The Role of Glycans in the Medicine of Tomorrow: Insights from 11 Leading Scientists

Podcast published on 8/29/2023 • Show notes written by Vanja Maganjic & Rina Bogdanovic

16 minutes reading time
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Episode summary

Is the future of medicine sweetened by the study of glycans? As GlycanHub rounds off its season, we've brought back the insights of 11 eminent scientists spanning from neuroscience to nanotechnology. Each guest delves into their vision of how glycans could shape medical advancements in their respective fields. Join Rina, our host, for a grand finale that paints a holistic picture of the promising horizon glycobiology is steering us towards.

Conversation timestamps

Answers to the question: What role do you think glycans will play in the future of medicine relevant to your area of study?

• Salome Pinho [01:21]
• Olga Zaytseva [03:04]
• Peter Joshi [03:51]
• Hudson Freeze [05:11]
• Samia Mora [06:11]
• Anna Halama and Karsten Suhre [08:09]
• Ronald Schnaar [12:03]
• Gordon Lauc [14:49]
• Louise Newson [17:35]
• Vered Padler-Karavani [18:47]

 

Episode transcript

Rina’s Intro

Rina Bogdanovic [00:05] Hello, hello, and welcome back to GlycanHub - the podcast in which we explore health, disease, and longevity through the lens of glycobiology. My name is Rina, and I am your host. Believe it or not, we have reached the final episode of this season, and for the grand finale, we decided to do something different. This season has featured 11 remarkable scientists from all over the world, spanning varied backgrounds from neuroscience, and immunology all the way to metabolomics and nanotechnology. Our guests represent the diverse intersections of the glycobiology field and its broad applications. Throughout this season, our discussions have revolved around the current state of glycobiology research, its potential challenges, innovative approaches, and the potential of glycans to revolutionise medicine. As we round off this season, we've asked each guest to answer a single, pivotal question: "What role do you think glycans will play in the future of medicine relevant to your area of study?" 

Salome Pinho’s Answer

Rina Bogdanovic [01:21] The first answer comes from Salome Pinho, the Immunology, Cancer and GlycoMedicine Group leader at the Institute for Research and Innovation in Health at the University of Porto as well as the affiliated Professor at Faculty of Medicine. During our conversation in the First Episode of this season we focused on the role of glycans in the immune system regulation both in the context of cancer and autoimmune disease. Here are Salome’s thoughts

Salomé Pinho [01:48] As I had the opportunity to mention, I believe that GlycoMedicine is a promising area that will have much potential to transform oncology but also to transform inflammatory diseases, autoimmune diseases, infectious diseases being actually at the frontiers of infection, inflammation, autoimmunity, and cancer. And GlycoMedicine, I'm talking about glycans as biomarkers of disease for risk stratification, for being included in the algorithm for clinical and therapeutic decisions of patients in many diseases, but also as a source of power. Therapeutic agents and the power of reprogramming or playing with the glycosylation signature of a specific cell, of a specific tissue will have a lot of impacts, not only in the immune response but also in other pathways associated with the biology of the cell. And of course of the tissue. Yeah, so I believe that GlycoMedicine is definitely a transforming area with many applicabilities in medicine.

Olga Zaytseva’s Answer

Rina Bogdanovic [03:04] Olga Zaytseva is a postdoctoral researcher at Genos – the leading laboratory for high-throughput glycomics. In Episode Two we talked about regulation of IgG glycosylation relevant to ageing and a range of chronic diseases. Let’s hear what Olga had to say.

Olga Zaytseva [03:23] I think that's actually in the future, we will see way more glycan biomarkers  in all kinds of diagnostics, way more than we are seeing now. I don't believe there will ever be a solo methods of diagnosing anything, but they definitely at least will be used in combination with current classic markers. Especially they will be important for cancer and autoimmunity I believe.

Peter Joshi’s Answer

Rina Bogdanovic [03:51] Peter Joshi is a tenured academic at the University of Edinburgh, and the Chief Scientist for Humanity Health, a company focussed on measuring and improving our rate of ageing. The focus of Episode Three was on biological age; we reviewed 11 different biological ageing clocks, taking into consideration their potential for clinical application. Let's now hear from Peter.

Peter Joshi [04:16] On the face of it, as we've been talking about, glycans are a marker of immunity and the immune system, and, you know, we've obviously got much greater thoughts about immunity and the immune system in front of our minds, following the recent pandemic. I also alluded to the fact and this data was gathered before the pandemic that it did look to us that glycans were a useful marker of real biological age, as opposed to simply measuring what we could measure any way from our calendars. And so I think there's a lot of prospects specifically there and in terms of prognostic tests for health, arising out of glycans, if we gather the data research, and it will be exciting to see how that goes.

Hudson Freeze’s Answer

Rina Bogdanovic [05:11] Hudson Freeze is the Director of the Sanford Children’s Health Research Centre and the Human Genetics Programme at Sanford Burnham Prebys Medical Discovery Institute. Our dialogue in Episode Four focused on the strides made in research and therapeutic interventions over the past three decades, focusing on congenital disorders of glycosylation. So, without further ado, here are Hudson’s thoughts 

Hudson Freeze [05:37] Glycans are everywhere. They do everything. We have to figure out what all their jobs are. First, as basic scientists, then we have to talk to physicians. We have to educate physicians and the families. Once they know that this is a glycosylation disorder, they're with us. So now I think that is going to be a big explosion. And it didn't hurt that Carolyn Bertozzi got the Nobel Prize and probably will give us a little boost.

Samia Mora’s Answer

Rina Bogdanovic [06:11] Samia Mora is a Professor of Medicine at Harvard Medical School and Director of the Centre for Lipid Metabolomics at the Brigham and Women’s Hospital in Boston, Massachusetts. In Episode Five, we discussed modifiable risk factors and the prevention of cardiovascular disease, as well as the potential of glycan-based biomarkers. Here is Samia’s answer to the question: What role do you think glycans will play in the future of medicine relevant to your area of study?

Samia Mora [06:42] I think it's going to be a very important area. Like I said, it's an explosion, it’s going to be an explosion, I think over the next decade because now we have the technology. And now you're ready to have many studies that will be investigating this kind of like what we have for the metabolomics and for the genomics and proteomics, I think this next decade is going to be the glycomics decade and the precision medicine, we're going to be able to incorporate glycomics also within the other omics. So we're going to see how does it relate to metabolomics and proteomics and genomics, and how can we put that all together, so we can more precisely tell for an individual whether it's their risk or their treatment for certain therapies or, over time how their profile is changing. So I think it's very exciting, Rina, and I do hope sincerely that worldwide there's going to be increased knowledge and understanding about the really key essential role of these simple sugar molecules that attach to proteins that we have just over the past few years really discovered what they do and these really promising results should be applied in the future to clinical investigations into clinical practice as well.

Anna Halama and Karsten Suhre’s Answer

Rina Bogdanovic [08:09] Karsten Suhre is the Professor of Physiology and Biophysics and the Director of Bioinformatics Core, and Ania Halama is an Assistant Professor in Research of Physiology and Biophysics at Weill Cornell Medicine in Qatar. In Episode Six, we explored the impending metabolomics revolution in research as well as its transformative potential in disease diagnosis and treatment. Here is what Ania and Karsten had to say. 

Anna Halama [08:38] I was not ignorant towards glycans, but I think the congress I attended last year, 2022 - The Third Human Glycan Project was kind of eye-opening for me and just even more strongly made me think that this will be also another step for me considering it for including in the cancer research, especially based on the hints which we were finding, looking at the molecular human, because we're having multiple interesting hits, which were relating to cancer. And this is something which I would like to investigate on the samples, the patient samples, which I'd have also would like to closely work with, glycomics community, you know, to make sure that whatever I'm doing, it's not something that shouldn't be done, because this is a very important thing. So I see that, first of all, making sure that there is some kind of mechanistic component to the things which we saw as hits in our molecule or human in the context of cancer, I can reproduce in the lab, but also to go further with the clinical samples which I have to do maybe some kind of fishing experiments, but I believe it will gonna bring me to another question and some kinds of answers which we started to see molecular human having this diabetic non-diabetic population, but in the cancer patient and non-cancer patients, right, we should see even stronger signals. So this is where we're, I would like to go and look up.

Karsten Suhre [10:15] I don't want to be cited as this IBM managers years back, who said there was no reason to have a PC in everybody's home. And nowadays, he has to swallow his words. At the moment, I don't think I mean, I would tend to say, there's not much I've seen until now in the clinic. But I think there is a real elephant in the room that some people just pretend glycans are not there. Like, I remember Gordan showed this on Twitter, the image of the COVID spike protein with and without glycans. And to see that some people just pretend they're not there, and others say they are there, there's definitely, I think, still a gap. And there will be probably some surprises there. So I think it's very hard to predict what the role of glycans in the clinic will be in a few years time. But I'm very curious about that. And I think, as we discussed before, the point is, you really need more comprehensive measures of glycans to actually show that they really play a role. And I think genome wide association studies are certainly the first step to that, to show that if I take over the genome, I tinker with something else. And maybe these genetic variants overlap with disease loci, I mean, then, I think the interest would really be kicked off in in these glycans. More studies are needed. But I'm still a bit hesitant because as I said, most of these glycans we're measuring they're just IgG glycans or just global glycans. And if there's really a glycan code or something like that, we're not there yet to understand that if the glycan code is really there and doing something, then it definitely will have a role in the clinic, but it still needs to be discovered.

Ronald Schnaar’s Answer

Rina Bogdanovic [12:03] Ronald Schnaar is a Professor and Interim Director of the Department of Pharmacology and Molecular Sciences and a Professor of Neuroscience at Johns Hopkins University School of Medicine. During Episode Seven, he introduced us to the role of glycans in healthy brain structure and function, as well as how glycan research reframed our understanding of the cause of Alzheimer’s disease. Let’s hear what Ron had to say.

Ronald Schnaar [12:31] There are multiple areas I think that are already being successfully addressed in medicine and will be in the future. One example is glyco-genes, they can have mutations that cause disease, and we already in the clinic, have enzyme replacement therapy for those. And I think in the future, those will be addressed by gene therapies. There are already what we call glycomimetics, those are drugs that mimic the shape of a glycans involved in a biological event. One that comes to mind is Tamiflu, which is an anti-influenza drug which mimics the sugar sialic acid. And that molecule can alter the course of infectious disease. There are others in the area of inflammation, that are also in the clinic, both sugar mimetics that can change inflammation, and glycan binding proteins taht can be delivered to change inflammation. And those are being tested now in the clinic for persistent short-term inflammatory diseases. So I think in the future, that's going to be the model, we're going to have easier and faster ways to build glycans, in shapes and formats that can be delivered as drugs, we're going to have glycans binding proteins, antibodies to glycans, and in that area that is going to be deliverable, replacement therapy, and of course, gene therapy. So I think it's a big area, and I think there are lots of ways that glycobiology can contribute.

Gordon Lauc’s Answer

Rina Bogdanovic [14:49] Gordan Lauc is a Professor of Biochemistry and Molecular Biology at the University of Zagreb Faculty of Pharmacy and Biochemistry and founder and CEO of Genos. He is also the chief scientific officer at GlycanAge. In Episode Eight, we reflected on the Covid-19 pandemic, focusing on how glycans have enhanced our understanding of susceptibility to Covid-19 and consequent disease severity. Here are Gordan’s thoughts regarding the question: What role do you think glycans will play in the future of medicine relevant to your area of study?

Gordan Lauc [15:29] This will take time. But eventually, glycans will become the most informative biomarkers, because glycans integrate genetic, epigenetic and environmental factors. Today, we use genes a lot to try to predict individual variation in the disease response or therapy response. And to some extent, this works. But the problem with genes is that genes do not change as we age, and the disease risk and the response to drugs are changing with time. So genes will always tell us a part of information. Glycans will have this genetic component, but to have also epigenetic and environmental components, so glycans in this respect, are more similar to complex diseases than any other set of molecules because the leaves are also a consequence of your genetic epigenetics and environment. Glycans are consequences of genetics, epigenetics and environment, we just have to find the right glycan to use as a biomarker for each disease. This will take time because glycome is several orders of magnitude more complex than the proteome. So we have 20,000 genes, maybe 100,000 proteins, we have 10 or 100 million different glycoproteins. So that's why I say it will take time for the technology to develop for the knowledge to be accumulated. And I think glycome today is where the genome was in the 90s. So it requires much more work, many more people working on it. But there is a bright potential because the glycome is the ultimate level of molecular complexity. So once we stop ignoring it and we start to research it more, this will become the most informative biomarker.

Louise Newson’s Answer

Rina Bogdanovic [17:35] Louise Newson is a GP and a Renowned Menopause Specialist. She is the founder of the balance app, The Menopause Charity, Newson Health Menopause Society, a bestselling author as well and a member of the UK Government Menopause Taskforce. Episode Nine unpacked the connection between perimenopause, menopause, and chronic diseases, the implications of HRT, and the emerging role of glycans as menopause biomarkers. Let's now hear from Louise.

Louise Newson [18:08] Well, I hope it will play a big role. Actually, I think it will enable women to have more control, which I think is really important. I think, if we work it out properly, it will be able to allow women to make the diagnosis of either perimenopause or menopause quicker, but it will also reshape their future health as well by allowing them to have an objective measurement of what their health is like, and hopefully improving as well in a way that we can't do otherwise at the minute so I think it's a really exciting time looking at GlycanAge with respect to female hormones.

Vered Padler-Karavani’s Answer

Rina Bogdanovic [18:47] Vered Padler-Karavani is the principal investigator in the Department of Cell Research and Immunology at Tel Aviv University. The season's Final Episode delved into xeno-auto antigens, illustrating the link between red meat consumption, inflammation, and cancer susceptibility. Here are Vered’s thoughts 

Vered Padler-Karavani [19:08] I think glycans have a major role. As I said, evolution has never been able to invent a cell that is not covered with glycans. So it has a detrimental role. And definitely, the crosstalk between glycans and the immune system is key to understanding the disease conditions in humans and also how to exploit that into therapy and diagnostics. And it spans everything in life because the sugars are really covering every cell, and most of the proteins, actually more than 90% of the proteins, are glycosylated. So I'm pretty sure it will play a key role. But it's yet, of course to be investigated.

Rina’s Outro

As we draw this exciting season to a close, I want to express my gratitude to all our guests for joining me on the show and helping us spread the word about this incredible field called glycobiology. If you haven’t already, I really encourage you to listen to these episodes. I have to say that regardless of how much I prepared for the interviews, I left every conversation having learnt something new or unexpected. To find out more about our guests, just follow the link in the description to the episode show notes at our GlycanHub page. I am very proud to say that GlycanHub is the first ever podcast focusing on the field of glycobiology, and I am very honoured for having had the opportunity to host it and bring such pivotal research into the spotlight. Of course, a huge, huge thank you to GlycanAge for making this podcast possible. To our listeners, thank you for tuning in and taking this journey with us. I encourage you to stay curious, keep exploring, and delve deeper into the fascinating world of glycobiology. As always, I hope you have a great day. Thank you for listening!

 

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Disclaimer

Please be advised that this show is for information only and should not be considered as a replacement or equal to medical advice.