UW Cardiovascular Pathology Training Program
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What we do
History
PNAS members
Translational research
CVP Applicant Responsibilities
Career preparation
Breakfast Club
Biomedical Research Integrity Lecture Series
Steering Committee
Other resources
Dealing with ethics or other issues
Other CVP trainee responsibilities
Expense reimbursement
      Travel
      Other expenses
Graduate training

KEYWORDS

HEART       BLOOD VESSELS     DISEASE     MOLECULAR BIOLOGY     DEVELOPMENTAL BIOLOGY       

MEMBRANE BIOLOGY     GENETICS     INFORMATICS     GENE THERAPY     STEM CELL BIOLOGY    

WHAT WE DO

CVP is a large, interdisciplinary training grant devoted to the basic science, the biology underlying cardiovascular disease. 

 CVP represents the major support for pre- and postdoctoral basic science training in vascular biology at the University of Washington.  The large number of investigators, (50 faculty members) in 14 departments, reflects the high level of NHLBI funding at the University of Washington.  In addition to using traditional cardiovascular labs as training sites, we place fellows in basic science laboratories where a cardiovascular disease project may only be one application of the principal investigator’s more basic interests.  These placements usually involve collaborations between senior investigators willing to co-mentor a fellow and have contributed to both our fellows’ growth and the development of interdisciplinary science within the cardiovascular community.  As a partial testimony to our interdisciplinary approach, 30 of the CVP faculty now participate in 17 large program project grants. Our research spans from basic to translational research.

The mixture of fellows, predoctoral, postdoctoral and MDs in our labs, is itself an asset as the trainees learn from each other.  At the predoctoral level, our fellows share formal, common course work in basic molecular cell biology.  Many of the postdoctoral fellows, especially those whose background is not in molecular biology, also take the UConjoint series in molecular biology.  To address vascular biology, all of our fellows participate in a weekly seminar called the “Breakfast Club".  The Breakfast Club is also offered as a formal course for predoctoral fellows (Path 552).  Breakfast Club has become known as a major seminar series of broad interest to the Medical school.  Weekly attendance ranges anywhere from 30 to 100 people.  In addition, as noted above, we have developed a new series of courses in cardiovascular biology.

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HISTORY

Modern vascular biology traces much of its origins about thirty years ago to the initial applications of cell culture, electron microscopy, and genetics to vascular biology in this Department, under Drs. Earl Benditt, the first PI of this training program, and Arno Motulsky, head of Molecular Genetics, and similar efforts at Harvard Medical School and the Department of Medicine at Cornell Medical School.  Besides their own work, Drs. Benditt and Motulsky mentored Drs. Russell Ross, Steve Schwartz, and Joseph Goldstein.  The tradition of innovation and mentorship has continued now for three decades.  Currently, the CVP faculty includes five Members of the National Academy and one Ed Krebs' nobel prize.

While the title of this grant reflects its historical origin in Pathology, in 1983 when Dr. Schwartz became Principal Investigator, he restructured CVP as an interdepartmental program that represented the collaborative nature of vascular biology research at our School.  Over the years, as vascular biology at the UW has evolved, areas have been added and removed from CVP.  This ability to grow and adapt is reflected in the extraordinary list of technologies pioneered in our program.  For example, work in Seattle was amongst the first to apply a long list of new methodologies to the vessel wall including: molecular biology and virology to the vessel wall, purification of a growth factor and its receptor, analysis by differential cloning and by array display, cell kinetic analysis in the vessel wall, use of in situ hybridization, identification of endothelial precursors in mice, identification of in vivo function of platelet-derived growth factor (PDGF), identification of heterotypic adhesion molecules, application of microdissection and molecular biology, cloning of coagulation proteins, development of the rat genetic linkage map, cell-based therapy in the heart, use of MRI to demonstrate a fragile plaque, analysis of vascular disease using SNPs, developmental analysis in chimeric mice, application of proteomics to the vessel wall and structural biology of channels.  This emphasis on cutting-edge technology continues with the current faculty. 

During the most recent five-year period, the program has also been greatly diminished by the loss of Dr. Russell Ross.  Dr. Ross died suddenly of pancreatic cancer in 1999.  This is a major loss to all of us, both emotionally and in terms of Russell’s role as a leading investigator in atherosclerosis.  His PPG (NIH 2 PO1 HL18645) has been renewed under Drs. John Harlan and Elaine Raines.  A happier change has been the retirement of a long-term member of this program Dr. Edwin Krebs.  Dr. Krebs, a Nobel Laureate, remains an active advisor and collaborator with CVP investigators.  We also lost one faculty member due to recruitment by another university.  Dr. Brad Berk left the University in 1999 to become chief of medicine at the University of Rochester.  In 2000, Dr. David Dichek was recruited to replace Dr. Berk as Director of Research in Cardiology.

We encourage our faculty to use CVP as a way to guarantee recruitment, but also to seek other sources of support.  Thus, some fellows recruited on CVP will end up supported by other sources.  We now have a clinically oriented grant that can accommodate MD postdoctoral fellows (9 positions).  During the current funding period, Dr. Brad Berk applied for and received a training grant directed at clinical investigators in Cardiology, Surgery, and Pathology.  This grant (Cardiovascular Research Training Program, NIH 5T32 HL07828), has been renewed under Dr. David Dichek of Cardiology with the assistance of Dr. Charles Murry of Pathology and Dr. Alec Clowes of Surgery.  The Cardiovascular Research Training Grant (CRTG) is complementary to CVP in several respects.  The CRTG emphasizes clinically-oriented research, does not support predoctoral students, and serves as the primary means of supporting MD postdoctoral fellows in Pathology, Cardiology, and Vascular and Cardiothoracic Surgery.  As such, CRTG is integrated with these residency programs and can serve the needs of resident physicians who would lack the research background for CVP.  Nonetheless, CRTG fellows work in the same laboratories as CVP fellows and will participate in our shared seminars and program grants.  CVP continues to serve MDs (especially MD PhDs) with more advanced research experience.  Currently, we have two MD PhD postdoctoral fellows in the program.

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Members of the national academy

Beavo, Joseph A.   Davie, Earl W.     Catterall, William A.    Glomset, John A.    Krebs, Edwin G.

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TRANSLATIONAL RESEARCH

Our program has always been multi-centered, something easy to do in Seattle, because of the proximity of independent institutions.  This application includes faculty from the Fred Hutchinson Cancer Center, The Hope Heart Institute and the Institute for Systems Biology.  Faculty from these institutions all hold UW appointments and participate in our joint research programs. 

We feel that the close ties between clinical and basic science activities are an important part of our continued success in training investigators who go on to successful careers as Principal Investigators and commit themselves to working on problems of cardiovascular disease.  This is especially true given our emphasis on basic science laboratories.

The following table lists CVP faculty with combined basic and clinical appointments.  The Department of Pathology plays a key role in these joint appointments.

Another way to illustrate our success in interdisciplinary research is our programmatic research career grants involving CVP faculty

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CVP Applicant Responsibilities

For consideration, CVP applicants must submit the following:

1.      Letter from the applicant stating planned area of research

2.      Letter from a mentor describing the qualities of the applicant

3.      Letter(s) of recommendation from one or two previous mentors

4.      Curriculum vitae

5.      Proof of USA citizenship, or permanent resident status (green card holder)

Career Preparation

We recognize that success as an independent investigator requires numerous skills beyond those required to design, execute, and interpret experiments.  These “survival skills” include writing manuscripts and grants, speaking, biomedical ethics, financial management, mastering of strategies for finding jobs in academia and industry, and learning to mentor trainees.  All fellows receive experience in grant writing.  For predoctoral fellows, all departments require submission of a grant application in the form of a proposed thesis project as part of the General Exam.  For postdoctoral fellows, we notify all fellows of non-NIH grant opportunities including AHA grants and starter grants available from the University Royalty Research Foundation and specific University Centers.  All fellows are asked to apply for such funding by the end of their second year of training.

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Vascular Biology Breakfast Club:  All of our laboratories participate in the Breakfast Club (PATH 552 Anatomic Pathology Course) once a week.  All CVP fellows must participate in this series.  Traditionally, there is a lot of questioning and interruptions are encouraged for fellows as well as any visiting speaker, is a lot of questioning; interruptions are encouraged.  Though listed as a course, Breakfast Club is actually an informal meeting that features invited lecturers, as well as UW faculty, fellows and CVP trainees.  Trainees are expected to present their research at Breakfast Club, which is held on Tuesday mornings during Fall, Winter and Spring quarters.  Special lectures may also be held on other days of the week and during the Summer quarter.  Check schedules at Breakfast Club.  Administrative support is provided by the Murry Lab and is funded by the Reaction to Injury Grant and the CVP Training Grant.

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Biomedical Research Integrity Lecture Series: All University of Washington School of Medicine trainees funded by NIH (both predoctoral and postdoctoral) are required to participate in the Biomedical Research Integrity Lecture Series, a series of seminars and discussion sessions on the ethics of biomedical research. The BRI Committee, composed of members of the Faculty Council for Research, directors of School of Medicine training programs, as well as postdoctoral and graduate student trainee representatives, recommends topics and formats for the lectures and discussions.  Topics vary each year and have included:  authorship, data ownership, conflict of interest, data handling, human subjects, scientific misconduct, mentoring, peer review, grantsmanship, genetic research, and use of animals in research.  Over 300 graduate student and postdoctoral trainees participate in the series each year, representing over 35 departments and degree granting programs.  Attendance is taken and reported to departments who monitor their trainees’ participation.  Trainees are allowed to participate in several BRI Series over the course of their traineeship, granting them a reasonable degree of flexibility in meeting the attendance requirement.  In addition, the BRI Series has a growing library of resources (video, texts, websites) that it makes available to departments and programs so that they may extend and tailor ethics discussion within their own programs.  Dr. Albert Berger, Associate Dean for Research and Graduate Education, welcomes student suggestions for this series.

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Other Resources: Some of the skills, such as grantsmanship and bioethics, are the subjects of formal lecture series.  For example, the UW Research Funding Service sponsors a monthly seminar series entitled “Grants for Lunch”.  This series covers grant writing skills and strategies for both public and private funding agencies, with an emphasis on NIH funding mechanisms.  The Department of Medicine sponsors a weeklong, biennial “Fellows’ Course”. Topics include scientific writing and oral presentations, grant writing, and an introduction to research mechanisms.  We also invite mentors to meet with students.

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Steering Committee: We require that all fellows be supervised by both their individual mentor and the Steering Committee.  The latter is most effectively done by the annual reports and by our requirement that fellows present in the Breakfast Club.

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Dealing with Ethics or Other Issues

CVP has a clear policy that encourages fellows to report any ethical concerns to their mentor or, if that is an issue, then to any member of the steering committee.  Our definition of ethics includes: intellectual property, fair pay, non-discrimination based on gender, race, religion, sexual orientation, authorship on papers

CVP Training Grant encourages trainees to use the faculty of the training grant as a resource for any issues which may arise vis-à-vis scientific integrity.  If for any reason a fellow feels uncomfortable discussing an issue of scientific integrity with his or her mentor, he or she may contact Dr. Schwartz, the Principal Investigator of this program.  Predoctoral fellows should contact their supervisory committees, which includes the official graduate faculty representative who has been appointed as advocate.  Fellows may also contact any other member of the CVP Steering Committee.

Possible issues requiring action include:

1.      Questions of accuracy of scientific data

2.      Questions of authorship of papers

3.      Relationships of academic to industrial research

4.      Patent issues

5.      Conflicts with PI about research direction

6.      Rights of fellows

7.      Rights of other lab personnel

At any time, fellows may also bring any issue to the attention of the Department Chair, or the Office for Scientific Affairs in the Dean’s office.

Issues relating to sexual, racial, religious or other conflicts may be brought to the same faculty or to the UW Ombudsman located in HUB 301, telephone 206-543-6028, or fax 206-685-6816.

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Other CVP Trainee Responsibilities

CVP fellows are required to submit annual progress reports during the period of Training Grant support.  In addition, as a condition of support, they must be willing to be contacted for up to ten years after termination of CVP support.  These reportorial requirements do not necessitate any complicated preparation of papers, but are merely submissions of summaries of work completed or in progress, papers authored under the grant, and reporting current personal information, such as positions held and other professional data, telephone and e-mail addresses or other contact information.

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Expense Reimbursement

Travel

Travel expense will be reimbursed if the CVP trainee’s mentor states that the travel fits in one of the following categories:

1.      The trainee will be giving a talk or presenting a poster;

2.      The meeting or course will provide critical insight or skills for the trainee; or

3.      The meeting will assist in job placement searches for the trainee.

CVP Trainees are not funded for general meetings, e.g. AHA or FASEB, unless one of the conditions above is met.

The CVP grant does not provide separate travel funds.  It does, however, provide approximately $500 per fellow per year to cover individual trainee’s travel expenses.  If required to travel, the trainee must submit a request stating the title of the meeting or symposium, the dates, the items requested (e.g. air fare, registration fees, cab fares, meals, etc.) and the amount, as well as attaching the necessary forms.  The grant administration will decide if and how much support will be granted.  Generally, support has been provided in the past to cover trips to meetings and courses which have been well-justified under the guidelines above.  Priority is given to trips for presentation of work done under the training grant and to attendance of specifically relevant courses.

Depending upon cost of travel, reimbursement will cover airfare, meals and accommodations up to the maximum limit.  Generally, however, mentors have used CVP funds to only cover shortfalls under other grants.

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Other Expenses

The CVP training grant may cover lab supplies, computers, office supplies, and books.

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Graduate Training within CVP

New departments added as of 2002 and not shown, include Biostatistics and Computer Science.  Traditionally, the two departments with the largest role in our predoctoral program are Pharmacology and Pathology.  As of this date, however, the distribution is changing.  We currently have only one student in Pharmacology, and two in Pathology.  Two students are in Bioengineering and we are adding a new student in Genome Sciences under Dr. Jarvik.

Biostatistics

The addition of Biostatistics to CVP reflects our growing interest in quantitative biology.  The University of Washington Department of Biostatistics’ predoctoral program already includes a specialty in cardiovascular biostatistics.  The program includes course work in both applied and theoretical statistics and biostatistics, including courses in statistical theory, introductory biostatistics, advanced applied statistics and linear models, design of medical studies, categorical data, survival analysis, multivariate statistical methods, statistical computing, design of medical studies, evaluation of new drugs and biologics in humans, and biologic courses.  First and second year theory and applied examinations, a cardiovascular biology project and a thesis are required as well.  Many students gain experience on ongoing projects including collaborative randomized clinical trials and epidemiologic projects (such as the Cardiovascular Health Study). 

Biostatistics already has close liaison with clinical cardiology via collaborations with the Division of Cardiology and the Cardiovascular Research Training Center in the School of Medicine.  The tie with CVP will encourage students to consider applying their skills to molecular biology.

CVP faculty in Biostatistics are Drs. Rossini and Kronmal. Dr. Rossini is a new faculty member who has been working with Drs. Schwartz and Jarvik on the problem of developing statistical models to link SNP data, clinical data and expression array data. Dr Kronmal has been Co-Principle Investigator and Co-Director of the Coronary Artery Surgery Study (CASS) Coordinating Center and Principle Investigator and Director of the Cardiovascular Health Study (CHS) Coordinating Center.  Dr. Kronmal is best known to CVP for his work as the coordinator of the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a 10-year observational study of the characteristics of subclinical cardiovascular disease in an ethnically diverse population-based sample of 6,500 men and women. From the CVP point of view, the MESA data set offers outstanding opportunities for collaborations between an epidemiologist and molecular biologists.

It is important to note that Dr. Kronmal’s training grant (Cardiovascular Biostatistics Training, NIH 5 T32 HL07183-26) already supports the cardiovascular path for Biostatistics students entering this program with an interest in epidemiology.  We expect, however, to use CVP to support the thesis and research efforts only of students choosing to work on projects in molecular biology labs.  CVP may also support collaborative programs for students from other departments who seek out mentors in Biostatistics for help with informatics.

Genome Sciences

The Department of Genome Sciences is a new addition to both CVP and to the School of Medicine.  Genome Sciences began in September 2001 by the fusion of the Departments of Genetics and Molecular Biotechnology.  The goal of Genome Sciences is to address leading edge questions in biology and medicine by developing and applying genetic, genomic and computational approaches that take advantage of genomic information now available for humans, model organisms and a host of other species.  Our faculty study a broad range of topics, including the genetics of E. coli, yeast, C. elegans, Drosophila and mouse; human and medical genetics; mathematical, statistical and computer methods for analyzing genomes, and theoretical and evolutionary genetics; and genome-wide studies by such approaches as sequencing, transcriptional and translational analysis, polymorphism detection and identification of protein interactions.  Our department includes both faculty with primary appointments in Genome Sciences, as well as adjuncts in other departments and Seattle institutions.  Eight faculty are members of the National Academy of Sciences, including 2001 Nobel Prize winner Dr. Lee Hartwell, who conducted much of his groundbreaking work in the Department of Genetics.  Graduate research in the Department leads to a PhD in either Genetics or Molecular Biotechnology and students in either PhD program can opt for a focus in Computational Molecular Biology.  Our department has about 60 graduate students.  CVP faculty includes Drs. Nickerson (a member of the Steering Committee), Dr. Aebersold, and Dr. Jarvik.

Computer Science

Computer Science is also a new addition as of this submission.  The University of Washington Department of Computer Science & Engineering includes roughly 35 faculty members, 150 doctoral students, and 425 undergraduate majors. Ranked among the top ten programs in the nation, we are active in most of the principal areas of the field, and are engaged in a broad range of interdisciplinary initiatives, including collaboration with eight other University of Washington departments in offering the interdisciplinary graduate program in Computational Molecular Biology (CMB).  Three faculty and about a dozen of the PhD students in CSE have their primary research interest in computational biology.  Quantitative and computational approaches are increasingly critical to biological research due to the explosive growth of genomic information and of high-throughput experimental technologies such as DNA microarrays.  The CMB program requires both course-work and lab experience spanning biological, statistical and computational fundamentals, and the PhD Qualifying- and General Exam projects of all recent CSE students interested in computational biology have included a substantive biological component.  Furthermore, we believe that active collaborations between computer- and biological scientists are critical to training the next generation of researchers, who will need to be versed in both fields to be successful.  The CSE faculty interested in computational biology are all strongly committed to fostering such collaborations, and most especially to fostering direct involvement by CSE students with biological researchers actively working on problems where new computational tools are needed.  We see great opportunities for such involvement within the context of the CVP training grant, with the likely outcome being the training of computationally oriented students with an interest in cardiovascular problems and of cardiovascular biologists with a much deeper insight into computational approaches.  As of now, CVP has only one Computer Science member, Dr. Larry Ruzzo.  He is a well-known investigator in arrays and is currently involved in cardiovascular projects that involve Drs. Schwartz, Byers, and Bumgarner.

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