Director’s Update – March 2015

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors.

Below, newly appointed co-director Martin Zand introduces himself and discusses his interest in informatics and population-based research methods.MartinZand

Martin, you’re not totally new to the CTSI, but I’m sure some people are more familiar with you than others. Could you tell us a little about your background?

Certainly. I started out as a transplant nephrologist — a medical kidney doctor who takes care of people with kidney transplants — and my clinical practice has been taking care of folks who have complicated immune issues for kidney transplantation. My laboratory, meanwhile, studies B cells — which make the antibodies that respond to vaccines and can cause kidney rejection. We are interested in learning more about how that biology works, how the cells differentiate, how many you need to create a rejection episode, what the molecular signals are for vaccine responses, and so on.

The tools we use in the laboratory involve many of the same mathematical methods used in data mining, which is the process of looking at complex data sets to reveal relationships between elements. We then go back to the bench and try to figure how these relationships work to create an immune response. And the mathematics used for that are, at their root, some of the same mathematics used in social network analysis. I realized that about two and a half years ago after reading a humorous article about finding terrorists in a network — the example was Paul Revere as the central revolutionary in his network — and I became very interested in clinical problems and population health problems that could be studied with the same methods.

Very interesting. So that system approach is what appeals to you most now?

Well, I’ve had, for a very long time, an interest in what people call computational biology — mathematical and computer analysis of data, and creating models of biological systems. I’ve always been fascinated by these models, because they give us a way of understanding how nature works, and, sometimes, how naïve we can be as scientists in terms of our theories.

So let me explain that. When you model a biological system — whether it’s vaccine response or kidney transplant rejection or development of B cells or the healthcare outcomes of a population of people — you begin with an idea of how the world that you’re studying works.  The model you build forces you to create an image of that world. If your models are quantitative and predictive, they provide a reality test for your ideas. What is really interesting is that the models are most useful when they’re wrong, because it tells you that the way you thought the world works is not the way that it really does. It tells you that you’re missing something. And then you can go look for that something. If you’re lucky, you find something really interesting.

Can you give a real-world example of this type of system-wide work?

One of our projects is looking at patients who go to the ICU, then get better and recover and are discharged to a medical floor, but then come back to the ICU because they’ve gotten sicker again. People who have that kind of pattern have a rather high chance of dying during their hospitalization. So we took some of the same methods used to look at patterns of gene expression and applied to the hospital admission and transfer data, and lo and behold, two things popped out.

The first was that we could graphically identify the patterns of who was returning to the ICU. They were a small fraction of those admissions, but accounted for a very large portion of our cost per patient. We are now using informatics to ask what medical conditions they had, what was going on right before they went back to the ICU. We want to put together a risk profile, an early warning system, that would tell us “This person has a high probability of ending up back in the ICU.” Then we can try to change the outcome.  That’s exciting, because we may have a chance to use data to save lives.

The second, really amazing thing, was that we were able to create a map — a flux diagram — of all the transfers within the hospital between the different floors and units. That kind of diagram is used in basic science to look at how organisms metabolize things by looking at all the nutrients and chemicals that go into a system, and how they’re shunted to various chemical reactions and come out as products. It’s also the same mathematics that FedEx uses to figure out how many planes they need and how much they need to load in each one, and so on. So with this map of the hospital, one project we’re working on now is to say “OK, we’ve got flu season here, and we’re going to overload this part of the hospital. What other parts are going to get stressed, and how could we creatively move patients around to provide better care, shorter ER stay times, and better outcomes?” The beauty of these approaches is they look at things as systems. It’s not just one part. Everything is connected to everything else.

This type of science, systems analysis, is very exciting right now, and we have a chance to see the world as a connected network using these tools.  My health informatics group, the Rochester Center for Health Informatics, is collaborating with the Institute for Data Science at the University of Rochester and Tim Dye’s CTSI Informatics group on these types of projects. Rochester is exactly the place where we can do this work.

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Previous director’s updates:
February 2015 – Nana Bennett discusses the CTSI’s Seminar Series on population health.
January 2015 – Harriet Kitzman reflects on her time as a CTSI co-director.
December 2014  – Karl Kieburtz offers his takeaways from the CTSI all-hands retreat.
November 2014 – Nana Bennett speaks to the expansion of the role of the CTSI’s Community Advisory Council.
October 2014 – Harriet Kitzman discusses the science of team science.
September 2014 – Karl Kieburtz talks about why the CTSI is beefing up its informatics team.
August 2014 – Nana Bennett discusses the new Population Health pillar.
July 2014 – Harriet Kitzman offers her takeaways from the Mini Summer Research Institute.
June 2014 – Karl Kieburtz gives an overview of the CTSI’s six pillars.

ACTS membership benefits

If you’re reading this, it means that you — yes, YOU — are a member of the Association for Clinical and Translational Science (ACTS).

That’s because the CTSI recently purchased an institutional ACTS membership, meaning that all faculty, post-docs, fellows, and students in the University of Rochester can access the association’s member benefits. Read more about those benefits below:

Translational Science 2015

ACTS’s annual conference, Translational Science, takes place April 16-18 in Washington D.C. and membership includes a registration discount. The conference is rife with useful presentations for young investigators and trainees — such as how to write R, K, and F grants — but this year, ACTS is making a push to broaden the conference to more seasoned investigators, and highlighting more topics across the field of translational science.

“This year’s meeting provides a program geared toward all investigators. Everyone should walk away from the meeting having networked with colleagues and with thoughts of new ideas and plans,” said Bushra Rehman, executive director of ACTS.

View the full schedule of presentations.

E-newsletter

ACTS publishes a newsletter called ACTS Connection that highlights translational science news, advocacy news, grant opportunities, and other relevant information. Going forward, the plan is for the newsletter to be published biweekly, with alternating content in each edition, said Rehman. One edition would summarize the goings-on at ACTS — meetings, work sessions and so forth — and the next would feature news from ACTS membership institutions. Look for content from the CTSI to show up from time to time!

If you’d like to receive it in your inbox, visit the association’s website and click on the “register” link in the upper right hand corner. Select member type “ACTS Individual from Institutional Member.” Registration will also enable you to access the members-only sections of the site.

Special Interest Groups, CTS Journal and Advocacy

Members are allowed to join certain Special Interest Groups, which are currently being developed. Investigators receive a reduced rate for publishing their articles in CTS, the official journal of ACTS. And finally, the university’s institutional membership also supports advocacy on behalf of translational science, and helps to fund a lobbying effort to ensure that the CTSAs remain healthy going forward.

For more information on ACTS membership, visit the association’s homepage.

CTSI revamps leadership structure

The Clinical and Translational Science Institute has reorganized itself to broaden the range of expertise among the institute’s top leadership.

Karl Kieburtz, M.D., M.P.H., senior associate dean for clinical research at the School of Medicine and Dentistry, who has served as director of the CTSI since October 2013, has been joined by Nancy M. Bennett, M.D, M.S,., and Martin S. Zand, M.D., Ph.D., and the trio are serving as the Institute’s co-directors.

MartinZand

Martin S. Zand

KarlKieburtz

Karl Kieburtz

NanaBennett

Nancy M. Bennett

The leadership change became effective on January 1.

“Karl has enormous experience in clinical trials, Nana brings her community perspective and population health expertise, and Martin brings informatics and data science, as well as a basic science background,” said Stephen Dewhurst, Ph.D., vice dean for research at the School of Medicine and Dentistry. “So they have different clinical interests, research interests and expertise, and put together, they make an extraordinarily broad and effective leadership group.”

This team approach is becoming increasingly common within the Clinical and Translational Science Award network. In Rochester, the diverse skill sets of the three co-directors allows for CTSI leadership to encompass the research spectrum, starting with basic science discovery and continuing through clinical trials and implementation on the population level.

“It really does bridge the molecules to populations theme that we’re trying to express. And the truth is, no single person can bridge all that — it has to be a transdisciplinary, multidisciplinary effort,” said Kieburtz. “So we’re doing it the leadership level, and showing that you can lead an institute effectively with a team.”

For the past year, Bennett served as a CTSI co-director alongside Kieburtz and Harriet Kitzman, Ph.D., but in a more limited capacity. Now her role comes with increasing importance, as the CTSI recently placed a renewed emphasis on improving the health of the population as a whole.

“As we try to accentuate the theme of population health in the CTSI, the new leadership structure will make it much easier for me to contribute in a meaningful way,” said Bennett.

Zand, meanwhile, brings informatics expertise, paramount when it comes to analyzing the big data needed for impactful research into population health.

“We want to use data science to identify questions that we’re not asking and identify data we don’t yet have. This will allow us to be in that space of discovery,” said Zand. “That way, we can translate data into real clinical and community interventions that improve the health of a population as a whole.”

The new structure also fosters an environment that will allow the CTSI to more easily integrate with several other centers within the university. Kieburtz also has strong ties to the Center for Human Experimental Therapeutics, Bennett heads the Center for Community Health, and Zand is the director of the Rochester Center for Health Informatics and co-director of the Center for Biodefense Immune Modeling.

In terms of operations, Kieburtz will remain the CTSI’s liaison to university leadership and to the National Center for Advancing Translational Sciences (NCATS), while Bennett will be the main interface with the community through the Center for Community Health, and focus on overall CTSI strategy and developing the population health science theme for the CTSI.

Zand will take on integrating informatics activities throughout the Medical Center and the newly created Institute for Data Science, have responsibility for the CTSI’s day-to-day operations, and will lead the grant-writing process when NCATS releases its call for renewal applications.

CTSI Pilot Program: “Accidental discovery” leads to new direction for research

In the hopes of better understanding microRNA’s function, Craig Morrell, D.V.M., Ph.D., infected mice lacking microRNA 451 with malaria, thinking the missing microRNA would cause the mice to succumb more quickly.

Craig Morrell, D.V.M., Ph.D.

Craig Morrell, D.V.M., Ph.D.

Instead, they all got better.

“So like most things we do, it was an accidental discovery,” quipped Morrell, associate professor of medicine in the Aab Cardiovascular Research Institute.

The discovery led to an application for a CTSI Pilot Grant, which allowed Morrell and Lesley Chapman, a fifth year predoctoral student in the translational biomedical science program, to further their study of microRNA 451, which plays a role in T-cell proliferation.

Normally, when the body fights a disease, T-cells help to identify and respond to the invasive microbe.

“We thought that platelets stuck to the malaria-infected red blood cells would deliver the microRNA and slow down the parasite growth, so we expected the mice without that microRNA to have a higher number of parasites,” said Morrell. “But it turns out that the whole animal is much more complicated. Without that microRNA, they cleared the infection.”

Now, Morrell suspects that the microRNA blunts T-cell proliferation in some way. While this could potentially lead to an effective malaria treatment, Morrell thinks that developing such a treatment would mean encountering some tricky socioeconomic barriers along the way.

But the research could lead to breakthroughs in other areas. One potential example would be the use of microRNA 451 to reduce T-cell responses following organ transplant, where one of the primary complications is an immune response to the new organ.

“It was really your classic pilot project,” said Morrell. “The CTSI got us started with a nice sum of money to really support some preliminary data, and now we can get that publication we need to move things along.”