Latest / Skin Anarchy / Dr. Ben Van Handel, PhD - Stem Cell Biologist and Co-Founder of HERAUXSKIN

Transcript

Dr. Ben Van Handel, PhD - Stem Cell Biologist and Co-Founder of HERAUXSKIN · Skin Anarchy

• 0:01
  SPEAKER_00: Yellow four has arrived.
• 0:03
  SPEAKER_00: The fourth world only you can get in their way.
• 0:07
  SPEAKER_00: Journey across the expansive open world sanctuary.
• 0:11
  SPEAKER_00: Five powerful classes of progressive figure play style.
• 0:16
  SPEAKER_00: The four-player co-op with cross play across progression on all platforms.
• 0:20
  SPEAKER_00: Welcome to Diablo 4.
• 0:23
  SPEAKER_00: Available now, rated and premature.
• 0:25
  SPEAKER_00: Cap the banner or visit this episode's page to learn more.
• 0:57
  SPEAKER_01: And I have an amazing guest today.
• 1:00
  SPEAKER_01: This is such a science-driven and really, really interesting uh line.
• 1:05
  SPEAKER_01: I love the science behind it, and I can't wait for um, you know, Dr.
• 1:09
  SPEAKER_01: Ben Van Handel, who is the founder of Hero Skin, to tell you guys all about it.
• 1:15
  SPEAKER_01: So welcome to the show, Dr.
• 1:17
  SPEAKER_01: Van Handel.
• 1:17
  SPEAKER_01: I'm so excited that you're here.
• 1:19
  SPEAKER_02: Please call me Ben Ecta, but thank you very much for uh for having me and giving us this opportunity to talk about uh the science behind Hero and a product that uh you know we think uh think is is the start of something uh pretty exciting for the future.
• 1:36
  SPEAKER_01: Yeah, no, I mean this is this is really extraordinary stuff.
• 1:39
  SPEAKER_01: And I and I want to really begin um with the the initial stages of your training and your graduate training, because I know that you know um it's very, very difficult, you know, to pick the route you want to go in in a PhD track.
• 1:51
  SPEAKER_01: So I want you to kind of tell us about yourself a little bit to begin, you know, how did you get involved with this kind of research in stem cell biology and all that good stuff?
• 1:59
  SPEAKER_02: Yeah, I, you know, I I went to undergrad in a tiny little school in the upper peninsula of Michigan, right on Lake Superior, Northern Michigan University.
• 2:09
  SPEAKER_02: Incredibly beautiful, right?
• 2:11
  SPEAKER_02: Um it snows a lot.
• 2:12
  SPEAKER_01: Oh my god, I'm from Michigan.
• 2:14
  SPEAKER_01: What the heck?
• 2:15
  SPEAKER_01: Are you serious?
• 2:15
  SPEAKER_02: Are you so you can't see me, but right now I've got my hand out.
• 2:19
  SPEAKER_02: Are you like the lower or the upper peninsula?
• 2:21
  SPEAKER_01: Uh East Lansing.
• 2:22
  SPEAKER_01: I've been in East Lansing, yeah.
• 2:24
  SPEAKER_02: Got it, got it.
• 2:25
  SPEAKER_02: Okay, well, that is that's a very small world, uh especially in that part of the world that it is quite small.
• 2:30
  SPEAKER_02: Uh but yeah, I went to NMU and um, you know, I I had no idea, like I think a lot of people at that age, um, what I was doing in college.
• 2:41
  SPEAKER_02: I think I started as a uh history major, then I switched to math and physics, then I think I went to just biology, and then finally, you know, in my junior year, I figured out, uh started to hone in on what I was thinking about and ended up switching again into biochemistry.
• 2:58
  SPEAKER_02: Um, so there was, you know, the college was sort of all over the place.
• 3:02
  SPEAKER_02: But you know, toward the end of undergrad, I started to realize that um, you know, I science was definitely the thing that I wanted to spend my life doing, but I still wasn't sure if I wanted to go to graduate school.
• 3:16
  SPEAKER_02: Um, and so I had a couple of really great mentors, Suzanne Williams, Frankie McCormick, John Rebers, all they all encouraged me to, you know, do uh maybe a master's uh degree at NMU and really get an idea if I wanted to continue.
• 3:35
  SPEAKER_02: Um and so I was about half a year into the program, and you know, I was working in Dr.
• 3:41
  SPEAKER_02: McCormick's lab.
• 3:42
  SPEAKER_02: Um, you know, the research labs are a little bit different.
• 3:44
  SPEAKER_02: They're they're you know, it's it's much smaller than let's say at a major research university, and everybody strapped for funding all the time.
• 3:52
  SPEAKER_02: But, you know, Dr.
• 3:53
  SPEAKER_02: McCormick had gotten a small grant, and so we were we we had resources and we were working really hard.
• 3:59
  SPEAKER_02: I mean, I slept in the lab most of the time, honestly.
• 4:02
  SPEAKER_02: Like uh I did have like a little office that I shared with another master's student, and I would just sleep on the floor in the crappy carpet, um, you know, in between my dad, by the way, Betty would love you because that's exactly what he did.
• 4:15
  SPEAKER_01: My dad has a PhD as well, and he was exactly what you just said.
• 4:18
  SPEAKER_01: He tells me all the time.
• 4:19
  SPEAKER_01: He's like, I used to sleep in the lab.
• 4:21
  SPEAKER_01: He's like, You kids nowadays don't know what hard work is.
• 4:24
  SPEAKER_02: Yeah, I think it's the scientist version of uphill both ways to school, um, is you know, uh walking uphill both ways to school.
• 4:31
  SPEAKER_02: I I think, you know, we we you we talk about how much uh time we spend in the lab sleeping on the floor or in the like lounge or whatever and never going home.
• 4:40
  SPEAKER_02: It's the same thing.
• 4:41
  SPEAKER_02: I I I'm I'm convinced of that.
• 4:43
  SPEAKER_02: Um yeah, and so you know, I think at that point I realized, wow, this is something I must really care about.
• 4:50
  SPEAKER_02: And um, you know, I'm I'm set.
• 4:53
  SPEAKER_02: I'm I'm I know I want to do science and I know I want to get an advanced degree.
• 4:57
  SPEAKER_02: So, you know, I started putting in applications uh to different graduate programs.
• 5:02
  SPEAKER_02: Um, and in the end, uh, you know, I have to say that those three people I already mentioned, they must have written phenomenal letters of recommendation because I didn't really have any research experience.
• 5:14
  SPEAKER_02: Like, you know, when I finally got to UCLA and I met my peers in my graduate class, a lot of them had already had their names on papers and had a ton of research experience.
• 5:24
  SPEAKER_02: And here I am, you know, I hadn't really done any independent research at NMU.
• 5:30
  SPEAKER_02: And so uh I don't know what the difference was, other it could the only thing I can think of is was the support of those three people.
• 5:37
  SPEAKER_02: And so, you know, it was uh I was really lucky uh to get into the program at UCLA.
• 5:44
  SPEAKER_02: Um, and um, you know, when I got here, it was a really interesting time in California Ecta because that was 2006, 2007, something like that.
• 5:57
  SPEAKER_02: And that was right after uh Prop 71 passed in California, which set aside three billion dollars of state funding for stem cell research.
• 6:07
  SPEAKER_02: Um wow.
• 6:09
  SPEAKER_02: Right?
• 6:09
  SPEAKER_02: And like, you know, I I didn't come to the university thinking, yeah, I'm gonna be a stem cell biologist.
• 6:16
  SPEAKER_02: I was like, oh, I I wanna I wanna be a virologist and I wanna study viral evolution and how you can potentially design evolutionary traps for infectious viruses so that you know we can reduce their pathogenicity and they just become endemic.
• 6:31
  SPEAKER_02: Now, who would have known, you know, 15 years later, maybe that would have been a good path too.
• 6:36
  SPEAKER_02: But, you know, I feel like that's brilliant, first of all.
• 6:39
  SPEAKER_01: Let me just say that.
• 6:40
  SPEAKER_01: Okay, you know, so he went from a brilliant idea, wanting to do something brilliant to something brilliant.
• 6:45
  SPEAKER_01: So it's okay, I get it.
• 6:48
  SPEAKER_02: I mean, all I can say is I was, you know, we had there the there was a talk at NMU when I was still there.
• 6:55
  SPEAKER_02: Um, this uh virologist came in, he gave a talk about the flu and studying the evolution of the flu and how it was becoming mostly over time less virulent.
• 7:05
  SPEAKER_02: And then um, you know, that just sort of got me thinking, well, what if, you know, we could promote something like that on our own.
• 7:12
  SPEAKER_02: But then that's fraught with peril.
• 7:14
  SPEAKER_02: Anyway, the point is, uh, you know, I came to UCLA thinking I wanted to be a virologist.
• 7:19
  SPEAKER_02: And then, you know, in the first year, when you get to these programs, um, you you would uh they set it up so that all the faculty members that are actively looking for new graduate students, they come and they give talks every week um so that the students can get acquainted with their research and then maybe start, you know, chatting with them a little bit, seeing if they want to rotate in their labs.
• 7:42
  SPEAKER_02: Um and, you know, so as I mentioned, this was right after Prop 71 passed in California.
• 7:49
  SPEAKER_02: And so UCLA had committed to recruiting, you know, what we called them the Fab Five at the time.
• 7:55
  SPEAKER_02: And I again I realize how dorky this sounds.
• 7:57
  SPEAKER_02: Like it's fine.
• 7:58
  SPEAKER_02: Just just it just go with it.
• 8:00
  SPEAKER_02: Please bear with me.
• 8:01
  SPEAKER_02: All of those are listening.
• 8:03
  SPEAKER_01: You can't get dorky enough for me.
• 8:04
  SPEAKER_01: Trust me, I'm like the mega dork of the world.
• 8:07
  SPEAKER_01: So it's okay.
• 8:08
  SPEAKER_02: Please continue.
• 8:09
  SPEAKER_02: So so we were comparing, you know, the these hotshot young scientists, of course, to like, you know, some um barnstorming band, you know, from the 60s and 70s.
• 8:19
  SPEAKER_02: Like it was ridiculous.
• 8:21
  SPEAKER_02: But, you know, these five people, they came to UCLA heavily recruited.
• 8:25
  SPEAKER_02: Um, and uh, you know, they were all stem cell biologists and were asking questions related to stem cell research and you know, how are stem cells specified?
• 8:34
  SPEAKER_02: How are they regulated?
• 8:35
  SPEAKER_02: How can we get the maximal regenerative potential out of them?
• 8:40
  SPEAKER_02: All of these really cool questions that at the time, you know, there wasn't a lot known about, but California had stepped up to the plate to provide funding on its own because at the time, you know, nationally the uh environment for stem cell research wasn't great.
• 8:53
  SPEAKER_02: This was the Bush years.
• 8:55
  SPEAKER_02: Um yeah, like you might remember, I don't know.
• 8:58
  SPEAKER_02: Uh, but no, I definitely remember.
• 9:00
  SPEAKER_01: Yeah, it was very hard to get uh funding for sure.
• 9:02
  SPEAKER_02: Yeah, yeah.
• 9:03
  SPEAKER_02: And so California just you know took it upon itself and really encouraged this.
• 9:08
  SPEAKER_02: And so, you know, it was one of those Fab Five, Dr.
• 9:11
  SPEAKER_02: Hanamikola, that was she gave a talk, uh, it was in October.
• 9:15
  SPEAKER_02: I remember it, which is ridiculous because it was forever ago.
• 9:18
  SPEAKER_02: But I remember she was talking about how blood stem cells are formed and um really trying to understand what are the environmental factors that contribute to their formation, and you know, can we can we apply this in a dish so that maybe we could culture them and expand them to treat diseases?
• 9:42
  SPEAKER_02: Um, because you know, at the time that was impossible.
• 9:45
  SPEAKER_02: We're closer, but it's still actually impossible.
• 9:47
  SPEAKER_02: Um, and you know, the I was just like, she was she was so eloquent, she was so passionate.
• 9:53
  SPEAKER_02: Like, I think the passion is what got me.
• 9:55
  SPEAKER_02: She was just, she's she's kind of like me, uh, like really high energy and really um just you know, just all over the map.
• 10:04
  SPEAKER_02: But you could tell that she cared more about this than probably most people care about anything.
• 10:10
  SPEAKER_02: Um it was just like, wow, all right, Hannah.
• 10:14
  SPEAKER_02: I mean, like I want to worship at your altar.
• 10:16
  SPEAKER_02: I want to learn from you, right?
• 10:18
  SPEAKER_02: Like this, this is it.
• 10:19
  SPEAKER_02: This is I I don't need to see anything else.
• 10:22
  SPEAKER_02: Um, if I can, you know, let's talk and and let's uh let's let's work together.
• 10:28
  SPEAKER_02: And you know, I was really lucky.
• 10:30
  SPEAKER_02: She she let me rotate in the lab, and it was like the fourth day that I was there, and it was 1.30 in the morning.
• 10:37
  SPEAKER_02: We're sitting by this machine called a flow cytometer, Hana and I, right?
• 10:42
  SPEAKER_02: My PI is there with me.
• 10:43
  SPEAKER_02: It's 1.30 in the morning.
• 10:45
  SPEAKER_02: We're both bleary-eyed and stupid, but we're having a great time.
• 10:48
  SPEAKER_02: And I was like, all right, yep, I made the right choice.
• 10:50
  SPEAKER_02: This is it.
• 10:50
  SPEAKER_02: Uh yeah.
• 10:52
  SPEAKER_02: So that's kind of how it started.
• 10:53
  SPEAKER_02: Uh, is just um, you know, I think I identified with someone that cared so much about what they were doing.
• 11:02
  SPEAKER_02: And then, you know, uh over the next couple of years with Hana and with our collaborators, we got to ask some really amazing questions.
• 11:09
  SPEAKER_02: Um, and I really uh really developed this interest in understanding the regulation of adult stem cells.
• 11:17
  SPEAKER_02: So, right, the stem cells that you and I have in our bodies, right?
• 11:20
  SPEAKER_02: Because we all have, you know, millions of stem cells in our bodies.
• 11:24
  SPEAKER_02: How can we support them or maybe manipulate?
• 11:29
  SPEAKER_02: I don't want to say it in the negative connotation, but manipulate them to achieve outcomes that may not normally be possible.
• 11:37
  SPEAKER_02: That's really, you know, what got me.
• 11:39
  SPEAKER_02: And I was like, that's that's I'm gonna spend the rest of my life doing this and I'm gonna be super happy.
• 11:44
  SPEAKER_01: That's so cool.
• 11:45
  SPEAKER_01: I love that.
• 11:45
  SPEAKER_01: And you know, I honestly I love a good, like true like lab story because I'm not gonna lie to you, like I was a year away from getting my PhD and I decided to just say no and get my master's and go to medical school.
• 11:58
  SPEAKER_01: So I understand, and I am so, so excited to hear that you, you know, you found someone who has such a great passion because honestly, that's what the best part of like I think uh biomedical research is, and that's something that I I try to push so much on my podcast is the understanding that like, you know, the people who are creating the pharmaceutical um solutions for us, whether it's in skin health or any other area or the PhDs, and we can't sit here, you know, like a lot of my clinician friends are like yes or no to things.
• 12:30
  SPEAKER_01: And I'm like, have you done the bench research?
• 12:33
  SPEAKER_01: Have you done the bench?
• 12:34
  SPEAKER_01: Have you been in the lab at 1 a.m.
• 12:36
  SPEAKER_01: looking, you know what I mean?
• 12:37
  SPEAKER_01: Looking at data, like, no, you haven't.
• 12:39
  SPEAKER_01: So you can't say yes or no to things.
• 12:41
  SPEAKER_01: So I really, really love that you went into that because I think it's very important for the general consumer to understand that the amount of work and passion that goes into research and development and really innovation is like, it's so much different than just going and seeing patients.
• 12:57
  SPEAKER_02: Well, and all I would the only thing I would add to that is like, you know, the the other thing I think that as a PhD, you have to really learn to integrate into your mindset is constant failure, right?
• 13:10
  SPEAKER_02: You have to, you're going to fail 98% of the time or more.
• 13:16
  SPEAKER_02: And so you need to learn like that most of your experiments, they won't be home runs.
• 13:21
  SPEAKER_02: They will, at best, if you've designed them well and you're lucky, give you clues as to what you should do for the next experiment.
• 13:28
  SPEAKER_02: But it's it's so rare to have that single experiment be like, you know, that moment of epiphany and you know, the angel or whatever lights shining down from above and you hear the noises, like, oh, like that never happens.
• 13:40
  SPEAKER_02: That never happens.
• 13:41
  SPEAKER_02: I mean, when it does, it you're uh you're you're floored, you're on your ass.
• 13:44
  SPEAKER_02: Like it's amazing, but it's not, you know, it's not common.
• 13:47
  SPEAKER_02: And I think I think it's it just takes because I'm sure you experienced it, like it just takes so much out of you, and you really have to learn to integrate that into your psyche.
• 13:58
  SPEAKER_02: And I think if you can, I think it's so rewarding.
• 14:01
  SPEAKER_02: But many people, it's a struggle because you know, we're we're we as humans aren't designed to work with failure.
• 14:07
  SPEAKER_02: It's just not.
• 14:08
  SPEAKER_01: Yeah, and it's it's about resiliency, right?
• 14:10
  SPEAKER_01: But I mean, it's like you have to be a resilient person.
• 14:13
  SPEAKER_01: So I completely, yeah, I 100%.
• 14:14
  SPEAKER_01: That's a great point.
• 14:15
  SPEAKER_01: And I'm so glad you're saying that because people don't like failure, you know.
• 14:19
  SPEAKER_01: It I can tell you honestly, in the clinical world, you know, as an MD, seeing my colleagues, especially, you know, in the field of surgery, they get very angry or they'll get, you know, they'll want to give up.
• 14:28
  SPEAKER_01: And it's like, are you serious?
• 14:30
  SPEAKER_01: Like, you gotta keep going, dude.
• 14:32
  SPEAKER_01: You know, you can't just say, no, screw it.
• 14:34
  SPEAKER_01: Like, this is that's the real crux of science.
• 14:36
  SPEAKER_01: That's the heart of science to keep trying.
• 14:39
  SPEAKER_01: So I completely, completely agree with you.
• 14:41
  SPEAKER_01: And I want to actually, I want to move forward and talk about your amazing discovery and your amazing line because the science that I was reading um, you know, behind this is truly something that I think the whole world needs to know about.
• 14:53
  SPEAKER_01: And I want you to really dive into how you um developed the HX1 molecule and you know, the lipid and how all of that started.
• 15:02
  SPEAKER_02: Yeah, uh, I mean, uh, it's uh obviously a story that I love telling.
• 15:05
  SPEAKER_02: And it I think it really encapsulates, you know, what we've already been talking about because you know, this took end to end 10 years, right?
• 15:14
  SPEAKER_02: And you know, it it's it, I I think the failure component, the failure quotient was extremely high the entire time.
• 15:23
  SPEAKER_02: Uh and yeah, that's that's it's incredibly frustrating.
• 15:26
  SPEAKER_02: But in the end, it ended up yielding something that you know we're really excited about.
• 15:32
  SPEAKER_02: And more importantly, I think even than us being excited about it and like knowing how it works, is that it has unlocked more for the future.
• 15:41
  SPEAKER_02: And you know, we'll we'll come back to that because I I need to stay on track, but um, please remind me if I forget, because that you know, we should talk about you know the the sort of iterative component of science that I think is so important.
• 15:56
  SPEAKER_02: Um, so yes, uh I was at UCLA uh, you know, in the midst of this stem cell research boom, uh, and you know, I met Dr.
• 16:05
  SPEAKER_02: Dennis Ovsenko, and he was really interested in stem cells in the joint and how cells in the joint um try to respond in the face of an injury or a bad environment and regenerate cartilage so that we don't get osteoarthritis.
• 16:25
  SPEAKER_02: But in the end, obviously, right, as you know, there are no disease-modifying therapies for osteoarthritis right now that are available to patients.
• 16:33
  SPEAKER_02: It's mostly palliative care where we treat pain and we try to, you know, which is obviously hugely important.
• 16:40
  SPEAKER_02: Don't get me wrong, like it's really important to make sure that, you know, uh patients with osteoarthritis aren't in pain.
• 16:46
  SPEAKER_02: But longer term, if we're gonna have a major impact, we need to be able to mitigate the degenerative milieu in the joint and allow for or even encourage the regenerative potential of the stem and progenitor cells in the joint and allow them to repair.
• 17:05
  SPEAKER_02: So that's what Dennis, that's the question he was asking.
• 17:09
  SPEAKER_02: How can we change this paradigm?
• 17:12
  SPEAKER_02: What are the what are the maybe major mechanisms driving this feed-forward degenerative process in osteoarthritis?
• 17:22
  SPEAKER_02: And can we, as a group of scientists and doctors, come up with a solution that could potentially greatly improve the quality of life for millions of patients worldwide?
• 17:33
  SPEAKER_02: I mean, so you can imagine I'm a young scientist, and it's like this this guy wants to do, you know, ask this huge question.
• 17:40
  SPEAKER_02: And I'm like, oh my god, yes, like I am on the let's do it.
• 17:45
  SPEAKER_01: Right, right.
• 17:46
  SPEAKER_01: That's like huge.
• 17:47
  SPEAKER_01: That's like literally like mind-altering, like different perspective needed to understand this.
• 17:53
  SPEAKER_01: Like, that's really big.
• 17:54
  SPEAKER_01: That's a big question.
• 17:55
  SPEAKER_01: So yeah, I can definitely see that.
• 17:57
  SPEAKER_02: And it just it just draws you in.
• 17:58
  SPEAKER_02: And so, you know, what what Dennis and I ended up doing over the next decade was really trying to understand mechanistically what would be potentially a major driver of the disease phenotype.
• 18:11
  SPEAKER_02: And what we landed on after, you know, understanding why cartilage can regenerate in you know, young people, but not older people.
• 18:21
  SPEAKER_02: Why is this capacity changing over time?
• 18:23
  SPEAKER_02: What we found is there's a huge, excuse me, inflammation has a huge influence on it.
• 18:29
  SPEAKER_02: Now, that's not new, obviously.
• 18:32
  SPEAKER_02: You know, everybody knows that inflammation um is a core component of the degenerative phenotype in osteoarthritis, but I think the paradigm shift was for us understanding that inflammation can greatly accelerate the aging process in semin progenitor cells in the joint and you know, essentially wipe out their capacity to respond to a bad environment very quickly because they sort of reverse Benjamin Button.
• 19:05
  SPEAKER_02: Like, you know, you get this injury, and instead of, you know, in that movie going back in time, they just slam on the gas and age so quickly.
• 19:14
  SPEAKER_02: And as we all know, you know, stem cells, older stem cells have a significantly reduced regenerative capacity.
• 19:21
  SPEAKER_02: And so it clear this link between inflammation and aging, which obviously people have coined the term inflammation in the biomedical world, um, you know, was becoming more and more recognized.
• 19:33
  SPEAKER_02: And Dennis and I decided, you know, what we were gonna do was specifically try to come up with a molecule or series of molecules that could target inflammation and protect stem and progenitor cells in the joint so that we could potentially stop the progress of osteoarthritis or maybe even reverse the course of it.
• 19:56
  SPEAKER_01: That's so interesting.
• 19:57
  SPEAKER_01: Now, see, here's the thing for me, I and from a science perspective, I've always had a hard time understanding like how you approach um a problem that is, you know, rooted in immunology.
• 20:10
  SPEAKER_01: Because, you know, the thing is immunology, when we learn it, for example, you know, I can tell you in the medical school curriculum, you know, it's a one course kind of thing.
• 20:20
  SPEAKER_01: You know, you learn about innate immunity and adaptive immunity, and they say, okay, uh, you're on your merry way, and that's all you need to know.
• 20:27
  SPEAKER_01: And it's like, you know, well, that's not even like a piece of the puzzle.
• 20:31
  SPEAKER_01: And so when you're and and that's why I'm I'm just so um, you know, my mind gets so boggled because how do you look at this overall state of inflammation um from like an aerial view and figure out where you want to target, right?
• 20:45
  SPEAKER_01: So, like how what was that process for you like in terms of like figuring out the the first steps of where you really wanted to, you know, like approach, like in terms of like which mech which uh pathways did you want to target?
• 20:57
  SPEAKER_01: What did you want to look at specifically?
• 20:59
  SPEAKER_02: Yeah, and and I I think you know you're giving us a lot more credit than we deserve in this situation.
• 21:07
  SPEAKER_02: So uh, because you are a hundred percent right, there are so many levers and pulleys and interdependencies and and uh matrix complexities, right, in different cell types of the immune system acting on resident cells in a tissue, and then obviously you throw a stimulative signal like inflammation into the mix, and yeah, it's bonkers.
• 21:31
  SPEAKER_02: Like there's no way you're gonna be able to tease out some sort of line to start following.
• 21:38
  SPEAKER_02: And so instead, we just took a shotgun approach.
• 21:41
  SPEAKER_02: What we did was a high throughput screen, right?
• 21:44
  SPEAKER_02: We were what we decided to do was essentially have a reporter in um cells like cartilage cells, chondrocytes, that if they're experiencing influences that drive.
• 22:00
  SPEAKER_02: them toward an arthritic phenotype, they upregulate a red fluorescent protein.
• 22:07
  SPEAKER_02: So essentially we have this screen.
• 22:09
  SPEAKER_02: So for those of you out there that have no idea what I'm talking about, which is I'm going to guess everyone because there's like that okay, so basically think about it this way there's a little plastic dish.
• 22:20
  SPEAKER_02: And that little plastic dish, there's like one thousand 1,536 little indentations in it.
• 22:26
  SPEAKER_02: And then we put cells in them that when they're experiencing inflammaging, they start glowing red.
• 22:34
  SPEAKER_02: If they're not, they will not have a color.
• 22:38
  SPEAKER_02: And so what we can do is squirt on some really bad, nasty proteins that make these cells drive toward inflammaging and turn red.
• 22:50
  SPEAKER_02: However, in each of those little indentations in the plate we also add a new molecule and see if it can limit the upregulation or turning on of that red protein.
• 23:04
  SPEAKER_02: And so by doing it this way, we can look at a quarter of a million new molecules in a relatively manageable amount of time to start identifying new potential molecules that could re-reduce or maybe even eliminate the inflammation response.
• 23:24
  SPEAKER_01: That's very interesting.
• 23:25
  SPEAKER_01: That's really that's really really cool actually I would love to see that actually in process.
• 23:29
  SPEAKER_01: I've never seen that done.
• 23:31
  SPEAKER_02: Oh CLA they have an amazing core the molecular screening core um Dr.
• 23:35
  SPEAKER_02: Demo was so he it like I mean a lot of the the bigger universities have these and it's exactly for the reason we're talking about if you don't know like it's and it's promulgated by your question if you don't know what you're looking for all right well then let's just spray a bunch of stuff at the wall and see what sticks and if you can if you can design an experiment like what we're talking about, you know, and you're lucky enough to like have the availability of the cells and the reporter you know that that protein that fluorescent protein that you can read with a microscope right so sorry to finish the experiment once you um once you uh add on the new molecules and you have the cells that can glow if they're experiencing inflammation you throw all of those plates now we're talking hundreds right because we're screening a quarter of a million new molecules you throw one by one all of those plates into an automated um fluorescent microscope so it's able to focus on each little individual indentation and see how much red uh fluorescence is coming from it and it can read all the wells uh all the little indentations and then give you a map and tell you okay these compounds look good or sorry these molecules look good or these don't um and that that's the way that we can get through that's essentially high throughput screening in case anybody in the world cared about that that's that's that's it in a nutshell that's so cool no I really I I love that so basically you guys then narrowed it down to 473 yeah then you're you're exactly right Ectus so after all of that um you we had like 473 of these new molecules that were very promising they were able to limit to some extent or maybe to a great extent the amount of red fluorescence that was present in the indentation and then you know we just kept winnowing down this is the this is the sloggy part of it right because you need to then take all of those 473 compounds and one by one test them in larger assays.
• 25:41
  SPEAKER_02: So it's a lot it's not nearly as high throughput we don't get to have robots and lasers involved and which I is awesome by the way can I just say that my life includes robots and lasers uh even though I'm just like some stupid scientist like I don't I like it's it's it's awesome.
• 25:58
  SPEAKER_02: Uh anyway um so so you know we got down to 473 and we kept winnowing it down and eventually we got down to three uh and then you know we had our prime candidate and that part that portion going from 473 to one took about two years in and of itself just because it's not at all high throughput um and you know it it takes a lot of effort uh to make sure that you're willing to throw away that molecule and move on to the next one because you just don't want to leave anything out on the field.
• 26:33
  SPEAKER_02: You want to be able to have a comprehensive evaluation of that prop of the properties of that molecule.
• 26:39
  SPEAKER_02: So we got down to one but of course because we're perfectionists and scientists and gosh darn it we want to make sure it's fully optimized we took that one little molecule and we started substituting and moving around atoms one position at a time and made 75 new analogs of it.
• 26:59
  SPEAKER_02: So wow because yeah that's who we are right like we wanted to make sure that you know this one was good but is there something even better within this I call it a molecular neighborhood right it's we start we stick with the base molecule but then we start making substitutions it at little spots or adding you know a few atoms here or there decorating it a little bit differently right you're optimizing it exactly optimizing the molecule yeah yeah absolutely and then you know eventually after that process you know which again took another year um you then you get down to HX1 um which is uh the molecule um that is in the hero face serum that we formulated um and can I just act is it okay like can I talk a little bit about you know uh HX1 itself we figured out exactly what it does um yes please yeah okay great because I'm I I I'm talking a lot and I don't know if that's okay.
• 27:59
  SPEAKER_01: No I want you to I'm letting you talk a lot because I want you to really go through the science and I love that you're doing it and so that's why I'm not interrupting you.
• 28:06
  SPEAKER_02: Okay great great yes it's not because of lack of interest trust me oh no no it's just can you get a word in edgewise is the real question.
• 28:15
  SPEAKER_02: Okay HX1.
• 28:16
  SPEAKER_02: So you know after all of that effort you know and I and the thing I'm the most proud of is not that you know we were flogging through and struggling and still maintained and still were able to come out with something I mean that's great but the thing that I'm most proud of uh and the group of scientists that contributed to this is that we were able to figure out what it does.
• 28:39
  SPEAKER_02: And the reason that that's so important is if you know what something does and how it acts biologically, that leaves further room in the future for additional iterations, additional innovation.
• 28:55
  SPEAKER_02: And I'll circle back to that um but you know I that's the thing that I'm so excited about with you know this this path of scientific endeavor was that we were really able to narrow or sort of um hone in on a mechanistic explanation for HX1 and then eventual family members that we've made since then um that uh influenced this pathway.
• 29:26
  SPEAKER_02: So okay Ecta, are you a Lord of the Rings fan?
• 29:29
  SPEAKER_02: Oh my god yeah okay are you kidding like I live for Lord of the Rings like what I would not be a dork if I wasn't Ben come on i i didn't want to judge or make any uh you know and uh I didn't have any I didn't want to have any preconceived notes everyone listening if you call yourself a dork and you don't like Lord of the Rings then you cannot call yourself a dork so I I second that motion yes uh be from from two dork's uh in uh in the ether uh I I second that motion um okay so Lord of the Rings right you know there's the ring right it's the one ring that rules them all and it has incredible capacity to you know modify and manipulate the environment and control the fate of of Middle earth uh you know and that's not an exaggeration go watch the movie read the books like right but anyway all right so one ring and rule them all turns out on the surface of stem cells and uh and other uh progenitor cells there is one protein that rules them all and this protein has an incredible job so when it's activated in one way uh and this is typically the way that it gets activated when we are young and our stem cells are super happy and healthy it promotes a regenerative a healthy regenerative response it tells the stem cells okay great life is good make more exact copies of yourself and also produce offspring that can repopulate damaged cells in the tissue that you're in but yeah yeah that yeah that's that's that uh sorry we actually didn't even cover that that's the real job of stem cells it's those two things um make exact copies of themselves or as best they can right eventually it's like a Xerox machine they they start to lose fidelity and those copies become you know uh worse and worse as we age um but I think that's reversible but it's another topic for another time or make what we call a daughter cell and so stem cells can make an exact copy of themselves or they can make a slightly different copy of themselves that then goes on to divide a bunch of times and then contribute to the tissue.
• 31:48
  SPEAKER_02: So you know there's a normal turnover of of cells and tissue cells live cells die they need to be replaced stem cells are responsible for generating offspring in order to replace those damaged cells or those naturally uh or in the case of an injury right then definitely stem cells need to get activated produce a bunch of offspring and drive um a healing response um in the tissue okay yeah yeah so I I realized I didn't know if we had covered stem cells and like uh I don't know how often you get to talk about them on your podcast.
• 32:21
  SPEAKER_01: No, I I love that you're doing this.
• 32:23
  SPEAKER_02: Yeah please like keep keep talking yeah okay just at any time just you know get the cattle prod out and get me back on the path.
• 32:30
  SPEAKER_02: But okay so so stem cells can with this one protein that rules them all they can either you know activate this sort of normal healthy regenerative response or if the environment around the stem cell is bad and there are a lot of pro-inflammaging pro-inflammatory proteins around what this protein is then responsible for is transducing this response inside the cell which then activates a bunch of further pro-inflammatory pro-inflammaging responses and so you know it's the same protein it's just when it interacts with different partners it can drive drastically different responses and so I think that's so amazing going back to the ring analogy right depending upon who's the bearer you can have an in you know a positive response or unfortunately you know you can give in to the ring and you can hear all of the weird and then do horrible things right so um you know that I so what we found out is that HX1 interacts with this one protein that rules them all and it does two things which is the coolest uh at all I mean at all possible not only does it prevent the protein from interacting with pro-inflammating factors so so essentially the stem cells are shielded from these pro-inflammaging factors and then they in turn the stem cells don't produce more of them they don't get involved in this feed forward loop of destruction instead they're shielded they don't feel the environment and whether or not it's crappy they're just sort of isolated in a good way from you know some of the stressors that might be in their environment now this doesn't impact their ability to differentiate at all no which is so that's it's that's actually a great question.
• 34:34
  SPEAKER_02: So this protein really isn't super involved in differentiation choices.
• 34:41
  SPEAKER_02: It's more of do I sort of regenerate and sort of uh essentially do what a stem cell does it it's more of controlling the capacity of the stem cell to maintain its stem cell identity.
• 34:57
  SPEAKER_02: And you know these these uh inflammatory and pro-inflammation factors they can you're absolutely right drive differentiation but you know that's only if they're present for long periods of time and in really high levels.
• 35:15
  SPEAKER_02: And so by shielding the stem cell from them we allow it to sort of just stay on the course of what it would normally do.
• 35:23
  SPEAKER_02: Um and then these optimizing I'd like optimizing the aging process basically that's exactly it's it's sort of just you know taking out some of the pro-aging or pro-inflammation factors that would accelerate the aging process of these stem cells.
• 35:41
  SPEAKER_01: That's exactly it yeah so like an analogy would be for everyone listening like if you smoke cigarettes, you know what I mean you're accelerating your process of getting cancer versus not smoking cigarettes versus not smoking.
• 35:54
  SPEAKER_02: Right.
• 35:55
  SPEAKER_02: Exactly yeah exactly and these stem cells they don't have that choice right they are you know they are just they're sort of at the mercy of whatever factors that would be negative and positive exactly in their environment.
• 36:08
  SPEAKER_02: So it's it's really important not only and we'll we can talk about this it's it's it's really important to try and reduce your systemic levels of inflammation in general that's just going to help you all across the board but what we found is a new little molecule that can help support stem cells so even if they are in maybe a less than optimal environment they have an extra layer of protection and you know what HX1 also does is it actually promotes a change in the shape of the protein and activates the protein in the way that it would be activated in sort of a normal healthy stem cell.
• 36:47
  SPEAKER_02: So we get some regenerative response as well.
• 36:50
  SPEAKER_01: That's very interesting and I'm really curious also in terms because you had mentioned like the overall milieu and how that really like plays a role in how we age and how that whole process takes place right of like stem cells doing what they're supposed to do.
• 37:04
  SPEAKER_02: I'm wondering if you know this molecule is also playing a role in in the recruitment of what kind of like inflammatory cytokines are coming to the scene versus not you know yeah it's like it's a great great question and again you know we were talking about like initially when we're thinking about getting you know taking a new look at osteoarthritis how do you choose amongst all these things that would be influencing the situation how do you choose just one to sort of to zero in on and you know I that's exactly where we're at right now is um looking at how these family of molecules the broader impacts rather than just the you know the the single cell biology aspect but really sort of looking more broadly what are the things how are they changing the microenvironment um to support healthy function of stem cells so yeah it's a great it's a great avenue and there's there's a lot that we're doing to to really address those types of questions.
• 38:07
  SPEAKER_01: Now one question I have um Ben is that like you know I'm gonna be you know very transparent here for everyone listening because I'm honestly getting sick of all of the um all of the products that are like well this is a stem cell product you know it has stem cells in it and it's like that doesn't mean jack shit okay if I'm not gonna put stem cells on the top of my skin and then expect my skin to all of a sudden be better.
• 38:32
  SPEAKER_01: You know what I mean?
• 38:33
  SPEAKER_01: Yeah so it's like can you please clarify that for everyone listening because this is so different.
• 38:38
  SPEAKER_01: That's what I want people to understand.
• 38:39
  SPEAKER_01: This is an actual molecule that's involved in the signaling that's occurring for normal stem cells to be protected.
• 38:46
  SPEAKER_01: So I want you to clarify that for people because I know there's a lot of products out there that are like well we have plant stem cells in our product and this is what you need.
• 38:55
  SPEAKER_02: So can you just talk about that a little bit definitely um and I I really appreciate the question Ecta because that you know I I I think the reason behind you know products talking about or or claiming to have let's say stem cells in them is because I think that it's you know it's it's a marketing term for most of these you know these brands or these products they want to you know they they want to take you know advantage of the zeitgeist that stem cells are important and that stem cells you know are are involved in maintaining our bodies I think I think a lot of people in in popularly in culture you know they understand that but you know these products like you were saying okay so let's take an apple stem cell for example right okay first of all I don't know what that is um I'm a stem cell biologist and I don't know what that is um because you know we have at least in the animal kingdom like in mammals we have a very strict definition of what a stem cell is and what a stem cell isn't so um I am I admit not horribly familiar with the plant literature on defining stem cells but I suspect it's not extremely robust.
• 40:18
  SPEAKER_02: So let's okay so putting that aside what is a plant stem cell let's just assume that they exist and that these um you know that we're able to somehow isolate them what again I feel like we're going out on a limb here but let's just say let's just say this is happening.
• 40:34
  SPEAKER_02: Okay so stem cells you know they themselves have important functions like we were talking about generating daughter cells and offspring that contribute to um tissue repair but they also have another important function which we touched on a little bit so you know I was talking about it in the negative context.
• 40:53
  SPEAKER_02: So if a stem cell is in a bad environment it ends up secreting a bunch of proteins that reflect that bad environment it tends to be feed forward.
• 41:03
  SPEAKER_02: They also try when they're when they if it's at a you know within a threshold that a stem cell can handle they will actually secrete anti-inflammatory proteins and you know regenerative proteins to try and counteract the signals that they are experiencing.
• 41:22
  SPEAKER_02: So I think when these products are saying that they're isolating you know stem cells they are trying to say that they're hoping that whatever they're putting in there will be cells that are secreting beneficial sort of like anti-inflammatory or pro-regenerative signals.
• 41:44
  SPEAKER_02: But I I think that's the that's what is the the premise behind it.
• 41:52
  SPEAKER_01: I do I think that doesn't even make any sense like you need to be in an actual like environment to even have that happen like like you're exactly right you drew the exact important connection there.
• 42:04
  SPEAKER_02: For a stem cell to have a you know an a very uh hyped up beneficial response it needs to be experiencing something you know mildly annoying or somewhat negative and so unless you're harvesting these apple stem cells after you've bruised the apple again I have no idea how this happens um I I I I have a I'm confused about you know what's going on there.
• 42:31
  SPEAKER_02: And then Ecta the point you made which I think again everybody that's listening has figured this out by now what we how we chose to approach this is instead of sort of just adding stuff on either extracts of stem cells or stem cells themselves what we're doing is the stem cells you already have in your own skin we're giving them tools to better deal with the challenges that they're facing and we're all we're you know kicking them into a regenerative response just by you know applying something topically well this is like you know this is for this is a terrible analogy but I'm just gonna run with it it's like the DARE program for like kids not doing drugs.
• 43:16
  SPEAKER_01: So like if you have little kids and you don't want them to do bad things then you tell them this is not something you should do and you give them tools that say you know that give them reasons to not do bad things.
• 43:27
  SPEAKER_01: So it's kind of like that you know it's like teaching them like teaching them like here you go this is a good example of what you should do with your life rather than giving them cigarettes and alcohol you know what I mean like don't give your stem cells cigarettes and alcohol give them HX1 instead exactly exactly no and you know actually I have one more I have a question for you about the um because I know a lot of clinicians love asking this question and it drives me nuts but I have to ask what is um the Permeability aspect of HX1.
• 44:03
  SPEAKER_01: How do we how does it go into the skin to the point where it actually reaches the stem cells?
• 44:08
  SPEAKER_01: And can you tell us about that?
• 44:09
  SPEAKER_02: Yeah, awesome question.
• 44:11
  SPEAKER_02: I don't mind that question at all.
• 44:12
  SPEAKER_02: In fact, I think, you know, you have to, as a either a potential consumer or as a as a formulator of a new technology, this is a critically important question.
• 44:25
  SPEAKER_02: You have to understand the solubility of the molecule that you're working with and create a formulation that enables it to get to where it needs to be through the stratum corneum and all the other things that are, you know, because the skin is literally armor.
• 44:45
  SPEAKER_02: We are wearing armor on the outside of our bodies.
• 44:48
  SPEAKER_02: It's designed to keep things out.
• 44:51
  SPEAKER_02: And so, you know, you, if you're going to, you know, apply something topically and expect it to get to where it needs to be, you have to take that into consideration.
• 45:00
  SPEAKER_02: So we actually spent a year formulating the serum as an emulsion so that we could allow this sort of amphopathic migration of HX1 into the deeper layers of the skin.
• 45:18
  SPEAKER_02: So yes, the answer is we we knew that you know HX1 itself is pretty hydrophobic.
• 45:25
  SPEAKER_02: Um, and so we needed to, you know, as a vehicle, give it some capacity that was hydrophilic.
• 45:33
  SPEAKER_02: Um and so it ends up being encapsulated in these little uh droplets um and that are inside out and uh are hydrophilic, and so it then it can penetrate into the skin where it needs to be and uh and then interact directly with the stem cells.
• 45:51
  SPEAKER_01: That's awesome.
• 45:52
  SPEAKER_01: I love that.
• 45:52
  SPEAKER_01: And by the way, everyone listening, ampopathic means that a molecule is both hydrophilic and hydrophobic and has properties.
• 45:58
  SPEAKER_02: Thank you.
• 45:59
  SPEAKER_02: I just I just got in now, jargon and thank you.
• 46:02
  SPEAKER_02: Thank you.
• 46:03
  SPEAKER_01: Just wanted to let everyone so that you can follow along.
• 46:05
  SPEAKER_01: But this is this is really, really cool stuff, Ben.
• 46:08
  SPEAKER_01: I mean, honestly, I I could talk to you for hours about this, and I would love to have like a part two because I think there's so much potential here, but I know you wanted me to remind you to come back to a topic.
• 46:18
  SPEAKER_01: So I want you to um, you know, close off and and make some comments on that aspect as well.
• 46:23
  SPEAKER_01: What you want to do?
• 46:24
  SPEAKER_02: Yeah, so I thank you again for for circling back.
• 46:28
  SPEAKER_02: So, you know, I what I you know, what I wanted to say is um, you know, why we were so excited about figuring out what HX1 does is it enables innovation and continued, uh we call it uh iterative medicinal chemistry.
• 46:45
  SPEAKER_02: Basically, doing that thing I was talking about earlier, where we continue to move atoms around or add additional functional groups to the molecule and test them to see if we can continue to elicit different properties from daughter molecules of HX1 or maybe even better properties.
• 47:05
  SPEAKER_02: And so the culmination of those efforts, you know, we have a molecule that is going into clinical trials next year at USC here in Los Angeles for mild to moderate osteoarthritis.
• 47:20
  SPEAKER_02: To sort of and I'm so excited about that because you know, the work that we've talked about today enabled that sort of circling back to what we were initially looking at, which was osteoarthritis.
• 47:33
  SPEAKER_02: So we have kept sort of on the path of developing new molecules to sort of get at our initial question, which is how do we interrupt the inflammation process so that we can allow for uh disease modifying activity in osteoarthritis?
• 47:53
  SPEAKER_02: Um, and so that you know, that clinical trial will start recruiting sometime late next year.
• 47:58
  SPEAKER_02: Um and you know, we're just I'm just so proud that to to contribute to something like that because yeah, I mean that is huge.
• 48:06
  SPEAKER_02: Yeah.
• 48:07
  SPEAKER_01: That's huge.
• 48:07
  SPEAKER_01: And I think that's really the for me, that's always been like the biggest attraction for biomedical research for me is um what it leads to.
• 48:17
  SPEAKER_01: You know, it's and it's and that's something I think a lot of people don't really grasp, like unless you're in the sciences, because it's like, you know, it's not about just one discovery, it's about one discovery leading to a domino effect, leading to huge innovations in like, you know, just diseases that we all deal with.
• 48:36
  SPEAKER_01: I mean, you mentioned osteoarthritis.
• 48:37
  SPEAKER_01: That's one of the most prevalent diseases for the elderly, you know, in our world.
• 48:42
  SPEAKER_01: And that's something that almost all of us will, you know, either experience or have someone we know experience.
• 48:47
  SPEAKER_01: So yeah, I mean, this is this is phenomenal science.
• 48:50
  SPEAKER_01: And I I'm so honored that you know you were able to come on the show and tell us about it.
• 48:54
  SPEAKER_01: I I wish Hero Skin nothing but the best.
• 48:56
  SPEAKER_01: Everyone, you need to go to www.herux skin.com and check out this product.
• 49:04
  SPEAKER_01: It's a phenomenal serum.
• 49:06
  SPEAKER_01: I've been using it, my skin's been loving it, and the science, like I said, is extraordinary.
• 49:10
  SPEAKER_01: So thank you so much, Ben.
• 49:11
  SPEAKER_01: This has been great.
• 49:12
  SPEAKER_02: Yeah, Ecta, thank you so much for having me.
• 49:14
  SPEAKER_02: And I very much look forward to part two.
• 49:16
  SPEAKER_01: Yes, absolutely.
• 49:17
  SPEAKER_01: Me too.
• 49:18
  SPEAKER_01: Uh, and everyone, leave us some comments and ask some questions.
• 49:21
  SPEAKER_01: And if you have any science-related questions, please leave them in the comments.
• 49:24
  SPEAKER_01: And I'm gonna try to pass them to Ben's team.
• 49:26
  SPEAKER_01: But yeah, definitely part two is coming very soon.
• 49:29
  SPEAKER_01: Because I'm not sure.
• 49:30
  SPEAKER_01: Yeah, and reach out to us.
• 49:31
  SPEAKER_02: Yeah, and reach out to us on Instagram if you have questions about the science.
• 49:34
  SPEAKER_02: I mean, or email, right?
• 49:35
  SPEAKER_02: Like we we clearly we love talking about this.
• 49:38
  SPEAKER_02: So thank you for the opportunity.
• 49:40
  SPEAKER_01: Yes, absolutely.
• 49:42
  SPEAKER_01: And I will be back soon.
• 49:43
  SPEAKER_01: Thanks, guys.
• 49:44
  SPEAKER_01: Hey guys, so I hope you love that episode.
• 49:47
  SPEAKER_01: Please make sure to hit subscribe if you're tuning in to us on any podcast platform.
• 49:52
  SPEAKER_01: We are available on so many different platforms.
• 49:54
  SPEAKER_01: So wherever it is that you're tuning in, just go hit subscribe.
• 49:57
  SPEAKER_01: You will be immediately notified when we publish new episodes.
• 50:00
  SPEAKER_01: This way, you're able to tune in to amazing insights from experts, brand founders, industry leaders, authors, all the wonderful people that we host.
• 50:09
  SPEAKER_01: And that's very important for me because I love to hear from you guys and really understand what you love and what you want to hear more of.
• 50:16
  SPEAKER_01: Also, make sure to give us a follow on all of our social media outlets.
• 50:19
  SPEAKER_01: We are available on Instagram, TikTok, X, you name it, we're there.
• 50:24
  SPEAKER_01: We also have a blog on Medium.
• 50:26
  SPEAKER_01: So if you're a reader and you love Medium blogs, check us out on Medium.
• 50:30
  SPEAKER_01: We publish some really great articles on there that do deeper dives than just what's available on the podcast, and it's really a great place for all of you science geeks out there that want to learn a little bit more.
• 50:40
  SPEAKER_01: We go above and beyond with our research and making sure we're bringing you information that you usually probably won't hear about in other outlets.
• 50:46
  SPEAKER_01: So check us out, leave us a comment, leave us a review, and we'll be back next time with another episode.
• 50:51
  SPEAKER_01: Thank you.