Dean's Newsletter

Archive of previous newsletters

The Aab Cardiovascular Research Institute

November 30, 2007

During the past 40 years, major advances in cardiovascular research have produced a better understanding of the pathophysiologic basis of diseases of the circulatory system.  This research has produced drugs, devices, diagnostic tools and preventive strategies that have saved lives.  Moreover, people with cardiovascular (CV) disease are living longer, and have an improved quality of life.

It is encouraging that the advances in CV diagnosis, prevention and treatment have led to a substantial decline in mortality—for example, deaths from coronary heart disease declined from a peak of 330/100,000 population in 1970 to 160/100,000 in 2005.  Yet, despite this tremendous progress, CV disease continues to impose a major burden on patients, their families, and the national health system. In 2005, it was the leading cause of mortality in the U.S., exceeding by 50% the second most common cause of death, cancer.

More photos can be found here

On October 22, 2007, the faculty and staff of the Aab Cardiovascular Research Institute (CVRI) began moving into their new facility on Bailey Road.  This newsletter will focus on the exciting work now being done in the Aab CVRI, and on the move into this state-of-the-art facility.

Mike Goonan, URMC CFO, remembers well the March 5, 2004 edition of the Rochester Business Journal, in which Wyeth-Lederle announced that the last remnants of its research program in vaccines would vanish from Rochester.  The company announced that it would relocate its remaining staff to sites in other states and close its facility.  A year earlier, a majority of employees at Wyeth's Bailey Road facility had been offered relocation packages to other Wyeth sites. The RBJ article indicated that Wyeth-Lederle was still "hunting for a buyer for its 84,000 square foot research site on Bailey Road." 

As I have discussed several times in the newsletters, research space at the medical school is now insufficient to accommodate our growth.  This is a good problem to have, in that our faculty have been successful in attracting new funding that requires additional space.  Therefore, when Wyeth-Lederle put the Bailey Road facility and site on the market, Mike was quick to convey our interest in the property.  This building—about half laboratory space and about half office and conference space, was originally designed and built for vaccine research and related regulatory and administrative support.  Among potential owners in Rochester, URMC was uniquely positioned to put the facility to good use.

According to Mike, the negotiations between Wyeth-Lederle and URMC considered many different options, ranging from outright gifting opportunities to an outright Purchase/Sales approach.  In the end, due to the long-standing and mutually beneficial relationship between the two organizations as well as the facility infrastructure and research space compatibility, a combined Purchase and Sale/Donation concept was negotiated.  We acquired the 84,000 sq ft facility and 62 acre-site for $4.5 million – a fraction of its book value of $14 million.  The cost to duplicate the facility, including equipment, was estimated to be approximately $30 million.  (Since then, we have added a 12,000 sq ft state-of-the-art mouse vivarium and have modified individual research laboratories to suit the needs of investigators.  The total cost of this facility, including the new vivarium and renovations, was about $18 million.  This translates to a cost of about $180/sq ft, which is still half to a third the cost of new laboratory space. 

It was now 2005.  We had a new facility, and a large new research space, but we had to find a program that wanted to move there.  Such a program would have to embrace the vision of an integrated research unit having a distinct identity, but detached from the mother ship.   So I shopped the idea around to a number of departments and centers.  Many of them had concerns about the distance from the medical center and its implications for graduate education and research interactions.  But one person saw the light.   Bradford C. Berk, MD, PhD, currently URMC CEO but at the time the Chair of Medicine and Director of the Center for Cardiovascular Research, understood the potential.  Working closely with Mark Taubman, Director of the Center for Cellular and Molecular Cardiology, Brad realized that the Wyeth-Lederle facility could be an incredible environment for a research program.  In particular, the growth of transgenic mouse models by cardiovascular researchers was straining vivarium resources and the inconvenience of multiple research locations for studying animals was significant.  Not all of the CCVR research faculty were equally enthused.  They had just moved from the Kornberg Building to labs in MRBX and felt that another move would be disruptive.  Like those in other departments and centers, many thought that that the off-site location would adversely affect graduate education and collaborative research.  But Brad, with Mark Taubman, MD (now Chair of Medicine) persuaded them that these problems would be addressed and that the benefits would far outweigh the inconveniences.

As Mark saw it, the CVRI afforded the CV research group the opportunity to continue to grow an already outstanding program in basic cardiovascular research.  It would serve as a focal point for developing new diagnostic and therapeutic modalities that could be rapidly translated to clinical practice.  Now that it has opened, with generous support from Richard Aab (see below), Mark believes that the Aab CVRI will be the base for developing an internationally recognized training program in cardiovascular research.  This will include enhancement of our Graduate Program in Cardiovascular Sciences in collaboration with the Department of Pharmacology and Physiology and the development of a Research Fellowship in Cardiovascular Sciences designed at attracting the most talented post-doctoral fellows and research-oriented Cardiology Fellows from around the world.  Mark anticipates that this will enable us to obtain an NIH Training Grant in Molecular and Cellular Cardiology, allow the Aab CVRI to serve as an incubator for junior faculty, and enhance the prestige of Rochester as a magnet for young scientists

Our ability to achieve the vision for the Aab institute that Brad and Mark articulate depends, of course, on the work of our faculty and staff, shown in the photo below.  Highlighted below are some of these faculty—the research they are conducting and their impressions of the move. You will see why we are so confident that the vision for the Aab CVRI will be achieved.

Burns Blaxall, PhD

Burns Blaxall, PhD

Burns C. Blaxall, PhD, is Assistant Professor of Medicine and of Pharmacology and Physiology, and is also Director of the Graduate Cluster in Cardiovascular Sciences.  Most recently, he won the American Heart Association's Outstanding Early Career Investigator Award for 2007 (Council on Basic Cardiovascular Sciences).  Burns, who joined us four years ago from Duke, has a long-standing interest in understanding the development, progression and regression (treatment) of heart failure, particularly as it relates to β-adrenergic receptor (β-AR) signaling. He and his group have recently identified several known and novel heart failure-associated genes by gene expression profiling of the normal, failing and "rescued" heart in both mice and humans.  Burns is pursuing three main projects based largely on genes identified in these studies.  These include functional investigation of two genes not previously associated with heart failure, as well as novel small molecule targeting of a gene previously known to play an important role in heart failure pathogenesis.  Investigational techniques range from in vitro biochemistry, pharmacology, cell biology and isolated adult cardiomyocyte contractility/calcium studies, to high-resolution in vivo cardiac phenotyping in genetic and surgical mouse models of heart failure, coupled with validation in human cardiac myocytes and heart failure samples.

Burns states that his move "was essentially painless. Our lab moved on a Monday, we were doing experiments by Wednesday."  While his group initially had concerns regarding extensive committee work and teaching responsibilities on the main campus, "they are essentially no different than they were previously.  The shuttle is terrific and always on-time."  Burns feels that ongoing collaborations have not suffered and that animal studies have been facilitated "due to our outstanding vivarium facilities, which we carefully designed to be state-of-the-art for cardiovascular investigation."

Regarding the educational mission, Burns states that: "The training environment is outstanding, and currently includes over 30 graduate students and postdoctoral fellows.  The labs and our research are highly collaborative and interactive, fostered in part by our program project grant.  Furthermore, Joe Miano and I initiated and co-organize the weekly Aab CVRI seminar series, as well as a weekly cardiovascular journal club for all trainees.  Video conferencing to numerous seminars and several courses is also provided.  Our Graduate Program faculty are highly dedicated to training the next generation of cardiovascular scientists.  In particular, Drs. Taubman and Berk are internationally recognized for their commitment to early career development.  Together they have trained dozens of current national and international thought leaders in cardiovascular research.   Dr. Taubman previously directed the Medical Scientist Training Program [MD-PhD Program] at Mt. Sinai, and remains highly involved with the MSTP at Rochester.  Dr. Berk was recently awarded SMD's Faculty Academic Mentor Award. Dr. Berk and I both recently gave invited addresses on early career mentoring to the American Heart Association Early Career Investigator symposium.  In summary, our world class faculty and facility provide an outstanding training environment." 

Burns concludes that:  "The new Aab CVRI provides world-class research facility and environment. With our newly renovated building, state of the art equipment and vivarium, peaceful setting with 62 wooded acres and 1.5 mile walking/running trail, it's tough to beat.  Coupled with our growth potential, outstanding training environment and camaraderie, it's a great place to work."

Joe Miano, PhD

Joe Miano, PhD

Joe Miano is Associate Professor of Medicine and Interim Director of the Aab CVRI.  He and his group begin with the supposition that "much of what predisposes us to disease relates to imbalances in gene expression control."  The Miano lab therefore focuses on how genes that are important in the cardiovascular system are turned on and off during development and in disease.  Within the vasculature, for example, smooth muscle cells (SMC) sometimes undergo "de-differentiation," which is thought to be an early event in the pathogenesis of vascular diseases.  An understanding of the molecular underpinnings of SMC differentiation has enormous potential for treating and possibly limiting vascular diseases as well as other SMC-associated diseases (e.g., asthma, Alzheimer's).  A wide array of research tools are used--ranging from computers to cells to genetically altered mice—all directed at delineating the discrete snippets of DNA (called regulatory elements) in our genome that direct the expression of genes.  Some of Joe's efforts "are directed towards the discovery of new snippets of DNA and ascertaining whether functionally important variants exist in human populations."  Other studies "test the hypothesis that retinoids (pro-differentiating agents used in cancer therapy) ameliorate vascular diseases through the coordinate expression of key target genes."

Regarding the move, Joe recognized that the new building had the immediate effect of expanding the overall space devoted to cardiovascular research.  Also, the presence of the Functional Genomics Core (which is co-located at the Aab CVRI), along with its infrastructure and personnel "provides a critical interface to augment our genomics efforts."   He is also appreciative of the new vivarium, immediately below his lab, which "has ample space for growth as we develop new mouse models, including 'humanized' mice for regulatory element analyses.  An added bonus is the serene campus and quiet atmosphere within the building."

Jim White, MD, PhD

Jim White, MD, PhD

When R. James White, MD, PhD, Assistant Professor of Medicine, began his pulmonary practice at URMC, there wasn't anyone in upstate New York with a large referral practice in pulmonary hypertension (PH).  PH patients in this area typically drove long distances to Cleveland or New York City.  To catalyze the process of drug development and to service a growing need in upstate NY, URMC launched a clinical research team four years ago to care for PH patients (now at the Mary Parkes Center).  The success of this team approach was recently highlighted nationally in the Pulmonary Hypertension Association's quarterly newsletter.  

A scientist and researcher by training, Jim earned a joint M.D.-Ph.D. degree from the University of Pittsburgh School of Medicine.  During his residency at the University of Rochester he became fascinated by pulmonary circulation, saying, "the understanding of what caused PH was so limited that I knew it would be an exciting area for research."  Regarding his laboratory research at the Aab CVRI, Jim's vision is to "create a premier lab for studying the vascular biology of pulmonary hypertension in a rat model that is highly relevant to the human disease.  To that end, we are combining classic histology techniques with cutting edge technologies like implanted flow probes for measuring cardiac output in conscious, behaving animals and micro-CT for visualizing the lung blood vessels.  We hope to use this animal model as a platform for testing novel drugs that might change the lives of patients with a devastating disease (pulmonary arterial hypertension, PAH)."

Jim believes that the move to Bailey Road will propel his program forward by allowing him to experiment in a premier vivarium designed specifically for rat and mouse cardiovascular physiology.  "The tight collection of a high resolution rodent echocardiography machine, multiple tools for invasive and non-invasive hemodynamic measurements, and several well-equipped operating rooms is optimal for my whole animal experiments.  We have also substantially upgraded our microscopy and histology cores to image processes in freshly prepared tissue and living cells.  Although the challenge of moving back and forth to the main medical center campus is real, we think the advantages of our upgraded facility will far outweigh the drawbacks and further, that the resources we have to offer will draw graduate students and faculty collaborators alike to Bailey Road."

Jim has a motivational message in his office that he looks at each day: "Excellence is the result of caring more than other think is wise, risking more than others think is safe, dreaming more than others think is practical, and expecting more than others think is possible."  He says that "sometimes I can't go to sleep, I'm so excited about this work."  But he's raring to go each morning—"The reason to do this work is that it gives me life."

Jinjiang Pang, M.D., Ph.D.

Jinjiang Pang, M.D., Ph.D., a post-doctoral fellow within the Aab CVRI, won the Cournand and Comroe Young Investigator Prize in Cardiopulmonary and Critical Care for her work on the genetic mechanisms that control how blood vessels form in the lungs during the postnatal period.  Her efforts could lead to a better understanding of syndromes like bronchopulmonary dysplasia, a problem seen in premature infants treated with ventilators who do not develop enough blood vessels to supply their lungs.  Pang won the award for her study, titled "GIT1 Is Required for Pulmonary Vascular Development," which was presented as an oral abstract at the 2007 American Heart Association (AHA) meeting and subsequently published in the AHA publication, Circulation. Specifically, her study results argue that a protein, G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1), is an important part of signaling pathways that drive the development of blood vessels in the lungs by employing growth factors.  Pang's experiments eliminating the action of GIT1 resulted in reduced blood vessel development in a mouse model.  Regarding the importance of this work, Dr. Miano states that it "exemplifies the power of mouse genetics to provide insights into basic human development and disease."

Dr. Pang's path to URMC and this award is very inspiring.  She received her MD from Shanxi Medical University and her PhD in Physiology from Peking Union Medical College.  She then moved to LSU for a post-doc in September, 2004.  Hurricane Katrina occurred a year later.  All of the cardiomyocyte samples she had worked so hard to generate over the previous year were gone.  At the same time, she was 8 months pregnant!  She and her husband, also a post-doc, moved to Texas A&M, but there was no long-term position there.  Hearing of this situation, Dr. Berk agreed to accept Dr. Pang into his lab as a post-doc, while her husband, Dr. Xiangvin Xu, obtained a position with Zheng-gen Jin, PhD, Associate Professor of Medicine, also in CVRI.  Moving here in February, 2006, Dr. Pang soon became very productive in this new environment, culminating in her AHA prize paper.

What about future plans?  Dr. Taubman, Chair of Medicine and Chief of Cardiology and cardiovascular investigator, plans to hire faculty in a way that will dovetail well with the goals of the new URMC Strategic Plan.  Recruitment will be focused in two broad areas: vascular biology and cardiac dysfunction.  "It is our goal to build on current strengths to establish an Internationally Pre-eminent Program in Vascular Biology.  This will include recruitment of faculty with expertise in atherosclerosis and plaque regression, macrophage/dendritic cell biology and matrix biology.  In addition we plan to establish a program in angiogenesis and vasculogenesis with recruitment of vascular stem cell biologists and developmental biologists.  Our second goal is to develop a nationally prominent program in Cardiac Dysfunction.  This basic research program will dovetail well with our strengths in clinical electro-physiology and heart failure/transplantation.  We plan to grow our program in Cardiovascular Ion Channel Biology by recruiting faculty with expertise in cellular electrophysiology and molecular biology, genetics, and cardiovascular development.  In addition, we will grow our program in Cardiac Muscle Biology by recruiting faculty with expertise in animal models of myocardial injury and heart failure, myocardial development, stem cell biology, and myocardial genetics."

I will end by abstracting part of the ribbon-cutting speech on August 21, 2007 given by Richard Aab, who provided the $5 million naming gift for the Aab CVRI: 

"There is no one here today who has not, in some way, been touched by cardiovascular disease.  Its reach is pervasive and deadly, particularly here in the U.S.  And while scientists' have evolved their understanding of the disease, thanks in part to the significant contributions of physicians like Drs. Berk and Taubman, we still have a long way to go to ease the suffering and human casualties caused by this disease.

"The good news is, there's new hope on the horizon.  As many of you might be aware, I was fortunate to be at the forefront of the telecommunications boom before the words broad-band, internet and cell phones invaded our vernacular.  It was the convergence of a series of new technologies that fed the global telecommunications boom, and I was one of the lucky ones able to see its potential.

"Today, I believe we are at a similar juncture with cardiovascular research.  New technologies and research developments are poised to make that miraculous discovery that will ease the pain and suffering caused by America's number one killer.  With Drs. Berk and Taubman, we have that capable leadership to make that next discovery right here in Rochester.  That's why I'm confident that my investment will yield the results that will make a real difference in the lives of thousands – perhaps even millions of families, and potentially put Rochester on the map as THE center for cardiovascular science.

Meliora,

David S. Guzick, MD, PhD
Dean, School of Medicine and Dentistry