Critical Roles of Clinical Laboratorians in Translational Research and Applied Sciences—Experts’ Insights and Experiences

Clinical laboratorians have been at the forefront of translating science into clinical practice, playing crucial roles in the development of techniques, instrumentation, and technologies that aid in patient care. Some noteworthy advances by laboratorians include the discovery of the Jaffe method for measuring creatinine, the Folin-Wu method for determining blood glucose concentrations, and Van-Slyke’s volumetric carbon dioxide gas analysis instrument. More recently, laboratorians have been instrumental in the development of assays for the detection of myocardial injury, informatics-based approaches for detecting laboratory error, and have stood at the forefront of omics-based approaches to diagnosis. In short, clinical laboratorians have been essential for the advancement of medicine and for providing timely, accurate diagnoses of medical conditions. The modern-day clinical laboratory looks dramatically different from labs of previous eras. The vast majority of laboratory-developed tests have been replaced with U.S. Food and Drug Administration-cleared instruments and assays. The implementation of laboratory automation has further mystified the testing process and has removed assay development from the hands of the laboratorian. The new laboratory structure has also necessitated a change in how laboratory directors are trained, requiring a greater emphasis on regulation and management, at times to the detriment of research and method development. Even in academic institutions, clinical laboratorians have limited protected time for research. Nonetheless, laboratory directors remain in a distinct position to impact patient care and to bridge the gap between research and clinical application due to their unique understanding of unmet clinical needs and technical expertise in laboratory testing. The ever-changing landscape of the clinical laboratory and increasingly clinical/managerial role raises important questions about the future of the clinical laboratorian in research, development, and translation of laboratory testing. Furthermore, it requires that new generations of clinical laboratorians are trained and prepared to meet these needs. In this Q&A, international experts share their experiences building translational research programs and establishing leadership in scientific subspecialties with the goal of determining the future role of the clinical laboratorian in translational research. Ann Gronowski: My research program is pretty modest compared to others, in terms of size and dollars. I would say that I have had three main areas of focus: (a) diagnostics for maternal–fetal medicine; (b) general laboratory medicine; and, (c) industry-sponsored projects. My passion is maternal–fetal medicine and this is the area in which I have published the most and the area for which I have written small grants and requested funding. I have undertaken some industry sponsored projects that have allowed me to accrue money that funds some of my own hypothesis-driven projects. The general laboratory medicine-based projects have their roots in interesting observations made during clinical service responsibilities. These interesting observations have informed my maternal–fetal medicine research and also lead to seemingly unrelated areas of research. For example, we recently published a study that examined the number and kinds of radioactive patient samples received by our hospital core laboratory annually. This grew out of a single event that occurred in the lab. It has resulted in improved safety for our lab staff, and improved communications with our radiation safety and oncology faculty, in addition to a publication. Fred Apple: I owe my success in clinical chemistry to my mentors, Drs. Jack Ladenson, David Dietzler, and Jay MacDonald, from my clinical chemistry fellowship training. Each provided doors to walk through and allowed me to pursue my passions in muscle biochemistry and toxicology. They also taught me that first and foremost was patient care, but to be successful in laboratory medicine in an academic setting one needed to focus on a primary research interest; and to pursue all the roads not taken until more questions arise that need to be answered. Professor Oliver Lowry took an appointment with me, and showed me the importance of learning and asking questions. It was clear that my need to balance clinical service, teaching, and administrative roles with my personal desire to initiate my own lab was what I wanted. It was also clear that it involved more than a 40-hour week. Building a research program started with my own hands-on experimentation and testing/validations, one assay and one instrument at a time. You quickly learn that studies require submitting grants, that reagents and glassware cost money, and this concept of overhead/taxation hurt. I remember hiring my first research technologist with my first funding, a 2-year project pertaining to creatine kinase MB. I thought I was rich, and went right out to the local pub for a scotch. Over time one employee led to two, and more, one technology led to others. At present my laboratory, the Cardiac Biomarkers Trials Lab of the Hennepin Healthcare Research Institute, has grown to 6 full-time employees and a diverse array of applied research studies. I got lucky. However, I never lost track of my hospital responsibilities in clinical chemistry, clinical and forensic toxicology, and point of care testing; all of these are my favorite subjects. You learn from other leaders, you listen a lot, but at the end of the day, it is critical that we establish ourselves with a seat at the hospital table with other clinical service directors. Being creative is important but following the science with a continuing growth of clinical knowledge to explain why we bring up certain tests to address disease processes needs to be an ongoing educational process; one that needs to be built with other clinical colleagues who use the laboratories we direct. Leadership, surrounding yourself with common sense, and engaging smart colleagues, especially in the pandemic world we practice in now, are key to being successful. Mari DeMarco: Experiences building research programs will vary widely based on factors like start-up support, availability of shared resources, mentoring support, time allotted for research, and the type of your institution. It is important to understand your situation before looking to others for guidance. If you are at a small community hospital and want to grow a research program, reaching out to a leading scientist at a top-tiered research school may not yield the best advice. To better understand my perspective, I work in a 550-bed, acute care hospital, and while it is a teaching hospital, it is far more on the clinical end of the spectrum than the research end. Within my own department, few of my peers engage in externally funded research, and none have independent labs. In that environment, it was critically important to build a research program that directly benefited the clinical lab. In that way, I could draw a direct line from my research program to innovations in the clinical lab. As structures were not in place in my department for someone with my career trajectory, there were many barriers to overcome. Through these challenges there are two lessons I have learned that I think are adaptable to various environments: Advocate for yourself. As you build your research program you will hear a lot of “no’s” to your ideas, whether it be from an administrator at your site or grant reviewer. Keep moving forward. If you get a definitive “no,” don’t wallow in defeat—move on to the next challenge. However, if you see a path forward, no matter how small, be persistent and advocate for yourself and your vision. Work with what you have. It took years for me to obtain the funding trifecta of personnel–operational–infrastructure support all working in harmony (i.e., money for people, consumables, and equipment). In the beginning, it seemed like an impossible task to get these key pieces in place. There was a time I had funds to hire a trainee but did not have any of the analytical equipment needed for the research; from that followed a time when I had equipment, but my personnel budget couldn’t keep up. What has served me well is understanding that whatever stage I am at and resources I have, I must make it work. Looking back, a few of our key outcomes as a research lab were borne directly from budgetary constraints that forced me to look at a research challenge differently. Yusheng Zhu: To build a clinical/translational reach program, a powerful research team is essential. Our team comprises principal investigators, technologists, post-doctoral fellows, nurses, and administrative staff. As a principal investigator, I oversee the research program, apply for funding, monitor the research activities and compliance with regulations, control budget, and work with sponsors. It is important to communicate with team members effectively. I have technologists who are dedicated to research projects. Postdoctoral fellows of our clinical chemistry fellowship also directly conduct research as a key component of their training. In clinical studies, patient recruitment is always challenging. Research nurses are crucial to effectively select, enroll, and consent research subjects. Finally, our administrative staff aid in Institutional Review Boards (IRB) application, funding management, and research reports. Paul Collinson: Individuals working in laboratory medicine are in a unique position as they are not limited to a single patient or a single type of patient but have a whole hospital to choose from. They are also scientifically literate, aware of the latest developments in diagnostic laboratory testing and what is in the development pipeline. As such, they know what tests need validation and evaluation. The first thing is to keep an open mind and always be on the lookout for unusual aspects of an individual patient’s test results. It is essential to build relationships with clinical and scientific colleagues so that they know you are available to assist in a diagnostically complex problem and can support them in any research endeavor, no matter how small. Importantly, always be proactive in seeking opportunities rather than waiting for them to come to you. Once you have a reputation as a proactive investigator, then people will seek you out. Accessibility and enthusiasm are the keys to building up research relationships. David Sacks: Building a research program requires resources, particularly money. This needs to be obtained from the department chair, grants (intramural or extramural), or other sources, e.g., collaborators. The specific approaches and resources needed for basic science and clinical research differ. Regardless of the research, one should integrate your program with the strengths of other departments and the institution. For example, if there is a cancer center, develop laboratory tests that support oncology. It is important to show others how you can leadership requires knowledge and will of opportunities that Ann Gronowski: This can be especially as your career advances and you more administrative responsibilities. Research is a team so be to build a with other and them how to and first of a of and questions as they to if you not have time to pursue and are looking for so when they come to you will have a of projects and waiting for Fred Apple: and work has been my balance has my the importance of the task at but track of the other challenges that need to be before the end of the For me, patient care and providing and laboratory has always been As a medical laboratory I have always been to have laboratory and in my clinical laboratory who have been in as a understanding when the of the medical is important is or with your staff to make they understand you have their when This up time in your day, you to think and and from your research a as a in your research laboratory with and personnel responsibilities as a to best your academic Mari DeMarco: If you are a and are in research, dedicated time for research activities as of your time between the of and it is important to have a clear and understanding of what of roles the time based on the of If you don’t know the this is the to reach out to your peers to get that there are always on clinical a or a new regulation requiring the time for all of dedicated academic what of this time can you out for research activities based on other academic responsibilities like If your responsibilities and the time are in If if you will have the time to build the type of research program you want while also all of your other and what other and may be available to get the time you Yusheng Zhu: This is a to all have clinical and and some may have teaching as I always clinical first it is a clinical primary with other clinical staff who directly can me understand the clinical needs so that I get new research I can basic and translational research with what is at the scientific in medicine is also a clinical so I any to conduct research. To have more time for research, I some administrative work that not require my to other staff. I to my time For example, I and my time to the of the work. Paul Collinson: This is the most single thing to The factors are being into place that make clinical and administrative as as and the to to others. and at the beginning, you will need to the you will have to some of your own time and you will be that are not You will have to the between out and in research. David Sacks: is a to The best to protected time for research is during the before one a and departments have different time for research. It is essential that the of the department the of research, particularly basic and who want to time to that funding your position to out time for research. and in the funding from sources, e.g., the of or as these funding for these are funds that are directly to the and are in addition to the money that the The time of basic and translational research the requires more and protected time. Ann Gronowski: In my laboratorians should a of laboratorian should be asking questions about unusual and they in their clinical of unusual and can lead to that should be shared publication. For this I think that laboratorians a diverse spectrum of research I think this should be not However, unusual may lead to one or two in an I think it is also for laboratorians to have one or two areas of research on specific so that they can and test and a area of Fred Apple: The is I was to a area that you are about and pursue all questions and of an on of the and the analytical and clinical aspects of this how you can with other experts in your of and the This not you be a diverse research working with your and fellows during their in the areas they choose to study and as well as work with medical staff colleagues in your who will always be on you as a laboratorian to their questions in their areas of research. At the end of the day, can as as your is and of publication. Mari DeMarco: I see to for different To build an externally funded research program a specific area or areas is It may be that you focus on an or analytical for The thing is that this not that you are a line of research. of that you would as successful and that have built the type of research programs you would like to would that you can their but you can also an of their research the it is important to build in your areas of research. You can make that on yourself if you to many For in my research lab we focus on with an emphasis on and clinical However, I an interesting clinical research challenge if it on a and can be with no matter what disease it This is how I more research into my lab from our core Yusheng Zhu: My research areas are and based on the clinical needs and research environment, but they are always in the of laboratory For example, my research areas include new assay development, clinical application of and Paul Collinson: It is to rather than to an However, the there are always opportunities for especially if there is the to use tests in a different The of should be by your and whether or not the is with It is to when there are few others working in your area of There will always also be In my own I was in the concept of in clinical resulted in a from with myocardial to proactive a need for diagnostic In there is a need to have some laboratory that you can your own and then to obtain funding. This can be with small projects tests which are in and then to grant and research David Sacks: It is important to knowledge and establish a reputation as an in a area of research for a successful research This to basic and translational research. In basic will you to for your and if you are an in an area of translational research, people will you for your into various from on and to to at and in or to make important must study important I to address a common disease with the could be In this if one the will be Ann Gronowski: people are to if you come to them with an The key is to be a what you from your through on what you be clear on from the beginning, be on and make to see the project through to the end. Fred Apple: I would that you not be to with a more in your of up the this individual and with them to questions. that they are open to listen and work with to share their and that will be educational in your growth and to a you initiate a meet to study written on and when to of important to be on time with the as this your Research like people who through on their It may but it is what many people it is important to make of all industry that may and funding. Mari DeMarco: my the most and industry have been by projects. by establishing my in our area of research, it has in a position to As such, many industry grew from programs of research in my lab. a think about what aspects of the study have for could be from a scientific to a new in diagnostic or I would that you directly your industry to you what aspects of the project are of the for them and the key knowledge they to a clear of will develop study that will lead to a If the are not in this is a project you a and a who may have an in this it be an academic or industry the best to more is to be a you to you through on specific you you any or other administrative that need to be the research team in the that are for you that were clear for all you project in a you work to keep the of Yusheng Zhu: To establish in I as many scientific and as I In this way, I can who have knowledge and needed in my research. I have with for my one has the I need and the other has in is a with a in a assay for industry it is a to reach out to In diagnostics to show your Paul Collinson: The most to is to a reputation as someone with an in the It is also essential to meet and with others who are working in the This and and to on projects. with industry the general but it is important that the is based on science and rather than However, a to and the to be to the needs of that are essential. David Sacks: are essential to This requires and to In basic research, one should scientific and to people at and be to your area of one to address not with the in own others about your work so they want to with you. For industry you establish a make you up and studies. establish a reputation as and are to you for Ann Gronowski: medicine will an important role in (a) of The pandemic has the importance of laboratory medicine in the of a is to be the pandemic and laboratorians will need to remember and apply the lessons they have (b) and to it is learning for detection of or of patient to analytical in in I that will an important role in (c) medicine is playing an important role in the of and through as This important work will to be by clinical in laboratory Fred Apple: I am about the role of laboratory medicine in research and development academic and and and medical in the next available for applied research are more to not all support applied research in place of basic are looking testing out to labs and not the hiring of and to develop and testing as a of patient care testing and Yusheng Zhu: medicine always critical roles in research. The most is the development of clinical assays for the and of during the In the next to we will to develop new assays to meet clinical needs. will that can be for the and of will to new as we will use learning and for Paul Collinson: There has been a in in the role of in disease and The clinical laboratory is the place basic and translational research is into clinical application at the patient This requires a with of concept then translation into studies of clinical application and clinical The most will have no application if it must be in and a medicine is the bridge that the whole of how a test may be in clinical work. new no matter how must meet can I it in my laboratory and what will you with the David Sacks: always to the is based on the Clinical laboratorians have unique which have been applied the years to patient care. For example, Jack assays to creatine kinase and which had impact on the of myocardial important by laboratory medicine has been of assays. working with laboratorians have and published to for laboratory analysis in development and of have led to in patient and The role of laboratory medicine in future research will on areas clinical laboratorians important challenge will be to of e.g., from or into an that will to make diagnostic and for their Clinical laboratorians are to lead these Clinical laboratorians should also apply their expertise to technology to develop and, in with new assays. they have to the of this and have the following (a) to the and of or analysis and of (b) or the for (c) of the published and to be for all aspects of the that questions to the or of any of the are and all the The no to the of this publication. of Clinical The of Clinical and and and The and and and

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