Latest / Minnesota Masonic Histories and Mysteries / Episode 146: Our Health Journey (ft. Dr. Silvia Balbo)

Transcript

Episode 146: Our Health Journey (ft. Dr. Silvia Balbo) · Minnesota Masonic Histories and Mysteries

• 0:00
  You earned your MS and PhD in medicinal chemistry at the University of Torino in Italy after completing part of your doctoral work in Belgium.
• 0:10
  Immediately after your thesis defense, you joined the International Agency for Research on Cancer in Lyon, France as a postdoctoral fellow.
• 0:20
  you then moved to work at the Masonic Cancer Center at the University of Minnesota, and in 2014 joined the faculty of the Division of Environmental Health Sciences in the School of Public Health at The U.
• 0:32
  Welcome, Dr.
• 0:33
  Silvia Balbo.
• 0:34
  Thank you.
• 0:35
  Thank you for having me.
• 0:36
  Your lab's research is focusing on mechanisms of carcinogenesis from environmental and lifestyle-related exposures.
• 0:45
  We're talking cancer.
• 0:46
  Using cutting-edge technology, I wanna hear about the development of innovative approaches in understanding causes of cancer and applying them to identifying people at risk, as the goal is to improve the prevention, detection, and treatment of cancer We met recently at the Masonic Cancer Center gala, the Illuminate Gala- Mm-hmm which was fantastic.
• 1:09
  We're looking forward to next year's already.
• 1:11
  I know you're extremely passionate about your research and the impact, and that you are constantly seeking better ways to effectively share with that broader audience the importance of the work done by scientists and researchers at our Masonic Cancer Center.
• 1:27
  What first made you want to understand why cancer develops and not just how to treat it?
• 1:35
  So it all started really, uh, with my experience in the International Agency for Research on Cancer, IARC, um, that is part of WHO, and it's located in Lyon, as you mentioned earlier.
• 1:48
  And it started from the fact that back there, I realized how much we know from the epidemiology about connections between exposures and cancer, and yet how little we know about really the mechanisms through which certain exposures are leading to cancer.
• 2:04
  So the steps, what is happening really at a molecular level.
• 2:09
  And so coming to the University of Minnesota and specifically to the Masonic Cancer Center, I was able to see how labs here were using technology to really try to dive deep into how these exposures are specifically leading to DNA damage, um, and then potentially mutations and ultimately cancer, and how we can use, um, these approaches to really understand those steps and these processes and try to clarify why certain people ultimately, even if exposed, are not developing cancer and others instead will.
• 2:44
  and so I really became fascinated by the ability of, of doing this kind of research.
• 2:50
  I realized that the Masonic Cancer Center was really a place unique in, in allowing me and, and the collegiality and the potential, that is available, um, at the cancer center and, and really allow me to think that I could make a difference in, in doing this kind of research.
• 3:09
  and so that's where my passion, um, started and, uh, and still is.
• 3:15
  Was there a particular person or experiment, maybe even an experience that made the work feel more personal to you?
• 3:27
  The experience really came from the fact of seeing that the work that I was doing could actually be meaningful and impactful immediately, or scientifically speaking immediately.
• 3:39
  Obviously, science takes some time.
• 3:41
  But, when I was at IARC again back in Lyon, we were looking at connections between alcohol and, uh, esophageal and head and neck cancer.
• 3:51
  And again, back at that point, we had a clear understanding of that connection from the epidemiology.
• 3:58
  But coming to the University of Minnesota, I started looking at using some of the techniques that were developed by, um, Dr.
• 4:06
  Steve Hecht, um, which is also in the Carcinogenesis and Chemoprevention program, where I'm now.
• 4:12
  And he was using mass spectrometry to really understand how alcohol, which is then turned into acetaldehyde, would become, connected or would react with DNA and lead to DNA damage.
• 4:24
  And so I was able to use his approaches to then look at samples from people that were exposed to alcohol and really try to understand that connection, if that connection is there, is real, and if we can use those methods to quantify it.
• 4:39
  Um, and so from work that we started back then, um- What year was that?
• 4:43
  That was 2008.
• 4:47
  Um, we started a project where we would have people coming, and they would drink alcohol, uh, in our clinical setting, and then we would take mouth, uh, wash and swabs, um, before and then after, different time points after the alcohol consumption.
• 5:03
  And we looked for that DNA damage.
• 5:05
  And we were able to see that actually it was really happening, that the alcohol that we were giving was increasing the acetaldehyde-derived DNA damage in people who were drinking.
• 5:15
  And this was depending on the amount that they were drinking, so there was a dose-dependent relationship.
• 5:21
  That work was used by IARC to then produce new guidelines and really produce information that would inform people about the fact that, yes, we have a connection that is epidemiologically seen, but we also have a mechanism that is supporting that connection.
• 5:37
  And if we have a mechanism, we can understand a little bit better how to interfere with it and what happens if that mechanism is taking place more in one person versus another one.
• 5:47
  And so with that, I saw that the work could really be used immediately, uh, for, you know, providing guidelines, for providing policies and so on and so forth.
• 5:57
  And so that is where I, I really had a, a trigger in terms of I wanna do this more, and, uh, I wanna do this for the rest of my life.
• 6:07
  When it comes to alcohol- Is it about understanding that it's a risk factor for certain cancers?
• 6:15
  How important, based on what you just shared too, moderation, reducing the amount that we ingest because there's other risk factors that are tethered to that.
• 6:25
  How, how much does that impact our bodies?
• 6:27
  Yeah.
• 6:28
  So alcohol obviously impacts our bodies in, in a multitude of ways, right?
• 6:33
  So we know that there are a lot of different effects, and we have been focusing mostly on the connection with cancer, and, and therefore the, the really, the, the processes and the mechanisms that could could result in, in cancers forming.
• 6:46
  Um, what happens is that we know that there is a connection.
• 6:52
  We know that we are trying and starting to understand better what the mechanisms are, but we're still very vague in the, um, recommendations in terms of how much we can drink or how much is considered to be safe, or are there instead people or situations where there is no safe level.
• 7:10
  And so we're trying to really dig further into these steps and mechanisms of the process so that we can be more clear in understanding exactly how much, uh, people should be or should not be drinking, depending on their risk factors and depending on their lifestyle choices.
• 7:28
  We all know that the pour that we give ourselves at home is different than what we would get in a restaurant or at a sporting event Is there a risk factor, a cause and effect with alcohol and breast cancer that you've seen?
• 7:42
  Yeah.
• 7:42
  I'm not focusing specifically on the connection between alcohol and breast cancer, but certainly the, um, most, you know, the, the evidence and the, the work that has been done by the International Agency for Research on Cancer, or more recently, the report from the surgeon general really shows and indicates that there is a connection between alcohol consumption and breast cancer, and this can be already seen for lower levels of consumption.
• 8:06
  So we know that there is, uh, a risk associated with drinking.
• 8:10
  and so because of that, I think that moderation is particularly, in this case, key.
• 8:16
  And when I talk about moderation, it's not elimination.
• 8:20
  It's not about all of a sudden stopping drinking.
• 8:23
  It's about thinking of how much we're drinking and potentially start reducing maybe the frequency, maybe the amounts, um, maybe alternating with days in which we don't drink, or just making choices knowing, um, better of some of the risks that are associated with alcohol.
• 8:41
  Because it is easy to get into a nightly habit.
• 8:45
  Mm-hmm.
• 8:46
  Are you saying seven nights a week is maybe not ideal, that that frequency factor is just as important as the quantity?
• 8:52
  I, I think so.
• 8:53
  I think that it's pretty clear that the frequency and the, not just in alcohol, in all sorts of exposures, if you have that constant frequent, what we would say chronic exposure, certainly that poses a risk.
• 9:06
  So you have the perception that you're not exposing yourself too much, but you are constantly doing it, and that is also, uh, a potential, uh, increase in risk.
• 9:17
  What would you recommend?
• 9:19
  if somebody were to share,"Maybe I'm having a bit too much during the week-" Mm-hmm.
• 9:24
  How, how do you either regiment or sk- I don't wanna say schedule that, but to, to figure out- No, yeah what, what works?
• 9:29
  'Cause I, I hear you.
• 9:30
  You're not trying to be the fun police.
• 9:32
  You're not advocating.
• 9:33
  No.
• 9:33
  Although, uh, pers- on a personal level, breaking up with alcohol almost six years ago was one of the best gifts I've ever given myself.
• 9:41
  But to those that wanna have a little imbibe here and there, what do you, what do you say?
• 9:45
  Yeah, so I usually recommend, and I've recommended this to myself, too, again, as I was saying earlier, to kind of break that daily consumption, to have maybe alternate days in which we don't have alcohol or maybe we have non-alcoholic, um, alternatives.
• 10:04
  Making sure that we are, um, eating while drinking, so having, um, you know, a, a drink while having a nice meal is different than having a drink without any kind of, uh, food, uh, coming with it.
• 10:17
  Um, making sure that we're drinking a lot of water.
• 10:19
  so there are a lot of different things that can be done to sort of reduce, um, the really, the, the amount and the, uh, frequency, that we are, um, drinking.
• 10:32
  You trained in Italy and Belgium and worked at the World Health Organization's cancer research agency in France, and then you came to Minnesota.
• 10:41
  How did that journey change the questions you wanted to answer or the areas you wanted to pursue?
• 10:49
  As I was saying earlier, that journey ended in, in Minnesota and specifically at the Masonic Cancer Center because I realized that I could ask questions that I could address with the technology and the techniques that were developed at the cancer center.
• 11:05
  I could further develop them and, and also turn them to different questions and really make an impact.
• 11:12
  And so I was able to really take my skills and the experiences that I have sort of collected in my journey and finally put them at use.
• 11:22
  And, and that was a great, really great feeling.
• 11:25
  And I feel like, again, here we're able to really make an impact.
• 11:30
  So the program that I mentioned earlier, their Carcinogenesis and Chemoprevention program at the Masonic Cancer Center, was really built on, uh, tobacco research.
• 11:41
  And the impact of the research that has been done here at the Masonic Cancer Center by the people that have been working on this has been really profound.
• 11:51
  and so we're using...
• 11:52
  That is still ongoing, obviously, but we're using-- and I've been able to use that as sort of a blueprint of saying,"Okay, the same methods, the same approaches we've used to understand what happens when people are smoking can be then used and applied to other exposures," and alcohol is one of them.
• 12:09
  But I've also been looking at, uh, for instance, um, genotoxins that are produced by microbes that we may be infected with.
• 12:16
  Um, so these can have an impact on colorectal cancer.
• 12:21
  we've been looking at, um, nitrosamine, um, contaminants in, uh, pharmaceuticals.
• 12:27
  So there are all sorts of different exposures that may have that interaction, chemical interaction with DNA, and ultimately that can lead to cancer that we can tackle and i- we can investigate.
• 12:38
  and that ability to do this, uh, is really what brought me here, kept me here, and is keeping me here.
• 12:48
  We've heard a recurring theme from several guests that have been on the podcast, Dr.
• 12:52
  David Largaespada, Dr.
• 12:54
  Zohar Sachs.
• 12:55
  There is a very healthy culture, the congeniality that you talked about, the sense of team collaboration.
• 13:03
  Those are often buzzwords in a lot of corporate or company settings, but it, it is the real deal at the Masonic Cancer Center here in Minnesota.
• 13:11
  Absolutely.
• 13:12
  It is truly something that I think the Masonic Cancer Center has been thinking about actively, has been investing in, um, and has been pursuing and fostering throughout.
• 13:26
  the building in which we are, the, Masonic Cancer Center research building is designed to have all the offices of the researchers sort of sharing the same hallway, and the labs are sort of one feeding into the other one.
• 13:42
  That kind of environment really helps collaboration, helps understanding what others are doing and try to understand if what they are doing can be helpful for what we are doing.
• 13:53
  Allows a collaboration, a level of collaboration that can be really synergistic, and I think it's quite unique.
• 14:00
  In addition to that, the Masonic Cancer Center has some shared resource, uh, facilities or core facilities where we can have access to cutting-edge technology, where we don't have to invest our own lab money for, for, you know, a brand-new instrument.
• 14:18
  We have access to instruments that we can then share with others, and that allows us to do cutting-edge work with the best technology, without having the burden of having to invest in it and then, you know, keep up with the maintenance or, upkeeping of instrumentation that can be extremely, uh, difficult and expensive and also time-consuming.
• 14:41
  And so we are put in a position where we have access to infrastructure and to resources that we can use efficiently, with, I think, the, the maximum outcome, which is, you know, making sure that we have the best, techniques and the best methods.
• 14:57
  and if there is any new technology coming in, that also is something that is always, uh, in, on the radar.
• 15:04
  And so these cores are constantly being updated and are constantly being really kept to the point where we can have access to the best, uh, approaches and best technologies.
• 15:16
  You study what happens when chemicals interact with our DNA.
• 15:21
  Can you walk us through that process as though we're standing beside you in the lab?
• 15:27
  So we usually are looking at-- We-- Everything starts from, um, really what the epidemiology is telling us.
• 15:36
  Is there-- If there's a link, if there's something that is-- seems to be associated, um, an exposure that is associated with a specific type of, of cancer or carcinogenic process.
• 15:47
  And we try to then bring that back into the lab, thinking about how we can test or measure that exposure and its interaction with DNA, and then see if we can a- if effectively see it, it's happening, it's true, and then if we can measure it.
• 16:05
  So we use usually then, um, animal models or cells, um, and have them, uh, have those exposed to that particular chemical that we're looking at, and then extracting the DNA, we look for those modifications using, mass spectrometry.
• 16:21
  And that allows us to really specifically look at the chemical modification of DNA that corresponds to that exposure.
• 16:28
  My lab, though, is always, and I know that other labs in the, um, Masonic Cancer Centers do that as well, always matches that kind of work in vitro or in vivo, but in the lab, with samples that come from epidemiological studies where we can just make sure that what we're seeing in our in vitro tests or in our animal models is actually something that we can also detect, uh, in people, so that we don't go down a rabbit hole of something that is, you know, meaningful but only for our, uh, laboratory, tests, but that is meaningful for a population too.
• 17:02
  And so that's where, for instance, the work that I was mentioning earlier on alcohol, uh, and effects of alcohol on d- on, uh, DNA, that's the reason why we went on and did this, um, clinical study to make sure that the interactions that we were seeing in our models would be also meaningful for, um, a study that would look at effects of alcohol, um, in, in people who are drinking and are consuming alcohol.
• 17:31
  So when you find chemical damage to DNA, what does that tell you exactly about cancer risk?
• 17:38
  Or maybe what does it not tell you?
• 17:41
  So it's part of a step, right?
• 17:44
  It's a part of a process that comes in steps.
• 17:47
  the first idea when thinking about chemical carcinogenesis is that you have an exposure, and that exposure is either directly activated and interacts with DNA, or it's metabolized through an active metabolite that can then lead to DNA damage.
• 18:04
  That DNA damage may happen, and we are, uh, well prepared to address DNA damage with a lot of systems in our body that are repairing DNA damage.
• 18:15
  The idea is, though, that if you have instead issues with repair, uh, or you have situations where that DNA damage is above a certain threshold, or you have other types of events that are not allowing the DNA damage to be eliminated or repaired, then that can continue lead to mutations and ultimately then lead to carcinogenesis.
• 18:36
  So it's a, it's something that is a, a process that is, is really, coming from a number of steps that have to happen.
• 18:44
  And so looking at the DNA damage, uh, interaction is our first step to understand whether this process is even happening.
• 18:53
  And so we're doing this to verify whether this is happening, and therefore, this kind of process is what we should look at, uh, to understand a little bit more what happens when we are exposed.
• 19:07
  Can you take us through a finding that genuinely surprised you from the original question to the moment the results showed up?
• 19:17
  I guess one example that was really incredibly exciting related to the genotoxin that comes from, uh, exposure to a particular type of E.
• 19:29
  coli, which is encoding for this toxin that has been associated with colorectal cancer, and this was work that we started, um, in a collaboration with, uh, Dr.
• 19:40
  Emily Balskus, at Harvard.
• 19:42
  And she knew from her work that there was DNA damage, and this was happening in models.
• 19:48
  and though this toxin is so reactive that they weren't able to really characterize it or, isolate it and understand the structure.
• 19:58
  But when, um, they sent us samples and we found that indeed we were able to identify the DNA damage that would come from this toxin, we were also able to basically, um, stabilize the compound on DNA.
• 20:13
  And so at that point, it was stable enough that we could then characterize it chemically, and we were able to identify it and get it to a real clear understanding of, of what it is.
• 20:23
  What was really amazing for us was that from this collaboration, then because, again, the Masonic Cancer Center is connected with a number of different researchers that are very keen in collaborating, I was able to set a collaboration with Dr.
• 20:40
  Alex Khoruts, uh, who is a, um, gastroenterologist who has been working on collecting samples from, um, biopsies that are collected through, during regular colonoscopies.
• 20:52
  And we were able to try to see if this toxin connected with DNA or reacting with DNA was even present in samples from people that potentially were exposed to this.
• 21:03
  after analyzing sample after sample after sample and having negative result, we were about to, you know, give up, and then all of a sudden we started seeing that there were some instead, spec-specific type of patients that were positive to this.
• 21:19
  And so all of a sudden, the work that was done, you know, in the lab at the bench became relevant to, uh potentially being able to better diagnose or to identify specific types of risk for patients, and that is something that is incredibly satisfying.
• 21:37
  What was also satisfying in that story was the fact that the collaboration with Harvard was supported by a NIH-sponsored funding, um, grant.
• 21:49
  But that additional side work, let's say, or testing on samples that were collected at the University of Minnesota came or was possible thanks to a smaller donation that my lab took or got from, a community in, uh, in Minnesota, in Renville County.
• 22:09
  Um, the Walk In The Park, uh, Foundation was able to give us, some funding for, a project that, again, was not part of a larger grant, and that allowed us to really make that breakthrough and that particular work that allowed us to understand that that was something that was real and was happening and was detectable in people and in patients.
• 22:31
  Um- So when you, when you have a large grant, is- Mm-hmm are there strings attached or stipulations that you have a more regimented course of action with something versus this gift from our friends in Renville County?
• 22:44
  Did that give you a little more autonomy to do what you wanted to do with- I- the money and the research and the equipment?
• 22:50
  Yes, absolutely.
• 22:52
  So the larger grants are coming in, to support work that oftentimes has required a lot of preliminary data, and rightly so.
• 23:01
  Those are larger grants, so they wanna be sure to give it to success, um, successful, uh, projects.
• 23:07
  So you have preliminary data, and you have a set of aims that you are, um, that you have to basically...
• 23:14
  that you're proposing and then you have to complete.
• 23:16
  So at times it's hard in those grants to include work that is maybe a side project where we, in that particular grant, we had not mentioned that we were gonna also test samples from, uh, patients, and we didn't have, uh, that part of the work that was described.
• 23:34
  And therefore, we couldn't really just take some of the funding and then apply it to this side project.
• 23:40
  The donations that are coming from philanthropy are really coming with that additional perk, which is the an- autonomy, the flexibility, really the ability to give us the opportunity to use funding for maybe projects that, again, are maybe more risky or maybe are just not part of a larger project that we have, uh, going.
• 24:02
  And so that is incredibly important because it allows us to then have preliminary data that we can leverage for additional larger funding or government funding.
• 24:13
  and so there is something about that that is truly important and, and crucial in the work that we do.
• 24:19
  and exciting too, uh, because it's wonderful to be able to, for me, to be able to go back, um, every year, to Olivia, Minnesota, and tell them about all the, work that we've been doing, thanks to their donations and thanks to their, um, commitment, to our research, and it's, it's incredibly satisfying.
• 24:40
  I think it's important that we acknowledge the fact of what you just shared, that sometimes those smaller gifts give you, the researchers in your team, the ability, freedom, and the autonomy to pursue something that's not part of a larger study with strings attached.
• 24:56
  I frequently hear from our brother Masons and members of the Masonic family, and those in the community that will say,"Well, will, will my smaller gift really make that much of a difference?" And the answer clearly is yes.
• 25:09
  As giving and donating to Minnesota Masonic Charities, and when we specify that donation to go to the Masonic Cancer Center or the Masonic Children's Hospital, you're doing amazing things and breakthroughs with a smaller study, could, could it be said equally impactful to some of the larger grant studies you're working on?
• 25:28
  Absolutely.
• 25:29
  And just to kind of continue on that, the impact of the work that we've been able to do by following, uh, and, and pursuing the smaller project, on the colibactin, um, genotoxin, has been putting us on the map, and has really been able to show how our techniques and our technologies and approaches can be used for this kind of work on a more international level.
• 26:00
  and that has led to our work being included and our team being included in a global effort, um, that has been turned into a proposal for the UK Grand Challenge, which we have, got, uh, just a few months ago, where we were part of the five teams that were selected out of 227, uh, applicants, to really tackle a grand challenge in, uh, cancer research.
• 26:27
  And again, that was$25 million grant.
• 26:32
  Obviously, that is a grant that is sponsored by the UK, uh, Cancer Research and the NCI, and is meant to be really focused on providing support to a global team, an interdisciplinary team, that will tackle a main challenge in cancer research.
• 26:52
  So the money is actually going to seven different teams, that are here in the US, in the UK, and in the Netherlands.
• 27:01
  And Masonic Cancer Center here in Minnesota is one of those recipients.
• 27:04
  Yes.
• 27:05
  My lab in the Masonic Cancer Center is one of the recipients, as well as the recipient of a specific part of that grant that is, meant to support the acquisition of a new instrument.
• 27:19
  And so it's allowing...
• 27:20
  has allowed us to purchase a new high-resolution mass spectrometer, the latest technology in that context, um, and, uh, the Thermo AstraZoom.
• 27:31
  And that allows us to really bring our analytical power to the next level.
• 27:37
  And can you say more about the, the machine- Mm-hmm in, in more of a layman's perspective of what, what does this entail?
• 27:42
  What does this look like and the impact it may have?
• 27:46
  Yeah.
• 27:46
  So these instruments are really based on amazing technology.
• 27:51
  They're mostly, they've mostly been developed for metabolomics, for proteomics, so characterization of proteins, characterization of metabolites, and we have been able to sort of use them for, our own, uh, application, which is characterizing DNA damage.
• 28:09
  And so we are using it in a, in a way that is not exactly what they've been designed for or what they have been meant for.
• 28:16
  Again, going back to what I was saying earlier, this is because our Masonic Cancer Center shared resources are allowing us to have access to instruments, but they are telling us also that we can actually use them beyond their regular, normal way of using it.
• 28:32
  You can really take advantage of that instrument and try to harness its power for your own analytical questions.
• 28:40
  That is not always the case for all core facilities.
• 28:43
  This is something that really speaks to the ability of, of- the, uh, Masonic Cancer Center to really foster that, synergy in interacting and using, um, common and shared resources.
• 28:57
  and so with that, those are, instruments that are allowing us to really characterize a chemical, um, uh, giving us the chemical formula and be extremely accurate and sensitive in detecting molecules and then telling us basically what they are.
• 29:16
  With that, we're able to analyze our DNA and look for the molecular modifications and the chemical modification of the sequence of the bases and, uh, and the nucleosides that are part of the DNA, and we're able to understand what is the chemical that has been, uh, reacting with DNA.
• 29:36
  How difficult is it to turn off your brain at the end of the day?
• 29:40
  Do you find yourself in the lab, in the office and looking at the clock thinking,"Just one more hour"?
• 29:47
  is it tough to stop for the day?
• 29:49
  So it's really hard to...
• 29:52
  I would say that it's really hard to leave the lab.
• 29:54
  So together with, a lot of success stories from the lab, there are also a lot of moments where you're doing troubleshooting, where you're not understanding what you're seeing, where you just need to do one more, one more analysis, one more thing.
• 30:07
  And so that leads to, to long hours, to just being in the lab for, for a long time trying to figure things out.
• 30:16
  And I feel like at that point, um, you really need to have a passion for what you're doing and to really see the value of it, because sometimes it's hard to, to be, um, constantly embedded in the research that you're doing.
• 30:32
  Uh, and it's not for everybody.
• 30:34
  Do you get stuck sometimes?
• 30:35
  Absolutely.
• 30:37
  Uh, we get stuck, and I think that the most important, characteristic that is, uh, really helping us move forward is the fact that usually people that are working, uh, in this context are extremely, tenacious.
• 30:52
  And the roadblock is just one more thing that you have to address before finally getting to a breakthrough, and it's just that oftentimes we do have to go through, and several roadblocks.
• 31:05
  Is, is the roadblock a motivator?
• 31:07
  It can be.
• 31:08
  You know, it depends on how many you're facing.
• 31:11
  Sometimes you're almost able...
• 31:12
  You know, actually, this is again another example.
• 31:15
  Back when I came to the Masonic Cancer Center, I was, working on a project that just...
• 31:22
  I was not able to, to, really to finish and to analyze a specific type of modification that, um, I was asked to detect and to, um, quantify.
• 31:35
  And I think that at, back at that point, we had tried all sorts of techniques and approaches.
• 31:43
  Finally, the Masonic Cancer Center analytical chemistry facility or core facility got a new instrument, And this was sort of like the first version of the one that we just purchased with the, UK Grand Challenge, uh, grant.
• 31:59
  And having access to that technology all of a sudden allowed me to have an instrument that was way more sensitive and accurate than what we had before, and all of a sudden my project, this was almost four years of work and roadblocks, all of a sudden saw a breakthrough because we were able to use that sensitivity and finally find and quantify and detect that modification that I was trying to get to.
• 32:23
  How did that feel?
• 32:24
  Amazing.
• 32:25
  It was truly amazing for me, and I guess also for my supervisor that kept on getting negative results from, uh, from me.
• 32:34
  So, I'm hoping that with the new instrument that we got, we're gonna be able to sort of follow on, on that experience and have many more breakthroughs just like that.
• 32:47
  What would have to happen for your lab's discoveries to become something a doctor could use to help a patient?
• 32:56
  our discoveries are really getting to turning that association that I was talking about earlier that comes from the epidemiology into causation.
• 33:08
  So that's when we can develop markers that we can measure and then help doctors understand more precisely what is a profile of a, of a patient's per- for instance, or of a, of a patient that comes with some questions about an exposure and define whether they are at higher risk or lower risk for developing certain ki- types of cancer.
• 33:29
  So the idea is really that we are able to develop markers that then can be used to better understand the risk and the susceptibility of people that may be exposed to some of the things that we're looking at When you look at what's possible now and what's still a research goal, do you see a difference between the two?
• 33:54
  Well, ultimately the research goal is to just stop cancer from happening in the first place.
• 34:01
  at least from a, you know, a prevention point of view From a clinical perspective, the goal is to cure cancer.
• 34:10
  And I think that these two goals are, are ahead of us, and I'm hoping that we'll be able to make, um, important contributions.
• 34:19
  Hopefully we'll get closer.
• 34:21
  I think it's gonna take some time to really get to, uh, achieve the goal So then what question about the causes of cancer would you most like to answer in the next 10 years?
• 34:34
  So the UK Grand Challenge that I am part of really focuses on looking at cancers that are showing specific mutations and a specific mutational signature, but that don't know-- the, it, but for which is unclear what the origin is.
• 34:51
  So an important breakthrough would be to use our interdisciplinary approach, and specifically the work that we're doing in, in my lab at the Masonic Cancer Center, to really help understand what those exposures or environmental factors are at the base of these type of cancers for which we really don't know what the s- the cause is.
• 35:15
  That would be a phenomenal achievement, and we're hoping to, to be able to contribute to, to this kind of work, uh, and to this kind of answers.
• 35:24
  And what do you think the impact would be in answering some of those questions for patients?
• 35:30
  The impact is that then you can inform patients of maybe some lifestyle, um, choice that they are, have been, uh, taking or maybe some environmental exposures that they are experiencing that they don't know are linked to the re- increased risk of cancer.
• 35:48
  And therefore, you can then put in place either remediation or you could also put in place, advices or information that then can be used for that particular population to reduce the, um, the risk.
• 36:01
  So again, just to go back to our example w-where we all st- our program started from, understanding better how tobacco leads to lung cancer or other cancer has led to making sure that people are invited to stop smoking, of course, but also to make sure that people who are not smoking are not exposed to environmental smoke.
• 36:24
  So there are a lot of different actions that can be taken to protect people if you know what you need to protect them from.
• 36:33
  When you talk about lifestyle, that leads me to have several questions.
• 36:36
  Mm-hmm.
• 36:38
  Cigar smokers will contend,"Well, I don't inhale it." Mm-hmm.
• 36:42
  And while we're at it, what about the vaping?
• 36:45
  Mm-hmm.
• 36:45
  The chemicals that are ingested, and I, I see people hitting that vape so hard What's your take on that?
• 36:52
  Yeah.
• 36:53
  So- The cigars are still made of tobacco, and so they s- they are still burning when you are, um, uh, smoking them.
• 37:05
  So there are some...
• 37:06
  the risk factors that come with, Inhaling even minimally or exposing yourself minimally to, to, uh, these products are still valid.
• 37:16
  Again, if you're smoking a cigar once or twice in your lifetime, it's probably gonna be okay.
• 37:23
  but that is where it becomes really hard to then understand whether people are doing it only, you know, at that low frequency of instead,"Oh, this is a minor thing," but then ultimately they're doing it every weekend, right?
• 37:36
  So again, it's that perception of moderation and that perception of, um, constant chronic exposure- Yeah um, that may be something that people think about or not.
• 37:49
  The vaping question is different because in vaping products there is no-- most, like, most often there is no tobacco, if it's not mixed or is not put on, in the, in the, uh, device.
• 38:02
  Um, oftentimes the chemicals that are coming from the combustion of the tobacco, are not there.
• 38:10
  But there are other chemicals that are also present in tobacco, but they're still present in e-cigarettes and, and, in the vapors that come from the vaping that can still pose some threats and can be a threat to health.
• 38:22
  The problem is that we don't have enough, evidence to understand exactly what, what they do.
• 38:30
  And so I think that the perception they're just safe just because they are compared to regular tobacco cigarettes is a misperception.
• 38:39
  Because ultimately they may pose different questions and different risks, we still have to understand what those are.
• 38:47
  would you say there would likely be some health implications as a result of the chemicals in vaping that we'll learn in the future as we go?
• 38:55
  Well, we know that there are a lot of, for instance, aldehydes that are present in the vaping.
• 39:00
  and people that are exposed to it are certainly experiencing the effects of those chemicals which we know are genotoxic.
• 39:08
  Some of them are mutagenic.
• 39:09
  Um, so certainly there are some health effects that are coming from being exposed to these kind of chemicals.
• 39:15
  And we have also know, that there have been reports of people that have been experiencing some, effects on their breathing ability and, and lung capacity.
• 39:24
  So I think that there is a lot that needs still to be understood on those products.
• 39:30
  But in general, just thinking that they are-- that something is safe because we don't know anything about it or we do- we know very little, or little compared to tobacco, uh, cigarettes, um, I think is, is just not a good way of approaching, uh, these products.
• 39:48
  when it comes to prevention, we talked about lifestyle choices a lot.
• 39:51
  Prevention isn't about developing a pill that you can take that will fix the problem per se.
• 39:58
  It's about gathering information that is good or detrimental to our health So much is related to a person's choices, and the person becomes the main actor in those choices.
• 40:13
  So tell us some good choices we should make.
• 40:15
  Is, is sleep important?
• 40:18
  Hydration?
• 40:20
  I know there's no guarantee that living this super clean, regimented, or being cognizant of these things in our lives isn't gonna guarantee we won't have some issue.
• 40:30
  But w- what do you suggest is a basic healthy lifestyle for men and women?
• 40:37
  So I think that there are certain things that we know, uh, are gonna put us in a, in a better position in terms of, of, cancer prevention.
• 40:45
  So certainly not smoking or quitting smoking if, if we are smoking is certainly a main, main aspect of, um, prevention.
• 40:56
  consuming alcohol in moderation, and again, that moderation is a few drinks a week.
• 41:03
  I think that- How many?
• 41:05
  That's very hard to say.
• 41:07
  I'm asking- I am- I'm asking an Italian- who does appreciate a good glass of wine.
• 41:13
  Absolutely.
• 41:14
  So, um, you know, the American Cancer Society reports one drink per day for women and two drinks per day for men.
• 41:26
  Uh, those are the recommendations.
• 41:28
  if you look at recommendations from, um, Canadian, government health a- agencies, they are reporting the same number but over a week.
• 41:39
  Hmm.
• 41:39
  Right?
• 41:40
  So one or two drinks per week.
• 41:43
  So clearly we are not doing a very good job in providing good, precise guidelines around, uh, around this kind of, uh, lifestyle, habit.
• 41:56
  I would say that, again, avoiding having a drink every day, I think it's really important.
• 42:03
  Even the two a day that you just described, that seems like a lot.
• 42:06
  It does.
• 42:07
  And that is from an older, uh, recommendation that just was really never changed.
• 42:12
  it's kind of interesting, and different countries have, as I just mentioned, the difference between US and Canada have different guidelines.
• 42:19
  The UK has a different guideline, uh, as well.
• 42:22
  So it's just, I think that going lower than one or two drinks per day, uh, is gonna be a, a good choice, and alternating that one event where maybe we have a good meal with a good glass of wine with maybe, um, you know, a few days in which we either choose al- alcohol-free alternatives or just stay away from alcohol is a, it's a healthier choice.
• 42:47
  Do you think people are truthful when they go to the doctor and the question is asked,"How many drinks do you have a week?" I think that that, uh, misrepresentation of the amount of alcohol consumed is a known, limitation, that all of the studies that have been collecting information on alcohol consumption are aware of, have to face, and have been addressing.
• 43:08
  and so that is part of the problem and the reason why doing research, just basing our understanding of the exposure from questionnaires is extremely difficult and imprecise.
• 43:21
  And that is the reason why developing methods like the ones that we are developing, where we can quantify something that is chemically detectable, allows us to be more specific and precise in that quantitation.
• 43:33
  Because the self-report is not just a matter of lying and feeling guilty about it.
• 43:38
  Sometimes it's just hard to remember, exactly.
• 43:41
  Some of these questions go back months or maybe even in the last year.
• 43:46
  I would have a really hard time, even knowing how important it is, to really document, uh, precisely my, my consumption and my habits.
• 43:57
  And we don't wanna make this into a lecture or scolding, but the Minnesota Freemasons have taken a step towards addressing health.
• 44:07
  and whether they're members of the Masonic family or our friends and neighbors or colleagues, we're surrounded by people with a ton of health challenges.
• 44:16
  But yet, well, what's the alcohol consumption?
• 44:18
  What's your diet like?
• 44:19
  How much sleep are you getting?
• 44:20
  How much water are you drinking a day?
• 44:22
  There, there, there's this long list of things that could be addressed that would clearly have a positive impact almost immediately on some of those preexisting conditions.
• 44:32
  maybe'cause as men we say,"Oh, it won't affect me," or,"I'll wait to do that someday." But, time and aging is also very humbling- Mm-hmm when it comes to the aforementioned items.
• 44:44
  Absolutely, and I think that it's a matter of shifting our idea from, again, the idea of the pill, of having something that is gonna fix our health issue, to taking in our hands the ability to make a difference in the way that we are addressing, uh, some of these habits and some of the things that we're doing, and taking our own, health journey in our hands, basically.
• 45:12
  And I think that that is something that if we have better information and if we have really good, solid, um, evidence of the importance of some of these changes, I think that that can also be easier, to do.
• 45:24
  And so that's where our work really comes in, is like to provide that information, uh, so that it can be used, uh, for this purpose.
• 45:34
  I think you've basically answered this question already.
• 45:37
  How do you explain cancer risk honestly without making people feel that everything around them is dangerous?
• 45:47
  This is a, a tough, tough question because I think that there are some psychological components that come into, to this.
• 45:56
  Uh, I think that, you know, having that perception that everything is bad for you is sort of like an easy way to just say,"So I'm not gonna even think about, what I can do to, prevent or to avoid, um, these effects." There are a lot of things that can be bad for us, is true.
• 46:19
  There are some that we cannot really change and address, and some instead where we have some power to address them, to change them, to modify them.
• 46:28
  And I think that with the idea of, again, taking in our hands our, our journey into getting healthier and being better, I think that we can focus on the things that we can change and that we can address, and just have the, the sense that by sort of creating more of a practice in terms of thinking about what we can do and how we can do better, um, there are potential effects that we can see that are not just on the long term, but immediately, perceived.
• 46:59
  And so if we sleep more, and if we drink less, uh, if we stop smoking, all of these things are gonna have immediate effects as well, and I think that that can be used as a way to incentivize this kind of approach.
• 47:12
  And again, it's not that everything can be changed.
• 47:15
  It's not that everything is bad for you.
• 47:17
  there are some things that we can do and that can turn into a better lifestyle or a better choice What wording do you wish scientists, and maybe even journalists for that matter, would stop using?
• 47:34
  I, I wish, it's not really a specific word, but I wish the media would stop treating science as a, um, a scandal or some kind of, you know, gotcha moment where,"Oh, we have figured this out," and we run with it.
• 47:52
  And, and it's either something that has been identified as a truth or something that has been identified as a, some sort of debacle, you know?
• 48:00
  And, and really help us instead do a better job in communicating the nuances around science, which are really hard to talk about, but it's very difficult to have a situation where scientific findings are black or white.
• 48:17
  It's a yes or no.
• 48:19
  It's a journey, it's a process, and we learn more as we go, and the things that we know now may be different or may be not complete compared to what we will know in the future.
• 48:31
  And so I wish, again, that the media and the news outlet would help us be better in communicating this process rather than just associating a headline to something that comes out of one study.
• 48:46
  That headline that comes out that looks like it has just established a conclusion when there's so much more to it.
• 48:51
  Exactly.
• 48:52
  That's exactly the problem, that sometimes these studies are long efforts that have come from work that has been done by a lot of different, um, researchers.
• 49:03
  When you actually look at the studies themselves and you really spend the time in understanding what they're saying, oftentimes they are producing some- they're commenting on some of the evidence that they have found, but they're also commenting on the limitations that maybe their studies are, characterized by.
• 49:19
  And so I think that that kind of approach on making sure that, yes, we have an indication of something being true, but there are also some limitations in what we've been looking at, is something that needs to be, um, talked about and, and, uh, that has to be represented as well.
• 49:38
  Do you have a favorite reliable source for medical updates, information in the world that you would lean on versus one versus another?
• 49:48
  Well, you know, for my work, I rely a lot on, um, looking at the literature and what is published.
• 49:56
  So obviously PubMed and, you know, any kind of, uh, source that leads me back to directly the studies and their publications is what I would use.
• 50:06
  But I understand that sometimes it's hard for people who are not, able to completely grasp the jargon or that are not scientists to really read this kind of, uh, of journals or of papers.
• 50:18
  Um- It's hard to read that when I have to look up every third or fourth word.
• 50:22
  Right.
• 50:22
  Exactly.
• 50:23
  Um, but there are some sources that are really breaking things down and, um, making, I think, a good summary, and some of them are through, you know, science and nature.
• 50:36
  oftentimes they are publishing articles, but then they have also commentaries that are more accessible, and I think that those can be really good sources.
• 50:43
  The Lancet I think does that, too When you think back on your journey, you studied internationally, you ended up in Minnesota, you've shared with me you love it here.
• 50:56
  What did you learn in one setting that you couldn't have learned in the other?
• 51:05
  This is a very difficult question.
• 51:08
  I have to go back to all the different places.
• 51:11
  so for sure, the experience at International Agency for Research on Cancer, which is a WHO research center that brings together people that are really coming from all over the globe.
• 51:27
  It's allow me to understand the importance of team science, of a global perspective when looking and tackling, um, complex, um, scientific questions that I don't think I would've been able to really appreciate and understand in any of the other places where I was the international student or the international researcher, but there was more of a homogeneous, um, community, let's say.
• 51:54
  And so that really opened my eyes to the importance of looking at things from s- different perspectives, and the, really the gain that comes from having this approach to looking at questions that are ultimately touching everybody globally.
• 52:10
  and so I think that there's a lot of, uh, important information that comes when we are bringing together people from all of the different places that are experiencing things maybe differently, but are bringing in maybe something that they've learned specifically in their different countries to a global, full, uh, understanding of the question or the problem.
• 52:30
  What does that feel like to be in a field where the work you do here at the Masonic Cancer Center in Minnesota is impacting the world?
• 52:39
  It's a global reach.
• 52:42
  It feels great.
• 52:44
  I think of myself as, you know, a, someone back in high school thinking,"I think I want to do research," but having really no clue of what direction I would take.
• 52:56
  And then now having the sense that obviously I'm one researcher of many, but what we're doing really matters, and it comes to provide additional information that can be really used by people and make a difference.
• 53:13
  And, and that is some sort of reward to all the time that I've put into first studying and then, uh, doing research and then, maybe spending time trying to, Write grants and, and, uh, um, get funding for the work that I do that really is, uh, a, a true reward.
• 53:35
  It's extremely rewarding And it's rewarding for the Minnesota Freemasons, and the Masonic fraternity for that matter.
• 53:43
  To look back on our 70-plus year history, the heritage we have with the university, we opened the cancer center in 1955.
• 53:52
  You fast-forward to today, it's nearly$200 million of investment for the Masonic Cancer Center, the Masonic Children's Hospital, the Masonic Institute for the Developing Brain, and there's more to come.
• 54:04
  and it's indescribable to be part of something where the investment is made in the best researchers and best physicians, like you and your colleagues are here just making these inroads.
• 54:16
  I can't describe how that feels for our organization and for those who support us, and who contribute to Minnesota Masonic Charities for the work that you do.
• 54:26
  Well, I can tell you that it, it makes me proud as well to be part of this community.
• 54:32
  Um, I'm wearing my Masonic Cancer Center pin right here on, on my dress.
• 54:38
  again, because it's just not doing research, it's bringing forward a community effort.
• 54:47
  And the fact that our work is so embedded into the community and, you know, really is thriving, thanks to the support of, of the people in Minnesota, it just changes the perception of how important it is.
• 55:03
  You feel more responsibility, but you also feel more inspired because it's sort of a community that is supporting you, and, and you have a responsibility towards that community and...
• 55:13
  But also pride of being their, you know, their, uh, uh, expression in a way, in, at least in research You describe the layout at the office at the Masonic Cancer Center as being somewhat communal.
• 55:28
  Everyone shares that space.
• 55:31
  I'm sure someone is playing Spotify or Apple or music during the day.
• 55:36
  What, what's the most annoying song to have stuck in your head?
• 55:42
  Someone playing loud Under Pressure.
• 55:45
  Queen and David Bowie.
• 55:47
  Yes.
• 55:48
  Just for the, uh, you know, the, the sense of, like, we're already quite under pressure regularly because of all the work that we are doing, and maybe some experiment not panning out as we wanted or we wished.
• 56:00
  And it's just like, ugh, I don't need that additional pressure coming in.
• 56:04
  Do people play that song?
• 56:06
  Sometimes.
• 56:06
  Really?
• 56:07
  Mm-hmm.
• 56:09
  tell us about the worst bad behavior that you've encountered in public There's a lot of crazy things happening on airplanes these days.
• 56:18
  I think I'm very sensitive to situations where I see someone being disrespectful, especially when it's disrespect towards someone that is doing their job.
• 56:27
  Um, and in those circumstances, I often tend to intervene.
• 56:34
  And yeah, so it's something that I have to be careful about because sometimes things get really, can get testy and, uh, yeah, something that I really though have a very low tolerance for.
• 56:47
  There's really nothing more cringe than watching someone shout at the gate agent because there's a mechanical issue with an airplane, or Mother Nature is delaying.
• 56:57
  Come on, really?
• 56:58
  Yeah, exactly.
• 56:59
  And again, when, especially when people are facing a lot of, uh, of people, all their needs, um, and there is also time, maybe time constraints, and they're just trying to do the best they can.
• 57:13
  That additional yelling is really not helping anybody other than the person that probably is just getting it off their chest.
• 57:22
  Who is your least favorite celebrity?
• 57:26
  Ooh.
• 57:27
  Um I think Meghan Markle.
• 57:31
  Why?
• 57:33
  I guess it comes from the fact that I like authenticity, and I really value that quite a lot.
• 57:42
  And someone being phony or, again, making up things and, and really not coming across as authentic is something that I have a hard time connecting with.
• 57:53
  that name is just one.
• 57:55
  I, obviously I don't wanna specifically- Oh, you could- point fingers at anybody, but- You can give another one if you want to but it's just the kind of a general sense towards anybody that is, uh, you know, that is like that and then I don't perceive as authentic.
• 58:09
  What's in style right now that you can't stand?
• 58:13
  And don't be worried if you insult a coworker with this.
• 58:15
  No, no, no, no.
• 58:16
  I'm just thinking.
• 58:17
  There's so many things.
• 58:20
  I think super puffy jackets are something that I just can't stand.
• 58:24
  They are back, aren't they?
• 58:25
  A little bit.
• 58:26
  They went- Yeah, I just saw one as I was coming here.
• 58:28
  Well, it's not even cold yet.
• 58:29
  Exactly.
• 58:30
  This is the best time of the year- I know.
• 58:32
  That, that's strange to see that- Yeah in October and not waiting for January.
• 58:37
  Exactly.
• 58:39
  What historic event do you wish you could have witnessed?
• 58:45
  I think, I don't know, something immediately popped out in my head is the French Revolution.
• 58:52
  I think that would've been really, really cool to witness.
• 58:56
  Cool to witness, a little terrifying at the same time.
• 58:58
  A little, exactly.
• 58:58
  Yeah.
• 58:59
  So I'm putting myself on a balcony from one of the- Yes of the In, in a safe spot.
• 59:05
  In a safe spot of one of the, um, you know, residences in, in Paris, just watching.
• 59:12
  Next to Victor Hugo.
• 59:13
  Certainly away from La Bastille.
• 59:15
  What do you find yourself dreading most often?
• 59:22
  I think that sometimes kind of more routine work that comes with what we do is something that I have...
• 59:29
  is less fun for me.
• 59:30
  And so sometimes if I keep on postponing things that need to be addressed, then I start dreading the moment in which finally I'll have to open that Pandora box and just start tackling them all at once.
• 59:44
  So- Like expense reports and administrative, right?
• 59:47
  Yes, exactly.
• 59:48
  Expense report- I'll do that later.
• 59:49
  Exactly.
• 59:50
  And then- Yeah, yeah and then when you sit down to do it, it's all day.
• 59:53
  Exactly.
• 59:56
  You mentioned the French Revolution.
• 59:58
  Let's fast-forward.
• 1:00:00
  What is the worst thing about 21st century living?
• 1:00:05
  I think at the moment, living in a world that is so polarized is something that is really, in a way, fearful.
• 1:00:14
  I, I really...
• 1:00:15
  It really does trigger fear, um, but also sadness, especially coming from an environment where we can do so much when we collaborate.
• 1:00:27
  We can do so much when we are bringing together different expertise and different points of view.
• 1:00:34
  And seeing that that is not really reflected or valued, um, in where we are currently is extremely troubling.
• 1:00:44
  And I think that that is maybe something that is a characteristic of this times that I think I am not particularly fond of.
• 1:00:55
  How do we get around that?
• 1:00:58
  That divisiveness, the polarization, the, you think or agree with that point of view?
• 1:01:03
  Well, then we can't be friends." It didn't used to be that way.
• 1:01:06
  Right.
• 1:01:06
  I think that is just by keeping on doing what we're doing and showing the value of it, just showing the, you know, providing that evidence that if we are coming together, if we do things in collaboration, uh, if we work, um, together, ultimately the outcome is much better than what would happen if we had, you know...
• 1:01:29
  I, I...
• 1:01:29
  It's even better than the sum of each of our contributions.
• 1:01:33
  And I think that showing and keeping on showing and insisting on it, is what we can do, and I think it has a value, and hopefully someone will pick on it and, uh, and then carry it forward.
• 1:01:48
  Dr.
• 1:01:49
  Silvia Balbo, the Masonic Cancer Center in Minnesota is very fortunate to have you on the team.
• 1:01:57
  I am very fortunate to be part of this team, and so I'm very grateful of being part of it, and I'm very grateful of all of the support that we have been getting in the past to create this, uh, this Masonic Cancer Center that I've been really, enjoying being part of, and the current support and the future support.
• 1:02:19
  This is a relationship really more than anything that is extremely, um, extremely valuable and unique in a way, too, and I'm very, very proud and honored to be part of it and to contribute to it