Cara Hatzinger from Rutkowski Lab just received an F31, Investigating the role of TLR5 signaling as a modulator of FLT3 ligand therapeutic efficacy for the treatment of ovarian cancer.

Ovarian cancer is the most fatal gynecological malignancy with most patients developing therapy resistance and recurrence, highlighting the need for more effective therapies. Patients bearing ovarian tumors infiltrated with high frequencies of T cells experience significantly enhanced survival, suggesting the potential for immune therapies. Despite this, therapies such as PD- L1/PD-1 blockade are largely ineffective for ovarian cancer. Because cross presenting cDC1s are fundamental in orchestrating anti-tumor immunity and response to immune therapy, expansion of this immune subset via the DC growth factor fms-like tyrosine kinase receptor 3 ligand (FLT3L) is an attractive strategy for enhancing immune therapy response. Unfortunately, FLT3L therapy has been largely ineffective in clinical trials, with mechanisms leading to the failure unknown. Here, we demonstrate that toll like receptor 5 (TLR5) signaling, the only known ligand for which is bacterial flagellin, mediates failure of FLT3L therapy. Culture of bone marrow cells with FLT3L during chronic exposure to bacterial flagellin promoted differentiation of cDCs away from mature functional cDC1s towards immature monocytes and macrophages expressing high-levels of PD- L1 and having a reduced ability to activate CD8 T cells. Importantly, in vivo expansion of cDC1s using FLT3L therapy in combination with PD-L1 blockade achieved long-term survival in 80% of TLR5 KO mice bearing aggressive orthotopic ovarian tumors. No survival benefit was observed in wild-type mice. These data suggest that TLR5 signaling is orchestrating the failure of FLT3L therapy by driving accumulation of immunosuppressive myeloid cells at the expense of mature cross-presenting cDC1s.

To watch more Research in Motion videos in this series, visit the School of Medicine website research landing page

A major new federal grant is set to advance research into respiratory immunity at the University of Virginia, where Harrison Distinguished Teaching Professor Jie Sun, PhD, has been awarded a $3.8 million from the National Institutes of Health.

The funding supports a five-year project titled “Decoding Cellular Networks Governing Respiratory Mucosal IgA Immunity,” aimed at uncovering how the body builds immune defenses in the respiratory tract following infection or vaccination.

Sun, who serves in the Department of Medicine’s Division of Infectious Diseases and International Health and Co-Directs the Beirne B. Carter Center for Immunology Research, said the work targets a critical gap in current immunology.

“Despite advances in vaccines and therapeutics, we still lack a clear understanding of how strong mucosal immunity—especially IgA responses—is generated in the respiratory system,” Sun said. “That knowledge is essential for designing the next generation of vaccines.”

Addressing a Key Immunity Gap
Respiratory mucosal immunity, particularly involving immunoglobulin A (IgA), plays a frontline role in defending against airborne pathogens. However, the biological mechanisms that drive robust IgA responses after infection or vaccination remain poorly understood.

This gap has become increasingly important in the wake of evolving respiratory viruses such as COVID-19 and its variants, where improved mucosal protection could significantly reduce transmission and severity.

The NIH-funded R01 project is built around the central hypothesis that effective respiratory immunity depends on localized interactions among pulmonary macrophages, CD4 T cells, and B cells within the lungs and airways.

Three Research Aims
The study will pursue three major objectives:

• Identify how respiratory CD4+ T cells promote IgA production directly within lung tissues.
• Examine how TGFβ-dependent interactions between macrophages and B cells regulate mucosal IgA responses.
• Define the molecular and functional characteristics of cross-reactive IgA-producing B cells that can respond to multiple respiratory pathogens.

Researchers believe these insights could pave the way for vaccines that provide stronger, longer-lasting protection at the site where infections begin.

Collaborative Effort
The project brings together a multidisciplinary team across UVA. Collaborators include:

• In Su Cheon, PhD, Division of Infectious Diseases and International Health
• Chongzhi Zang, PhD, Department of Genome Sciences
• Justin Taylor, PhD, Division of Infectious Diseases and International Health

Implications for Future Vaccines
By decoding the cellular networks that drive mucosal immunity, the research could inform the development of next-generation vaccines designed not only to prevent severe illness but also to block infection at the point of entry.

Such advances may prove critical in combating emerging respiratory threats, including new variants of SARS-CoV-2 and other airborne pathogens.

“This work has the potential to reshape how we approach vaccine design,” Sun said. “Ultimately, our goal is to enhance protection at the mucosal level and strengthen public health defenses against respiratory diseases.”

See link for full details: https://www.immunology.virginia.edu/event/the-annual-meeting-of-the-aai-located-in-boston-ma/

2026 AAI Meeting Website: https://immunology2026.aai.org/

Look for these CIC members at the 2026 AAI meeting presenting their research.

A vibrant exchange of scientific discovery and potential strategic collaboration took place February 23–24, 2026 at the University of Virginia, as researchers from AstraZeneca met with faculty from across the School of Medicine. 

The Robert M. Berne Cardiovascular Research Center and the Beirne B. Carter Center for Immunology Research hosted the two-day event, that brought together members of AstraZeneca’s Cardiovascular, Renal and Metabolism (CVRM) team, alongside its Respiratory & Immunology (R&I) team — including representatives from the company’s Open Innovation and Corporate Affairs teams— with UVA investigators and leadership from the School of Medicine (SOM) and the Office of the Vice President for Research (VPR). 

Strong Institutional Engagement 

The meetings reflected deep engagement on both sides. More than 60 UVA faculty laboratories submitted one-page proposals outlining innovative research programs and potential areas for collaboration with AstraZeneca. Following review, 33 labs were selected to present their science and participate in focused discussions about how future collaborations could be structured to accelerate discovery and therapeutic development. 

The breadth of science represented underscored UVA’s strengths across cardiovascular, renal, metabolic, respiratory, and immunologic research. Topics ranged from inflammatory drivers of cardiometabolic disease and immune-mediated tissue injury to biomarker discovery, advanced human model systems, translational data science, and novel therapeutic targets. 

UVA School of Medicine and Office of Research leadership were in attendance throughout the program, signaling institutional commitment to fostering high-impact academic–industry partnerships and supporting pathways that move discovery from bench to bedside. 

Science at the Interface of Disciplines 

A recurring theme of the meetings was the growing intersection between immune biology and cardiometabolic disease. Investigators from across the school of medicine highlighted advances in heart failure, vascular biology, thrombosis, and metabolic regulation. Other colleagues presented cutting-edge work in immune signaling, inflammation, host defense, and tissue homeostasis. 

AstraZeneca scientists engaged deeply with presenters, exploring how UVA’s mechanistic discoveries could align with the company’s global capabilities in drug development, translational medicine, and clinical trials. The presence of AstraZeneca’s Open Innovation Team created opportunities to discuss flexible partnership models, while Corporate Strategy leaders examined long-term alignment and portfolio integration. 

From Dialogue to Discovery 

The format emphasized interaction. Following each presentation, robust scientific discussion focused not only on experimental findings but also on practical next steps — from target validation and preclinical modeling to biomarker strategy and patient stratification. 

Networking sessions and smaller breakout meetings allowed faculty and AstraZeneca representatives to explore specific collaboration concepts in greater depth. Conversations centered on building sustainable connections designed to generate new discoveries and ultimately improve outcomes for patients worldwide. 

With strong participation, engaged institutional leadership, and cross-disciplinary scientific exchange, the February gathering marked an important milestone in strengthening ties between UVA and AstraZeneca. Participants left with a shared sense of momentum — and a commitment to advancing innovative science through collaboration in service of global patient care.

Link to Article on the UVA Research Website

Harrison Distinguished Teaching Professor of Medicine Jie Sun, PhD, in the UVA Beirne B. Carter Center for Immunology Research and the Department of Medicine’s Division of Infectious Diseases and International Health, has secured two new five-year NIH R01 awards totaling $6.2 million. Dr. Sun’s projects aim to unravel why some people, especially older adults, never fully bounce back after severe respiratory infections such as COVID-19 or influenza and to develop strategies that restore healthy lung function.

The first grant, funded by the National Institute of Allergy and Infectious Diseases, focuses on the lingering lung problems that plague many “long-COVID” patients. Dr. Sun’s team has discovered that an immune alarm signal called interferon-gamma can remain switched on after the virus is gone, prompting a prolonged conversation between lung-resident T cells and macrophages that fuels scarring. Over the next five years, the researchers will pinpoint exactly how interferon-gamma from T cells sparks this chronic inflammation, test whether blocking its partner pathway (STAT1) in macrophages prevents long-term damage, and chart the entire molecular chain in search of drug targets.

The ultimate goal is to lay the groundwork for therapies that can stop, or even reverse, persistent lung injury after COVID-19 or other severe respiratory viral infections, common in the elderly.  -Jie Sun

The second award, from the National Institute on Aging, tackles a different piece of the puzzle: why older lungs heal more slowly after infections. Alveolar macrophages, the lungs’ resident cleanup crew, normally self-renew and calm inflammation, but with age they lose this “stem-like” vitality and adopt a senescent, inflammatory profile. Dr. Sun’s lab has shown that two key proteins act like a molecular seesaw that determines whether these cells repair tissue or exacerbate damage. The new study will decode how that balance is lost during aging, explore the consequences for influenza and COVID-19 recovery, and test an inhaled RNA therapy approach that delivers key proteins to rejuvenate macrophages and speed healing in older adults.

“Together, these complementary projects approach the same public health challenge from different angles to help ensure full recovery after infections,” said Dr. Sun.

By clarifying the immune circuits that derail healing and piloting targeted interventions, Dr. Sun and his collaborators at UVA and the Mayo Clinic aim to pave the way for precision therapies that let patients breathe easier long after the virus has cleared, while training the next generation of scientists in cutting-edge immunology and aging research.

View the article at the SOM website

The Recognition Award for Scientific Accomplishments recognizes outstanding scientific research contributions in basic or clinical arenas to enhance the understanding, prevention and treatment of respiratory disease, critical illness, or sleep disorders and recognizes exemplary professionalism, collegiality and citizenship through mentorship and scientific involvement in the ATS community. Awardees are selected based on contributions made throughout their careers or for major contributions made at a particular point in their careers.

The American Thoracic Society improves global health by advancing research, patient care, and public health in pulmonary disease, critical illness, and sleep disorders. Founded in 1905 to combat TB, the ATS has grown to tackle asthma, COPD, lung cancer, sepsis, acute respiratory distress, and sleep apnea, among other diseases.

2025 AAI Meeting Website: https://immunology2025.aai.org/

2025 AAI Meeting CIC Gallery:

See link for full details: https://www.immunology.virginia.edu/event/the-annual-meeting-of-the-aai-located-in-honolulu-hawaii/

2025 AAI Meeting Website: https://immunology2025.aai.org/

Look for these CIC members at the 2025 AAI meeting presenting their research.

I study B cells, which are part of the immune system, which make antibodies that recognize pathogens and protect us against infections. —Loren Erickson, PhD, Associate Professor, Department of Microbiology, Immunology, and Cancer Biology

To watch more Research in Motion videos in this series, visit the School of Medicine website research landing page