Chris Pastore, a 4^th-year graduate student mentored by Anner Sperling, PhD, is studying the lung’s healing processes. Treating mice with an immune protein, Interleukin 5 (IL5) after lung damage protects them against further injury. Pastore is investigating the lung epithelium, the cells lining the airways, and the lung immune cells themselves. “The F31 specifically focuses on B Cells in the lungs and how they respond to IL5,” explained Pastore. “The model I use is very broad, so it can be relevant in a lot of different contexts, including infection and smoking.” By using advanced genetic models, Pastore can compare lung and B cells with and without IL5 receptors, teasing out the difference between different immune processes.

The F31 will facilitate Pastore’s aspirations to continue in academic research. “I spent six years between undergrad and grad school, and those experiences have taught me that I really love the academic environment,” he said. An appointee to the Infectious Disease Training Program, Pastore credits part of his success to being exposed to new ways of thinking about problems. “Immunologists tend to think about entire systems, but infectious disease researchers think on much smaller scales, and sometimes that perspective opens up new lines of thinking for me.”

Rossymar “Ross” Rivera-Colón is engineering the immune system to better destroy cancerous tumors. Tumors produce adenosine, a compound that suppresses immune activity. By blocking adenosine, Rivera-Colón, mentored by Kristin Anderson, PhD, aims to improve the quality of treatment available to patients. “Adenosine suppression hasn’t been explored in ovarian cancer, and cellular therapies are ineffective. This could be a new combination therapy,” she explained.

For Rivera-Colón, writing the grant application was an opportunity to practice science communication skills. “I learned how to write a research plan and communicate my science to other scientists,” she said. Rivera-Colón noted training in science communication she received through the Cancer Research Training Program as an important element of her success in applying for funding.

Cara Hatzinger, a 4^th-year graduate student advised by Melanie Rutkowski, PhD, is studying the role of the gut microbiome in ovarian cancer. Specifically, she studies the importance of a receptor on the surface of cancer cells that responds only to the flagella that bacteria use to move. Removing this receptor in mice helps them survive cancer and respond better to immunotherapies. Hatzinger seeks to understand the mechanisms of this effect with the hopes of one day being able to develop a method to improve immunotherapies for cancer patients.

Hatzinger previously interned at Johnson & Johnson, working on immunotherapy development in the corporate sector, an experience that led her to Rutkowski’s team. “Everyone in this lab is very collaborative, technically and emotionally, and Melanie’s been such a great mentor,” said Hatzinger. “I’m honored that other scientist think this project is as cool as she and I do.”

Emily Grayson, supervised by Anne Sperling, PhD, studies environmental triggers for asthma. Her research took an interesting dimension when she noticed that her mouse models behaved differently depending on where the mice lived. She eventually traced the disparity to differences in the mouse gut microbiome, which was being influenced by the different buildings where the mice were housed. Mice from different facilities showed different populations of bacteria in their guts, which in turn affected their responses to allergens. “I hope that this work can help inform therapeutic interventions and advance our understanding of microbial influences on treatment strategies,” says Grayson. A member of the Immunology Training Program, Emily received guidance from a variety of mentors in preparing her application. Her success in this grant application mirrors her success in UVA’s Three-Minute Thesis Competition, further demonstrating her skills as a scientific communicator. “I have learned so much from the whole CIC community here at UVA, and I’m thankful to have their continued support to grow as a scientist and develop this project,” she says.

The award from the Lupus Research Alliance is a supplement to Zegarra-Ruiz’s existing award that will support a promising trainee’s career in lupus research. The recipient, Maricielo Vaella Alarcon, is a graduate student who had previously worked with Zegarra-Ruiz as a Lab Specialist. Alacron will study how typically harmless bacteria that “leak” through the gaps between cells in the gut can contribute to lupus development by promoting inflammation and activating the immune system around the body. Diet is an important factor in controlling against such leaks and will be an area of study for Vaella Alarcon.

 The second award, from the Lupus Foundation of America, is the Gina M. Finizi Memorial Student Summer Fellowship, awarded to Gillian McClennen. The award provides funding for research-related activities that will enhance McClennen’s work, such as additional training or conference travel.  

Respiratory infections, including influenza and COVID-19, are important conditions affecting approximately a billion people globally each year. Millions of these people will go on to develop severe illness requiring medical intervention, and according to the World Health Organization, hundreds of thousands of these patients will die as a result. Vaccines for the flu are readily available, but influenza viruses are particularly good at evading them. This is partly because vaccines train the immune system to recognize proteins on the viral surface, and influenzas mutate those proteins frequently, preventing a strong initial immune response to prevent illness. Another concern is that vaccines are administered via the blood, which generates a strong immune response in the circulating immune system—the immune cells residing in the bloodstream. However, respiratory viruses primarily infect the cells within the lung tissue, where the vaccine-induced immune response is weaker.

The structure of lung tissues makes them unique immune environments. The immune cells residing in lung tissues include a class of T cells that acts as first responders to viral infection. Interestingly, these cells remember the specific viruses they have encountered and can react against new infections, making them interesting targets for respiratory vaccinations. Li will comprehensively study their behavior to understand their broad protectivity with an eye towards developing vaccines that produce a strong response in lung tissues specifically.

Taylor is an expert in B cell biology, studying and engineering antibody-producing immune cells. His existing projects include understanding the immune system’s response to vaccination, targeting cancers with immune cells, and engineering white blood cells to protect against infectious disease. With the funding from the Pinn Scholar Award, Taylor will begin studying autoantibodies against cytokines.

In its normal functions, B cells will produce antibodies to identify foreign cells or substances. These marked cells and substances will be destroyed by other immune cells. When antibodies target the body’s own cells, autoimmune diseases follow, such as lupus, rheumatoid arthritis, and multiple sclerosis. In cases where antibodies target cytokines, immune signaling molecules, the body develops “blind spots” for certain illnesses, weakening an individual’s ability to fight them off. “This became really apparent during the COVID-19 pandemic,” said Taylor. “Researchers found that up to 20% of the people who died from COVID and 10% of those hospitalized produced antibodies against cytokines associated with protection against viral infections.” Taylor and his team will trace such antibodies back to their B cells of origin and identify what breakdown occurred in the body’s mechanisms that prevent the immune system from targeting itself.

The project is highly collaborative, using the COVID-19 biobank developed by UVA’s Judith Woodfolk, MD, PhD. The biobank contains samples from patients with autoantibodies, which the Taylor lab will use to study this condition. Additional samples will come from a COVID-19 biobank at the University of Washington, where Taylor was affiliated prior to joining the CIC. Finally, Taylor will work with Paul Nghiem, MD, PhD, at the University of Washington and Aaron Ring, MD, PhD, at Fred Hutchison Cancer Center to study the role of autoantibodies in Merkel Cell Carcinoma. “It’s a complex project, and the pieces have all fallen in place for what we think is going to be a really impactful study,” Taylor said.

In addition to his research, Taylor is also proud of his contributions to the scientific community through his service and mentorship. “In order to have scientific excellence, you need to have talented mentees to do the experiments and develop ideas beyond where the projects may have started. I’m proud that the people in my lab have gone on to do great things, including leading their own labs in academia and biotech. The same is true of service— I rely on my colleagues for feedback and collaborations that elevate us all and stimulate new ideas,” he explained. “If you take one of those pillars out, the whole system falls down.”

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.

Dr. McKee, mentored by CIC Co-Director Coleen McNamara, MD, is deeply involved in community engagement efforts both within UVA and beyond. She received her medical training at the University of Otago in New Zealand before pursuing a master’s degree in Immunology and Inflammatory Disease at the University of Glasgow, Scotland. While presenting to the approximately 40 high schoolers attending her talk, she used her experience in both clinical and research settings to help delineate the two perspectives. “Imagine a cliff,” Dr. McKee explained. “Clinical medicine is like an ambulance that treats people who fall off the edge. Research science tries to build a fence to stop people from falling in the first place, and there are pros and cons to each approach.” She also described her current research and the importance of being an advocate for science in a national climate increasingly skeptical of research.

Speaking at Monticello High School is Dr. McKee’s latest community engagement effort. She has also volunteered at events that brought middle schoolers to Grounds, UVA’s Discover Medicine program, and Charlottesville’s local Big Brothers Big Sisters chapter. Community service is one of Dr. McKee’s core values, having volunteered in international medical efforts and local programs throughout her professional and personal life.

Her efforts to bring UVA and the Charlottesville community together are already building new bridges. Dr. McKee’s Discover Medicine mentee attended her talk at Monticello High School. Another student who attended that talk subsequently sought out a clinical research rotation and will work at iPRIME this summer.

Community outreach and engagement is a core value of the CIC and its researchers. Students and faculty interested in additional outreach opportunities should contact Dr. Christos Baryiames.

Bryant and Erickson will investigate alpha-gal syndrome, a unique allergic condition that can develop following a tick bite. People with alpha-gal sensitivity can experience allergic reactions to foods such as beef, eggs, and milk. Erickson and his collaborators have also linked alpha-gal sensitivity to cardiovascular disease and atherosclerosis. Bryant plans to continue her career in biomedical research, bridging fundamental immunology and its application to human health. The Immunology Innovation Fellowship allows her to remain at UVA, join the CIC, and continue developing as an independent scientist – all while significantly advancing Erickson’s research program. Trained in human immunology, Bryant strengthens a growing area of focus in the Erickson Lab. Her expertise will enhance the team’s human sample collection and processing efforts, bring advanced biostatistical approaches to their analyses, and drive the incorporation of imaging mass cytometry for spatial proteomics analysis of the immune response to tick bites in skin. Little is known on how a tick bite can lead to the development of alpha-gal syndrome, so anything gained from Bryants’ work will greatly advance the field. “This project is extremely complex – technically, analytically, and logistically,” says Erickson. “Naomi brings strengths in all three areas. There’s no way I’d be able to do this without her”.

In turn, Erickson is providing Bryant with opportunities to expand her technical skill set, gain experience in mentoring, and build the foundation for an independent research career. Having focused on T cell immunology in her doctoral training, Bryant will now broaden her expertise to encompass other components of the immune system through her work on the alpha-gal project. “Through the Immunology Innovation Award, I have been given the opportunity to explore new areas of scientific research which leverage cutting edge technologies” says Bryant.

Fitzsimmons and Ewald are studying Toxoplasmosa gondii, a parasite that infects humans and causes chronic infections that last a lifetime. Ewald and coworkers have previously shown that nitric oxide synthetase (iNOS) plays an important role in controlling and clearing T. gondii infections. Fitzsimmons is an expert in how iNOS and nitric oxide can control bacterial infections, like Salmonella and Rocky Mountain Spotted Fever. His experience has allowed him to make an immediate positive impact in the lab. “For 30 years, we have known that nitric oxide shapes parasite biology,” Fitzsimmons explains. “No one knows how or why. Sarah’s and my expertise will allow us to answer those questions.”

“Liam is the one of the strongest postdocs my lab has seen,” says Ewald. “This award recognizes his excellence and will support his future grant and career opportunities.” Fitzsimmons looks forward to a career as an independent researcher and is using his time in the Ewald lab as an opportunity to build the skills he needs for his next career stage. He identifies factors including an independent research environment, mentorship opportunities, and a supportive mentor as making the Ewald lab an ideal fit.

Immunology Innovation Awards are available for postdocs mentored by CIC resident or advisory committee members on a rolling basis. Interested parties should contact Justin Taylor, PhD, for more information.

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