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 .

The five-year grant from the National Institutes of Health (NIH) is an extension of a��Center of Biomedical Research Excellence (COBRE) grant awarded in 2018��to study the connection between those microorganisms — such as bacteria, yeasts, fungi, viruses and protozoans — and disease. The work could lead to discoveries in, among others, Alzheimer’s disease, heart disease, diabetes, periodontitis and colorectal cancer.

The grant will support research by three faculty members focused on microorganisms in the mouth, GI tract and the blood-brain barrier, said Richard Lamont, principal investigator for the grant and chair of School of Dentistry Department of Oral Immunology and Infectious Diseases.

“Collectively, these three projects provide innovative approaches to an increased understanding of the host-microbe interface as it defines health and disease and these advances will establish the basis for new therapeutic approaches,” Lamont said.

The School of Medicine’s Department of Microbiology & Immunology also is involved in the COBRE research, including interim chair Haribabu Bodduluri, the center’s co-director.

“An essential feature of these awards is the support of shared resources for development of new research areas,”��said Bodduluri.��“In the past few months since the renewal, we were awarded supplemental funding to the COBRE that enhances the research core facilities and initiates a novel��‘Team Science’��project.”

Gerry Bradley, interim university provost, said the NIH grant allows UofL to further the COBRE’s groundbreaking research, development of new innovations and training the next generation of scientists.

“This huge commitment from the government reinforces that UofL is one of the top dental schools in the United States in terms of the value of research work conducted here and research funding dollars,” he said.

The original COBRE grant allowed UofL to establish an interdisciplinary research program to study associations linking microbiome with inflammation and disease. The grant provides junior research faculty with seed funding to build potential for independent research funding. The first five faculty researchers involved are successfully continuing their research with other financial support.

“As a top-tier research institution, UofL works to expand understanding and find solutions to important problems,” said Kevin Gardner, executive vice president for research and innovation. “The work of Drs. Lamont and Bodduluri, along with their��team, for example, could lead to life-changing therapies, treatments and more that could dramatically improve the lives of people living with numerous conditions.”

Kevin Sokoloski, assistant professor in the Department of Microbiology & Immunology and participant in UofL’s initial COBRE grant, said the program helped his research by connecting him with a robust scientific community focused on inflammation and pathogenesis.

“Our ongoing involvement in the COBRE program has accelerated our success and continues to enhance our scientific mission,” Sokoloski said.

The newly funded researchers are:

• Fata Moradali,��(Oral Immunology and Infectious Diseases), who will address periodontitis, a common condition driven by a synergistically virulent bacterial community that triggers destructive inflammatory responses in the periodontal, or gum tissues.
  ��
• James Collins,��(Microbiology & Immunology), who will investigate the GI tract pathogen��C. difficile, an evolving organism whose ability to cause disease can be enhanced by the nutritional microenvironment.��
  ��
• Yun Teng,��(Department of Medicine), who will focus on the blood-brain barrier (BBB). Increased permeability of the BBB accelerates the aging process and the progression of age-related diseases.��

View the press conference .��

Watch the press conference:

A family of proteins known as interferon lambdas produced by epithelial cells in the mouth serve to protect humans from viral infection, but the oral bacteria Porphyromonas gingivalis reduces the production and effectiveness of those important frontline defenders.

“Our studies identified certain pathogenic bacterial species, P. gingivalis, which cause periodontal disease, can completely suppress interferon production and severely enhance susceptibility to viral infection,” said Juhi Bagaitkar, assistant professor in the UofL Department of Oral Immunology and Infectious Disease. “These resident oral plaque bacteria play a key role in regulating anti-viral responses.”

Bagaitkar and Richard Lamont, professor and chair of the UofL Department of Oral Immunology and Infectious Disease, led the work, with first author Carlos J. Rodriguez-Hernandez and other colleagues at UofL and at Washington University in St. Louis. The findings were published

The mouth often is a gateway into the body for viruses that infect the gastrointestinal tract and lungs such as SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex and cancer-causing viruses such as human papillomavirus (HPV).

P. gingivalis, a common oral bacterium that causes periodontal disease, has been linked to numerous other diseases, including Alzheimer’s disease and rheumatoid arthritis. Recent clinical studies have shown that immune suppression in patients with periodontitis can enhance susceptibility to HIV, herpes simplex and HPV.

Improved understanding of how interferons provide broad antiviral protection and activate antiviral genes to protect us from viruses, as well as how P. gingivalis compromises their protection, may lead researchers to clinical approaches to increase that protection.

Research at UofL has revealed connections between P. gingivalis and multiple other diseases and conditions, including rheumatoid arthritis, Alzheimer’s disease and esophageal cancer.

Bagaitkar was one of the first junior faculty members whose research was supported by the Center of Biomedical Research Excellence (CoBRE) for research in microorganism disease research funded by the National Institute of General Medical Sciences.

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.”

The researchers at UofL have determined that Urolithin A (UroA) and its synthetic counterpart, UAS03, mitigate IBD by increasing proteins that tighten epithelial cell junctions in the gut and reducing gut inflammation in animal models. Tight junctions in the gut barrier prevent inappropriate microorganisms and toxins from leaking out, causing inflammation characteristic of IBD. Preclinical research published today in shows the mechanism by which UroA and UAS03 not only reduce inflammation and restore gut barrier integrity, but also protect against colitis.

“The general belief thus far in the field is that urolithins exert beneficial effects through their anti-inflammatory, anti-oxidative properties. We have for the first time discovered that their mode of function also includes repairing the gut barrier dysfunction and maintaining barrier integrity,” said Rajbir Singh, PhD, a postdoctoral fellow at UofL and the paper’s first author.

Venkatakrishna Rao Jala, PhD, assistant professor of microbiology and immunology at UofL, led the research, conducted by Singh and other collaborators at UofL, the Institute for Stem Cell Biology and Regenerative Medicine (inStem) in Bangalore, India, the University of Toledo College of Medicine and Life Sciences, and Dalhousie University in Nova Scotia. Jala, Singh and other researchers at UofL have been investigating how metabolites produced by the human microbiota – bacteria, viruses and fungi that inhabit the human body – affect many areas of health. By understanding the effects of specific metabolites, they hope to use them directly as therapeutic agents in treating disease.

It has been reported that the microbe Bifidobacterium pseudocatenulatum INIA P815 strain in the gut has the ability to generate UroA from ellagic acid (EA), a compound found in berries and pomegranates. Variations in UroA levels, despite consumption of foods containing EA, may be the result of varied populations of bacteria responsible for the production of UroA from one individual to another, and some individuals may not have the bacteria at all. While encouraging natural levels of UroA in the gut by consuming the appropriate foods and protecting populations of beneficial bacteria should have positive health effects, the researchers believe the use of the more stable synthetic UAS03 may prove to be therapeutically effective in cases of acute colitis. Further experiments and clinical testing are needed to test these beliefs.

“Microbes in our gut have evolved to generate beneficial microbial metabolites in the vicinity of the gut barrier,” Jala said. “However, this requires that we protect and harbor the appropriate gut microbiota and consume a healthy diet. This study shows that direct consumption of UroA or its analog can compensate for a lack of the specific bacteria responsible for production of UroA and continuous consumption of pomegranates and berries.”

Haribabu Bodduluri, PhD, professor of microbiology and immunology at UofL and an author of the article, said another key finding of the research is that UroA and UAS03 show both therapeutic and protective effects. Administration of UroA/UAS03 after the development of colitis reverses the condition and administration prior to development of colitis prevents it from occurring.

This research was facilitated by funding from the National Cancer Institute to Jala and the , established at UofL in 2018 with funding from the National Institute of General Medical Sciences.