Meet the winner of “America’s Got Regulatory Science Talent”

Corey Hoffman, a predoctoral student in the Medical Center, was the winner of the second annual “America’s Got Regulatory Science Talent” student competition held on Feb. 10 at the Clinical and Translational Science Institute. Hoffman will soon travel to Maryland to speak with the Food and Drug Administration about his project. This competition is organized by the University of Rochester Regulatory Science program, led by Joan Adamo, Ph.D. and Scott Steele, Ph.D. and held in conjunction with the Center for Excellence in Regulatory Science and Innovation at the University of Maryland.

Hoffman recently spoke with CTSI Stories.CoreyHoffman

Tell us a little bit about your proposal.

Right now, there are certain areas in regulatory science where the FDA wants to advance science, and within each area there are a few more specific focuses. The focus that stuck out to me is a clinical one that centers on personalized medicine, and looking for new types of biomarkers.

So what we want to know is: Is there something within the human body, a protein or DNA sequence that might be different in a healthy individual than someone who might be at a predisposition for a disease or who might have a disease. And how can we identify methods for finding these and then validating them?

Can you give an example of that?

There was one study on people with leukemia, and there was a small subset of patients that had a more aggressive disease and didn’t respond to chemotherapy. So the study was asking if there was something genetic that was different in those individuals, and it showed that there was indeed a commonality. So that was the example I used in the presentation.

What I’m proposing is to take advantage of all the clinical trials being done that are using sequencing like that, and put them all into a database. This could allow others to prevent redundancies in future trials and could be a reference point for future clinical studies or basic science studies.

Very cool. In a perfect world, what do you see as the potential outcomes from this type of database?

There are two potential outcomes that I could see. The first is that you could screen a patient’s genome, so that when patients do respond well in a trial, maybe there’s a genetic element that they share. Or, if there’s a commonality in people that don’t respond, then you could screen future patients ahead of time before you even offer the treatment. That way you wouldn’t have to put them through something if you knew ahead of time that they weren’t going to respond.

Secondly, certain individuals don’t respond well to certain drugs because of how their body metabolizes the drugs. This is determined by things called CYP genes, and certain people have mutations in these genes which affect how they respond to the drug. So you could screen people for mutations in their CYP gene to give indications for drug response, and who is and isn’t a good candidate for a certain drug.

Are there any challenges you see to developing a database like this?

I think the biggest concern before a database is ever constructed is protecting the patient health information of these genetic sequences, and I think that’s something that remains unexplored. There needs to be efforts that go into de-identifying the genomes. I’m not a geneticist, but it seems possible that a certain sequence of DNA could be unique to an individual that it could tell you who that person is. So, how can we take advantage of genetic information without putting any risk to the patients? And if these genome sequences are in the database, who has access? Those are two things that need to be considered.

 

Med Center Research Associate receives NSF grant to help fight Ebola

What if everyone in Nigeria had a smartphone with an app where they could input abnormal health symptoms? What if health care workers could monitor all the information in real time, and direct resources to people and places before an Ebola outbreak got out of control?

SolomonAbiola

Solomon Abiola, MS, is hoping to answer these questions, at least on a very small scale, in the next few months.

A research associate in the Medical Center, Abiola recently received a $130,000 grant from the National Science Foundation to develop a smartphone app that can track the symptoms of a population in real time. He leaves for Nigeria to begin implementing his idea in the next month.

The app works like this: A cellphone user living in a region with a dangerous epidemic downloads the program. Every morning, the app sends the person a series of questions about how they are feeling and prompts them to seek help if certain criteria are met.

“So a big component for Ebola was your temperature,” said Abiola. “The app could ask ‘Do you have a fever?’ and if you answered that your fever was 103, it would tell you to come in and get screened. That way you can get in front of a health care worker instead of waiting, which might cause you to spread your disease to your family or anyone else you encounter.”

The grant covers a field study with up to 200 participants. Health-related studies that track cellphone data in an attempt to map a population have been done before, said Abiola, but previous studies have been done retroactively, which can create legal issues and issues of informed consent.

“A lot of studies that use cellphones are doing it passively. They’ll look at the cellphone tower information or, after the fact, they’ll download a bunch of data from a carrier, which can create other obstacles because none of those users have given consent to use their data,” said Abiola, who collaborated with Henry Kautz, Ph.D., director of the Institute of Data Science, and Ray Dorsey, M.D., director of the Center for Human Experimental Therapeutics, on the grant.

“But through this, by downloading the app, you’ll be able to give informed consent, and the app will give health care providers real-time information.”

Though the Ebola crisis is one of the more pressing global health crisis he said that the app could potentially be used to track any future outbreak, or aid in current efforts to combat malaria and HIV/AIDS. In developing countries, where health care professionals are scarce, the app could be used to direct the limited health resources into regions that need it most. But in more developed countries, it could also be used as a form of telemedicine, allowing doctors to check in on patients who live in rural areas; or aid in tracking infectious diseases within the hospital system, such as MRSA and C. diff.

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.”

Director’s Update — February 2015

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

Below, Nana Bennett discusses the spring CTSI Seminar Series on population health, and the CTSI’s emphasis on this field of growing importance.NanaBennett

Tell me a little about why this topic is so important.

The United States spends more money per capita on healthcare than any country in the world, and yet our health outcomes are very poor relative to most other developed nations. Overall, it’s evident that we, as a country, have not done well improving the health of our residents.

The CTSI is increasingly focused on health improvement and the ways in which research can contribute directly to population health improvement.  We initially described this approach as  pillar of the CTSI, but increasingly we are viewing it as an overarching goal.  Through the CTSI seminars, we hope to give everyone an introduction to population health, which is a way of thinking about how to increase the health of all of our citizens by addressing certain key issues. The US government has set a triple aim: to improve health, improve health care, and reduce cost, and in order to do that, it’s becoming more and more critical for both health care systems and health research to embrace a population health approach.

Why is there such a gap between what we spend and our outcomes?

There are a number of reasons. First, our system is set up to treat individuals, rather than populations. This means we spend a lot of money on new technologies and expensive treatments for individual problems, rather than allocating resources to prevention which will help the population’s health improve.

Additionally, it’s currently believed that the health care a person receives only accounts for about 10 percent of the health of that person. Behaviors, meanwhile, account for 40 percent. So we spend a lot of money treating the consequences of some widespread problems, such as obesity and tobacco-use, which could be more efficiently dealt with by addressing behaviors on the front end.

Those are a few examples from the clinical enterprise. On the research side, we’ve always focused on basic science discovery and exciting technologies. However, we have not ensured that our research dollars support studies that address the most important determinants of health and can be quickly translated into health improvement for the population as a whole.

With that as a backdrop, what is the CTSI doing to address population health?

The CTSI is formulating ways to place population health at its forefront. We want everything we touch — whether it’s our pilot grants, our education and career development, our research support programs — to somehow be moving towards the goal of improving the population’s health. We want to make translation into clinical and community solutions our primary goal. And, of course, this lecture series will introduce key concepts of population health and population research. We want to give everyone a grounding in this work in the hopes that they will consider this paradigm as they pursue their own interests.  We do not want to, in any way, diminish the importance of basic science, but rather hope to articulate the road to its translation into better health.

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Previous director’s updates:

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.