Tell us about your early days
I was raised in a small town in Western Kentucky, where I played soccer and basketball and ran track in high school. The outdoors interested me early on. Up through junior high school, I pursued traditional rural southern activities, such as hunting and fishing, quite a bit. However, I have not been hunting since I was 14, and I do not have the patience for fishing anymore. I also did a fair amount of canoeing in the Appalachians and Ozarks while growing up. Now, I much prefer hiking, mountaineering, skiing and observing wildlife (I find it hard to believe that I ever hunted) when I head outside.
Did you have a particular career wish as a child?
To be an explorer of the American west, like Meriwether Lewis or William Clark (Lewis and Clark). Too bad, I was born 150 years too late!
When did you first get interested in science?
I first became interested in natural science while growing up in rural Kentucky. The outdoors were a natural laboratory for me. Later, I became interested in geology as my contact with mountains (both the Appalachians and the Rockies) increased on backpacking trips. My interest in biomedical science emerged while I was in college.
When did you decide to become a scientist?
As an undergraduate at Williams College, I majored in philosophy and chemistry. I was offered a fellowship at Christchurch College, Oxford University to pursue a DPhil in Philosophy and Theology. Instead, I decided to pursue an MD-PhD degree in the Medical Scientist Training Program at the University of Washington. I think that I made the right decision.
Tell us about your education and experiences at university
As an MD-PhD student at the University of Washington, I received my graduate education in the Department of Pharmacology in the laboratory of Dr. Neil Nathanson. Initially, I thought that I wanted to be a neurosurgeon, so my PhD thesis was on the cellular and molecular regulation of the neuronal muscarinic acetylcholine receptor (we thought there was only one type/subtype back then!). As I progressed through medical school, I realized that I was not interested in neurosurgery (or neurology) as a career. I ended up finishing the MD and PhD degrees in 6.5 yrs, so I had an extra 0.5 yrs to pursue some ‘postdoctoral research’ before residency. Neil is a generous and kind guy, and he allowed me to begin doing work in inflammation in his laboratory, even though he had no real interest in innate immunity/inflammation at the time. I am grateful for his support during this 6-month “post-doc.”
Where did you perform your internship/residency and what field of specialization did you choose?
I completed my internship and residency in internal medicine at Massachusetts General Hospital. I can't think of a better place for residency training in medicine. Afterwards, I completed my sub-specialty training in infectious diseases at the University of Washington, where I completed the research portion of my fellowship in the laboratory of Dr. Seymour Klebanoff, a real pioneer in the fields of host defense, innate immunity, and infectious diseases.
What do you like most about your work as a physician?
The human interaction, and seeing the application of science in medicine. Helping individuals to cope with and overcome infections. I also enjoy using my basic science background to help patients understand their underlying diseases and our approaches to therapy. In addition, I do appreciate the challenge of figuring out the cause of an enigmatic fever of unknown origin (FUO) in a patient and the opportunity to see individuals with tropical medicine disorders (a special interest of mine) and travel-related infections.
How can one successfully combine working in the clinic with heading a research lab?
My clinical work has guided and inspired me in my research. My laboratory has always strived to take a comprehensive “bench-to-bedside” and “bedside-to-bench” translational approach to research.
What was your first position after university?
My first tenure track position was as an Assistant Professor in the Division of Allergy and Infectious Diseases in the Department of Medicine at the University of Washington.
When and where did you start your own lab?
I “graduated” from the laboratory of Dr. Seymour Klebanoff (with whom I did my fellowship research) and started my own laboratory in 1996 at the University of Washington in the Division of Allergy and Infectious Diseases of the Department of Medicine.
What is your position at your institution?
I currently am Professor of Medicine and Associate Chair of Medicine at the University of Washington. I am also an Adjunct Professor in the Departments of Pathology, Pharmacology, and Global Health. I returned to the University of Washington in 2012 from the University of Toronto, where I was Vice-Chair and Professor of Medicine (and served approximately 1 year as Acting Chair of Medicine), Director of the Division of Infectious Diseases, and the Canada Research Chair in Infectious Diseases and Inflammation. At the University of Washington, I also serve as Co-Director of the Molecular Medicine Training Program, Co-Director of the Molecular Medicine and Mecahnisms of Disease (M3D) Graduate Program, and Interim Director of the Center for Lung Biology at the University of Washington. I am also an elected member of the Association of American Physicians (AAP) and serve ast the President and Secretary-Treasurer of the Western Association of Physicians (WAP). I have published more than 215 peer-reviewed manuscripts and approximetly 40 book chapters and books.
What areas or topics does your lab currently focus on?
The overall mission of my research program is to investigate clinical problems at the bench, in order to gain novel insights into disease pathogenesis and to develop novel therapeutic approaches to important clinical problems. My laboratory focuses on the role of dysregulated host responses in the pathogenesis of infectious diseases of public health importance. A guiding principle of my research program is rapid translation of experimental insights and advances gained in the laboratory to the clinical bedside. Areas of current research include: 1) the molecular immunopathogensis of malaria, one of the major causes of infection-related morbidity and mortality worldwide; 2) sepsis, a major cause of tissue injury and organ dysfunction in patients hospitalized in intensive care units; 3) hemolytic-uremic syndrome (HUS); 4) severe influenza; 5) acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS); and 6) the role and regulation of endothelial activation/dysfunction in life-threatening infectious diseases. The role of innate immunity and inflammation in the development of effective acquired/adaptive immunity to infectious diseases is an emerging interest in my laboratory, as is prognostic host-derived biomarker discovery. My research utilizes a variety of molecular and cellular biology technologies (e.g., transfection/transduction strategies, real-time PCR, siRNA technology, Western blot, ELISA, etc.), expression microarray technology, mesenchymal stem cell and adoptive cell transfer technology, cell culture, work with patient specimens, and clinically relevant mouse models of malaria, sepsis, shock and acute lung injury. I collaborate extensively with University of Washington Investigators in the Center for Lung Biology, Institute for Stem Cell and Regenerative Medicine, and Bloodworks Northwest (formerly Puget Sound Blood Center).
Do you have partners that are important for your research projects?
Yes, my research has almost always been conducted with valued colleagues and collaborators in diverse fields, ranging from infectious diseases to pulmonary and critical care medicine, hematology, surgery, pathology, cardiology, immunology, and bioengineering. Currently, I have on-going collaborations with Dr. Kevin Kain (University of Toronto), Dr. Claudia dos Santos (University of Toronto), Dr. Shahid Husain (university of Toronto), Dr. Mark Wurfel (University of Washington), Dr. Bill Altemeier (University of Washington), Dr. Michael Mulligan (University of Washington), Dr. Jose Lopez (University of Washington and Bloodworks Northwest), Dr. Ying Zheng (University of Washington), Dr. Susan Graham (University of Washington), Dr. Jonathon Himelfarb (University of Washington), and Dr. Eliot Melendez (Boston Children's Hospital), Dr. Andrea Conroy (Indiana University), and Dr. Michael Hawkes (University of Alberta). Earlier during the course of my career, I have enjoyed productive collaborations with Dr. David Dale (University of Washington), Dr. Bill Henderson (University of Washington), Dr. Gus Matute-Bello (University of Washington), Dr. Tom Martin (University of Washington), Dr. Duncan Stewart (University of Ottawa), Dr. Lena Serghides (University of Toronto), Dr. Phil Marsden (University of Toronto0, Dr. Warren Lee (University of Toronto), Dr. Tom Wadell (University of Toronto), and Dr. Malak Kotb (University of Cincinnati), and many others. In my opinion, multidisciplinary collaborations produce the most innovative, interesting, and impactful contributions to science. My collaborations have taken my research in directions that I would never have anticipated.
What are your main goals for the next five years?
To develop a point-of-care device incorporating both pathogen diagnostics and clinically informative prognostic biomarkers;
To determine the critical elements of innate immunity and inflammation that drive appropriate adaptive immune responses in infectious diseases, especially malaria;
To develop novel adjunctive therapeutic strategies to prevent and/or limit organ injury and dysfunction and improve clinical outcomes in sepsis and malaria;
To continue progress in understanding the role of microangiopathy and endothelial activation/dysfunction in the pathogenesis of infectious diseases;
To help young physician-scientists in the transition from trainee to successful principal investigator.
Tell us about the most important stages of your professional career
One of the most important stages in my career was the decision to move to the University of Toronto in 2006. The move allowed me to assume administrative leadership roles that I had not previously experienced. This experience laid the foundation for my current professional career. Under the guidance of Dr. Wendy Levinson who was Chair of the Department of Medicine while I was in Toronto, I assumed the roles of Director of the Division of Infectious Diseases and Vice-Chair of Medicine, and served as Acting Chair of Medicine for approximately 12 months while Wendy served major leadership positions in the American Board of Internal Medicine.
Who were your mentors?
It is widely acknowledged that mentorship and wise counsel play critically important roles in the career development of successful physician-scientists. I have had the fortune to receive invaluable guidance from a number of outstanding mentors during the course of my career. In terms of research, Dr. Neil Nathanson, Dr. Seymour Klebanoff, Dr. David Dale, and Dr. Tom Martin played important roles in my career development. In terms of my academic career, I have received invaluable guidance at various stages in my career from Dr. Paul Ramsey, Dr. Walt Stamm, Dr. Wendy Levinson, and Dr. Bill Bremner. I can only hope that my mentorship to my trainees approaches the quality of mentorship that I received from my mentors during the course of my career. It's a tough road out there for physician-scientists, and it's only gotten harder since I was in training.
What makes a good mentor?
A good mentor is someone who guides but does not dictate. A good mentor also allows the trainee the opportunity to propose new hypotheses and explore new avenues of research. A good mentor is also able to provide constructive criticism and have the ‘hard talk’ with the trainee when appropriate.
What advice would you have to junior people entering the field?
Don't do research just to do research! I advise junior investigators to pursue research that really interests them, and not to be attracted to an area of research that appears just to be easy. For physician-scientists, I encourage them to pursue investigation with real (not just hypothetical grant-oriented) translational potential – in other words, fundamental disease-oriented research that may lead to significant paradigm-shifting advances in clinical medicine. It is no mystery that the laboratory-based physician-scientist is an endangered species, but we must not lose sight of the fact that physician-scientists can play a critical role in the integration of scientific advances into clinical medicine.
What do you think you would do if you were not an MD or a scientist?
Instead of my career as a physician-scientist, I can imagine that I might have considered a large animal veterinarian (influenced by my upbringing in an agricultural area). The possibility of being a ski mountaineering guide has also crossed my mind, although I think that I definitely chose the right career path for me.
What do you do for fun?
As mentioned above, I enjoy outdoor activities away from work, especially skiing, ski mountaineering, hiking and scrambling. Since 1994, ski moutaineering (also known as backcountry skiing) has been a major part of my life. I have climbed and skied in the western US (Washington, Oregon, Idaho, Montana, Utah, Colorado, California, and Alaska), in western Canada (British Columbia – especially the Northern Selkirks and Monashees where I have skied for 21 straight years – and Alberta), and the Alps in Europe.
At the end of April, 2015, I literally had a life-changing event - a very bad ski mountaineering accident in Switzerland. Unfortunately, I slipped on ice while skiing down a steep couloir and fell over a 50–60 foot cliff onto rocks below. I should have died, but thanks to quick actions by the Swiss helicopter rescue system (REGA) and excellent surgical and critical care in Chur, Switzerland, I survived after 9 surgeries, one month in the ICU, and 3 months in the hospital. I had a polytrauma score that is associated with about 70% mortality, but I should be back to near pre-accident baseline level of functioning by the spring.
My list of injuries:
Bilateral hemothoraces;
Right tension pneumothorax;
Fractured right pelvis and large hematoma/hemorrhage;
Comminuted sternal fractures;
Flail chest due to 10 widely displaced rib fractures on the right and 4 rib fractures on the left;
Grade 5 right shoulder separation/acromiocla-vicular dislocation;
Basilar skull fracture, with associated right occipital stroke causing loss of a small portion of my left eye visual filed;
Odontoid fracture;
T10 vertebral compression fracture;
Multiple vertebral transverse process fractures.
And that's not all. I developed disseminated intravascular coagulation (DIC), bacteremic sepsis, an infection of a seroma in my right pelvis, and heparin-induced thrombocytopenia (HIT) with multiple DVTs. In terms of surgeries, I underwent internal fixation and reconstruction of my right hip, replacement of my sternum with a metal plate, internal fixation of my right chest, and reconstruction of my right shoulder. I've got metal in my right pelvis, right chest, and sternum. I was on IV antibiotics for 10 weeks. I received chest tubes and was intubated in the helicopter, which was forced to land at their base en route to the hospital because of refractory hypotension – there, I received 9 units of O negative blood. At the hospital, I received more blood, fibrinogen concentrate, platelet transfusions, and recombinant activated factor VIIa. Remarkably, I did not develop ARDS, ALI, or myocardial damage, although I had almost every risk factor for ARDS, etc., although I did develop bad ICU psychosis/encephalopathy.
Fortunately, I received outstanding surgical and critical care in both Switzerland (Kantonsspital Graubunden; Chur, Switzerland) and Seattle (Harborview Medical Center and Skyline Skilled Nursing Facility) following my transfer back to the US. I have recovered to what I would estimate to be approximately 85% of my pre-accident baseline. I resumed working full-time at the University of Washington at the end of September, 2015, and I have resumed hiking. I plan to resume skiing at ski areas in the spring of 2016. My wife is looking forward to me skiing groomed intermediate ski runs with her for a change. If all goes well, I should resume backcountry skiing during the 2016–2017 season, although my choice of routes will not be as “hardcore” as in the past.
I would not have been able to make the reovery that I have without the tremendous support that I have received for the past 6 months from my family, friends, colleagues, and co-workers. Really, the support has been awe-inspiring, and I am grateful and indebted to them all.
Figure 1. About W. Conrad Liles. Dr. Liles received his graduate education from University of Washington School of Medicine and Department of Pharmacology (1987), and postgraduate training and medical residency at the Massachusetts General Hospital (1987–90), and University of Washington Medical Center (1990-94). He has held faculty positions at University of Washington since 1996 with an intermission as a Professor of Medicine at University of Toronto (2006-12). Currently, he is a Professor of Medicine and Associate Chair of Medicine at the University of Washington, and serves as the Director of the Center for Lung Biology and Co-Director of the Molecular Medicine Training Program. He is also an Attending Physician at the University of Washington Medical Center. Dr. Liles has received numerous honors and awards including the Western Society for Clinical Investigation Outstanding Investigator Award (2004) and was elected to the Association of American Physicians (AAP) in 2014. He has authored more than 250 articles and book chapters. His research focuses on diverse aspects of host response to life-threatening infections, including sepsis, hemolytic-uremic syndrome and multiple organ dysfunction syndrome, and the pathogenesis of and host response to malaria.
