The Center for Genomic Pathology (CGP) is a not-for-profit educational foundation whose goal is to collect, integrate and disseminate knowledge about Genomic Pathology. The CGP is designed to support educational activities of the Academy of Genomic Pathology (AGP). CGP will provide training and expertise in comparative pathology with an emphasis on the pathobiology of the genetically manipulated laboratory mouse as applied to human disease. Our objective is to train the next generation of comparative pathologists their students and staff helping them meet the needs of the scientific community with accurate interpretation of the diseases produced in mice through experimental and genetic manipulation. This objective is being realized using remote and on-site training based on our annotated, digitized images and databases coupled with modern telepathology and Distance Learning systems. A network of international expert comparative mouse pathologists (AGP) provides interactive training and consultation.
Genetically engineered mouse (GEM) mutants are rising substantially in number and complexity. However, the scientific community lacks a sufficient workforce with expertise in comparative pathology to effectively characterize and validate these model animals.
Following large-scale mouse mutagenesis programs and expansion of Genetically Engineered Mice created by individual scientists, the National Institutes of Health (NIH) is embarking on the “knock out mouse project” (KOMP), aiming to knock out all functional mouse genes. Similar large-scale efforts are underway in Canada (NorCOMM: North American Conditional Mouse Mutagenesis Project), Europe (EUCOMM: European Conditional Mouse Mutagenesis Programme) and Asia. These programs, now amalgamated as the “International Mouse Knockout Consortium”, are creating a critical, but unmet, need for expert comparative pathologists who are knowledgeable in mouse biology and human disease.
Comparative pathologists are the gatekeepers of translational research. Effective mouse pathology requires a global understanding of mouse biology. Comparative mouse pathology requires a unique set of skills and a knowledge base that is not possessed by most investigators or, for that matter, most service pathologists. The lack of pathologists qualified to serve biomedical research, and mouse-related research in particular, is also emphasized in recent reports from the U.S. National Academy of Science, American College of Veterinary Pathologists and PRIME.
The advances in the understanding and manipulation of the genome have created a new field of pathology aimed at understanding the effect of specific changes in the genome on disease processes, Genomic Pathology. For the first time in scientific history, specific changes in the genome can be experimentally correlated with specific changes in disease processes. Cancer biology provides one example in which genetic manipulation results in very specific and unexpected tumor phenotypes. While this information is widely dispersed, it is not systematically taught in most residency, or other training programs resulting in service pathologists unprepared for current and future needs as well as being untrained to guide their research staff in use of GEM. The use of untrained pathologists has already led to numerous egregious errors appearing in publications.
Although recognizing the problem, NIH has not committed adequate resources for addressing this shortage. Furthermore, NIH funding mechanisms do not allow for training in pathology. Where are the mouse pathologists of the future and who is going to train them? Who is going to train technical staff researchers?
One solution is to develop an “electronic consortium” of existing “experts” in mouse pathology whose collective wisdom and resources can be systematically collected, integrated, and disseminated. More important, their expertise now can be shared with interested young pathologists and staff using appropriate distant-learning tools. While the technology for a distance-learning consortium is available, a stable funding base needs to be identified and developed.
Scientists involved in creating this huge mouse population must also recognize the need, and help to seek a solution. The government is funding the generation of GEMs, but is failing to create the necessary human resources. A potential solution is a partnership between academia, industry and government. We have asked that the scientific community recognize the impending crisis and help address the issue before it becomes catastrophic.
The Center for Genomic Pathology is designed to provide a center of international cooperation and resource-sharing for education in Comparative Pathology. To this end, we have:
- Received the certificate registering a not-for-profit 501(c)(3) corporation with the State of California.
- Named a Board of Directors
- Engaged a business agent
- Engaged a law firm
- Approved bylaws
- Established a Board of Scientific Advisors who will also contribute to our “Academy of Genomic Pathology”
- Held the first annual meeting of the CGP.
- Received certified tax exempt status from the State of California and the USA Internal Revenue Service
- Developed a curriculum with the UCD Extension Distance Learning.
The CGP is administered by the Director and the Board of Directors. CGP is “Affilliated” with the University of California, Davis so that CGP can utilize its infrastructure and resources. Initially, the CGP will rely on the extensive annotated databases and image archives developed by Dr. Robert D. Cardiff in the Center for Comparative Medicine (CCM) and will be the basis for our educational/training programs. These resources will expand and improve as additional models are placed in the repository.
The Academy for Genomic Pathology
The Academy for Genomic Pathology is the major resource for this educational effort. The Academy is composed of internationally recognized experts in comparative pathology who have agreed to participate in this innovative program. The Academy members were chosen based on their dedication to our educational goals, experience with genetically modified mice, expertise in specific areas and willingness to participate in our training programs (see appendix). Ten senior members include experts in infectious disease, GEM tumor pathology, dermatopathology, toxicology, neuropathology and lymphoma/leukemia. The expertise of the ten senior experts is represented by a combined 2500 publications referenced in Pub Med and over 100 chapters and monographs. In addition, we have nominated more faculty for the Academy for Genomic Pathology and can call upon a network of colleagues with expertise not found in one academic institution.
Access to the CGP knowledgebase and AGP expertise is an unparalleled opportunity for education and collaboration with an interactive group of Comparative Pathologists. The CGP Experts are always interested in expanding the CGP resources and knowledgebase. The CGP provides powerful potential for collaboration with peers in academia, industry and government in our ongoing efforts to expand and improve the databases and related reference materials.
The Knowledge Base
The collection, integration and dissemination of information concerning Genomic Pathology will be based on the collection and integration of information currently dispersed in a number of publically accessible databases including the current UCD databases: TGmouse (http://tgmouse.compmed.ucdavis.edu) and TVmouse (http://tvmouse.compmed.ucdavis.edu). The data will be integrated so that it is a useful reference source for Comparative Pathologists and trainees. Since pathology is primarily a visual discipline, the major effort will be to provide gross and microscopic images that are useful for interpretation of cases and integrated with the appropriate genomic and molecular data. We started one type of image archive for the National Cancer Institute using high resolution whole slide digital imaging that has been very useful but has never been updated, audited or expanded (http://imagearchive.compmed.ucdavis.edu). This type of image archiving can provide the foundation for Genomic Pathology but it needs continuous management to provide accurate, up to date and searchable data.
Other knowledge bases can be found using the CGP MouseCrawler which indexes the content found on the web and displays it in a searchable format. A PubMed crawler is planned to index and update all GEM-based literature.
The training will be based on “Distance Learning” with the web-based interactive telepathology and teleconferencing applications developed and utilized by Dr. Cardiff and his colleagues. The curriculum is implemented and presented with the UCD Extension. However, on-site, face-to-face training sessions are encouraged when necessary and can be arranged.
The primary tool will be weekly Internet-based meetings/conferences with the trainees and the CGP “Academy of Genomic Pathology.” These will be similar to the traditional apprenticeship training sessions using “cases” viewed on a multi-headed microscope or video projection. However, the slides will now be reviewed using digitized “whole slide images” and interactive internet teleconferencing applications. Each case will be presented by a specific expert for discussion by the faculty. Student trainees will actively participate in the conferences. The students will be assigned slides and background in advance of each conference and will be expected to present and discuss specific cases with the faculty. Students will be encouraged to prepare and present materials from their own institution or company. The student also will be able to present and discuss specific cases with individual experts.
In addition, PowerPoint-based lectures covering various topics in Comparative Pathology will be available to the enrollees. These are based on a Pathobiology course given at UCD and by other members of the faculty. The lecture series will include materials that the faculty deems essential for applied Comparative Pathology. They will be updated and filmed for easy and asynchronous access by the students. Reading lists and reading assignments will help provide background information. The student trainee completing the assigned lectures and required coursework and an examination will receive a certificate of completion from the University of California.
The curriculum is multi-tiered to benefit all levels of scientific personnel engaged in the research process, from laboratory technicians to comparative pathologists.
Tier I: Pathobiology of Laboratory Mice is suitable for all levels but primarily intended for technical personnel who support biomedical research and need to understand the animals they are handling as well as how to assist the investigators in characterizing the mice. You will learn good laboratory practice and animal husbandry, how to perform and accurately describe meaningful, thorough necropsies, how to prepare and process tissues for microscopic examination and how to correlate microscopic findings to the clinical and gross observations.
Tier II: The Pathology of Genetically Engineered Mice is designed for the trained scientist (Ph.D., M.D., D.V.M.) with exposure to but little training in comparative pathology using genetically engineered mice to model human disease. You will learn to recognize and interpret the significance of the clinical, gross and microscopic findings in your mice and to compare and contrast diseases found in mice to those found in other animals including human.
Tier III: Genomic Pathology is designed for the veterinary and medical board-certified/eligible pathologist, or equivalent, who desire expertise in recognition of the unique differences in disease in the GEM and other models of human disease. You will perform special projects and participate in advanced seminars and focused discussion groups with expert faculty aimed at building your expertise in genomic pathology.
Tier I The Pathobiology of Laboratory Mice
Section A. (30 Hours)
Topic 1: Mouse Husbandry (4 Hours)
Topic 2: Mouse Anatomy (10 Hours)
Topic 3: Principles of Pathology (12 Hours)
Topic 4: Basic Necropsy and Surgical techniques (4 Hours)
Section B. (30 Hours)
Topic 1: Endogenous and Opportunistic Infections (4 hours)
Topic 2: Genetic Engineering (4 hours)
Topic 3: GEM Basic Pathology (9 hr)
Topic 4: Mouse Immunology (4 hr)
Topic 5: Mouse Physiology (3 Hours)
Topic 6: Design of Animal Experiments (2 Hours)
Topic 7: Fundamentals of Toxicology (2 Hours)
Topic 8: Ethical and Responsible use of Mouse Models (2 Hours)