PROVIDENCE – Last week, Women & Infants Hospital and Rhode Island Hospital received more than $10 million in combined new federal research funding, through the National Institutes for Health’s Center of Biomedical Research Excellence, or COBRE.

[Gov. Gina Raimondo and Stefan Pryor, CommerceRI czar, please take note: the $250 million-a-year research engine driving Rhode Island’s biomedical industry cluster is alive and well – and prospering.]

Both hospitals received Phase Three awards, focused on supporting the future sustainability of the research centers.

The COBRE awards are an integral part of NIH’s efforts to build research capacity in states that historically have had low levels of NIH funding. The research awards support basic, clinical and translational research, faculty development and infrastructure improvements.

The first Phase Three award, for nearly $5 million, announced on June 3, was an Institutional Development Award for Women & Infants Hospital and its Center for Perinatal Biology, the only COBRE in the nation specifically focused on developmental research.

The second Phase Three award, for $5.8 million, announced on June 5, was another Institutional Development Award for Rhode Island Hospital’s Center for Cancer Research Development. [A news conference was held that day where that award was hyped by Rhode Island’s congressional delegation.]

What the news media missed, however, was the salient fact that the principal leaders of the two research centers – Dr. James Padbury, pediatrician-in-chief, chief of Neonatal/Perinatal Medicine at Women & Infants Hospital and professor of Pediatrics at the Alpert Medical School at Brown University, Surenda Sharma, Ph.D., a researcher scientist at Women & Infants and also a professor of Pediatrics at Brown, and Dr. Bharat Ramratnam, director of the Center for Cancer Research Development at Rhode Island Hospital, an attending physician at Miriam and Rhode Island hospitals, and an associate professor of Medicine at Brown – see themselves as colleagues and collaborators, not competitors, according to Padbury.

“We have similar stories,” Padbury told ConvergenceRI, describing the two COBRE centers that received Phase Three awards in the same week. “We work together; we help each other's programs, we review each other’s pilot programs.” In turn, Padbury urged ConvergenceRI to call and interview Ramratnam, providing the direct telephone number. [ConvergenceRI did follow up, but had not received a response by the newsletter deadline.]

That reality of collaboration, not competition, between the top doctors and researchers at Rhode Island’s two largest hospital systems, Care New England and Lifespan, at the cutting-edge of perinatal biology and cancer research, speaks volumes about the culture change now underway in Rhode Island’s innovation ecosystem.

Voracious intellectual appetite
ConvergenceRI took advantage of the COBRE Phase Three award announcement to talk with Padbury, who had spoken with ConvergenceRI a year ago. [See link below to ConvergenceRI story.]

Padbury spoke at length about the work supported by the COBRE funding in Sharma’s laboratory, and what have been described as “novel new insights” into the pregnancy disorder known as pre-eclampsia, or pregnancy-induced hypertension.

The research has demonstrated that the disorder originates as a result of the misfolding of a protein, transthyretin; further, there appear to be mechanistic similarities between the pre-eclampsia and Alzheimer’s disease.

Work is underway to develop a rapid diagnostic test to confirm pre-eclampsia earlier in pregnancy.

“I have a voracious appetite, including things that I’m not working on directly,” Padbury told ConvergenceRI. But the Phase Three award, he continued, is part of a trajectory, really focused around perinatal biology, building the future sustainability of the center.

Given Padbury’s intellectual appetite, ConvergenceRI began the interview on a tangential note, asking about a new study published in Nature that identified, for the first time, the existence of a lymphatic system in the brain.

ConvergenceRI: Congratulations on your new COBRE award. Did you happen to see the recent study published in Nature about the existence of a lymphatic system in the brain, in the meninges, the tissue that surrounds the brain? The authors say that now, all the textbooks will have to be rewritten?
PADBURY: Not yet. Can you send it to me?

ConvergenceRI: Be happy to. Can you describe the importance of the new award and what it means to the Perinatal Biology Center, and for Rhode Island?
PADBURY: This is an IDeA grant, an Institutional Development Award. Only certain states are allowed to apply, and Rhode Island is one of 23 of these. This is the third in a series of grants for the Center of Biomedical Research Excellence in Perinatal Biology.

Bharat Ramratnam, director of the Center for Cancer Research Development at Rhode Island Hospital, also just got a Phase Three award.

Rhode Island currently has eight COBRE research centers, which is really spectacular.

From the perspective of the emerging Rhode Island context, consider how extraordinary these awards have been in bringing resources, supporting research laboratories, and sponsoring young investigators.

The COBRE mandate is to create something sustainable that wasn’t there before, to promote biomedical research, and to enable young investigators to become established.

In Phase One awards, only young investigators are funded; in Phase Two awards, there is funding for some established investigators. In Phase Three, the [goal] is to finish creating the essence of what you’re trying to build – a center, an institute, a new department.

[Through the COBRE grants], we have created a research institute for perinatal biology, we have an energetic environment and can support investigations beyond in perinatal development; we’ve accomplished that.

The latest award allows for a last phase of sustainability – one-third goes toward administration, [another third] goes to molecular biologic imaging, and the rest to small pilot program grants.

[The Phase Three award] will enable us to upgrade and replenish our equipment, to replace our laptops, to [acquire] a new consul microscope.

ConvergenceRI: Can you talk about the significance of the identification of the protein involved with the hypertension disorder in pregnant women and its potential relationship to Alzheimer’s disease?
PADBURY: We screened serum from women with severe cases of pre-eclampsia and from women with normal pregnancies. Through proteomics, we identified a protein, transthyretin – which had been altered, it was misfolded. It couldn’t carry out its main biological function to cargo [other] proteins around and scavenge some of the bad actors.

[As a result], when transthyretin is misfolded, it precipitates cellular injury.

[Research has shown that] the misfolded protein is a player not only in Alzerheimer’s disease, but in other neurodegenerative diseases.

We went over to the memory clinic at Lifespan, and we got some serum from Alzheimer’s patients, and in about a third of the samples [tested], it induced pre-eclampsia.

ConvergenceRI: Are you working on a rapid test for pregnancy-induced hypertension?
PADBURY: We’ve published, we can identify [pre-eclampsia] at 12 weeks of pregnancy. That’s really important from a translational medicine standpoint, for interventions, drug trials. [By using recombinant techniques], we [believe] can reverse the effects of the misfolded protein.

ConvergenceRI: There is work underway in Rhode Island to focus on the phenomena of toxic stress, adverse experiences that cause trauma to the developing brain, and to develop a diagnosis for screening, treatment and referral. Should your research become part of the conversation?
PADBURY: When we as research scientists talk about stress, the things under our immediate consideration are cellular stress, and environmental stress from pesticides.

Others may think of toxic stress as emotionality and life circumstances.

We see this as a secondary confounder; we don’t see that it is a primary indicator.

There is an entire field of research, called psycho-neural endocrinology, with its own journal and academic departments, which is exactly in that wheelhouse.

ConvergenceRI: It terms of moving from the laboratory to clinical applications in the market, are there potential partnerships in the works regarding the center’s work with the misfolded protein?
PADBURY: We’ve been in conversations, I can’t say more than that, with commercial entities. We need to further enhance the research.

ConvergenceRI: What are some of the other research being conducted at the Perinatal Biology research center?
PADBURY: We’re looking at how signal pathways inform the mechanics of cardiac development. We’re investigating, using stem cell models, the signal pathways for cardiac injury, in the high level of cell proliferation in fetal and newborn development. We have developed some valuable insights into myocardial infarction.