On every third Thursday of the month, Devil’s Krafthouse is host to Research on Tap: a series that gives Duke researchers, from undergraduates to postdoctoral fellows, the opportunity to present their work in a casual setting. It may seem odd for the procedures of academia to make their way into a space for socialization and entertainment, but this situation allows individuals to practice speaking publicly to a general audience under a short time limit–good conditions for developing their “research elevator pitch.” These were the pitches on October 17:
Jacqueline Trujillo, a Ph.D. student in the Department of Molecular Genetics and Microbiology, who is part of Dr. Edward Miao’s lab, presented her research on immune cell response to the bacterium Chromobacterium violaceum (Cv). Being an environmental pathogen, Cv usually resides in the soil of tropical and subtropical areas. While disease in humans is rare, the mortality rate is high in immunocompromised individuals.
“The Miao Lab was initially studying pyroptosis, a form of cell death that occurs during infection, when they discovered Cv-induced granulomas,” Trujillo said. Granulomas are specialized structures that are formed to contain and eradicate pathogens, but they can range in the arrangement and type of cells they consist of; one induced by tuberculosis infection, for example, would include adaptive immune cells like T and B cells. However, when the pathogen inducing them is Cv, only innate immune cells are present: neutrophils in the inner cluster and inflammatory macrophages in the outer cluster. When Cv is detected, neutrophils are the first to flock to the site of infection in a “toxic swarm.” The neutrophils themselves are typically able to effectively kill microbes even before granuloma formation. “These are one of the most toxic defending cell types in the immune system,” Trujillo said.
Despite this, the lab observed something unusual: these neutrophils failed to kill off the Cv bacteria, which continued to replicate despite the swarm. The lab ultimately saw Cv eliminated by the innate granulomas within about 21 days, but the ability to survive the neutrophils is what Trujillo now aims to understand. Such a feat from an environmental bacterium comes as a surprise, being “something more characteristic of the causative agent [Yersinia] of the bubonic plague,” Trujillo said. A comparison between the proteins CopH and YopH, virulence effectors in Cv and Yersinia respectively, reveals lots of similarities between the two. Trujillo hypothesizes that CopH is part of the secret to how Cv disarms the immune system’s defenses.
The role of virulence effectors is generally “aid[ing] in survival, invasion, and suppressing immune responses.” Through needle-like structures, bacteria inject these proteins into a host cell. A cell responds to this in two main ways. It dies–initiating pyroptosis to prevent the pathogen from replicating inside the cell. Second, it signals for help by making chemical messengers called inflammatory cytokines. Investigating the first response is what led the Miao Lab to Cv-induced granulomas.
Now, the lab is interested in understanding the regulatory signals that form the granuloma–and the role that inflammatory cytokines might play, if any. In addition to testing her hypothesis on CopH, Trujillo intends to determine if neutrophils respond to Cv’s initial survival by producing the cytokine IL-18, thus recruiting immune cells to the infection site. This would help the Miao Lab confirm their idea that the neutrophils’ failure to clear Cv is what prompts the process of granuloma formation.
With much still unknown in the area of granuloma biology, Cv provides an “excellent model for studying immune cell biology and characterizing bacterial virulence effectors,” Trujillo said.
Though it happens that many Research On Tap speakers are in the sciences, the program isn’t discipline-specific. Our second researcher of the evening, Sungil Kim, studies a far different field from Jacqueline.
As a Ph.D. student in Finance at the Fuqua School of Business, Kim is looking at the effects of a growing trend in recent years: private equity (PE) firms acquiring healthcare companies. His focus is on what’s known as the “buy-and-build”, as this business strategy is often used by such firms entering the healthcare sector. The scenario typically looks like this: a private equity firm first acquires a large existing company, called the platform company or “first deal.” They’ll then acquire several smaller companies, or “add-on deals,” in order to expand the platform company’s operations.
Since private equity firms buy businesses with the eventual goal of selling them at a profit, their primary focus is increasing efficiency to reduce costs. On one hand, these buyouts might be seen as beneficial for languishing businesses in need of operation enhancements. But within the healthcare sector, many worry the resultant cost-cutting will lead to declining standards of care for patients.
Kim set out to investigate if operational improvements are sustainable across multiple acquisitions within the buy-and-build framework. The simple answer? No.
Kim confirmed that, on average, private equity firms improve the operational performance of hospitals without hurting quality, “a finding that agrees with some of the previous literature.” Yet, one only needs to take a closer look into the sequence of deals to uncover a different, more complicated story.
To arrive at his answer, Kim considered three main factors–operational efficiency, profitability and quality–in both the platform company and add-on companies. Platforms, or first acquisitions, did see success in performance, but this came with what appears to be a trade-off, as the first two factors increased while quality went down. As in, quality of healthcare. From one of Kim’s graphs, it was apparent that occurrences of four of the six health outcomes measured, including mortality and remission of heart failure, increased in such first deal situations.
Meanwhile, results for the add-ons changed little before and after the buyout, meaning that the initial success from the platform didn’t carry over to later acquisitions, even as reduced costs did. A potential reason for this inability to replicate success, Kim explained, is that these cost savings may come from reducing the number of patients and services, instead of truly improving the efficiency of operations.
In contrast to academic journals that display research that’s been in the works for years, Research on Tap brings us closer to working papers in their ongoing, exploratory stages. While it’s difficult to draw wider conclusions from Kim’s findings just yet, and important to remember the specific first deal context of this study, research like his helps us further understand the issues facing improvement of our healthcare system and where private equity plays a role.
If you’re interested in learning something new and free Krafthouse bites, swing by and attend a session–the next one occurs on November 21, 2024 at 5 p.m. The program welcomes prospective speakers to place themselves on the waitlist for a spot.
