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ASIP.org > BLOG > December 2015

ASIP Pathogenesis Blog, December 2015

President's Perspective. . Educating the Next Generation of Experimental Pathologists
William B. Coleman, PhD, ASIP President

More so than ever before, human health is in the forefront of the public consciousness. While much of the discussion of human health is centered on healthcare and provision of healthcare benefits to all people, there is also a heightened level of interest in biomedical research - disease risk and causation, disease prevention and wellness, and disease diagnosis, prognosis, and treatment. Over the last decade, the National Institutes of Health (and other research funding agencies) have adopted a greater focus on translational research with the goal of bringing basic science discoveries more quickly to the clinic for the improvement of human health. Experimental pathologists play important roles in translational science, and make critical contributions to the whole spectrum of research from basic to clinical. With the changing landscape of human health and disease, it is worthwhile to consider the role of the experimental pathologist in basic science research, how the work of these scientists impact translation of basic science discoveries into the practice of clinical medicine, and how experimental pathologists are trained.

Pathology - The New Biology
In recent years, some have referred to pathology as the new human biology. This statement reflects both the general interest of many in disease and disease causation, as well as changing paradigms in how we teach students about human disease. In the past, normal human biology and physiology were taught as the primary curriculum. Students would then learn about disease based upon this foundation, but largely in isolation. More recently, normal biology and abnormal biology (disease) are taught with greater integration focusing on the comparison of the two. Hence, the emergence of pathobiology as a field of study and a conceptual framework for training students in disease-related topics. For graduate students pursuing experimental pathology or pathobiology, curricula are generally based upon three pillars - (i) pathology, (ii) pathogenesis, and (iii) pathophysiology. Pathology represents the description of disease - what it looks like, what features are abnormal, and how we distinguish it from normal. Pathogenesis represents mechanisms of disease - where it comes from, what cellular or tissue injury or responses to injury caused the disease, and how the altered pathways differ from normal. Pathophysiology represents the adverse effects of disease on the patient - how disease alters cellular or tissue function, how altered cellular or tissue functions contribute to abnormalities in the systemic physiology, how the abnormal physiology differs from normal.

Training Experimental Pathologists
Experimental pathologists are concerned with mechanisms of disease causation, and are basic scientists by training. Basic scientists are equipped with the tools of laboratory investigation that encompass several fields of research - molecular biology, cellular biology, genetics, biochemistry, and so on. Experimental pathologists bring these tools to bear on the study of diseases - in some cases using model systems, and in others using human tissues or cell lines. Some experimental pathologists are also physician-scientists or veterinarian-scientists who have expertise in clinical medicine or laboratory animal medicine. The training of experimental pathologists is built upon the foundation of disease and therefore most curricula include formal coursework on mechanisms of disease and organ-based pathology, along with teaching laboratories where students see gross and microscopic pathology. In addition, students are trained in the other basic science disciplines, in some cases with a specific emphasis (like biochemistry or genetics). Hence, the training of experimental pathologist is diverse, but with the common feature of disease focus. Experimental pathologists emerging from formal training programs are equipped to address a range of questions and problems that impinge upon our fundamental understanding of human disease, through direct experimentation in human tissue systems or using model systems such as genetically-modified mouse models. Of course not all experimental pathologists are formally trained - some are trained in another area of specialty in basic science and then acquire a working knowledge of disease through their research programs and in collaboration with physician and physician-scientists. Irrespective of the training pathway, experimental pathologists are experts in basic science methods and approaches and apply these to clinical problems associated with specific diseases. As such, experimental pathologists have discovered molecular and cellular players and pathways that contribute to the development of disease, characterized and explored these players and pathways in detail, and in many cases identified players and pathways that can be exploited in disease detection, diagnosis, monitoring, or treatment.

Experimental Pathologists Are Translational Researchers
Translation is a popular concept with various funding institutions despite the general lack of understanding of the definition of this term and how this concept is manifest in the real world. Translation represents the bridge that crosses the large chasm that exists between basic science research and clinical research. As mentioned, basic science research seeks to identify and characterize the players and pathways that constitute mechanisms of disease. On the other hand, clinical research occurs in the realm of applied science and directly involves human patients. Clinical research has an obvious impact on human health and treatment of disease. Clinical research encompasses clinical trials of new drugs (or the use of old drugs with new purpose), examination of new methods for disease detection and diagnosis (through new imaging methods or the use of biomarkers), development of companion diagnostics (biomarkers for personalizing drug therapy), and others. Compared to clinical research, basic science research is often mistakenly perceived to be esoteric. However, this is far from the case. Drugs that make it to clinical trials and eventually into clinical practice often emerge from studies that identified molecular players or pathways that were good drug targets. Likewise, new molecular diagnostics (with multiple clinical uses) are based upon identification of disease markers in basic research studies. Finally, effective biomarkers used as companion diagnostics are often evaluated for efficacy in preclinical models prior to testing in humans. Hence, there is a necessary linkage between basic research and clinical medicine. Historically, basic science discoveries were very slow to emerge from the research laboratory and there was no direct pipeline to the clinicians and the clinic - the bridging of basic science into clinical medicine was ineffective. Translational research involves the intentional development of basic science discoveries into applications that are useful in clinical medicine. Hence, translational researchers are those that are working on a clinically-relevant problem from the perspective of basic science with the end-goal of improving the practice of medicine. This definition of translational researcher precisely describes experimental pathologists who are trained to address disease-related problems (i.e. , clinically-relevant problems) using the tools and approaches of the basic scientist, but always with a clear objective to apply what is learned for improvement of clinical medicine.

Experimental Pathology - At the Translational Crossroads
Experimental pathologists are extremely important to ongoing pursuit of translational research in all areas of biomedical science. Not only are experimental pathologists uniquely trained to address clinically-relevant problems in the basic science laboratory, experimental pathologists are translational researchers and so supply the required bridge to translate basic science discoveries into clinical medicine. In addition, experimental pathologists are essential members of the collaborative teams that work on clinically-relevant problems. Experimental pathologists are able to bridge the gap between clinicians and other scientists because they speak the language of disease in addition to understanding disease models and possess the basic science tools and approaches of the research laboratory. Experimental pathologists can see the whole picture and connect the patient's disease to a model where hypotheses can be tested and refined. Experimental pathologists are key to the effective flow of information and ideas between the two worlds represented by basic science and clinical medicine, and it is important to note that this exchange of information and ideas is not limited to the paradigm of bench-to-bedside, but also includes bedside-to-bench. The experimental pathologist represents an effective translator in both directions, and is capable of identifying clinically-relevant problems (in conjunction with clinician collaborators) and appropriate model systems for research (in conjunction with basic science collaborators).

Effective Training of Experimental Pathologists
It is clear that the experimental pathologist plays a special role in basic science research that addresses clinically-relevant problems, both as a researcher (with basic science research skills) and as a collaborator (as a bridge between clinicians and basic scientists). As such, students that are pursuing experimental pathology research (no matter their major or specialty field) require enhanced training programs to provide development of the necessary skills to effectively manage collaborative teams that cross traditional boundaries between basic science and clinical medicine, and address research projects that bridge from bench-to-bedside and/or bedside-to-bench. Enhancements to training extend beyond the classroom exposure to disease and the basic science research training in the laboratory. These enhancements are based upon interactions with clinicians and clinical exposure. Trainees that are embedded in programs within Departments of Pathology often interact with physician-scientists and other clinicians on a regular basis through collaboration and these collaborating clinicians typically serve as members of doctoral committees. Hence, from an early stage of training and development, experimental pathologists-in-training interact with clinicians and through these interactions learn the language of medicine and gain insight into the diseases they study. In some cases, programs require trainees to have a clinical co-mentor for this expressed purpose, and often the trainee will gain access to clinical case conferences, shadowing opportunities in the clinical setting, and guidance related to useful seminars and symposia. In contrast, trainees in many of the traditional basic sciences are not exposed to clinicians in this manner and miss the opportunity to benefit from the interaction. Nonetheless, many trainees in the traditional basic sciences will become experimental pathologists (in a practical sense) as they refine their research projects and collaborative teams. Hence, we have the responsibility to provide good training to these scientists while they train as students, while they perform postdoctoral research, and as they transition into independent investigators. It is now common for non-pathology students to take formal courses related to mechanisms of disease or systemic pathology, and the curriculum should be designed to benefit all these students equally without compromise of rigor. Likewise, Directors of Graduate Studies should create opportunities and facilitate interactions between non-pathology students and clinicians or physician-scientists.

Pathology Education Through the American Society for Investigative Pathology
Educating the next generation of experimental pathologists requires concentrated efforts at our individual academic institutions, but these efforts can be magnified through the efforts of the larger scientific community. The American Society for Investigative Pathology (ASIP) has a long history of promoting pathology education through the Annual Meeting, special educational course offerings, and on-line resources. Some of these educational offerings and opportunities are described here. Each year at the Annual Meeting, the ASIP Education Committee holds a meeting of Directors of Graduate Studies and others involved in graduate education where various issues are discussed related to the training of experimental pathologists, including best practices, innovative teaching methods, educational collaboration with industry, integration of relevant subject matter, and others. The Workshop on Graduate Education in Pathology at Experimental Biology 2016 is focused on “integration of clinical and anatomic pathology." The ASIP Education Committee provides several other sessions in 2016 that are of specific interest to trainees, including the Pathobiology for Basic Scientists course on metabolism and systems biology and a Lunch and Learn on the appropriate use of statistics in research. In addition, several career development sessions will be offered for trainees, organized by the ASIP Committee for Career Development and Diversity. Beyond these sessions, the Annual Meeting provides ample opportunities for discussion, interaction, and establishment of collaboration among investigators and trainees. The ASIP also provides resources for education that are useful for educators and trainees alike. These resources include the ASIP Digital Library which provides access to presentations made at the Annual Meeting (courses and award lectures), and access to lectures from the ASIP Summer Academies. Recognizing that professional development is very important for trainees and others, access to career development resources is provided through the ASIP website. All of these resources are available to members of the ASIP and we encourage our members to utilize them for teaching or personal benefit.

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