Absolute Gene-ius

A passion for cfDNA analysis is in her blood

Episode Summary

This episode gets personal quickly when our guest talks about how her husband is now benefiting from methods her and her colleagues have developed over her career in developing organ transplantation compatibility assays.

Episode Notes

Organ transplantation is a modern marvel, with more than 157,000 solid organ, and more than 9,000 marrow and blood transplants occurring worldwide in 2022. Organ donor and recipient matching and compatibility screening has progressed significantly in recent decades as molecular methods have progressed rapidly to support this and other fields. Specifically, typing of human leukocyte antigens (HLAs) has expanded to consider ethnic population variation and cell free DNA (cfDNA) monitoring is now being used to monitor recipients for biomarkers that indicate organ rejection.  

Our guest for this episode, Dr. Lee Ann Baxter-Lowe, Director of the HLA Laboratory at Children's Hospital Los Angeles has been working in the field of transplantation science for virtually her entire career. Join us for a great explanation of the science and a first-hand recounting of developing the assays, from decades ago, before thermal cyclers existed, to her cutting-edge work using digital PCR to progress the field even further. 

Lee Ann also shares very personal aspects of her career journey in her conversation with Cassie. This includes her describing the scientific “studies” of her and her cousin as children, her venturing into the world of HLA typing when it was emerging, and the role her family has played in her career, which gets personal quickly when she shares that her husband is currently dealing with a blood malignancy. 

Visit the Absolute Gene-ius page to learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

Episode Transcription

 

Cassie McCreary 00:00

Snaps. Snaps. Snaps. Jazz hands. 

 

Jordan Ruggieri 00:03

It's a snap clap, a snap clap.

 

Cassie McCreary 00:06

That's it. I like the snap clap. Also known as a slap. 

 

Jordan Ruggieri 00:27

Welcome to Absolute Gene-ius, a podcast series from Thermo Fisher Scientific. I'm Jordan Ruggieri.

 

Cassie McCreary 00:32

And I'm Cassie McCreary. And it's our pleasure to welcome Dr. Lee Ann Baxter-Lowe to the show as our esteemed Gene-ius of the day.

 

Jordan Ruggieri 00:39

Lee Ann is the director of the HLA laboratory at Children's Hospital, Los Angeles. And she has contributed to an incredible amount of research and scientific discovery over her decades-long career. We're so thankful to learn from her about both her research and her clinical work, as well as the incredible stories about how her innovation has impacted lives around her. Thanks so much for joining us today, and we hope you enjoy it.

 

Jordan Ruggieri 01:06

Leanne, it is a pleasure to have you with us on Absolute Gene-ius today, we're super excited to have you on your research is really, really interesting. Can you maybe just give a little bit of background on yourself and what type of research you're involved in?

 

Lee Ann Baxter-Lowe, PhD 01:19

For the most part, I work in transplantation. And I came to this field many decades ago, because of my interest in being able to develop new technologies and new laboratory tests that could be used ultimately, in clinical care, although my work is at the research stage. Eventually, actually, I evolved into having dual roles. I have a research laboratory and I also have a separate clinical laboratory. And one of the advantages of that is that allows me to translate some of the things I do ultimately into practice. 

 

Jordan Ruggieri 02:01

That’s amazing. Can you elaborate, how does this research work? Are you looking at how a subject might accept or reject a transplant? Can you elaborate on that a little bit?

 

Lee Ann Baxter-Lowe, PhD 02:13

Most of my work involves compatibility in some way. In the early days of my work, I did research to better understand matching of HLA between donors and recipients and how that impacts blood and marrow transplants. And that, over decades has evolved in standard practice for testing that's done now by sequencing, nucleotide sequencing. But I was in the early days of the work even involved in sequencing some of the alleles and developing methods. So, it was just great fun for me and very rewarding. And then to see it ultimately move into clinical practice and change lives, it's been extraordinary, I feel very lucky. Today, I'm still working with compatibility. Some of the work that we've recently published involves understanding why the HLA alleles in the population differ in ethnic groups and how that impacts the ability of a clinical laboratory to measure certain endpoints and clinical tests that are important for assessing compatibility. But I'm most excited about a project we're doing to look at cell free DNA (cfDNA) after transplantation. Cell free DNA in itself is absolutely amazing and provides a lot of opportunities for future diagnostic tests. There are some diagnostic tests already available for cell free DNA. But I believe that we've only just touched the surface of what's possible there.

 

Jordan Ruggieri 03:56

Cell free DNA is amazing. What is cell free DNA? And what exactly do you look for, you know, in that particular type of DNA? 

 

Lee Ann Baxter-Lowe, PhD 04:06

Cell free DNA is something that gets released into the circulation when cells die. And the nature of that cell free DNA can vary depending upon the process that caused the death of the cell. So, that's one of the opportunities to get additional information. In my laboratory, we're looking for assays that can allow us to distinguish donor-derived cell free DNA from host-derived cell free DNA. There's a lot of interest in using donor-derived cell free DNA and the levels of donor-derived cell free DNA to detect when an organ that's been transplanted is being damaged. And there's growing evidence that there is a correlation and that perhaps, you know, monitoring the levels of cell free, donor-derived cell free DNA, could be useful to detect organ damage very early in the process that would allow early intervention to prevent the severe damage from ever occurring and we think ultimately can result in much longer graft and patient survival. 

 

Jordan Ruggieri 05:19

Is there any challenges looking at donor-derived cell free DNA versus host cell free DNA? 

 

Lee Ann Baxter-Lowe, PhD 05:26

Tremendous challenges. That's what makes it fun. It's extremely challenging. First, the levels of cell free DNA in the blood are, are very low, a zero to 100 nanograms per mil, very little. And in a situation such as ours, we're interested in studying pediatric samples. So we want to be able to get results from a milliliter of blood. So that means we have to have an assay that can work with very little DNA input. Beyond that, when you're looking at the amount of donor derived cell free DNA in the midst of all the host cell free DNA, there isn't very much most of the time. So if you have a healthy graft, some of the literature suggests it might be as low as point 2%. So you can imagine why I think digital PCR is a godsend.

 

Jordan Ruggieri 06:28

Definitely. How is this looked at, let's say prior to digital PCR, how and even maybe some of these techniques, how would somebody determine that there might be a response against that transplanted organ? Is it done molecularly? Or is it done, maybe proteomics, immunology? How does that work?

 

Lee Ann Baxter-Lowe, PhD 06:56

Historically, well actually still, a standard practice would be to use some sort of markers or indicators of organ function and they're very insensitive. So, in the case of kidney transplantation, serum creatinine is used as a biomarker. And then an invasive biopsy is generally used to determine if there's some pathology in the organ. There's a lot of new things coming out. There are assays that are looking at RNA, either in biopsy material or in blood. And looking at whether or not they can be useful biomarkers. It's a rapidly advancing field and very exciting. It's providing new insights into the diagnosis of rejection, and the pathways involved in rejection. And ultimately, we believe that it's going to lead to better therapeutic interventions, as well as preventing damage in the first place.

 

Jordan Ruggieri 08:02

I can just imagine. Talking a little bit more about some of your workflow. Can you talk a little bit about how the assays work? Are you looking at a particular biomarker for say, donor-derived, then you are looking at host-derived? Is there any multiplexing or somewhere around there?

 

Lee Ann Baxter-Lowe, PhD 08:25

That's exactly what we've been working on is multiplexing. And developing primers and probes that can be used to differentiate donor and recipient. We are using indels, insertions and deletions. And the alleles that we're using now have been selected so that they're between 0.5 or 0.6 frequency in the population. The goal there is to have as many informative markers as we can. And we started by trying to develop a whole new approach to digital PCR that allows us to multiplex beyond what's been available before. We've recently published a paper in Frontiers in Genetics describing this approach in detail. Interestingly, what we did in the first demonstration is that we could detect 12 different targets in one well, instead of one. It would be very difficult to do but we think it could be done that you could get up to 25 targets per well. And then, you know, if you use, you know, multiple wells for one sample, then you can also increase the number of targets beyond that. But in measuring donor-derived DNA, it's my observation that having many targets and being able to average them is beneficial because you're working at something that's just so, such a low level and improves precision and accuracy when you have multiple informative targets.

 

Jordan Ruggieri 10:10

Yeah, makes sense. Let's transition over to digital PCR. We'd love digital PCR at Absolute Gene-ius, I'm sure you know. How does digital PCR play a role in your research?

 

Lee Ann Baxter-Lowe, PhD 10:20

For us, we think it's perhaps the only useful platform to be able to test samples that have only one milliliter of blood and to isolate cell free DNA from them. But we're not going to have very much DNA to work with and we're going to be measuring very small quantities. And when you have a very low copy number of something in a mixture digital PCR is really the best approach. It helps you to get a much lower baseline. You know, for some of the probes we've been working with, if we just see one positive signal, we can be pretty confident that there's one copy there. 

 

Jordan Ruggieri 11:04

You mentioned NGS, and using some NGS is kind of an industry standard or a direction that the industry is going in. Is there any differences or do they, any differences between the two in terms of your research? Are they complementary? How could you maybe use NGS versus digital PCR? When might it be useful to use one or the other?

 

Lee Ann Baxter-Lowe, PhD 11:27

Clinically, we're using NGS. Our research involves digital PCR. So you know, our long-term goal would be to see this technology move into the clinic. 

 

Jordan Ruggieri 11:39

And is it simply the just the ease of use and, that digital PCR offers? Or turnaround time? What are some of the benefits of using digital PCR?

 

Lee Ann Baxter-Lowe, PhD 11:52

The list is long. The ease of use is amazing. For our research assay, the setup is 30 minutes. And it doesn't require much expertise at all. One of the students working in our lab had never taken a lab course, she was a major in public health. And she wanted to volunteer to work in our lab, we were very fortunate to have her, and her first assay looked great.

 

Jordan Ruggieri 12:24

Amazing.

 

Lee Ann Baxter-Lowe, PhD 12:26

Yeah, so it's really easy to use. Another thing is the speed. Here, we can just do one sample at a time if we wish. And for the assay we're working with, it takes about, if we had a whole plate of 16 samples, it would take 30 to 60 minutes to set up and to two and a half hours to run. But if we have only one sample, it's 30 minutes and a shorter run time as well. 

 

Jordan Ruggieri 12:55

Makes sense. I can imagine holding samples, especially cell free DNA, you run into issues with potential freeze thaw and degradation. And this is something you come up against frequently as well?

 

Lee Ann Baxter-Lowe, PhD 13:08

We've been, I think, successful at being able to store samples. But we're looking for something that ultimately will be used clinically. And one of the drawbacks of the a lot of the current options are that it takes days or longer to be able to get the results. So when I discussed our research at clinical meetings, I can't tell you how much positive feedback I've gotten from the clinician saying, you know, having a true same day assay would be extraordinary, and it would really change their ability to manage patients.

 

Jordan Ruggieri 13:48

Can you talk a little bit about multiplexing as well? How does that look on digital PCR as opposed to maybe a real time PCR platform or a different platform?

 

Lee Ann Baxter-Lowe, PhD 13:59

The work we're doing is in collaboration with a company who holds the patent for this technology, and we've been the first group to be able to explore it. I'm really thrilled about having that opportunity. It's an amazing probe design that allows us to multiplex. And the way it works is that the probe itself forms a hairpin. And the target region of the probe has a ribobase incorporated into it at the five prime end there's the dye that we use to detect the presence of the probe. And when there's no part target present, it's in this partial hairpin conformation, and you see the, you detect the fluorescence. Then when you go through cycling, what you can do is that is the denature, the hairpin loop in the presence of your target DNA. When it hybridizes to the target that presents so the ribobase allows cleavage by ribonuclease. Then after the cleavage, that hairpin loop piece comes off, and the other part stays with the target DNA. Now you add polymerase and it extends it. And that dye at the five prime end has an ISO-C. And in this polymerization, you add an ISO-G with a quencher attached. So, now you're going from a signal to no signal quite different than most of the technologies that are out there. But because we can control the melt temperature, we can use several different probes that melt at different temperatures during a single cycle.

 

Jordan Ruggieri 15:52

Very, very interesting. Anything else, science wise or digital PCR wise that we might have missed or that you wanted to talk about?

 

Lee Ann Baxter-Lowe, PhD 16:00

No, I really like working with technology. And I feel very fortunate that for most of my career, I got to do this. This is my idea of fun. And the wonderful aspect of the area that I work in is that a lot of my work has ultimately evolved into clinical practice, and you know, knowing that it's affected the lives of people is really rewarding.

 

Cassie McCreary 16:30

We hope you're enjoying this episode of Absolute Gene-ius. We're huge fans of digital PCR here and want to tell you about Applied Biosystems™ QuantStudio™ Absolute Q™ dPCR system. This instrument enables quantification of your targets without the need for standard curves with excellent precision in only 90 minutes.

 

Jordan Ruggieri 16:48

You could say that again Cassie!

 

Cassie McCreary 16:49

Okay I will. Get dPCR data in only 90 minutes.

 

Jordan Ruggieri 16:54

Unlike other digital PCR systems, the Absolute Q dPCR instrument does not use emulsion or other droplet-based methods to compartmentalize reactions. Rather using distribution channels on a microfluidic array plate (MAP), the reagent is consistently delivered to physical micro chambers. That technology utilizes more than 20,000 micro chambers with the coefficient of variation of less than 1%. 

 

Cassie McCreary 17:18

Another feature we're excited about is that the Absolute Q dPCR system analyzes more than 95% of the loaded sample, ensuring highly accurate digital PCR results. No more wasting upwards of 60% of your precious samples when loading, which is especially critical for rare targets.

 

Jordan Ruggieri 17:35

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Cassie McCreary 18:25

Now, back to our episode.

 

Cassie McCreary 18:30

Leanne, welcome to Cassie's Career Corner. We just talk about fun, warm, and fuzzy career things and advice and all kinds of fun stories. So, uh, you know, we've spoken a lot about your passion around this and how much it excites you and how happy it makes you everything. What is it about it that you're so passionate about? Or what is it they you so connect with? And like, was there anything early in your life that made you think kind of more broadly, I really want to go down the route of science and research? 

 

Lee Ann Baxter-Lowe, PhD 19:03

When I was a little girl, I didn't want to play with dolls. I love experimentation, not like having a kit, but actually observing the world around me and categorizing it. I used to do things, my favorite thing to do was to go to my aunt's farm. And she had like a lot of cats. So I, my cousin, and I would collect all the cats and then test them to see what would they eat and then take, make records of it. Or what was their tolerance to various noises or various stimuli. 

 

Cassie McCreary 19:41

I have one right here. I’m going to do that later. 

 

Lee Ann Baxter-Lowe, PhD 19:43

And that was, that was my idea of fun. You know, I think there's something to be said for there's, you know, we're each meant to do something. And maybe you can even go back to your early parts of your life and think about what was event and have that guide you into a career. For me, I also like writing a lot. And then when I went to school, I was actually an editor in my college newspaper as well. So, I was thinking about a writing career, but then I love science. And ultimately, the more involved I became in science, there really wasn't time for the journalism part of my inclination anymore. When I started as a graduate student, I was really interested in enzymatic pathways and their regulation and hardcore biochemistry. But I love everything I learned about, with two exceptions. I thought antibodies were pretty boring. And I also wasn't very interested in nucleic acids either. So, that was those were like the only two areas I thought I could say, “Never.” And then I actually became interested in gene regulation, understanding, you know, some enzymology that was created some changes that were related to alternative splicing of the enzyme itself. And that led to really becoming immersed in molecular biology and learning a lot of technology and all of a sudden, that became my passion. So, so much for not being interested in molecular biology, that one was gone. So, I was doing molecular biology. That's what brought me to this field of HLA. At the time that I entered the field, in transplantation differences in HLA between individuals were determined using serological methods. And I entered the field at just the right time because the molecular biology hadn't yet been explored to any great extent. And so I got the opportunity to be involved in developing molecular methods for doing typing that hadn't historically been done by these serological methods. That led to incredible discoveries, not by me personally, but this large field of people pursuing the same technology. What we thought used to be maybe 100 types, turns out to be millions of alleles. And all of this is important in clinical transplant settings, and even other settings like a person's ability to fight an infection. It's really been a lot of fun. But in working in transplantation, another part of compatibility is that the immune system can develop antibodies against the graft. And as my clinical lab was evolving, we were also testing for antibodies. So, I also became passionate about antibodies. And so now you will, if you look at my publication record over the last few decades, it's all either molecular biology or antibodies. 

 

Cassie McCreary 23:18

Isn't that funny how that works out? So, going back to the beginning a little bit, what did you study in school? Because they you said kind of at the beginning, you were more heavily steeped in bio, like the biochemistry side of things. Is that Is that what you studied or?

 

Lee Ann Baxter-Lowe, PhD 23:34

As a graduate student, I worked in the lab of Hector DeLuca, who was responsible for discovering some of the vitamin D metabolites. 

 

Cassie McCreary 23:43

Oh, awesome. 

 

Lee Ann Baxter-Lowe, PhD 23:43

And we were doing some of that work while I was a graduate student. And so I was doing assays, studying the hydroxylases. For vitamin D, there's one hydroxylase, a 24-hydroxylase and 25-hydroxylase. And so I was studying those and it was a really exciting time. When I finished my graduate work. I started thinking that I plan to stay in the vitamin D field. But I thought that maybe vitamin D was like estrogen in that it regulated gene expression. So, then I did a postdoc in a lab looking at regulation of gene expression by estrogen, which is what brought me to molecular biology. 

 

Cassie McCreary 24:32

There we go. It's all connecting. So, kind of a theme, throughout our show has been the discussion of the importance of finding mentors over your career in your studies, or networking or things of that nature. Would you say that any of that has played a crucial role for you over the course of your past?

 

Lee Ann Baxter-Lowe, PhD 24:52

Oh, certainly. I think my advisors through my training definitely played a role. And then later, especially when I took a deep jump into this HLA field. I was actually surprised to get hired to work in this field. What happened is that I had been doing a lot of molecular biology and I had moved away from the regulation and things that were clinic, potentially clinically relevant, to some more hardcore enzymology and looking at these isoforms. Although I was doing well, I didn't feel as passionate about what I was doing as some of my earlier work, and I decided I wanted to do something that had more clinical relevance. And so I started thinking about my skill set and looked at this HLA situation with the typing. And I thought there was this fabulous opportunity to apply molecular biology to HLA typing and also to understanding what the difference was between those HLA types. I applied for a job at the Blood Center of Southeastern Wisconsin to establish the first clinical laboratory to do DNA based HLA typing. And they hired me, even though I knew nothing about HLA, so it was, or transplant or anything. So, I was on a steep learning curve, and I had a lot of mentors there that were extraordinary, really helped me along my career path.

 

Cassie McCreary 26:31

I think it's very natural for a lot of people over the course of their career, or even their studies, in one format or another to experience kind of some self-doubt. What's your kind of advice, or any sort of tricks or tips that you've discovered as like a workaround for a situation like that when you're sitting, and you're just kind of like, I don't know if I can do this?

 

Lee Ann Baxter-Lowe, PhD 26:54

Well, in that situation when I went to the Blood Center, it really did happen. Shortly after I started work within, I think the first week or two, the Blood Center sent me to an international workshop, which is a major meeting in the HLA field where the most recent discoveries of the fields are presented and, and the experts in the fields are giving lectures, and the latest technology is being presented. And I went to that meeting, and I had no idea what anyone was talking about. There was so much jargon, I mean, I was just clueless. So, I was blown away, I went back to the Blood Center, and it was the same thing I would go to, you know, seminars for the experts in the field at the time, and I wouldn't know what they were talking about. I had my little like, my little molecular biology corner, and I was isolating DNA and doing PCR back before there were thermal cyclers. And about the six-month point, I thought "This was just such a mistake I'll never understand". And then suddenly, it all cleared up. It just happened. It was just, I think my brain was overwhelmed with all the new information and it took some time to learn the jargon. You know, since then, it's just been fabulous.

 

Cassie McCreary 28:21

Yeah, well, I mean, there's a lot that can be said for just recognizing even that things take time, like most things in life are an adjustment and come with kind of a learning curve. And that's, you know, not something that's just exclusive to careers or anything like that. We like to get into the nitty gritty, fun, maybe embarrassing things here on Absolute Gene-ius. You don't have to share with us, but we'd love to hear, over the course of time what is your most embarrassing lab moment?

 

Lee Ann Baxter-Lowe, PhD 28:53

You know, I don't have any, like a really dramatic event where something went wrong. No, just you know, the usual things because we're all humans and occasionally we pipette something incorrectly. We have you know; we've pipetted the wrong sample; we've omitted one of the components or something. It happens to everybody. My approach to having that happen is that there's something wrong with the system that allowed me to do it. 

 

Cassie McCreary 29:27

Ah, okay. 

 

Lee Ann Baxter-Lowe, PhD 29:30

So, then I focus on what the system is, and how did that contribute to my making the error. So, you know, for my work, and most of the people who work with me, we have checklists to prevent those errors. And we take a lot of steps to prevent the person from being able to make a mistake.

 

Cassie McCreary 29:51

Yeah, especially since what you're working with is such a, I mean, it's delicate, it's a rare commodity, it's a you know, these are these are samples that you really can't mess up with, you know. How about a moment in time when you thought to yourself, you know, “Wow, I've really made it” or “This is, I feel very happy, I feel very content with where I've reached” or “I'm super proud?”

 

Lee Ann Baxter-Lowe, PhD 30:13

You know, as time went on, and my research continued, I was invited to give lectures around the world at large audiences. I thoroughly enjoyed doing that. And some of those crowds were really quite large. Actually looking out on the audience and realizing that they're all totally engaged and excited about what I had done. I would say that would be it. 

 

Jordan Ruggieri 30:40

Amazing.

 

Cassie McCreary 30:41

What an evolution, right? Because we just went over how you went from not having any idea on what a lot of people were speaking about back when you're at the Blood Center to confident and comfortable to speak to large audiences about all kinds of, you know, really important topics that good for you what an evolution, right?

 

Lee Ann Baxter-Lowe, PhD 30:56

It was quite an evolution it again, when I started out as a graduate student, I thought I would just have a career in academia and do some research and publish some papers. And I really didn't think much about public speaking. But I ended up doing that. And it was a wonderful part of my career. 

 

Cassie McCreary 31:18

Yeah, that's excellent. You are clearly balancing a lot. Everybody needs a break from work and research and all these fun things. What do you like to do in your spare time to give yourself a little bit of a mental break from all of this, like heavy duty thinking that you're inevitably doing?

 

Lee Ann Baxter-Lowe, PhD 31:35

I actually don't take many breaks, 

 

Cassie McCreary 31:37

You're like, I don't have anything. 

 

Lee Ann Baxter-Lowe, PhD 31:41

This is my idea of fun. You know, I might like to pick up an issue of Science, 

 

Cassie McCreary 31:45
Okay.

 

Lee Ann Baxter-Lowe, PhD 31:46

And just read something outside my field. I guess, you know, my husband and I do like, gourmet food. So, we like going out to restaurants and cooking fun things. But, you know, and then there's family, of course. So that's also a big commitment. I think, by the time you know, you've finished with time for your family and the basics of living and doing research, that's, there isn't any time left. At least for me.

 

Cassie McCreary 32:18

Fair enough. Jordan, do you have any more fun questions? Otherwise, I'm good.

 

Jordan Ruggieri 32:23

I have you know; I have two, not necessarily fun, but two that I was thinking about just talking. You know, I mean, we talk about HLA quite a bit in in the podcast. Can you describe just for the listeners and the capture of what HLA is and how does that play a role in your research?

 

Lee Ann Baxter-Lowe, PhD 32:40

So, HLA is human leukocyte antigen. This is a group of proteins that are expressed on the surface of the cell. They are involved in discriminating self from non self in the immune system. When you get infected with a pathogen, for example, the HLA proteins bind peptides derived from those pathogens. And this complex of the HLA molecule with a peptide derived from the pathogen is recognized by T-lymphocytes, and that's what allows the immune response to target that pathogen and destroy those cells and ultimately, for you to be, have the infection resolve. The problem with it in transplantation is that now when you transplant the organ, if the HLA proteins of the donor organ, or the donor marrow, or the donor blood are different, your immune system is going to recognize that as foreign and something to kill. So, that's why the HLA matching between the donor and the recipient is one of the important factors in compatibility. That said, now, physicians have developed a lot of protocols and there are therapeutic alternatives to try to overcome that. So, a patient who gets a solid organ transplant will be on lifelong immunosuppression to prevent the immune cell system from recognizing those differences. I have spent my career, much of it developing HLA, molecular HLA typing methods. Um, chimerism tests to be able to monitor engraftment after blood and marrow transplant. And so my family's well aware of this and we've been talking about transplant my whole life. And this year, my husband developed a hematological malignancy. And as a result, a lot of the things that I've developed are actually being used for my own family. Really kind of surreal.

 

Cassie McCreary 34:57

Well, it's a good thing you develop them.

 

Lee Ann Baxter-Lowe, PhD 35:00

Well, I wasn't alone. Those advances are, you know, the product of many people making some little incremental difference and then it all comes together. But I did play a role in it. And, you know, my children grew up with, you know, doing the first sequencing of HLA genes, I used to have them read the autoradiograms, this is when we did P32 labeling. So, they helped me read the sequences.

 

Cassie McCreary 35:32

Who needs ABCs when you can do that?

 

Lee Ann Baxter-Lowe, PhD 35:36

And we were just talking about this a few nights ago, and they said, you know, it was really surreal that they were now donating, they're having their samples sent for HLA typing. And they could remember how we were working out the technology to get it to work from buccal swabs. And I did a lot of work with the National Marrow Donor Program in developing the registry and getting the donors typed. And my husband found a match donor through the National Marrow Donor Program. So, you know, things that I was very involved in are actually influencing us.

 

Jordan Ruggieri 36:16

It's absolutely incredible. And thank you so much for sharing. On behalf of Cassie and I, and Matt and Sarah as well, who are in the background, you know, our best wishes to you and your family. And, I mean, but what a story and you know, something that you saw that and thought that you could help improve. I mean, you know, being affected by that now is, it sounds surreal. And, yeah, but we're with you and your family and really grateful for all of the work that you've done as well.

 

Cassie McCreary 36:45

Just an excellent discussion. We really, really appreciate your time. This has been great.

 

Jordan Ruggieri 36:50

Thank you very much for being on Absolute Gene-ius, and the podcast. Absolutely enjoyed our conversation. And thank you very much for your time and your personal stories as well. We really appreciate that. We know our listeners do, too.

 

Lee Ann Baxter-Lowe, PhD 37:01

Yeah. And if you can guide people to our digital PCR paper, 

 

Jordan Ruggieri 37:07

You bet!

 

Lee Ann Baxter-Lowe, PhD 37:07

I'm pretty excited about it. And I think it has such great potential but it's just like, you know what I talked about in HLA typing; everybody does some little part and then it blossoms, and it really takes a village and a lot of people to, you know, make that happen. We've shown it can be done, but there's so much more work to be done.

 

Cassie McCreary 37:36

That was Dr. Lee Anne Baxter- Lowe, director of the HLA laboratory at Children's Hospital Los Angeles. Absolute Gene-ius is produced by Sarah Briganti, Matt Ferris, and Matthew Stock. Thank you so much for joining us for today's episode. We hope you're enjoying Season Two of our show so far. And that you're as excited as we are for the remaining episodes. Stay curious and we'll see you next time.

 

 

Jordan Ruggieri 37:58

I'm going to have to take a piece of your advice there. I have a six-month-old, we've just had a, my wife and I just had a baby this year, so he might be getting read some scientific journal articles, as well. 

 

Cassie McCreary 38:10

That's right, like who needs See Spot Run when you can just go straight to the scientific journal articles. Forget it. Just going to skip over it.

 

Lee Ann Baxter-Lowe, PhD 38:19

Then you could say "And then look with that virus did. That was a bad virus."

 

Cassie McCreary 38:24

The virus, look what the virus did. Yeah.

 

Jordan Ruggieri 38:29

That is amazing.