Get More Out of Your CTSI Grant Applications

Junior Investigator Funding Pathways blog image
The CTSI is implementing a new forum this May to help junior investigators become independently funded. In addition, several “funding pathways” will be introduced that set a framework for investigators to revise their scientific proposals for KL2 Mentored Career Development and CTSI Pilot awards into proposals for K or R21 awards from the National Institutes of Health.

The twice monthly Research Methods Forum will focus on multidisciplinary research methods and will offer investigators the opportunity to share research ideas and receive constructive criticism from their peers. The forum is open to investigators of all ranks whether or not they are applying for CTSI funding. However, junior investigators will particularly benefit from the opportunity to interact with potential collaborators and receive thorough feedback on their proposed research early in project development.

Of course, the main goal and benefit of the forum is to help junior investigators obtain funding and progress to independence and the CTSI’s new funding pathways will facilitate this. The pathways guide investigators through a process to repurpose existing CTSI grant proposals for new funding opportunities. Timelines are also included in the pathways to ensure investigators don’t miss important submission deadlines. That means an investigator could submit a KL2 application in November, and use it for the base of a K08 or K23 application in February.

Funding pathways currently exist for both NIH K award-eligible and non-eligible investigators and both pathways encourage submission for NIH awards while the CTSI award applications are still under review. CTSI funding decisions will not be influenced by whether an investigator also applies for a NIH award.

Junior investigators interested in applying for funding through one of these pathways must present their research ideas at the Research Methods Forum at least 2-4 months prior to submitting their KL2 or CTSI Pilot award applications. Watch the CTSI weekly update for reminders about upcoming Forums.

To learn more about CTSI funding opportunities and pathways or the Research Methods Forum, contact researchhelp@urmc.rochester.edu.

Career growth

CTSI Pilot Program: Vitamin D metabolization in pregnant women

Eva Pressman, M.D., discusses her CTSI Pilot Project, Vitamin D Kinetics During Pregnancy.

Dr. Pressman is The Henry A. Thiede Professor and Chair of The Department of Obstetrics and Gynecology at The University of Rochester.

Video by Susanne Pritchard Pallo.


If you’d like to see your research featured in the CTSI blog, email Sean_Dobbin@urmc.rochester.edu.

Success Stories: Pilot Grants lead to R01, new business

Lisa DeLouise, Ph.D., M.P.D., associate professor of Dermatology, has received two Pilot Grants from the CTSI, each of which helped to support a line of research that blossomed into much more. She shared her experiences with CTSI Stories.

LisaDeLouise

Thanks for taking the time to chat! Tell us a little about the Pilot Grants you’ve gotten through the CTSI.

The first one I got was in 2007, and it was for nanoparticle skin research. I look at cosmetic products to see if they have efficacy and any unintended toxicity issues, and back in 2006, I got involved in the question of whether nanoparticles that are increasingly formulated into various topical cosmetic products have any of these side effects.

In sunscreens, for example, there are ingredients that can have unintended biological consequences, so I was looking at a couple compounds used in sunscreens – titanium oxide and zinc oxide – which absorb UV light so your skin is protected. When these compounds were first used, they were approved by the FDA at the micron level – so, relatively speaking, the particles were too large to seep through skin.

But in the 1990s, manufacturers learned to make the metal oxide particles on the nano-scale – 1,000 times smaller. Since it was the same elemental composition,  it didn’t have to go through rigorous FDA testing again, but scientists became concerned that the nano-sized particles might have different properties than the micron-level ones. Some compounds, for example, can become more optically and electrically active, or more likely to catalyze reactions that could cause oxidative stress in tissues

It seems like they might be more susceptible to being absorbed by skin.

Yes, that was also a concern – whether they could go through the skin barrier. So that’s what really launched my interest in this field of nanotoxicology, and I got some funding from the CTSI Pilot Program to look at this in the early going.

I was also questioning whether people with skin diseases – who tend to have defects in their skin barrier – could be more susceptible to penetration of these materials. So in collaboration with Lisa Beck, M.D., we made some of these comparisons.

What did you find?

Well, much of the research is still ongoing, because thanks in part to the early data gathered from the CTSI from 2007-2008, I was able to get an R01 grant in 2011. So I’m in my fourth year of that. But we do know that nanoparticles go through the skin and more easily through barrier impaired skin. The titanium dioxide has the tendency to conglomerate on the skin surface, so it loses it’s nanomaterial status. The zinc oxide, though, does get into the body, though it’s still unclear whether it’s penetrating the skin as nanoparticle or in another form such as a dissociated ions.

Very interesting. How about the second CTSI Pilot grant you received in 2011?

In 2011, the CTSI supported an application of microarray technology that allowed us to sort and enrich rare cells in the blood. The award was critical to fostering a collaboration between myself and James Kobie, Ph.D. We haven’t landed the R01 yet – we’re still trying – but the big success story is that the application of the technology has proven very positive.

In cancer, a lot of tumors are infiltrated with B-cells, which are antibody-making cells. So understanding the antibodies and other proteins secreted will help us understand the disease and why the B-cells are there sometimes and not there other times. Also, in cancer therapeutics, the field seems to be headed toward controlling the immune system and training it to fight the cancer in a more effective way.

So with the microarray technology, we were able to prove that you could look specifically at these human B-cells and their secretions. Earlier this year, we started a company named Nidus Biosciences to explore the potential of this technology. The CTSI is what really kept us going with momentum in that crucial early stage.

CTSI Trainee Pilot supports better understanding of lupus

by Samreen Jatana
Special to the CTSI Stories Blog

Lupus is a devastating disease that affects around 1 in 2,000 people in the U.S., and involves chronic inflammation and tissue damage in various organs including the skin, kidneys, and joints. Although the mortality rate for lupus has improved in recent decades, a diagnosis of lupus often means elevated risk of early mortality and lifetime of immunosuppressive therapy, which can carry significant side effects.

AnnaBirdAnna Bird wants to improve treatment options. Bird, who is currently working towards a doctorate within the Immunology/Microbiology (IMV) graduate program in the laboratory of Jennifer Anolik, M.D., Ph.D., was recently awarded a CTSI Trainee Pilot Grant to study the immunologic mechanisms underlying the autoimmune disease, systemic lupus erythematosus (SLE).

Improving treatment options requires the development of more specific, targeted therapeutic approaches. But to make those improvements, researchers require a better understanding of the factors driving lupus pathogenesis, a project that Bird seeks to contribute to in her graduate research.

Specifically, she is using the CTSI Trainee Pilot as an opportunity to define the mechanisms underlying pathology observed in an under-characterized tissue in lupus: the bone marrow. Bone marrow in lupus often produces functionally abnormal or inadequate numbers of immune cells, and is a site where tissue necrosis and bone thinning are commonly observed. Evidence is accumulating that dysregulated cell production by the marrow contributes directly to lupus pathogenesis in peripheral tissues, as well as the high rate of infection that lupus patients experience.

Although it is poorly understood why lupus patients show marrow abnormalities, the work funded by the CTSI Trainee Pilot seeks to illuminate the mechanisms driving lupus pathogenesis within the bone marrow.

The CTSI project focuses on the neutrophil as a likely contributor to pathology in lupus marrow. Neutrophils contribute to inflammation in peripheral tissues including the vasculature and kidneys, and have been identified as a source of dying cell material and type I interferon, as well as B lymphocyte proliferation factors that are known to be central in driving B lymphocyte reactivity against self-tissues in lupus. Neutrophils develop abnormally in lupus and may be acquiring premature effector function that is responsible for elevated cell death seen in lupus marrow.

“Ultimately, this project will both assess whether neutrophils contribute to pathology in the marrow, as well as identifying the mediators responsible for abnormal neutrophil development in lupus,” said Bird. “This Pilot has provided a great opportunity for a translational investigation, incorporating a highly novel characterization of human bone marrow in lupus in combination with a murine model, which will allow me to tease apart the mechanisms underlying neutrophil defects in lupus.”

The CTSI Trainee Pilot has also provided a platform for collaboration between researchers in Hematology/Oncology, Immunology/Microbiology and the CTSI, as well as a foundation for generation of preliminary data that Anna can use to apply for the NIH K mechanism for future post-doctoral studies.

Success Stories: Pilot Program furthers Thy1, diabetes research

The CTSI’s Pilot Program offers researchers the chance to compete for pilot grants up to $50,000. Sherry Spinelli, Ph.D., received one such award in 2014, and spoke with CTSI Stories about her research.

SherrySpinelli

Thanks for taking a minute to chat, Sherry. Tell us a little bit about yourself.

I’m a research associate professor in the Department of Pathology and Laboratory Medicine, working with Drs. Neil Blumberg in transfusion medicine and Richard Phipps in environmental medicine. My main research pursuit is the study of platelets and inflammation, and I have a keen interest in the role of platelets in pathological processes such as Type 2 Diabetes. And that research brought me to the CTSI. I wanted to develop a translational project looking at platelets and their role in type 2 diabetes and obesity, and the CTSI has provided the support and resources I needed to jumpstart this project.

What was the focus of the study?

I’m studying a protein called Thy1, which was originally identified as a surface marker of unknown function, but recently, Dr. Phipps and colleagues have shown that this protein plays an essential role in fat formation. So in layman’s terms, if Thy1 is lacking, you get fat, and if it’s present, you don’t get fat. An over simplification, but you get the idea.

Once that discovery was made, I wondered if this protein was found on platelets and further whether extracellular vesicles, small cellular fragments shed by platelets, contained Thy1 and could be taken up by other cells in the circulation to influence the recipient cell’s function. So if Thy1 is normally present on platelets and vesicles, what happens when it is not? We found that Thy1 levels are much lower in type 2 diabetic platelets and in the vesicles shed by these platelets.

So this was very exciting because we thought this might be a mechanism by which platelets could promote the chronic inflammation and obesity often associated with type 2 diabetes and cardiovascular problems.

Stepping back a little bit, what happens with Thy1 in a normal, healthy person?

In short, Thy1 expression is present in normal, healthy individuals, but we do not yet know what signals cells to lose Thy1. The funds from this CTSI pilot study have allowed us to begin to characterize the role of Thy1 in platelets and extracellular vesicles, and the consequences of the loss of Thy1 that lead to the disease state.

And from a clinical standpoint, the idea would be to alter the biology so that doesn’t happen?

Yes. Hopefully in the future, we’ll develop a therapeutic that would allow us to regulate or restore levels of Thy1, with the goal of reducing obesity. This is an important consideration as there are over 25 million diagnosed type 2 diabetics in the United States, and it’s an escalating problem.

We also feel Thy1 might be a good biomarker. We haven’t looked at this yet, but it might be the case that Thy1 expression is lost before you see other symptoms of diabetes. So perhaps it could be a flag we can use for early diagnosis.

What’s the next step?

So the pilot grant was wonderful in terms of allowing us to get that early data to go forward and get more funding. We’re also getting ready to publish a paper, which, of course, is key to getting a larger grant.

Success Stories: Trainee Pilot Program helps launch a career

The CTSI’s Trainee Pilot program offers aspiring researchers the chance to compete for a 1-year grant of up to $25,000. Courtney Jones, Ph.D., received one such award in 2012, and spoke with CTSI Stories about how the subsequent research helped shape her career.

Courtney Jones, Ph.D.

Courtney Jones, Ph.D.

Tell us a little about your research.

My dissertation centered on risk stratification of older adults with injuries. Certain hospitals, like Strong Memorial, are designated trauma centers that have specialized resources for the care of injured patients, and when we’re making a decision on where to send a patient, we want to make sure we choose the correct facility. We don’t want to send every injured patient to a designated trauma center, because then those centers may become overwhelmed. And we don’t want to send patients who are at high risk to a community hospital because they might not have the necessary resources to care for that person.

So when the ambulance arrives on the scene, it’s really about identifying where a patient should be transported. Previous research has shown that older adults are less likely to receive trauma center care than their younger counterparts, even if they have similar injuries. We really didn’t know why that was the case.

How did you come to work with the CTSI?

I was a Ph.D. student in epidemiology when I looked into the Trainee Pilot program, and it seemed really aligned with what I was doing because my research is very translational — it has the potential to really impact patient care. So the study that I proposed to the CTSI was to evaluate two hypothesized mechanisms that we thought were at play.

First, we knew there was this age based disparity in who receives trauma center care. There are national guidelines that EMS providers follow that outline things like systolic blood pressure, respiratory rate, and how the injury occurred — was it a high speed motor vehicle crash, or did they fall off a roof, for example — that determine where a patient should be transported.

The national guidelines are structured toward the most severely injured patients — the high-risk motor vehicle crashes, falls off a roof, the incidents that you might think about being on the 5:00 news. But in older adults, we know that even a simple fall can result in a pretty high risk of mortality and the need for substantial medical resources. So we’ve hypothesized that those guidelines just don’t work as well at identifying who is high risk.

We also evaluated this phenomenon where EMS providers might perceive older adults differently. There was some preliminary research done on the west coast that Identified potential reasons why older adults are more likely to be undertriaged – our goal was expand upon this previous research.

Very interesting. Can you describe your methods?

We created a quantitative survey that we administered to 600 EMS providers across the region, and we used a factorial survey method. We presented the EMS provider with a clinical scenario with different random patient characteristics. So one provider might get a vignette with a younger adult in a motor vehicle crash who had normal systolic blood pressure. And another EMS provider would have a different patient and scenario. And we’d ask: Would you take this patient to a trauma center? Then we analyzed the statistics and evaluated how they incorporated age into their decision.

The CTSI was great because it provided us the funds to do this complex, novel study in which we evaluated multiple components of decision-making, and it especially helped in recruiting the local providers to participate in the focus groups. We were able to provide food and beverages at each of the focus groups, and we provided incentives for participation, and I don’t think I would’ve had the same success — recruiting 600 EMS providers from a fairly small region — without the incentives and the support of the CTSI.

Any results you’d like to share?

What we found in the preexisting dataset is that the national guidelines don’t work as well among older adults. The sensitivity — or the ability of the national guidelines to correctly identify severely injured older adults — for individuals less than age 55 is about 80 percent, but for people over age 70, it’s only about 52 percent. And there’s a statistically significant linear decrease in sensitivity as age increases.

So that’s quite remarkable when you think about it. It has huge implications, because if the protocol they’re using in the field doesn’t work as well among older adults, then that might explain why we see that older adults are less likely to see trauma center resources.

The focus groups and factorial surveys we did with EMS providers also generated some interesting data. We failed to find a statistically significant difference in trauma center decision making between age groups, but the protocol states that age greater than 55 should be a special consideration. So if they were following the guidelines explicitly, they should’ve been more likely to transport the older patients to the trauma center. But, in fact, we failed to find such a difference.

The surveys also generated some interesting responses, such as the notion that injuries are just expected among older adults — that grandmas just fall out of bed sometimes – and as a result these injuries may not elicit the same response from providers. So that’s interesting because it speaks to what the next steps might be. Do we need to educate EMS providers? Do we need to structure the guidelines differently such that there are separate guidelines for older and younger adults?

How has your research progressed since then?

After completing the CTSI award, my primary mentor, Manish Shah, M.D. and I applied for an NIH R03 which evaluated a similar research question. We also got a CDC U01 grant that aligned perfectly with our previous research— it was an RFA for field triage decision-making for older adults taking anti-coagulants and platelet inhibitors. So in the U01 application we put a whole section of preliminary data that was essentially the findings and methodology I used in the CTSI award.

I also used the data as the basis for my future research which I outlined in NIH loan repayment award application, where they pay a portion of your student debt for you, and that was fantastic.

Overall, the CTSI was great because it was a catalyst — it was enough seed money to really show this was a worthy topic, and we got some really exciting findings which put me on a trajectory to really make this my career. We have presented the findings at numerous conferences and have manuscripts in-press and under-review.

Also, I was a Ph.D. student at the time so it was a really great opportunity for me to be a PI, if you will, before I became a faculty member. Because as a student, that’s an experience that often gets overlooked. You’re focused on your coursework and writing your dissertation, but grants management is never really part of your education. So just learning about the budgeting and the paperwork you have to fill out, that was something very complementary to my education and was a piece I wouldn’t have received otherwise.

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.”