Center for Infectious Diseases Research takes aim at pediatric pathogens

At the beginning of the 20th century, 1 in 5 children under the age of 5 was killed by infectious diseases in the United States. Despite the advent of antibiotics and vaccines, microbial infections still account for 6 of the top 10 causes of death in children under 5 globally. According to The Lancet Global Health, the second leading cause of death among children under 5 is lower respiratory infections, and malaria and diarrheal diseases are the fourth and fifth leading causes, respectively.

Immunocompromised children, including the patients undergoing life-saving therapies at St. Jude, are especially susceptible to infections. The leading cause of treatment-related mortality in pediatric cancer patients is infections, and the rise of antimicrobial resistance is increasingly limiting treatment options for many bacterial and fungal pathogens. There is an urgent and unmet need in infectious biology research to combat resistance. In 2021, a study in The Lancet reported 4.71 million deaths were associated with resistant bacteria and, by 2050, that number could be as high as 8.22 million.

To address this, Victor Torres, PhD, Department of Host-Microbe Interactions chair, created the Center for Infectious Diseases Research (CIDR). “The solution against antimicrobial-resistant pathogens and against infectious diseases is not a simple one. We need a multidisciplinary approach to tackle the problem from different perspectives,” said Torres, who also serves as the Director of CIDR. The purpose of CIDR is to bring together the research community at St. Jude around the common goal of conducting world-class research in infectious diseases affecting children.

CIDR bridges infectious disease research across St. Jude

The development of novel therapeutics for infectious diseases is a complex endeavor for academic research institutions to tackle. According to Torres, it requires a combination of research focused on the development of antibiotics, vaccines and biologics, but he questions, “Who has the capacity to combine all those disciplines as a single lab or even as a single department?”

That was the impetus for creating CIDR within the unique St. Jude ecosystem. Torres found the perfect partner to carry forward this vision in Octavio Ramilo, MD, Department of Infectious Diseases chair.

“Using state-of-the-art technology in genomics, cell biology, structural biology, data sciences, chemistry and pharmacology, and by partnering with the Department of Infectious Diseases for clinical care, we’re able to unleash a framework that has not been done before,” said Torres.

With CIDR, Torres is bringing together people across departments with diverse backgrounds to create a community of individuals who want to prioritize infection research within St. Jude. Any St. Jude faculty member can join CIDR; in fact, there are currently 11 clinical and fundamental science departments across St. Jude with CIDR members.

Daniel Blair, PhD, Department of Chemical Biotechnology & Therapeutics, joined CIDR because he finds the best ideas come when you get lots of different people together. “We’re molecule makers, so we’re at the front lines of making the things that are functional, while others are on the front lines of what’s actually affecting people in the clinic,” he said. “Getting those two groups of people together is what allows you to pinpoint where you can be uniquely impactful.”

Peijun Ma, PhD, Department of Pharmacy & Pharmaceutical Sciences, shares a similar sentiment about why she joined CIDR. “CIDR provides a structure where basic scientists and clinicians are thinking about infectious diseases together,” she said. “A major long-term goal of my lab is to connect mechanistic insights to real patient outcomes.”

To spur new ideas and collaborations — and to get members out of their comfort zones — CIDR holds monthly update seminars. “It’s a great forum where you get feedback from people from many different disciplines,” said Torres. “We have faculty present out-of-the-box ideas and projects that they haven’t launched yet because they don’t have the expertise or they need extra help.”

Salvador Almagro-Moreno, PhD, joined the Department of Host-Microbe Interactions last year and has found the CIDR seminars to be a great way to learn about St. Jude research outside the department. “It’s infectious diseases from a more holistic standpoint. Every time I go to a CIDR meeting, I see one or two layers above the problem I’m focusing on,” said Almagro-Moreno.

For Stacey Schultz-Cherry, PhD, also of the Department of Host-Microbe Interactions and on the executive committee of CIDR, “the works in progress seminars have led to new collaborations with people in the Department of Structural Biology and have strengthened ongoing relationships with people in the Department of Surgery.”

CIDR membership also provides access to collaborative centers within Host-Microbe Interactions. These world-class centers provide “an extra workforce for CIDR projects and investigators to push their science forward,” said Torres. These include:

• Antibody Discovery Collaborative Center
• Microbial Metabolomics/Lipidomics Collaborative Center
• Microbial Biorepository Collaborative Center
• Microbial Computational Genomics Collaborative Center
• BSL2/3 Flow Cytometry Collaborative Center

CIDR funds collaborative science with therapeutic potential

More than just convening researchers, over the past two years, CIDR has funded 10 collaborative projects that cover a range of topics. “The funding framework is ideal for a foundational project where you could do one or two big experiments, and the success rate might be low, but if you succeed, the outcome could be massive,” said Torres.

For Almagro-Moreno, who studies the emerging bacterial pathogen Vibrio vulnificus, CIDR funding has been key for getting a labor-intensive project off the ground. “The question that we were trying to address is really fundamental, so it helps to have internal funding,” said Almagro Moreno. His project aims to identify V. vulnificus virulence factors that allow the bacterium to transition from its natural environment in warm coastal waters to a human host.

Developmental funding from CIDR has also allowed Blair to pursue resource-intensive ideas. “The catalytic support from CIDR to explore high-risk ideas has been helpful and impactful,” said Blair. His project aims to combat antimicrobial resistance by developing a high-throughput screening platform to identify new antimicrobial molecules. Blair is collaborating with Christoph Gorgulla, PhD, Department of Structural Biology, on the research. “We’ve already got a list of likely candidates, and now we’re just building up the chemical synthesis strategies and tools that will let us figure out which are the best ones,” said Blair.

In line with Blair’s project, a project proposed by Schultz-Cherry and Andrew Davidoff, MD, Department of Surgery chair, also aims to develop novel monoclonal antibodies for influenza. This builds off previous collaborative work to create a new influenza vaccine.

In addition to helping get promising research off the ground, CIDR is also facilitating the bench-to-bedside pipeline that is a hallmark of the St. Jude approach. “We can identify the problems that matter most to the doctors at St. Jude and bring them into the lab to generate potential lifesaving treatments and preventives,” said Torres.

For example, through CIDR support, Ma is studying why antibiotic treatment sometimes does not work. To do so, she is working with Josh Wolf, PhD, MBBS, Department of Infectious Diseases, and Randall Hayden, MD, and Heather Glasgow, PhD, both of the Department of Pathology, extending the work into patient-derived strains and clinically relevant contexts. “These interactions have been essential for defining clinically meaningful questions and for accessing samples that allow us to test mechanistic hypotheses in real-world contexts,” Ma said.

A vision for collaboration and progress

As CIDR continues to grow and evolve, Torres hopes to measure the Center’s success in the generation of new antibiotics, vaccines and biologics. “At St. Jude, we’re all about generating knowledge. We’re all about tackling catastrophic diseases, and there is no catastrophic disease with a bigger impact than infectious diseases,” said Torres. “I want to use CIDR as the vehicle to translate fundamental findings into actionable therapies or preventives. That’s my goal and vision for this new Center.”