That work will continue and expand at UofL thanks to $11.5 million in new funding from the National Institutes of Health. The funding will support continuing research in the CCII to investigate therapies that activate the immune system against cancer and to train the next generation of cancer researchers and oncologists.

Since its launch, the CCII has helped four young researchers obtain independent federal funding and doubled the immune-oncology faculty at UofL from 10 to 20 members. The center’s faculty and research facilities also support highly successful clinical trial program.

“The power and impact of our clinical and translational research in cancer immunotherapy are undeniable. This work provides hope for people facing a cancer diagnosis,” said UofL President Gerry Bradley. “I am grateful to our researchers and clinicians who devote their careers to advancing innovative therapies that benefit cancer patients in Kentucky and beyond and I am excited to see what the next phase brings.”   

The CCII was created with an initial five-year Center of Biomedical Research Excellence (CoBRE) grant of $11.5 million in 2020. The new $11.5 million CoBRE grant announced today will support the center’s work for an additional five years.

An essential component of the CCII’s mission is translating research into the clinical realm, making UofL Health an essential part of its work. CCII supports and is supported by Brown Cancer Center.

“UofL Health – Brown Cancer Center has been developing novel immunotherapies since the early 2000s and our collaboration with UofL’s research and educational programs has translated into lives saved not only in our region but also throughout the country,” said Jason Smith, chief executive officer of UofL Health. “This grant highlights the advantage of academic health care. We are able to leverage life-changing research from the University of Louisville and elsewhere, and put it to work to save and improve the lives of our patients.”

UofL and UofL Health – Brown Cancer Center are leaders in translating scientific discoveries to patient care and conducting clinical trials that bring new therapies to patients and improve chances of recovery for patients. Brown Cancer Center has led multiple clinical trials of tumor-infiltrating lymphocytes (TILs) therapy, and in 2024, the cellular therapy was for metastatic melanoma.

“The UofL Health – Brown Cancer Center has been a leader and innovator when it comes to novel therapies like TILs,” said Jason Chesney, director of Brown Cancer Center and . “We started offering TILs in clinical trials back in 2016. We have seen many patients who were told elsewhere that they had no other options, but they’ve come to us, and their lives have been extended for years. This grant has allowed us to continue this research so more of our patients can make it to weddings, graduations and meet their grandchildren.”

Julie Reynolds, 69, was the first patient treated with commercial TILs for metastatic melanoma after its FDA approval in February 2024. The retired teacher and Indiana resident was treated at Brown Cancer Center with TILs therapy in June 2024 and is alive and well today.

“The clinical trials of TILs that were conducted by Dr. Chesney at UofL Health – Brown Cancer Center led to the FDA approval of TILs last year which in turn led to me being alive so that I can enjoy spending more time with my family,” Reynolds said.

Training the next generation of investigators

One key goal of CoBRE programs is to train talented young investigators to become the next generation of research leaders. At CCII, young investigators benefit from project grants and mentoring by senior investigators, supported by CoBRE funding. All four of the young investigators who led projects under the first round of center funding have now obtained major federal funding of their own, including:

• Chuanlin Ding
• Qingsheng Li
• Corey Watson
• Kavitha Yaddanapudi

“When we launched this center, our mission was ambitious: to build a vibrant community of scientists who could bridge fundamental immunology with translational and clinical research, ultimately bringing new hope to patients with cancer,” said Jun Yan, director of the CCII. “Through this next phase, we will continue to provide a nurturing environment where junior investigators can develop cutting-edge research programs, gain access to advanced technologies and receive the mentorship and resources they need to succeed.”

As a first-round project leader in the program, Yaddanapudi’s translational research supported the clinical immunotherapy program at Brown Cancer Center. She investigated immune checkpoint inhibitor resistance in lung cancer patients to improve treatment and worked with the TILs clinical trial team. Now, Yaddanapudi is a mentor for other young investigators in CCII as they build their research programs.

Junior investigators currently receiving support and training include:

• Sharmila Nair
• Jian Zheng
• Joseph Chen

The center also houses research instruments in its Functional Immunomics Core facility. The equipment supports research by the CCII faculty, the junior researchers and other investigators at the university. It houses a Helios CyTOF instrument and a Hyperion Imaging Mass Cytometry, among other resources. To date, investigators within the program have secured approximately $33 million in research grants made possible by the core.

As part of its next phase, the CCII plans to add a tumor organoid fragment culture platform. The platform uses human tumor specimens and mimics the human body environment for more precise testing.

View photos from the announcement on .

Immunogenomics combines the fields of immunology (study of the immune system) and genomics (study of the genetic changes in cancer). According to the proposal submitted for approval, researchers are just now uncovering the extent of immunogenetic diversity among human populations. Genetic diversity in immune genes significantly impacts individual immune responses, with critical implications for how people develop and administer novel vaccines and therapeutics, as well as characterize complex and dynamic immune responses in infection, autoimmune disease and cancer.

School of Medicine Interim Dean Jeffrey Bumpous said that the university is well-prepared to support this research with equipment that other research institutes do not have, and the new endowment will accelerate efforts to understand the rapidly expanding field of immunogenomics.

Funding for the endowment comes from the estate of Carolyn S. Browning ($934,498.15) and the estate of Clifford Ernst ($65,501.85). UofL will request the gifts be matched by a contribution of $1 million from the Commonwealth of Kentucky Research Challenge Trust Fund, resulting in a total contribution of $2 million.

Browning, the endowment’s namesake, was a longtime Louisville resident, teaching music and Spanish for more than 30 years. Her husband, Harold Alonzo Browning, Jr., was a city editor for the Louisville Times. The Browning estate has provided gifts to other medical schools as well as the American Diabetes Association, memorial Sloan Kettering and St. Jude’s Children’s Research Hospital.

University of Louisville researchers recently have shown that beta-glucan, a natural carbohydrate, can generate enhanced immune responses to cancer in the pancreas and may lead to improved efficacy of immunotherapy for pancreatic cancer.

Jun Yan, chief of the Division of Immunotherapy in the Department of Surgery at UofL, said one of challenges for pancreatic cancer is that natural immune cells are unable to enter the pancreas to combat the growth of tumors, creating an immune desert.

“These tumors lack quality effector immune cells that can kill them,” Yan said. “In addition, pancreatic cancer has a unique tumor microenvironment that prevents the influx of anti-tumor immune cells.”

In new research published this month in , Anne Geller, an MD/PhD student, and a research team at UofL led by Yan demonstrate that a type of beta-glucan derived from yeast can alter the environment within the pancreas to promote anti-cancer immune cell migration to the site of the cancer. Beta-glucan, a naturally occurring carbohydrate found in plants, bacteria and fungi, is known to induce trained immunity, stimulating an immune response to a specific stimulus, such as pancreatic tumor cells.

Trained immunity is a new concept in the field of immunology and is the idea that innate immune cells possess a form of “memory,” which typically only has been considered to be a feature of adaptive immune cells such as T-cells. Using animal models, Yan and his team found that when they injected particulate beta-glucan into the peritoneal area, it accumulated in the pancreas and promoted anti-cancer immune cell migration to the area. These immune cells were found to have a trained immunity phenotype and effectively inhibited pancreatic cancer growth.

“This research demonstrates that a natural compound can stimulate trained immunity in pancreas,” Yan said.

The researchers also found that beta-glucan-stimulated trained immunity can enhance PD-1 antibody therapy in pancreatic cancer. Anti-PD-1 immunotherapy has been approved to treat many types of cancer including melanoma and lung cancer. However, this therapy has failed in treating pancreatic cancer. This research could be a breakthrough in successfully applying immunotherapy to pancreatic cancer.

“This research has a great potential for clinical translation as it elucidates a strategy for delivering therapeutics directly to the pancreas, identifies a mechanism of enhancing anti-tumor immune responses against pancreatic tumors and provides insight into ways of unleashing the awesome power of immunotherapies against PDAC,” Geller said. “This could be a breakthrough in treating the deadly cancer that has evaded so many other forms of treatment.”

Yan, director of the Immuno-Oncology Program at and study coauthor, and surgical oncologist Robert C.G. Martin II are conducting a clinical trial using beta-glucan in pancreatc cancer patients as a proof-of-concept study.

“This publication demonstrates that a simple yeast-derived beta-glucan supplement has the potential to enhance a patient’s immune system and then respond more effectively to therapies in pancreatic cancer. The concept that patients’ immune systems can be ‘trained’ to see their pancreatic cancer as abnormal or foreign could be a crucial step in enhancing a patient’s overall survival and thus quality of life,” said Martin, professor and director of the UofL Division of Surgical Oncology and a co-author on the study.

According to the , more than 60,000 adults are expected to be diagnosed with pancreatic cancer in the U.S. in 2022 and nearly 50,000 patients will die from the disease. Alex Trebek, long-time host of the game show “Jeopardy!” shared his pancreatic cancer diagnosis and treatment journey beginning in 2019. Trebek died in 2020, just over 18 months after announcing his diagnosis.

“UofL is committed to solving big, global challenges through research,” said Kevin Gardner, UofL’s executive vice president for research and innovation. “This work, leveraging the power of the immune system to better treat pancreatic cancer, could have a big impact in helping people live lives that are not just longer, but healthier and more resilient.”

Building on more than two decades of success in cancer research, the University of Louisville is poised to advance immunotherapy with a grant of $11.5 million from the National Institute of General Medical Sciences to establish the (CCII). The new center will develop and improve strategies that use the immune response to fight cancer. The five-year grant also will allow UofL to establish the CCII as a National Institutes of Health-designated Center of Biomedical Research Excellence (CoBRE) to support young investigators and develop additional basic, translational and clinical research at the .

“One of the university’s Grand Challenges is to advance the health of all people,” said UofL President Neeli Bendapudi. “Through this center, our cancer researchers will grow the field of immunotherapy, saving the lives of many more patients with cancer in the future.”

“Our mission is to harness the power of the immune system to eradicate cancer,” said Jason Chesney, director of the Brown Cancer Center. “The University of Louisville, UofL Health and the Brown Cancer Center have been at the forefront of the clinical development of a new generation of immunotherapies that have been proven to increase the survival of cancer patients. This grant from the federal government leverages our existing strengths in cancer immunology and clinical trials to accelerate the development of new immunotherapies that will translate into lives saved across the globe.”

Cancer survivor Jeff Habermel received two different immunotherapies at Brown Cancer Center in the course of treatment for three different cancers, including metastasized melanoma.

“I consider myself very fortunate to have the type of care that Dr. Chesney and Dr. (Donald) Miller and the whole staff provide at the Brown Cancer Center. We have a world-class facility right in our backyard,” Habermel said. “I truly feel I am the luckiest man in the world to live in a time when we have such technologies and such amazing abilities to treat cancer in these ways.”

The newest cancer treatments often are available at Brown Cancer Center through clinical trials before they are available anywhere else. One such treatment is CAR T-cell therapy, in which a patient’s own immune cells known as T cells are modified in the lab to more effectively attack cancer cells. UofL announced the creation of the at UofL in October.

“Our leading-edge cancer program improves access for patients in our region, giving them the opportunity to benefit from life-saving immunotherapies through clinical trials,” said Tom Miller, CEO of UofL Health. “Thousands of our cancer patients – our neighbors and family members – are alive today because of this early focus on drugs that activate immunity against cancer.”

Researchers within the CCII will build on expertise and resources gained from previous research at UofL to develop better cancer immunotherapies. This will be achieved in part by enabling talented junior investigators who have not yet obtained major funding to advance their research and subsequently obtain major grant awards of their own.

“One of the major goals of the center is to cultivate the next generation of cancer scientists in immunology and immunotherapy,” said Jun Yan, professor, director of the CCII and chief of the UofL Division of Immunotherapy. “Starting in year two, we will call for pilot projects that will bring in more researchers and investigators to work on immunotherapy and immunology.”

The young researchers are provided funding, mentorship and access to sophisticated facilities to advance their research. Once CCII-supported researchers obtain their own funding they rotate out, allowing new investigators to come in to the program.

“It’s training a cohort of new investigators who will have their own large grants and expertise,” said Paula Bates, professor of medicine and co-investigator for the CCII along with John Trent. “We are building a critical mass of well-funded researchers in the area.”

Senior UofL faculty members Robert Mitchell, Nejat Egilmez, Haribabu Bodduluri, Huang-Ge Zhang and Bing Li will serve as mentors and core directors for the CCII. In the first year of the program, four junior researchers at UofL are conducting projects to improve the effectiveness of immune therapies.

• Chuanlin Ding is investigating the impact of chemotherapy on anti-tumor immunity in breast cancer order to discover effective combination regimens that improve conventional chemotherapy.
• Qingsheng Li is exploring a method to improve immune checkpoint inhibitor therapy for non-small cell lung cancer. Immune checkpoint inhibitors are a type of immunotherapy that blocks proteins (checkpoints) made by immune system cells, such as T cells. The checkpoints can prevent T cells from attacking cancer cells.
• Corey Watson is studying immune cells to determine which of these cells are beneficial to lung cancer patient outcomes and how they may help kill tumor cells.
• Kavitha Yaddanapuddi is studying immune checkpoint inhibitor resistance in lung cancer patients. This will help in developing therapies that reduce resistance and improve treatment.

This grant may be extended for two additional five-year phases. A previous CoBRE program for cancer research at UofL was extended through all three phases, lasting 15 years. That program significantly expanded the contingent of both junior and senior investigators at UofL, including Chesney, Trent and others whose research was funded by the previous program.

“This type of funding has been truly transformative for this cancer center,” Trent said. “The research for the current generation of immunotherapeutic checkpoint inhibitors was done more than 18 years ago. This grant’s research will feed into the clinical work in time. These grants lay the groundwork for the next generation of therapies.”

To extend the impact of the CCII still further, Kosair Charities has provided an additional $200,000 to facilitate the discovery and development of immunotherapy drugs for children with cancer. This gift bridges the CCII and the UofL Kosair Charities Pediatric Oncology Research Program, allowing the CCII to focus also on immuno-oncology for children.

“Kosair Charities is proud to be the first community partner to support the UofL Center for Cancer Immunology and Immunotherapy,” said Kosair Charities President Keith Inman. “The UofL Kosair Charities Pediatric Cancer Research Program will allow this new center to include crucial pediatric cancer research as well as expand the scope to all people living with cancer – children and adults alike.”

Yan, an immunologist and researcher with the , along with UofL Professor of Anesthesiology Jiapeng Huang and MD/PhD student Samantha Morrissey, conducted a patient study to better understand the most severe cases of COVID-19.

Approximately 20% of COVID-19 patients experience severe disease, including pneumonia and acute respiratory distress syndrome (ARDS). In some of these patients, the rapid influx of immune cells to the lungs to fight the infection leads to complications in the lung and blood coagulation disorders, resulting in heart attack, pulmonary embolism, stroke or deep vein thrombosis.

To better understand these serious complications, Yan’s team evaluated levels of various immune cells in blood samples of COVID-19 patients and compared those levels with those of healthy individuals. They discovered that one type of immune cells, low-density inflammatory neutrophils, became highly elevated in some patients whose condition became very severe. This elevation signaled a point of clinical crisis and increased likelihood of death within a few days.

Neutrophils are one type of immune cells that serve as the first line of defense in the body. When an individual acquires an infection, neutrophils rush to the site to clear the pathogen causing the infection. However, if their presence is persistent or there is a very high volume of cells at the site of infection, in this case the lungs, they can cause unwanted adverse effects. In the case of patients with severe COVID-19, a blood clotting disorder known as coagulopathy occurred, that can manifest as pulmonary embolism, heart attack or stroke.

The study, as a preprint, details shifting levels of these neutrophils and other immune cells through repeated blood samples from study participants, correlated with improvement or worsening of the patients’ condition. If clinicians could detect a rise in these cells, they may be able to provide therapy to prevent the potential life-threatening conditions associated with them.

“Based on this study, we believe that the low-density inflammatory band neutrophil population contributes to COVID-19-associated coagulopathy (CAC) and could be used as a clinical marker to monitor disease status and progression,” Yan said. “Identifying patients who are trending toward a cellular crisis and then implementing early, appropriate treatment could improve mortality rates for severe COVID-19 patients.”

To provide additional clinical options for physicians in addressing these crises, Yan is now working with other researchers at UofL to test potential therapies.

“Billions of cells die daily as a consequence of regular wear and tear, tissue turnover and during an inflammatory response. The body dedicates a significant amount of energy in the specific recognition and uptake of these dead cells via specific pathways,” said Juhi Bagaitkar, PhD, a researcher in the University of Louisville School of Dentistry’s Department of Oral Immunology and Infectious Diseases. “If you don’t bury the dead cells, they can burst open and cause harm, however the underlying mechanisms are incompletely characterized.”

Bagaitkar, along with researchers at Washington University, Indiana University and University of Michigan, recently published a paper in , demonstrating the importance of oxidants in the digestion of apoptotic, or dead cells. 

Specifically, the research uncovers how NADPH-oxidase is activated to generate reactive oxygen species (ROS) in macrophages, a kind of white blood cell that eats dead cells. These cells also are involved in getting rid of viruses and bacteria.

The presence of ROS is critical as its generation drives additional mechanisms involved in the digestion of cellular corpses to perform at an optimal level. This allows the macrophage to complete the digestion process of efferocytosis, meaning “to bury the dead.”

“Independent of their role in microbial killing, we are gaining even greater appreciation of ROS for their huge role in the regulation of host immune response,” Bagaitkar said. “Uncovering this role of ROS in the clearance of dead cells sheds some mechanistic insights on how oxidants function in limiting of host inflammation rather than activating it.

“When our bodies produce too much or too little ROS, we become pre-disposed to autoimmune disease and chronic inflammation. Producing just enough – the optimal level – is what’s needed,” she said.

To further understand these associations linking the microbiome — bacteria, yeasts, fungi, viruses and protozoans — with inflammation and disease, the University of Louisville has received an $11.2 million federal grant over five years to establish an interdisciplinary research program.

The grant, awarded through the National Institute of General Medical Sciences, establishes a Center of Biomedical Research Excellence (COBRE) and pairs well-funded scientists with junior faculty in the Schools of Dentistry, Medicine and Engineering. This arrangement facilitates the career development of junior faculty, and aims to advance the study of the interface between microbiome, inflammation and disease development.

“Although the microbiome contributes to many beneficial aspects of our physiology, when these communities are out of balance, or dysbiotic, they are implicated in an array of diseases such as inflammatory bowel disease, periodontitis, vaginosis, colorectal cancer, and distant sites like rheumatoid arthritis, even neurological disorders like Parkinson’s disease and autism spectrum,” said Richard Lamont, PhD, chair of the School of Dentistry’s Department of Oral Immunology and Infectious Diseases and principal investigator for the grant.

Furthermore, Lamont said, inflammation is a process that provides the mechanism connecting the microbiome and disease.

“The interplay of the pro and anti-inflammatory components of the immune system with microbes often dictates whether a person remains healthy or develops a disease, as well as controls aspects of recovery, chronic infection and the level of tissue destruction,” he said.

Microbiology and Immunology in the School of Medicine is the other primary department participating in the COBRE. Researchers in the J.B. Speed School of Engineering’s bioengineering department will provide expertise as possible new discoveries show potential for new therapeutic technology against disease.

“This program will synergize with, and augment, existing research priorities at UofL centered around microbial community-associated diseases,” said Greg Postel, MD, interim UofL president. “We are confident that establishing a critical mass of investigators with unique complementary expertise will propel UofL to a position of preeminence in this important field.”

“We are thrilled to add this COBRE multidisciplinary program in research, education and mentoring to facilitate and accelerate the transition of junior faculty to independent extramural funded status, advancing our overall research enterprise,” said T. Gerard Bradley, BDS, MS, Dr.Med.Dent., dean of the School of Dentistry.

The grant will support five junior faculty and their specific research focused on the mouth, GI tract, arthropod (flea) vector environments, vagina and lungs:

• Juhi Bagaitkar, PhD, will study how oxidants change neutrophil, or white blood cell, responses in the mouth. She is focused on inflammatory pathways regulated by Reactive Oxygen Species essential in host responses to oral bacteria. She hopes to provide insights into neutrophil biology, and enhance the understanding of immune pathways related to inflammation of the gums and the interface with microbes.

• Venkatakrishna Jala, PhD, will investigate the beneficial effects of the microbial metabolite, uronlithin A (UroA) and its structural analogue UAS03 in inflammatory bowel disorders. He will examine their impact on both immune responses and maintenance of the epithelial barrier in the gastrointestinal mucosal membrane.
• Matthew Lawrenz, PhD, will study the pathogenic mechanisms of pestis, a bacterium that causes bubonic plague. Humans can become sick after being bitten by a rodent flea. Lawrenz will further investigate several mechanisms, including how Y. pestis evades macrophages, a kind of white blood cell first on the scene of infection. As the project develops, Lawrenz also hopes to explore the relationship of Y.pestis and microbial communities of the flea, which may impact colonization and transmission.
• Jill Steinbach-Rankins, PhD, will investigate a new nanotherapeutic approach to treat bacterial vaginosis (BV), a dysbiotic condition where vaginal microbial communities are disrupted. With expertise in materials science engineering and biomedical engineering, Steinbach-Rankins aims to develop targeted community engineering to restore the balance between the microbiome and host to prevent the manifestation of disease.
• Jonathan Warawa, PhD, will investigate Burkholderia pseudomallei (Bp), the bacterium responsible for respiratory melioidosis, an inflammatory disease of the lungs that progresses into a fatal systemic disease involving major organs. This project drills down into innate immune responses contributing either to protection and resolution of diseases or to increased morbidity. Through greater understanding of immune responses, therapeutic intervention is possible.

The COBRE also helps establish a functional microbiomics core research facility at UofL. The facility will provide germ-free animal facilities, oxygen-free culture capability, microbiome sequencing and bioinformatics, assessment of inflammatory markers and pathology services. 

Check out more from the press conference below: