Getting the Diagnosis Right: Sarah Wheeler

Sarah: I do have a passion for diagnostics because if you get the diagnosis right at the beginning, then things down the line go much better. It’s fewer interventions for patients if the diagnosis is right up front. It’s less cost to health care system if we get that right from the beginning.

Mike: From CTSI, this is the Products of Pittsburgh. A show about the people in Pittsburgh – innovators, scientists, community leaders – and the remarkable stories behind how they came to be and the work they’ve produced. I’m Mike Flock. On the show today, we catch up with Dr. Sarah Wheeler, Assistant Professor of Pathology at the University of Pittsburgh.

Mike: The clinical laboratory is at the heart of hospital systems because it’s responsible for the majority of medical diagnoses and decisions. Lab tests can detect and confirm diseases, which helps inform individualized treatment plans. This real-world application drew Sarah to clinical chemistry and ultimately landed her in Pittsburgh, where today she is both a translational researcher at the University of Pittsburgh and the medical director for multiple UPMC testing laboratories. Her expertise in diagnostics, though, may be rivaled by her talent as a competitive dancer. When Sarah returned to Pittsburgh in 2017 to become a faculty member, it wasn’t the first time that she came back…..

Mike: Where did you grow up? Where are you originally from?

Sarah: I don't know if the “Pittsburgh vortex” is a common phrase for you but I've often heard about the “Pittsburgh vortex” that once you move to Pittsburgh, you’re stuck in Pittsburgh.

I actually lived here until I was about five. My dad was a mining engineer and then we moved to the West Coast to Washington state where I grew up and spent most of my time, but I have some extended family in the area. So, when I was looking at graduate schools, University of Pittsburgh was top three for the biomedical research I wanted to do so I came here for that and then got re-sucked into the “Pittsburgh vortex” so I am kind of an ultimate boomerang story. Ironically, I was born in Mercy Hospital before it was UPMC Mercy and now I oversee the clinical labs there.

Mike: Now, that's a small world.

Sarah: Yes, very small world.

Mike. You said your dad was a mining engineering?

Sarah: Yea, so lots of geology in his background.

Mike: Any of that rub off on you in terms of interests?

Sarah: Um, not necessarily in terms of rocks but definitely in general scientific method. So, always looking for evidence and trying to make sure that the data is there and that I don’t allow the things that I’m working on to be clouded by what I want the story to be but that I really look at what the data is. That was definitely a part of growing up with an engineer.

Mike: So, when you were growing up, let's say middle school, high school, did you have an idea what you wanted to do in terms of a career?

Sarah: Yeah, I really wanted to be a civil engineer and work in developing countries on their infrastructure. It was definitely what I wanted to do. I was in international baccalaureate honors in high school and took Spanish. So, I had some Spanish speaking when working in South America and also took chemistry. When I got to the University my first year, I decided I really hated calculus much more than I thought I did, so civil engineering was maybe a poor choice. And, actually, found myself tutoring a few of my contemporaries that were in the dorms with me in their chemistry work and realized I missed chemistry and went back to chemistry.

Mike: Sarah graduated in 2006 from Brigham Young University with a degree in biochemistry. She also minored in Spanish and spent a couple years volunteering in Argentina, which has proven to be valuable as she continues to this day working with South American countries. Sarah was interested in chemistry but wanted to be able to apply it to patients and the community, and engage in translational research, which is what brought her back to Pittsburgh, where it all started. She would go on to receive her PhD in cellular and molecular pathology at the University of Pittsburgh, and then completed a combined basic research and clinical fellowship in metastatic breast cancer and clinical chemistry. Sarah was becoming an expert, and in that process, learned some things the hard way….   

Mike: Was there anything during your PhD that you found particularly challenging and didn’t anticipate that were difficult for you?

Sarah: Yes. So, three years into my PhD. I guess first, I was super lucky to be in the laboratory of Jennifer Grandis. She was MD head and neck surgeon. Still is, although she moved to UCSF. She was an absolute powerhouse. When you would meet with her, she was a complete whirlwind of energy and enthusiasm and new ideas. I started work in her lab on a variant of epidermal growth factor receptor and we had to construct models because it wasn't preserved when you tried to take it out of people's tumors or try to take people’s tumors and grow them, you would lose this variant and so we had to construct models. And 3 years into my PhD, we found out that the cell line that we've been using to construct our models have been contaminated with a different cell line that was not head and neck cancer but was actually bladder cancer which does not contain this variant. And so, we were back at ground zero. We had a paper that had been submitted and reviewed that we had to come back. They gave us three months to redo all the work in the paper and get all of the data again. Super lucky, Jennifer was very supportive and provided me all the resources I needed to be able to get to work the done. But it was definitely a moment when you go, is it is it worth continuing this if like, if all that work was just lost, but we did continue it. A year and a half later, I finished my PhD. Partially because the environment of that lab was so great that there were other junior faculty members that had me help them on their work so that I could also keep publications going and expand my interest.

Mike: Once you received your PhD, what did you do next?

Sarah. So, when I finished my PhD, I thought I wanted to go into industry. I wasn’t really sure kind of what the next step would be. So, there was postdoc in a lab where I had received my PhD who had become pregnant at an older age and had to have a lot of genetic testing done and she noticed that the signature on her genetic testing was signed by a PhD not a MD. And so, she looked into it said, hey there's this whole field called laboratory medicine, you should look into it. So, I looked into it and heard just about the medical genetics which is PhDs who do clinical training and then do genetics interpretations and I looked at that and it didn’t seem like a great fit because I’m chemist not a geneticist. But then I found out that there was the bigger umbrella of laboratory medicine and they did do chemistry. And I met Dr. Octavia Palmer who does amazing translational research and is a clinical chemist, and she told me about laboratory medicine where after you get your PhD you do two years of clinical fellowship, possibly a post doc, as well, and then sit for a board exam to be certified to practice clinical chemistry in clinical labs. So, I did my training at the University of Pittsburgh as well as a postdoc at the same time.  

Mike: You decided after your postdoc to go into industry, how did that happen?

Sarah: So, I finished up my clinical fellowship and my post-doc and I was trying to decide what to do next. It was also kind of on the heels of Theranos. So, the big Theranos thing, it was during the boom time of that, not during the bust time of that. That is very specifically my field, diagnostics on blood products is clinical chemistry. And I felt like there was a company that approached for a position that had some really amazing technology that I was excited about and they wanted to also start a clinical lab. So, I could be involved in research working on these cutting-edge diagnostics tests to bring to patients, as well as starting a clinical reference lab for them so it seemed like a no-brainer and it was. I worked there for a couple years and really enjoyed that.

Sarah: After two years there, we had continued assays going, lots of exciting things happening and it turned out that I didn’t like managing people, to be honest, it was not my favorite part of my job. But we all have parts of our job that we don’t like…

Sarah: But there was an opening at the University of Pittsburgh. They called me to see if I would be interested. I was very interested. I missed the kind of more direct patient contact that I had when I was a fellow finishing up my clinical work and there were also some new things that I wanted to work on in my research. Some translational things that it was just difficult to do from the industry side, but I could do from the kind of academic medical center side. We also, when we were looking at it, we lived in Washington, DC, so we did industry in DC which is really great but ended up being a little farther from family than we had anticipated. There was also a draw to the city, as well.

Mike: In 2017, Sarah returned to the University of Pittsburgh as an Assistant Professor in the department of pathology while also taking on the role of directing diagnostic testing for multiple UPMC laboratories. A major focus of her work is to improve current diagnostics and develop new diagnostics in order to provide better patient care. One recent example is a computational project on HIV testing. Early detection of recent HIV infection represents a critical preventive approach and could help decrease the spread of HIV.

Conventional HIV tests provide accurate results, but it can take hours and sometimes days to receive them. So, with Drs. Michael Shurin and Alex Star, Sarah entered the Pitt Innovation Challenge in 2019 and won an award for the project HIV Detective, a rapid HIV test that can detect early infection at the point of patient contact with healthcare providers, which allows for real time interventions. Soon after the team got started on the project, though, there was a new virus and a pandemic looming. Sarah’s expertise in diagnostic testing became a critical asset to the Pittsburgh community.      

 
Sarah: Two weeks before the pandemic came to Pittsburgh, we realized that we needed to have antibody testing available. So, infectious serology or detecting antibodies against foreign pathogens is one of the clinical areas I oversee, most of my diagnostic work focuses on infectious disease serology. Usually when we implement a test it has to be FDA-approved so a company has worked on it, they vetted it, they've done a clinical trial and that shows up in our lab and we make sure it works, we see how we are going to use in our patient population, make sure it’s appropriate for our patients, do any tweaking we need to do and then implement it.

Instead, knowing that we’re going to have COVID in Pittsburgh at any time now and that the only real therapy that we have available to us is convalescent plasma or blood products from people who have had COVID and then have recovered as our only kind of hope that might be helpful intervention as we try to get a hold on it so, that means we need to test people’s plasma for that.

So, we worked with a few vendors that we already knew, got some test products from a test assay from Germany and had to do extensive internal work up, kind of our own internal clinical trials to get that up and running before we even had cases to try it on. We had a lot of work to do and then when we finally had cases, every case that came through the door, we made sure that we got any remnants that we could so that we could validate this to be able to use for convalescent donation, so we ended up being, as far as I’m aware, UPMC was actually the first organization in the US to offer antibody testing. Within the same week several organizations went live but I'm pretty sure we ended up being the first because of, kind of, all the work of the entire laboratory of medicine team in doing that.

Mike: The COVID-19 pilot program that CTSI launched in March of 2020, I know you received some support through that mechanism, focused on the pediatric side of things. Could you elaborate a little bit on what that work entails?

Sarah: Once we made it past the first wave and we had these assays that we could actually use and they weren’t widely available assays, because I oversee children’s hospital, I worked with ID physicians there, there were two ID fellows that noticed that we weren't doing a lot of swabs on kids because we didn’t have enough test kits to test everybody so we were only doing symptomatic people which made use think that perhaps we were under estimating what the prevalence was in children. So, we got together to try to figure out what is the sera prevalence in children, particularly at the time we were trying to figure should kids go back to school, should we keep them doing home schooling and some decisions to be made about that. Are kids really driving infection? Because they tend to run around, talk to a lot of people, climb on their parents’ laps, and things like that. It seems like they could be a serious source driving infection and so we had a lot of kind of outstanding questions around what was happening in kids and there weren’t any pediatric studies happening so kids were included in a couple of the large NIH studies but they were really were very small portion of that population. And so, we used remnant specimens from kids that were seen at UPMC Children’s and already had to have blood draws taken.

Sarah: We had a few exclusion criteria: Obviously, if they weren’t underage of 18 years. We did not include them. Also, kids that have actually been in the community was what we were after. We did two windows. One during a red phase lock down phase, one during yellow phase. We also specifically made sure we did a subgroup analyses on kids that were immune compromised because we see a lot of immune compromised kids at Children’s and we wanted to see if, we knew in adults that we were seeing worse outcomes and transplant patients and others that had immune disorders but we didn’t feel like we were seeing that in kids anecdotally, but we wanted to see what was the case. What we did find is that it appears that kids don’t have the same or as robust of an antibody response as adults. So, detecting antibodies in kids actually may not be as accurate for looking at prevalence rates as doing PCR because our current understanding is we think their immune system takes care of COVID so quickly that they never have to build an antibody response to get rid of it. And looking at kind of the subset of children that had immune dysregulation they didn't really do any worse than healthy kids which was really great news because that was not what we were seeing in the adult world. That was very reassuring for us and for parents and great to share.

Mike: What has been challenging for you? You're very much involved in the testing and having a role in helping support testing, is there certain aspects of your work that have been difficult to kind of maintain during this time?

Sarah: I think one of our challenges has been that COVID is not the only sickness happening in the world right now and not the only thing we have going on, and this has been a problem for all health care workers and health care systems, is that we have to manage the COVID workload on top of our existing health care workload. So, I think that has been the challenge universally. I don’t think that is any way special to me. All of the COVID antibody testing and the COVID antibody research that has been very important to do has been on top of the other work that I have to do. And that health care systems and physicians and nurses and all of the people that support us being able to treat people or keep people well is the same thing that they are experiencing.

Mike: Health care workers and the many individuals who support health care systems have been in high demand. For many, it has been a difficult and overwhelming time, particularly for those on the front lines putting themselves and their own families at risk in order help others.  Fatigue, depression, anxiety, burnout. One large national study found that 42% of doctors reported being burned out; the poll came out, though, in January 2020, before the pandemic.  

The toll on mental health that the pandemic has taken cannot be understated, and it goes beyond health care workers. Reaching out to friends, family, and neighbors, as a quick check-in could spark conversations that relieve stress and help cope with challenges everyone is facing. Fortunately, the tide is turning on this devastating virus and there is a light at the end of the tunnel. Finding time for personal interests and hobbies will be important to restoring some level of normalcy and for Sarah that means dancing!  

Mike: Outside of the work that you do, any particular hobbies or interests in your free time?

Sarah: Yea, not really during COVID. I’m going to be honest. 2020 was not the best year for hobbies for me, but definitely when we are allowed to interact with human beings my husband and I are actually professional dancers. So, we do partner dancing and we compete internationally and we teach. We do a dance style called West Coast Swing, danced to contemporary music. And ironically when we first determined that we needed to do antibody testing, I was at a competition in Washington DC and spent like half the weekend in the hotel room working and the other half down in the ballroom dancing. So, that was like the last time that I really did dancing but we’re very much looking forward to getting back to that.

Mike: That’s cool. How did you get involved in dancing? How did that come to be?

Sarah: When I first moved to Pittsburgh, I didn’t know anybody here and I didn’t have any friends. So, you know you meet people at work, which is great. But you know, they are all science-y people, if you want to meet some other people you have to look for ways to do that. And I decided to try dancing. A couple of people that I met were also part of the dance community and I went with them to a few things and then found that it was a really great stress outlet, a great way to meet people kind of outside of my daily sphere and obviously a good way to stay active. So, it checked a few boxes of socialization and activity. After my first year, I went to this new dance that had come to Pittsburgh called West Coast Swing and I actually met my husband in that dance class and that has solidified our dancing addiction.

Mike: It was the West Coast Swing.

Sarah: It was.

Mike: You met your husband through dance, what does he do for a living?

Sarah: He was in information technology when I met him. Actually, when we made the decision to come back to Pittsburgh, he decided to pursue a PhD in the information science department. So, he is getting his PhD in computer vision, specifically in information science. Occasionally I snag him to help with some of my projects, too.

Mike: Ha, of course you have to.

Mike: If you could select one word to describe yourself, what would that one word be?

Sarah: That’s a hard question. I kind of feel like I should have something, some like deep word but I think probably just “spunky” is probably the word that gets like used on me the most, no matter what part of life it is.

Mike: Spunky. Alright, so you bring some energy to what you do?

Sarah: I think so.

Mike: In your career, do you see yourself 10 years from now being in this diagnostic space or do you see other areas of interest you feel like you might explore?

Sarah: The diagnostics space is definitely where I see myself being. Nobody’s career is ever linear because I definitely did not see this particular place 10 years ago, but I do have a passion for diagnostics because if you get the diagnosis right at the beginning then things down the line go much better. It’s fewer interventions for patients if the diagnosis is right up front. It’s less cost to health care system if we get that right from the beginning. So, I am hoping to shift more into computational modeling and computational ways to assess our existing diagnostics we’ve done a remarkable amount with biomarkers, with next gen sequencing, we have the ability to really dive into biomarkers. But my sense is that we can continue to chase biomarkers, but we also have so much information that we're currently not using. So, instead of trying to find necessarily more tests, in some cases I believe there will be more tests that are going to be helpful and there will be more tests that we need to track diseases and things like that but I also think that there is this wealth of information that we are not tapping into. And if you run just a basic metabolic panel and a CBC on a patient, which is kind of baseline, somebody comes into a hospital, you run these two things, you have a whole list of data and there's so much more that we could mine into that than we currently are. Also, to provide decision support because there's so much information coming at our clinicians now that being able to integrate that into something that's a little more human interpretable. For me in the next 10 years, that’s where I’d like to expand a little be bit more.

Sarah: Another area that has been getting some of my attention lately is how we can use that data to reduce health disparities because a lot of the health disparities that we see can to some extent have some mitigation happening through clinical testing because we can get earlier diagnosis to get earlier intervention. I had the opportunity to collaborate with Dr. Palmer on two pieces where we looked at how the clinical laboratory actually can play a role in unfortunately exacerbating health disparities but also the opportunities we have to intervene and reduce health disparities. One that’s got a lot of attention this year is removing the race correction factor from the glomerular filtration rate. Basically, we use a common blood component to assess people’s kidney function and that happens through a very complex algorithm. One of the parts of the algorithm involves a race correction, specifically for Black. And there is a lot of controversy around using that race correction, what assumptions are in that race correction, and the lack of data to support that. We are actively removing the race correction at UPMC but also we are just starting the project to look at when we remove that, what is the outcome effect on patient care? Do we see, which is what we are hoping to see, that we get more patients appropriately assigned to the transplant list, more patients appropriately receiving the interventions they need. Or not receiving medications that might cause renal compromise.

Mike: So, it sounds like an ultimate goal for yourself is improving diagnostics for improving better care for everyone.

Sarah: Yea, I mean you know at the end of the day, I want everybody to get perfect medical care. And the perfect medical care that they need and not over burden the health care system and keep people well and do it kind of perspectively. But I, as an individual, cannot do that. But in terms of diagnostics, I would love to see us being more proactive about peoples’ care.

Mike: Sarah Wheeler, Ph.D., Assistant Professor of Pathology and Medical Director of the Automated Testing Laboratories at UPMC Mercy and UPMC Children’s Hospital of Pittsburgh, and Associate Medical Director of Clinical Immunopathology at UPMC.

That’s our show. Thank you for listening to the Products of Pittsburgh. Be sure to check out our website at http://www.ctsi.pitt.edu/podcast/ to hear more episode as well as learn about CTSI programs and services. I’m Mike Flock along with Zach Ferguson, until next time on the Products of Pittsburgh.