Yale News

Three Yale professors received $1.5 million through the coveted 2022 New Innovator Award by the NIH’s High Risk-High Reward Program, which provides funding for high-impact, visionary undertakings in the biomedical, behavioral and social sciences. 

Luisa Escobar-Hoyos and Berna Sozen, assistant professors at the School of Medicine, and Nathan Grubaugh, associate professor at the School of Public Health, were each given this award to pursue projects that have the potential to redefine the future of research in pancreatic cancer, embryonic development and genomic epidemiology. 

All three professors expressed gratitude for the efforts of the researchers in their labs. Escobar-Hoyos further encouraged all scientists to take intellectual risks, in line with the spirit of the award.

“For scientists like me, or a junior […], you shouldn’t put too much pressure or prevention to your ideas,” Escobar-Hoyos said. “I think you need to think about them. Try them and see what happens because that’s the only way that you get to do this. […] Risks [are] important.”

Luisa Escobar-Hoyos: RNA and pancreatic cancer

Escobar-Hoyos, assistant professor in the department of therapeutic radiology at the School of Medicine, received a grant for two joint projects centered around antitumor immune response. For the first project, Escobar-Hoyos’s lab gathered preliminary data by observing RNA immune cells — specifically T cells — isolated from pancreatic cancer tumors. 

The group subsequently found that the splicing process, which transforms precursor messenger RNA into mature mRNA, was under great stress in these T cells.

“The [T cells] are not really processing these RNAs well, and they are impacting the function of proteins that are required for antitumoral immune response, so they have a splicing stress that is preventing them from being active,” Escobar-Hoyos said.

To unravel the mystery behind this irregular splicing process, the lab will use their own patented RNA-based therapy, called slicing hit oligo therapy, or SHOT, to reverse the defects and correct the protein’s function.

Escobar-Hoyos’s second project is based on data that originally defied expectations: while conducting preliminary research, the group found that when pancreatic cancer patients were previously infected by a pathogenic bacteria called Streptococcus pyogenes, their T cells were better equipped to kill tumor cells.

The surprising correlation between bacterial exposure and heightened antitumor response was due to striking similarities in certain sequences of keratin 17, a protein expressed in aggressive forms of pancreatic cancer, and M6, a protein found in the cell wall of the S. pyogenes.

“[This relationship represents] a phenomenon […] called antigen mimicry, which is the most fascinating thing that I’ve encountered through my career, which is that there are some proteins in the body that look like bacteria proteins,” Escobar-Hoyos said.

The T cells mistook the tumor cells for bacterial cells and, based upon the memory they had acquired against S. pyogenes, were better able to combat tumor cells. If successful, this project could revolutionize pancreatic cancer therapies, according to Escobar-Hoyos.

Escobar-Hoyos recalled that she “just couldn’t believe it” when opening the letter the NIH sent to award recipients.

“I’m originally born and raised in Columbia, South America, but my parents were here, and I had told them about this award,” Escobar-Hoyos said. “We were all tearful. For me, it was such a pleasure to be able to learn about this important news with my parents by my side because they have given everything to help my education when I was training, so to pay them with this news was a great feeling.”

Nathan Grubaugh: Dengue virus

Grubaugh proposed a project based upon the genomic evolution of dengue virus — a highly infectious, mosquito-borne disease that infects around 400 million people worldwide annually and primarily impacts lower-income communities in tropical regions.

“There are some really great efforts being made to help control dengue, especially with vaccination,” Grubaugh said. “But going along with those vaccinations, we don’t yet have the ability to monitor if there are different variants of dengue that are easier to control or less easy to control.”

Grubaugh is an associate professor in the department of epidemiology of microbial diseases at the School of Public Health.

With the NIH grant, Grubaugh plans to construct a global dengue virus genomic surveillance program that will allow him to track the rapid branching of dengue variants, based on data extracted from hotspots like Colombia and Puerto Rico. The program will adopt and generalize the COVID-19 surveillance framework that his lab developed during the height of the pandemic.

For the NIH project, Grubaugh’s lab will work closely with collaborators across the globe, including academic groups in the Dominican Republic and Jamaica, training them to use virus sequencing tools and host pilot trials in dengue-affected communities. The data will be gathered and processed in Grubaugh’s lab, with the goal of making an online viral surveillance platform accessible worldwide.

Grubaugh noted that part of his motivation comes from thinking about the far-reaching impacts of his research, especially in middle and lower-income communities.

“In a lot of situations, you have this cycle between the economy and disease: it’s hard to bolster the economy when the disease burden is so high, and it’s hard to relieve that disease burden when your economy is low. So thinking about these things that we can do to help with one aspect of it could have a huge positive effect throughout all of it,” Grubaugh said.

Berna Sozen: Stem cells and embryonic development

Sozen, an associate professor in the departments of genetics and reproductive sciences at the School of Medicine, plans to use stem cells — the cells from which all other cells in the body are derived — to study human embryonic development, a topic that originally piqued her interest when she was in college.

“I developed a fascination with embryogenesis during my undergraduate studies,” Sozen wrote in an email to the News. “How a single cell — the fertilized egg — evolves into a complex, multicellular organism allured me.”

Building upon her early research interests, Sozen will undertake a project to investigate an event in embryonic development called gastrulation, a critical juncture occurring fourteen days after fertilization during which the basic body plan is determined.

To study gastrulation, Sozen’s lab plans to advance existing in vitro embryonic stem cell model systems, which provide a viable alternative to unethical experiments performed on embryos within the uterus. With their model, the group will mimic cell fate decisions — how a cell develops into its final form — that occur in the womb, examining the impacts of genetic and environmental aberrations on the embryo.

“We hope to shed light on the unknown regulatory mechanisms by which the human body plan is created and the ways in which this can go awry, which will be critical for predicting the origins of human developmental pathologies and cancer,” Sozen wrote.

This year, 72 researchers from across the nation were presented with the Innovator Award.