Pelayo Correa, MD, professor emeritus of Medicine and Pathology, Microbiology and Immunology, at Vanderbilt University Medical Center, and John Kuriyan, PhD, dean of the Vanderbilt University School of Medicine Basic Sciences, have been elected to the 2025 class of fellows of the American Association for Cancer Research (AACR) Academy.
John Kuriyan, PhD
The mission of the fellows of the AACR Academy is to recognize and honor extraordinary scientists whose groundbreaking contributions have driven significant innovation and progress in the fight against cancer.
Fellows of the AACR Academy constitute a global brain trust of leading experts in cancer science and medicine, working to advance the AACR’s mission to prevent and cure all cancers through research, education, collaboration, communication, advocacy and funding for cancer research.
Fellows of the AACR Academy are nominated and elected through a peer-reviewed process that rigorously evaluates each candidate’s scientific achievements and contributions to global cancer research. Only those whose work has made a profound and lasting impact on cancer research and related fields are considered for election and induction into the AACR Academy.
Correa was recognized for his “illustrious work defining the histological stages of gastric carcinogenesis through the ‘Correa Cascade’ and establishing the link between Helicobacter pylori infection and gastric cancer, fundamentally advancing the understanding of the pathology, epidemiology, and prevention of this disease.”
Kuriyan, Mary Geddes Stahlman Chair and University Distinguished Professor of Biochemistry, Chemistry, and Cell and Developmental Biology, was recognized for his “heralded contributions to cell signaling and kinase biology, including the elucidation of the switching mechanisms of tyrosine kinases such as SRC and EGFR, which has advanced the fundamental understanding of signal transduction regulation and informed the development of kinase-targeted therapies for cancer and other malignancies.”
Correa and Kuriyan are among 33 new fellows who will be recognized at the AACR Annual Meeting on April 25-30 in Chicago. Including this year’s class, only 375 cancer researchers have been named fellows of the AACR Academy.
Colorectal cancer is the second most common cause of cancer-related deaths worldwide, according to the World Health Organization. Understanding factors that contribute to the development of colorectal cancer could point to new targets for treating the disease at earlier stages, when survival rates are highest.
Nicholas Markham, MD, PhD
Nicholas Markham, MD, PhD, assistant professor of Medicine, and colleagues are exploring how bacteria in the colon may contribute to cancer development. They previously showed that C. diff (Clostridioides difficile) isolated from human colorectal cancer samples accelerated tumorigenesis in the colon in a mouse model of intestinal cancer.
Now, they have combined single-cell RNA sequencing, spatial transcriptomics and immunofluorescence to build a multiomic atlas of gene expression and protein abundance in C. diff-associated colorectal tumorigenesis.
They report in The Journal of Pathology that the protein DMBT1 (Deleted in Malignant Brain Tumors 1) shows striking differences in regulation in areas of the colon with inflammation versus dysplasia (abnormal cellular changes). DMBT1 is a protein with roles in mucosal immune defense and epithelial cell differentiation.
In a mouse model, the researchers found that expression of DMBT1 increases in normal absorptive colon cells exposed to C. diff, but that its expression is reduced in dysplastic areas compared to normal adjacent tissues.
Immunofluorescence studies confirmed that DMBT1 protein was downregulated in dysplastic regions from three mouse models of colonic tumorigenesis and in colorectal precancerous adenomas from human samples. Using mouse and human organoids, the researchers implicated WNT signaling in the downregulation of DMBT1 mRNA and protein.
The findings suggest that loss of DMBT1 could be a mechanistic link between bacterial infection and colorectal cancer development. Further studies will explore how DMBT1 might function to limit tumorigenesis.
Emily Green, a graduate student in the Molecular Pathology and Immunology program, is the first author of the study. Collaborators at Johns Hopkins University School of Medicine contributed to the study. The research was supported by grants from the Department of Veterans Affairs (BX005699, BX002943) and the National Institutes of Health (P30DK058404, P30CA068485, R00CA230192, P50CA236733).
An ambitious project led by Vanderbilt University Medical Center investigators aims to use artificial intelligence technologies to generate antibody therapies against any antigen target of interest.
VUMC has been awarded up to $30 million from the Advanced Research Projects Agency for Health (ARPA-H) to build a massive antibody-antigen atlas, develop AI-based algorithms to engineer antigen-specific antibodies, and apply the AI technology to identify and develop potential therapeutic antibodies.
ARPA-H is an agency within the U.S. Department of Health and Human Services that supports transformative high-risk, high-reward research to drive biomedical and health breakthroughs to benefit everyone.
Ivelin Georgiev, PhD
“Over the last few decades, monoclonal antibodies have started playing an important therapeutic role in a wide range of disease settings, but we’re just scratching the surface. Monoclonal antibody discovery has the potential to impact a lot of different diseases where currently there are no therapeutics,” said Ivelin Georgiev, PhD, professor of Pathology, Microbiology and Immunology, director of the Vanderbilt Center for Computational Microbiology and Immunology, and the project principal investigator.
Traditional methods for antibody discovery are limited by inefficiency, high costs and fail rates, logistical hurdles, long turnaround times and limited scalability, Georgiev said.
“What we’re proposing to do is going to address all of these big bottlenecks with the traditional antibody discovery process and make it a more democratized process — where you can figure out what your antigen target is and have a good chance of generating a monoclonal antibody therapeutic against that target in a very effective and efficient way,” said Georgiev, who is also professor of Biomedical Informatics, Computer Science, and Chemical and Biomolecular Engineering.
Antibodies are part of our immune system. They are proteins produced by white blood cells (B cells) that bind to and inactivate antigens — targets on viruses, bacteria and even our own cells. Antibodies are effective as preventive and therapeutic treatments against viruses, cancers, autoimmune disorders and other diseases.
To identify a candidate therapeutic antibody, researchers generally screen and test thousands of antibodies against an antigen target, looking for the “needle in the haystack” that binds to and neutralizes the target. The traditional discovery process requires specific types of biological samples. For example, to find antibodies against an infectious disease pathogen, blood samples from people or animal models exposed to the pathogen are required. And then, if the pathogen mutates, a therapeutic antibody may become ineffective.
“With a computational approach, you’re no longer dependent on access to biological samples or multiple screening cycles,” Georgiev said. “You can simulate variants and generate antibodies ahead of time before the variants arise.”
Georgiev and his colleagues are engaged in three tasks as they work toward developing computational approaches for antibody discovery:
Generation of an antibody-antigen atlas of unprecedented size and variety
Development of AI-based algorithms for extracting information from the antibody-antigen atlas and engineering antigen-specific antibodies
Proof-of-concept studies to apply the AI technology to identify antibody candidates against antigen targets of biomedical interest
For the first task, the researchers are using a technology they developed called LIBRA seq (Linking B-cell Receptor to Antigen specificity through sequencing) that enables high-throughput mapping of antibody-antigen interactions for many antigens and B cells at the same time.
“For computational methods to work, we need to have a lot of data,” Georgiev said. “The scale of data that’s available for antibodies and antigens is lower than in other fields, which has been one of the limiting factors when it comes to developing AI approaches.
“If we train algorithms on the data that exists currently — much of it is for SARS-CoV-2, flu and HIV — the algorithms may be accurate for these targets, but they are less likely to be successful in extrapolating to a new target. We need to train them with a more diverse set of antigen targets, which is where LIBRA-seq comes into play.”
The investigators aim for the atlas to include hundreds of thousands — and potentially over 1 million — antibody-antigen pairs, compared to approximately 15,000 pairs currently available from published data, providing an unparalleled resource for researchers worldwide.
The team is already moving forward on the second task of building computational models, which they will improve as they populate the antibody-antigen atlas. For the third task, they will apply the AI technology to develop antibodies against cancer antigens and bacterial, viral and autoimmune targets. They will select one candidate antibody for preclinical development up to and including IND (investigational new drug) application.
“Our project will be providing a platform that can be used for a variety of different diseases, not just the specific targets we’re interested in,” Georgiev said. “Our team has spent many years trying to discover antibodies against a variety of indications, and it’s such an inefficient process with a lot of failure. If we can help change that, that’s going to be huge — not just for us, but for the entire field and for people with diseases where antibody therapies can make a difference.
“It’s going to be hard. It’s not an easy problem, but I think we have a good foundation for it, and we’ll do the best we can to make it work.”
Collaborators on the project are: Ben Ho Park, MD, PhD, Sarah Croessmann, PhD, Eric Skaar, PhD, MPH, Maria Hadjifrangiskou, PhD, and Jeremy Goettel, PhD, at VUMC; Tedd Ross, PhD, and Giuseppe Sautto, PhD, at Cleveland Clinic; and Maria del Pilar Quintana Varon, PhD, and Lars Hviid, PhD, at the University of Copenhagen. The Brock Family Center for Applied Innovation, a catalyst for advancing translational research to market, has engaged with and supported the Georgiev team.
Vanderbilt University and VUMC shared resources that are critical to the project are: VANTAGE (Vanderbilt Technologies for Advanced Genomics), ACCRE (Advanced Computing Center for Research and Education), and FCSR (Flow Cytometry Shared Resource). Wheeler Bio will participate in IND-enabling studies, cell line development and manufacturing activities.
Jeffrey Rathmell, PhD, founding director of the Vanderbilt Center for Immunobiology and a pioneer in immune and cancer cell metabolism research, this summer will begin a new chapter in his career at the University of Chicago.
University officials announced March 3 that Rathmell has been named chair of the Ben May Department for Cancer Research and director of the Ludwig Center at the University of Chicago, effective July 1.
Rathmell currently holds the Cornelius Vanderbilt Chair in Immunobiology and is professor of Pathology, Microbiology and Immunology, and of Molecular Physiology and Biophysics in the Vanderbilt University School of Medicine.
“Dr. Rathmell’s impact on immunology and cancer metabolism research at Vanderbilt has been remarkable,” said Jennifer Pietenpol, PhD, Chief Scientific and Strategy Officer and Executive Vice President for Research at Vanderbilt University Medical Center.
“His leadership in building an immunology community, advancing translational research and mentoring the next generation of scientists has left a legacy,” said Pietenpol, who holds the Brock Family Directorship in Career Development. “While we will greatly miss his leadership at Vanderbilt, we know his impact will expand in these prestigious roles at the University of Chicago and the Ludwig Center.”
The Ludwig Center at the University of Chicago, one of six Ludwig Centers nationwide, is focused on finding ways to stop the spread of cancer.
Rathmell earned his PhD in immunology from Stanford University, did postdoctoral work in immunology and cancer biology at the University of Chicago and University of Pennsylvania, and was on the faculty at Duke University before coming to Vanderbilt in 2015.
As director of the Vanderbilt Center for Immunobiology, he has led growth in basic science and translational immunology at Vanderbilt, with an emphasis on the research of immune-related diseases and building an immunology community.
A co-leader of the Host-Tumor Interactions Program in the Vanderbilt-Ingram Cancer Center, Rathmell helped define the metabolic mechanisms that control inflammatory diseases and cancer.
He also led initiatives, as associate director of the Molecular Pathology and Immunology PhD Program and of the Vanderbilt Institute for Infection, Immunology and Inflammation, to strengthen basic science immunology education and position Vanderbilt as a leader in immunology research.
Rathmell said he is looking forward to working in collaboration with the University of Chicago Comprehensive Cancer Center to advance understanding of the tumor microenvironment and the role that immunity plays in cancer growth and response to therapy.
