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Name:
Discovery and clinical implementation of pharmacogenomics
Description:
Discovery and clinical implementation of pharmacogenomics
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https://cadmoremediastorage.blob.core.windows.net/c2bc5425-7397-4d67-8374-bbe4f037520d/videoscrubberimages/Scrubber_15.jpg
Duration:
T00H09M50S
Embed URL:
https://stream.cadmore.media/player/c2bc5425-7397-4d67-8374-bbe4f037520d
Content URL:
https://asa1cadmoremedia.blob.core.windows.net/asset-52be19b9-8b4b-4bef-a2fb-917b8b85e7be/Jun Yang - Interview V3.mp4
Upload Date:
2020-01-27T00:00:00.0000000
Transcript:
Language: EN.
Segment:1 Introduction.
JUN YANG: My name is Jun Yang. I'm a faculty member at the pharmaceutical sciences department at St. Jude Children's Research Hospital in Memphis, Tennessee, USA.
Segment:2 Can you tell us about your presentation?.
JUN YANG: So I'm actually giving a talk today in their pharmacogenetics session. I will specifically talk about the discovery science in pharmacogenomics and also its clinical implementation using one gene that we have been studying for the past four years as example of how things translate from the lab all the way to the clinical practice.
JUN YANG:
Segment:3 What are the challenges in translation of pharmacogenomic discoveries into clinical practice?.
JUN YANG: That's actually a very good question. I think it's a somewhat complicated scenario or a question, if you well. I think there are at least two things that are very important. Number one is we need to do more discovery. We need to identify more pharmacogenetic variants associated with drug response. The challenge there sometimes it can be very challenging or difficult to really identify the intra-patient variation in drug response, because it can be subjective in many different ways.
JUN YANG: So we have to find the perfect solution to really standardize the way that we measure drug response across different settings. So when we're able to do that, we're able to look across different cohorts, different patient populations and really to do large scale pharmacogenetic discovery. So I think that's challenge number one in terms of the discovery.
JUN YANG: But maybe even more significant a challenge is the clinical implementation or translation. You can identify a pharmacogenetic variant, especially with the response of a specific drug. But oftentimes when you put that into clinical practice, it becomes a lot more difficult, especially for people who are not trained in pharmacogenetics to understand. You can say that I have identified variants.
JUN YANG: Then I push that out into the clinical laboratory for people to sequence that variant or genotype that variant. But once the result comes out, it's up for the physicians to really understand what that means. I think there is quite a significant gap in terms of what we understand as people doing pharmacogenetic discovery and what the practice of physicians can understand in terms of the results from pharmacogenetic testing.
JUN YANG: I think it was maybe about 10 years ago there was definitely a huge recognition of this issue and a new response to the unmet needs. They formed what we call CPIC-- Clinical Pharmacogenetics Implementation Consortium. It's a group of investigators, in academia primarily, really get together, try to put together this consortium and try to address that specific need. They develop what we call clinical guidelines for pharmacogenetics implementation.
JUN YANG: So they have already identified the gene-drug pairs for which there is a very clear clinical implementation or need for clinical implementation. And they develop very specific guidelines for you to not only interpret the pharmacogenetic testing results, but also to tell you how to use the result to guide the therapy-- either as to give a different dose of the same drug or to use a different drug altogether.
JUN YANG: So I think that type of effort is actually incredibly important in terms of moving pharmacogenetics from discovery into clinical practice. I think that we need more of that in the next few years as we make more and more discoveries.
Segment:4 Pharmacogenomics in precision medicine.
JUN YANG: Of course, I'm biased, because I study pharmacogenetics. I feel pharmacogenetics-- of the entire genetics field, pharmacogenetics is probably amongst a small group of fields or area where we're actually very, very close to the front-line of precision medicine.
JUN YANG: So once you identify genetic variants, specifically related to a response to a drug, there is a very strong clinical implication. So I cannot stress enough how important pharmacogenetics is in the entire context of precision medicine. I think in the next few years, as we make more discoveries in pharmacogenetics, as we expand the CPIC guidelines, I think you will see more and more incorporation with pharmacogenetics in clinical practice that can really push the field of precision medicine in a very significant way.
JUN YANG:
Segment:5 Techniques in pharmacogenetics.
JUN YANG: That's a very good question. I think the field evolved quite a bit. Back in the days when I first started, people were doing a lot of genotyping. People know, for example, if a specific enzyme is responsible for the metabolism of a specific drug. And they just to sequence or genotype that specific gene. And then as I started my lab about 10-something years ago, there was a lot of GWAS going on.
JUN YANG: So there, people are moving above and beyond what they knew already. They really start taking agnostic approach to look at a variant across the entire genome using their genome-wide association study approach. And as a result, we have identified many, many new variants in new genes that are related to drug metabolism and drug response, which we didn't know before.
JUN YANG: But now, I think the field moved even further above and beyond that. People are doing whole actual sequencing, whole genome sequencing to look at even broader space of genetic variants. A particular advancement I'm very excited about in the past couple of years is the exhaustive muta-genesis approach. So traditionally, we identify one variant in one patient, and we know it's related to a response to a specific drug.
JUN YANG: But the more patients you sequence, the more variants you identify. It becomes very, very difficult to study the function with specific variants one at a time. So a couple of years ago, a number of labs in the US started looking into this issue and developed functional genomics tools to be able to look at all possible variants of a given gene in a comprehensive and exhaustive way.
JUN YANG: So now we have a couple of genes where we have this preemptive sort of lookup table. You have the function of all possible variants within the same gene. I think having that sort of information really helps the clinical implantation moving forward. I think this, to me, is a pretty significant breakthrough in terms of pushing pharmacogenomics into the future for the next few years at least.
JUN YANG:
Segment:6 The future of pharmacogenomics.
JUN YANG: In terms of patient care, I really hope that we can move above and beyond just testing one gene for one drug. I think everybody in the health care system, for example, should get their genotype done at birth. And then you have all the information-- either its whole genome sequencing or whole actual sequencing.
JUN YANG: And then you have this information of your genetic makeup that will go with you for the rest of your life. And instead of you take this drug, you have this toxicity, and then you go back to check whether you have the genetic variants. What if we can just do sequencing or pharmacogenetic testing up front preemptively? Then we have the information in your medical records.
JUN YANG: And I think that can actually improve the efficiency of the health care a very substantial way. So that will be a huge step forward if it can realize that. And also I think on the discovery side, we need to really ramp up the efforts to do a better job at genotyping drug response and to do a better job of standardizing the way that we phenotype patients and to have a more unified or a collaborative way to look across different patient populations, different race ethnicities, and to really empower the scientists to do more pharmacogenomic discovery.
JUN YANG: I think that, in the next few years, will really move the field forward.
Segment:7 Heroes and inspirations.
JUN YANG: When I was finishing up my PhD, I thought about doing pharmacogenomics because I had a background in human genetics for my master's degree and I studied pharmacology for my PhD. I thought it would be very natural to marry the two together.
JUN YANG: I specifically reached out to Dr. Mary Relling and Doctor Bill Evans at St. Jude Children's Research hospital, because they are very well recognized pioneers in the field of pharmacogenetics. So when I reached out to them, they really embraced this idea of having me in the lab. And it's interesting-- although I had a background in genetics and pharmacology, I had no idea about how to do pharmacogenetics.
JUN YANG: So I really want to thank them for taking me in, although I had very little background in pharmacogenetics specifically. Over the years, they taught me exactly how to do it. And I cannot really thank them enough for really taking me on-- maybe going a little bit on a limb given the little background on that in pharmacogenetics. And I think they had a very, very significant and positive impact on my career.
JUN YANG: And I could not be happier that I decided to train with them.
Segment:1 Introduction.
JUN YANG: My name is Jun Yang. I'm a faculty member at the pharmaceutical sciences department at St. Jude Children's Research Hospital in Memphis, Tennessee, USA.
Segment:2 Can you tell us about your presentation?.
JUN YANG: So I'm actually giving a talk today in their pharmacogenetics session. I will specifically talk about the discovery science in pharmacogenomics and also its clinical implementation using one gene that we have been studying for the past four years as example of how things translate from the lab all the way to the clinical practice.
JUN YANG:
Segment:3 What are the challenges in translation of pharmacogenomic discoveries into clinical practice?.
JUN YANG: That's actually a very good question. I think it's a somewhat complicated scenario or a question, if you well. I think there are at least two things that are very important. Number one is we need to do more discovery. We need to identify more pharmacogenetic variants associated with drug response. The challenge there sometimes it can be very challenging or difficult to really identify the intra-patient variation in drug response, because it can be subjective in many different ways.
JUN YANG: So we have to find the perfect solution to really standardize the way that we measure drug response across different settings. So when we're able to do that, we're able to look across different cohorts, different patient populations and really to do large scale pharmacogenetic discovery. So I think that's challenge number one in terms of the discovery.
JUN YANG: But maybe even more significant a challenge is the clinical implementation or translation. You can identify a pharmacogenetic variant, especially with the response of a specific drug. But oftentimes when you put that into clinical practice, it becomes a lot more difficult, especially for people who are not trained in pharmacogenetics to understand. You can say that I have identified variants.
JUN YANG: Then I push that out into the clinical laboratory for people to sequence that variant or genotype that variant. But once the result comes out, it's up for the physicians to really understand what that means. I think there is quite a significant gap in terms of what we understand as people doing pharmacogenetic discovery and what the practice of physicians can understand in terms of the results from pharmacogenetic testing.
JUN YANG: I think it was maybe about 10 years ago there was definitely a huge recognition of this issue and a new response to the unmet needs. They formed what we call CPIC-- Clinical Pharmacogenetics Implementation Consortium. It's a group of investigators, in academia primarily, really get together, try to put together this consortium and try to address that specific need. They develop what we call clinical guidelines for pharmacogenetics implementation.
JUN YANG: So they have already identified the gene-drug pairs for which there is a very clear clinical implementation or need for clinical implementation. And they develop very specific guidelines for you to not only interpret the pharmacogenetic testing results, but also to tell you how to use the result to guide the therapy-- either as to give a different dose of the same drug or to use a different drug altogether.
JUN YANG: So I think that type of effort is actually incredibly important in terms of moving pharmacogenetics from discovery into clinical practice. I think that we need more of that in the next few years as we make more and more discoveries.
Segment:4 Pharmacogenomics in precision medicine.
JUN YANG: Of course, I'm biased, because I study pharmacogenetics. I feel pharmacogenetics-- of the entire genetics field, pharmacogenetics is probably amongst a small group of fields or area where we're actually very, very close to the front-line of precision medicine.
JUN YANG: So once you identify genetic variants, specifically related to a response to a drug, there is a very strong clinical implication. So I cannot stress enough how important pharmacogenetics is in the entire context of precision medicine. I think in the next few years, as we make more discoveries in pharmacogenetics, as we expand the CPIC guidelines, I think you will see more and more incorporation with pharmacogenetics in clinical practice that can really push the field of precision medicine in a very significant way.
JUN YANG:
Segment:5 Techniques in pharmacogenetics.
JUN YANG: That's a very good question. I think the field evolved quite a bit. Back in the days when I first started, people were doing a lot of genotyping. People know, for example, if a specific enzyme is responsible for the metabolism of a specific drug. And they just to sequence or genotype that specific gene. And then as I started my lab about 10-something years ago, there was a lot of GWAS going on.
JUN YANG: So there, people are moving above and beyond what they knew already. They really start taking agnostic approach to look at a variant across the entire genome using their genome-wide association study approach. And as a result, we have identified many, many new variants in new genes that are related to drug metabolism and drug response, which we didn't know before.
JUN YANG: But now, I think the field moved even further above and beyond that. People are doing whole actual sequencing, whole genome sequencing to look at even broader space of genetic variants. A particular advancement I'm very excited about in the past couple of years is the exhaustive muta-genesis approach. So traditionally, we identify one variant in one patient, and we know it's related to a response to a specific drug.
JUN YANG: But the more patients you sequence, the more variants you identify. It becomes very, very difficult to study the function with specific variants one at a time. So a couple of years ago, a number of labs in the US started looking into this issue and developed functional genomics tools to be able to look at all possible variants of a given gene in a comprehensive and exhaustive way.
JUN YANG: So now we have a couple of genes where we have this preemptive sort of lookup table. You have the function of all possible variants within the same gene. I think having that sort of information really helps the clinical implantation moving forward. I think this, to me, is a pretty significant breakthrough in terms of pushing pharmacogenomics into the future for the next few years at least.
JUN YANG:
Segment:6 The future of pharmacogenomics.
JUN YANG: In terms of patient care, I really hope that we can move above and beyond just testing one gene for one drug. I think everybody in the health care system, for example, should get their genotype done at birth. And then you have all the information-- either its whole genome sequencing or whole actual sequencing.
JUN YANG: And then you have this information of your genetic makeup that will go with you for the rest of your life. And instead of you take this drug, you have this toxicity, and then you go back to check whether you have the genetic variants. What if we can just do sequencing or pharmacogenetic testing up front preemptively? Then we have the information in your medical records.
JUN YANG: And I think that can actually improve the efficiency of the health care a very substantial way. So that will be a huge step forward if it can realize that. And also I think on the discovery side, we need to really ramp up the efforts to do a better job at genotyping drug response and to do a better job of standardizing the way that we phenotype patients and to have a more unified or a collaborative way to look across different patient populations, different race ethnicities, and to really empower the scientists to do more pharmacogenomic discovery.
JUN YANG: I think that, in the next few years, will really move the field forward.
Segment:7 Heroes and inspirations.
JUN YANG: When I was finishing up my PhD, I thought about doing pharmacogenomics because I had a background in human genetics for my master's degree and I studied pharmacology for my PhD. I thought it would be very natural to marry the two together.
JUN YANG: I specifically reached out to Dr. Mary Relling and Doctor Bill Evans at St. Jude Children's Research hospital, because they are very well recognized pioneers in the field of pharmacogenetics. So when I reached out to them, they really embraced this idea of having me in the lab. And it's interesting-- although I had a background in genetics and pharmacology, I had no idea about how to do pharmacogenetics.
JUN YANG: So I really want to thank them for taking me in, although I had very little background in pharmacogenetics specifically. Over the years, they taught me exactly how to do it. And I cannot really thank them enough for really taking me on-- maybe going a little bit on a limb given the little background on that in pharmacogenetics. And I think they had a very, very significant and positive impact on my career.
JUN YANG: And I could not be happier that I decided to train with them.
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