Space for Hearts: The evolution of Dalton Cardiovascular Research Center
Story by: Jeff Sossamon
Photo: Angela Bruno
Feb. 19, 2019
“The relationship of the University [of Missouri] to the national space effort has been under discussion and development ever since the National Aeronautics and Space Administration was formed in 1958…”
So began a working document written by Ward J. Haas, associate professor of management and director of the Space Sciences Research Center. Written in 1967, Haas highlighted the collaborative nature of the research conducted at Mizzou more than 50 years ago involving “more than one faculty member, discipline, department, or college of the university,” a hallmark and centerpiece of what would later become known as the Dalton Cardiovascular Research Center.
Ultimately named for MU grad Gov. John Dalton, the Center’s focus areas have a varied past—what began as a NASA-affiliated research facility focused on space, hypoxia and altitude research, and eventually led to environmental research and its current mission, which is to create the research collisions needed in medical pharmacology and physiology, veterinary biomedical sciences, biological engineering, and arts and science.
Michael A. Hill, serves as the interim director of Dalton and is a professor of medical pharmacology and physiology in the MU School of Medicine. Hill’s original research interests included vascular complications associated with diabetes, which took him to Texas A&M University where he focused on the ways in which circulation is controlled in very small blood vessels.
In a recent conversation, Hill described how his research is evolving, breakthroughs and shared research facilities at Dalton, and the Center’s upcoming jointly-hosted signature event, Cardiovascular Day, which is slated for Feb. 26 at the Reynolds Alumni Center.
JS: How has your research evolved?
MH: At the moment one of our major areas of interest relates to vascular complications associated with diabetes. This is particularly relevant as our population in general is becoming more obese, a major risk factor for developing diabetes. Blood vessels in people with diabetes become stiffer and this impairs their function while decreasing their ability to control blood flow. That might be in the vessels of the heart, for example, which in turn leads to stiffening of the tissues in the heart than can ultimately contribute to cardiomyopathy and heart failure. We have a real team approach with the research representing collaboration between multiple Dalton Investigators and researchers across MU. Key to this work is James Sowers, professor of medicine; Luis Martinez-Lemus, professor of medical pharmacology and physiology; Jaume Padilla, an assistant professor of nutrition and exercise physiology, and Camila Manrique, associate professor of medicine. Collaborations also occur with researchers at the VA and other institutions including Tuft’s Medical Center, Boston and the University of Pittsburg.
Additionally, we’re studying how blood flow and pressure are controlled at a local level – for example, when you exercise the muscles in one hand, how does the body know to in crease blood flow in that hand and not the other? These mechanisms have fascinated us over the years and involve a process we refer to as mechanotransduction which we know depends on how the cells and blood vessels respond to physical forces like pressure. We are now translating some of this work back into back into clinically relevant situations including diabetes, obesity and aging. Importantly, this involving substantial collaboration between Dalton Investigators and researchers across MU.
JS: Why are multidisciplinary teams at Dalton important for grant funding?
MH: Historically, people work in their respective laboratories and seek individual funding through granting agencies such as NIH, the American Heart Association, and NSF. As grant money is getting harder to obtain, these funding agencies are looking for team-based research, so multidisciplinary teams are key to attaining those research dollars. Also, we’re focused on our core facilities where researchers share their expertise as well as the equipment.
JS: Can you explain some of the science occurring at Dalton now?
MH: Firstly I’d like to emphasize that researchers can learn from other disciplines, so we do quite a bit more than might first be considered as cardiovascular research—people bring in new techniques and new approaches that inform how others conduct their science and that’s a definite strength of our multidisciplinary institute.
We have people who are interested in vascular complications associated with aging, diabetes, cancer and hypertension—some of the classic disorders that are affecting society these days. Salman Hyder, is the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine. He is studying what at first looks like cancer, but he is actually exploring how cancer cells and tissues interact with their own vasculatures during the cancer development process. Slava Glinskii, associate professor of pathology and anatomical science, and Olga Glinskii, assistant research professor of medical pharmacology and physiology are also studying the vasculature in cancer, in particular as it relates to how cancer cells travel to distant sites within the body.
Shinghua Ding, professor of biomedical, biological and chemical engineering, is conducting research related to cellular mechanisms underlying the catastrophic vascular disorder, stroke, while Chetan Hans, assistant professor of medicine is studying how potentially lethal aortic aneurysms form and rupture.
Lakshmi Pulakat, a professor of medicine, is another of our investigators studying cardiovascular disease in diabetes while also having a major interest in drug delivery.
We have researchers working on cardiac development. Chris Baines, associate professor of biomedical sciences, and Maike Krenz, associate professor of medical pharmacology and physiology, are studying how cardiac development functions, and what events underlie certain genetic cardiac diseases. We have people who are interested in cardiac failure, again another major problem in Western society.
A very active group of researchers Cheryl Heesch, Eileen Hasser, David Kline, all professors of biomedical sciences, and Kevin Cummings an assistant professor of biomedical sciences, are tackling problems associated with how the nervous system interacts with blood vessels to control blood flow, pressure and respiration. These studies are relevant to adaptations to low oxygen (hypoxia), sleep apnea and sudden infant death, for example.
Additionally, we have a couple of research groups. T.C. Hwang, professor of medical pharmacology and physiology, and Lane Clarke, professor of biomedical sciences, are interested in Cystic Fibrosis, which doesn’t necessarily seem to be a cardiovascular disease; however, they study fundamental processes which are very relevant to the cardiovascular tissue. Cystic Fibrosis, itself represents a major genetic disorder that needs basic research to identify strategies for developing new, and improving existing, treatments
Several of our scientists including Kevin Gillis, professor of biomedical, biological and chemical engineering and Andrew Gu, associate professor of biomedical, biological and chemical engineering; Luis Polo-Parada, associate professor of medical pharmacology and physiology, are performing basic research in the area of ion channels and the exchangers that move substances across cell membranes, these processes are fundamental to all cells and tissues within the body.
Finally, not all of our scientists are ‘bench-based.” Xiaoqin Zou, a professor of physics and biochemistry, uses computer-based methods to study how proteins interact with other proteins and small molecules. Such work is integral to the rationale design of novel drugs.
That’s quite a group, but I should also point out that Dalton has a number of very active non-resident investigators from across the Campus. We also have very talented and vital administrative and support staff who we could not function without.
JS: What are some of breakthroughs that have resulted from Dalton research?
MH: It’s hard to pick individual examples because I’m proud of all the investigators we have. Their success is evident in the funding obtained, the publication of quality manuscripts and, importantly, through the training of Ph.D./MS students and postdoctoral fellows.
One historic breakthrough relates to former Dalton director Dean Franklin who contributed to ultrasound techniques that have led to advancements in measurement of blood flow and how we quantify dimensions of the heart and vasculature. He was the first person to develop telemetry and we’ve built on that technology to this very day.
Some of our recently developed core facilities are very much based on that technology.
JS: Let’s talk a little about the new Dalton imaging facility.
MH: As well as being a multidisciplinary Center, we try to maintain and enhance the core facilities we have that bring value to other investigators throughout the research enterprise at Mizzou. As such, we have focused on our core imaging facilities including very sophisticated modes of microscopy, such as multiphoton microscopy, confocal microscopy and, more recently, atomic force microscopy, which lets us look at live cells and understand their structure and function.
Recently we’ve placed an emphasis on making measurements in live animals so that we can follow disease processes like hypertension or blood vessel complications associated with heart disease or diabetes. These occur over time, so being able to follow the process in live animals is a very powerful method of research.
Some of the techniques we’ve set up include high-frequency ultrasound, which allows us to get excellent images of the heart and blood vessels in animals. In addition, we have photoacoustic imaging which allows us to combine the ultrasound with measurements of tissue metabolism.
JS: What else should folks know about Dalton?
MH: Well, we have a number of national and international collaborations. Dalton helps to promote and encourage people coming from other countries to continue and develop their work here. We have formal interactions with institutions in China, Sheffield in the UK, and the University of Calgary in Canada. We also have collaborations with industry as well as the Missouri Life Science Incubator, and the Nano and Molecular Innovation Center will share some of our animal and microscopy facilities. They will develop radiopharmaceuticals which will be tested in our facilities.
JS: Governor Parson has declared February 26th as Cardiovascular Day. Could you tell us about the event and the speaker?
MH: The 26th Annual Cardiovascular Day (Tuesday, February 26 at Reynolds Alumni Center) is a yearly event jointly sponsored by the Department of Pharmacology and Physiology in the School of Medicine, Biomedical Sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center. The event is a high quality symposium that highlights research advancements in all studies of vascular function.
Ernesto Schiffren, professor of medicine at McGill University, is an expert on hypertension. He will discuss the interaction that occurs between the immune system and hypertension. We now realize that immune cells directly interact with the cardiovascular system in both good and bad ways. Dr. Schiffren will address how immune cells affect hypertension.
Also, on that day we’ll have eight local speakers, from Mizzou who will promote the research of recently appointed faculty and their trainees. Additionally, that afternoon we’ll have a poster session where post-graduate students and fellows present their work in poster format. We find that CV Day helps younger faculty develop their presentation skills as they receive feedback from a large audience.
We hope everyone can join us.
In addition to Cardiovascular Day, Dalton hosts a monthly Cardiovascular Forum at 5 p.m. every third Thursday of the month. The idea is to bring researchers together to become aware of vascular research on campus and encourage collaborations. We generally have two people present early phase research results or the aims and hypotheses section of their grant submissions so they can get feedback from other investigators on how to make their grants more competitive. Normally the talks go for about 10 minutes, and the discussion goes on for 30 minutes more.
The Annual Franklin Endowed Lecture, named after Dean Franklin, former director of the Dalton, was established to recognize his role in the field of animal research and instrumentation.
The final thing I’d like to mention is that Dalton plays an important role in education and training. The Center is not just comprised of senior investigators. In fact, we have post-doctoral fellows, medical fellows, and Master’s and doctoral students who conduct their entire research programs here. We also have undergraduate, high school, and international trainees who participate in research at Dalton.
There’s no shortage of ingenuity at the Dalton Center.
For example, in conjunction with Dr Xu Han, Hill and William Fay, professor of internal medicine and senior associate dean for research at the MU School of Medicine, are co-principal investigators for developing a heart cryopreservation technology that has been supported by Coulter Translational Partnership Program funding in 2018. Donated hearts can currently only be stored for a maximum of six hours. This “nano-ice forming” medium would maintain the viability of donated hearts for days and possibly weeks.
And Dalton researchers Luis Martinez-Lemus, and Christopher Foote, an instructor of biochemistry, have developed a new therapeutic for the treatment and prevention of cardiovascular disease. Both innovations are available for licensing through MU’s Technology Advancement Office.
For more information on shared resources, multidisciplinary research opportunities and academic events at Dalton, please contact Dr. Mike Hill at email@example.com.