from [Music] airway epithelial cells so dr goto has developed a efficient method to differentiate ips cells into airway epithelial cells and dr sakai showed that these cells epithelial cells from ips cells can be infected by cytoscope 2 very very effectively but at the same time making uh serious lung epithelial cells from ips cells is a lot of work it's a labor intensive so as an alternative dr takayama is trying to use undifferentiated ips cells in viral research so we found that undifferentiated ips cells express very low level of uh s2 so undifferentiated ips cells cannot be infected by cytoskop2 but by introducing transgene human is to transgends into undifferentiated ips cells dr takayama showed that these s2 amps cells can be transfected by steroscope 2 as effectively as viral cells ex over expressing team press too so depending on the applications we can we can utilize either undifferentiated ips cells or by expressing s2 or lung airway epithelial cells differentiated from ibs cells so i really hope these systems will contribute to the understanding of copy 19 and the development of new effective drug in the near future so once again we are suffering from nearly identical virus but we are seeing very different outcome in each country so we should learn from each other i i think this is very important in this pandemic era so let me move on the other important application of ips cells which is regenerative medicine the biggest advantage of ips cells is that we can utilize autologous ips cells ips cells from patients on blood cells however this process is very labor intensive and also very expensive so as an alternative we have been working on ipso stock for for regenerative medicine so in this strategy we have been using hla homozygous super doughnuts so if we identify this kind of hla homozygous donors we can cover uh many uh patients many recipients very effectively this one homozygous donors can match these four recipients out of 10 because they have red and something else whereas actually homozygous donors have read along so by getting a huge support from japanese red growth society we have been able able to identify multiple hla super donors and so far we have generated emp grade research grade ips cells from four hcra hyper types these four exterior prototypes along can cover up to 40 percent of all the japanese population we started shipping the first line uh almost five already five years ago so many clinical research and clinical trials are being conducted by using our ipswell stock including age-related macular degeneration corneal epithelial stem cell exhaustion parkinson's disease and ischemic cardiomyopathy in addition some other applications also or in clinical trial including retinitis pigmentosa head and neck cancer it's a cancer immunotherapy using ips cells and also platelet transfusion we can now make our colleague doctor cause eto or his team can make functional platelets from human ibs cells so all these in blue are already in clinical trials spinal cord injury and athletic disorder which are in euro their clinical trials have been approved by the japanese government because of the copied 19 the surgeries have been postponed but hopefully sometimes this year they can start clinical trial and other applications such as type 1 diabetes and leukemia this is again cancer immunotherapy these are very close to clinical trial so once again uh only by just four or hla super donors can cover up to 40 percent of japanese population but how about the remaining 60 percent and how about other population like u.s and uk so in order to cover uh the remaining japanese population we would need more than 150 april types and in order to cover world population we would need more than 1000 april prototypes and it's next to impossible to prepare this large amount of hla prototypes so as an alternative approach thanks to geneva wagner we are now using this approach genome editing approach so in our approach we look out c2ta active co-activator in order to suppress all class 2 msc and we knock out hra and hrab leaving intact hlac we need hlc to suppress nuke cell based immuno immunoreactivity so actually by using our h3 homozygous ips cells it's much easier to generate this kind of hlac on the ips cells because we would need only three guide rna by using hra homozygous ips cells so this is a huge plan for ips cell cell phase currently we can cover up to 40 percent of japanese population but since last year we have started distributing research-grade genome-edited ips cell line and this year we are trying to generate gmp grade genome editing ips cell stock so as small as 10 lines would cover most of wild population but for some patients and for some applications autologous ips cells may be required so for those patients we are trying to shrink the time and cost of autologous ips cell generation so that within five years we can generate patient owned ips cells my ips cells with affordable cost and within one or two months so this is our ultimate goal and uh these lines we have been talking to fda and we hope we are confident that these cell lines should be uh utilized to be uh approved by fda in the very near future we are still talking discussing with fda but we are very optimistic so with this i'd like to finish my talk i would like to thank uh all my collaborators both in japan and in grad gladstone uh this is my small lab at gladstone this picture is a bit old i need to update this picture but in order to update this picture i need to be in san francisco so i really hope we can overcome this pandemic situation as quickly as possible thank you very much

Channel: Gladstone Institutes

Views: 310

Rating: 4.5999999 out of 5

Keywords: Science, Research, Stem Cell, Cardiac, Neuro, Virology, Immunology, UCSF, Gladstone Institutes, Data Science, Biotechnology, Biomedical Science, Biotech

Id: rEPsI5dyLFY

Length: 26min 33sec (1593 seconds)

Published: Fri Feb 19 2021