Researchers from Vanderbilt-Ingram Cancer Center will present findings from clinical trials, laboratory discoveries and innovations in caring for patients with hematologic cancers and other blood diseases at ASH 2025 in Orlando, Florida, Dec. 6-9. 

ASH 2025 is the American Society of Hematology Annual Meeting and Exposition. Established in 1958, ASH is the world’s largest professional organization for clinicians and scientists who study blood diseases.  

Three of the presentations from Vanderbilt-Ingram researchers will focus on chimeric antigen receptor T-cell (CAR-T) therapies, a form of immunotherapy that involves treating cancer with white blood cells that have been reengineered to attack cancer cells. Vanderbilt-Ingram is an international leader in advancing the efficacy of and expanding access to CAR-T therapies.

Olalekan Oluwole, MBBS, MPH, associate professor of Medicine, who leads the cellular therapy research program at Vanderbilt-Ingram, will present data on health care resource utilizations of the therapies in U.S. patients treated at newly authorized treatment centers. He will also provide an overview of outcomes for inpatient and outpatient CAR-T treatment. Grace Mercadante, MD, will present data on the impact of clonal hematopoiesis on CAR-T therapy. 

Michael DeBaun, MD, MPH, the J.C. Peterson, MD, Professor of Pediatrics and founder and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, will speak at a special session focusing on ASH’s sickle cell disease initiative. He will present findings from “Sickle Cell Trait Does Not Cause ‘Sickle Cell Crisis’ Leading to Exertion Related Death: A Systematic Review.” 

Other topics researchers will address include acute myeloid leukemia, myelodysplastic syndrome, drug resistance, potential adverse reactions and risk comparisons of treatments, pediatric blood disorders, multiple myeloma, bispecific antibody treatment, and graft-versus-host disease. 

A complete list of presentations from Vanderbilt researchers follows: 

Sally Momoh, MD – Sex-related differences in silent cerebral infarction burden among adults with sickle cell disease 

Jamila Mammadova, MD – Behind the blood-brain barrier: Contemporary screening practice patterns and trends of central nervous system involvement in acute myeloid leukemia treated with intensive regimens and hypomethylating agent/venetoclax 

Alyssa Jarabek – Impact of innate immune memory on myelodysplastic syndrome progression by TET2-driven inflammation 

Raymond Zhang – VISTA contributes to disease progression in high-risk myelodysplastic syndrome 

Mattew Villaume, MD, PhD – EB2023 primes mitochondria for BCL2 dependence and induces pyroptotic cell death via AMPK signaling and the unfolding protein response 

Grace Mercadante, MD – The impact of clonal hematopoiesis on CAR-T cell therapy outcomes: a single-center analysis 

Ghadeer Dawwas, PhD, MSc, MBA – Risk of serious bleeding with concomitant use of apixaban or rivaroxaban with amiodarone compared to flecainide or sotalol in patients with atrial fibrillation  

Olalekan Oluwole, MBBS, MPH – Real-world health care utilization following CAR-T cell therapy in U.S. patients treated in newly authorized treatment centers 

Erin Christensen, MS, DO – A case series of pediatric patients with congenital thrombotic thrombocytopenia purpura treated with recombinant ADAMTS13 

Andrew Jallouk, MD, PhD – Real-world outcomes of mosunetuzumab use in indolent and aggressive lymphomas  

Bhagirathbhai Dholaria, MBBS – Characterization of a population with newly diagnosed standard risk multiple myeloma by 2025 ims/IMWG definition with exceptional long-term outcomes after fixed duration therapy 

Y. Emily Chu – The acute myeloid leukemia microenvironment is defined by ineffective immune surveillance despite the presence of activated, clonally-expanded CD8 T cells with preserved effector function 

Michael DeBaun, MD, MPH – Findings from “Sickle cell trait does not cause ‘sickle cell crisis’ leading to exertion related death: a systematic review ”

Mattew Villaume, MD, PhD – F1 subunit-specific ATP synthase inhibition disrupts AML mitochondrial metabolism distinctly from other electron transport chain inhibitors 

Lauren Klein, MD, – Early weight gain predicts nutritional recovery in children with sickle cell anemia and severe acute malnutrition in Nigeria 

Olalekan Oluwole, MBBS, MPH – U.S. cost consequence and time toxicity model for advanced therapies in the treatment for relapsed/refractory third-line or later diffuse large B-cell lymphoma: a comparison of axicabtagene ciloleucel with bispecific antibodies 

Olalekan Oluwole, MBBS, MPH – Outcomes of inpatient and outpatient CAR-T in newly authorized treatment centers in the United States 

Elizabeth Pollard, MD – Leukapheresis for acute leukemia with hyperleukocytosis: line complications, resource utilization, and early mortality outcomes 

Carrie Kitko, MD – Long-term treatment duration and safety of axatilimab among patients with chronic graft-versus-host disease in AGAVE-201 

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Researchers at Vanderbilt University Medical Center and the University of Calgary have established an analytical framework that integrates genomic, proteomic and electronic health record data to identify cancer risk proteins and therapeutics for cancer prevention. 

Their study, reported Dec. 2 in the American Journal of Human Genetics, identifies previously unreported protein biomarkers and candidate drug targets across six major cancer types and highlights approved drugs with potential cancer preventive effects.

To date, genome-wide association studies (GWAS) have identified several hundred genetic variants associated with increased risk for breast, colorectal and prostate cancer, and several dozen risk variants for other cancers, including lung, pancreatic and ovarian cancer. 

“Previous research, including our work, has identified hundreds of putative cancer susceptibility genes that could be regulated by these risk variants; however, most dysregulated gene expression has not been thoroughly investigated at the protein level,” said Xingyi Guo, PhD, associated professor of Medicine in the Division of Epidemiology at VUMC.

Guo is a co-senior author of the current study with Zhijun Yin, PhD, MS, associate professor of Biomedical Informatics at VUMC, and Quan Long, PhD, associate professor of Biochemistry and Molecular Biology at the University of Calgary. 

“To deepen the understanding of causal mechanisms and enhance drug discovery efforts, it is imperative to explore data from transcriptomic to proteomic studies,” Yin said. 

In the current study, the investigators integrated large GWAS data for breast, colorectal, lung, ovarian, pancreatic and prostate cancers and population-scale proteomics data from over 75,000 participants (combined from the Atherosclerosis Risk in Communities study, deCODE genetics, and UK Biobank Pharma Proteomics Project) to identify risk proteins associated with each cancer. 

They identified 365 proteins associated with cancer risk, and through further analysis narrowed the list to 101 proteins, including 74 not reported in previous studies. Using a variety of pharmaceutical databases, the researchers comprehensively annotated the risk proteins as therapeutic targets of approved drugs or drugs in clinical testing. The idea, they said, is to find drugs that can potentially be repurposed for cancer prevention. 

“Traditional drug discovery faces challenges of escalating costs, lengthy timelines, and high failure rates. Drug repurposing is a promising strategy to identify new applications for existing drugs with well-documented characteristics,” Guo said. 

Among the 101 risk proteins, the researchers identified 36 druggable proteins potentially targeted by 404 drugs already approved or in clinical trials. Nineteen of the druggable proteins were targeted by drugs approved or in trials to treat cancer. The researchers compared drug effects using data from more than 3.5 million electronic health records (EHRs) from VUMC. They demonstrated in simulated trials with EHR data that several approved drugs, for example the diuretic medication acetazolamide, were associated with reduced colorectal cancer risk. 

“Our findings offer additional insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention. It is essential to evaluate the effects of the reported candidate drugs through both in vitro and in vivo assays in future research,” Yin said. 

Co-first authors of the AJHG paper are Qing Li, PhD; Qingyuan Song; and Zhishan Chen, PhD. The research was supported by the National Institutes of Health (grants R37CA227130, R01CA269589, R01CA297582).

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Vanderbilt University Medical Center offers access to new resources that help relatives connect and join forces to protect their families from inherited diseases. 

VUMC is one of the first cancer centers to partner with the ConnectMyVariant program, which offers resources for families with hereditary cancer risk. The resources make genetic medicine approachable, can help people discover distant relatives they didn’t know before, and can assist families in talking across dinner tables about a potentially sensitive topic. It’s akin to an ancestry game that allows people to amplify the family benefits of cancer prevention, and the person who starts it can be a superhero. 

To launch a connection search, someone with a specific gene variant signs up to meet others who share that variant. When people have the same gene variant, there is more than 90% chance they are related, even if it is several generations back. This begins the process of sharing stories with others who are likely to be relatives, discovering new connections with unknown relatives, and encouraging family members to get tested. The program is designed around the perspective and experience of lay people — not clinicians. It is an innovative approach to encourage genetic testing, and it’s needed, said Tuya Pal, MD, professor of Medicine in the Division of Genetic Medicine and Clinical Pharmacology at VUMC. 

“Family communication, which is the basis of what we call cascade testing, is hugely important,” said Pal, who is also Ingram Professor of Cancer Research and an associate director at Vanderbilt-Ingram Cancer Center. “BRCA genes were identified 30 years ago, but we’ve found maybe 20% of adults who are at risk for cancer. There’s a lot of adults walking around with a BRCA mutation. They could get ongoing prevention, but they don’t know it. This is a challenging nut to crack, but it is of huge public health relevance. If we can get to these people, we can save lots of lives.” 

BRCA1 and BRCA2 gene variants, which increase risk for breast, ovarian, pancreatic and prostate cancer, have received the most media attention. However, in recent years, several other gene mutations have been discovered that can also put people at risk for cancer. Pal stressed that people should seek genetic testing from reputable and accredited laboratories, which are different from many direct-to-consumer testing companies that offer testing for “recreational genetics.” While direct-to-consumer labs offer ancestry testing, sometimes they also delve into other genes; however, the quality of the data they provide is not always accurate for disease risk. For this reason, it is important to get tested through providers knowledgeable about genetic testing options, such as the Vanderbilt Hereditary Cancer Clinic. Insurance typically covers the cost for those at high risk, such as those with a personal history of specific cancers (and diagnosed at certain ages), family history of specific cancers, and those who already have a relative found to have a gene mutation. The tests, which can be done with either blood or saliva samples, cost about $250 for self-paying patients.  

Pal likens a gene mutation to a spelling mistake. 

“When we’re talking about an inherited predisposition, you can think of each gene as a big book, and a mutation is like a ‘spelling mistake’ in that book — leading to the gene not working quite right and thereby raising risk of certain cancers,” she said. “If you’ve got the same spelling mistake between two people, they are somehow related. People sometimes have trouble sharing broadly with family members, so this tool can make this experience of family communication and testing more enjoyable. You can connect with people you don’t know that are related from maybe eight generations ago.” 

ConnectMyVariant, which is operated as a nonprofit organization, was developed by Brian Shirts, MD, PhD, associate professor of Pathology, Microbiology and Immunology and of Biomedical Informatics, who was recruited to VUMC in December 2024. He is the service medical director of the Molecular Genetics Laboratories. 

“Scientific modeling has shown that if we could reach out to second and third cousins effectively of people with known variants, we could identify everyone who has a hereditary cancer risk,” said Shirts, who is also President of ConnectMyVariant’s Board of Directors. 

However, he stressed that ConnectMyVariant is not a research program or a direct clinical resource.  

“It’s an educational program,” Shirts said, noting that people should schedule a visit with a genetic counselor affiliated with a medical provider if they discover they have relatives with mutations that put them at increased risk for cancer.  

ConnectMyVariant offers educational resources for adult-onset hereditary diseases for which there are established preventive actions people can take. It is not intended for use by people younger than 18, so it does not offer resources for autosomal recessive pediatric diseases.  

“The way I like to think about what we offer is ‘If I talk to my relatives, are they going to be able to do something?’ If the answer is yes, and they can get genetic testing and do something that will improve their health, then that’s included,” Shirts said. 

The ConnectMyVariant program also offers participants access to resources for ancestry research, such as professional assistance from the Center for Family History and Genealogy at Brigham Young University.  

For individuals with inherited cancer predisposition, Vanderbilt-Ingram has the Inherited Cancer Registry (ICARE), which Pal founded in 2010. It has grown into one of the largest registries for inherited cancers, with almost 8,000 participants enrolled to date. Through the registry, the latest care and research updates are shared with participants by newsletter, email and links to presentations, and it is a way for people to be part of the larger research mission. 

Pal serves as vice chair of the National Comprehensive Cancer Network Genetics/Familial Guidelines Committee for Breast, Ovarian and Pancreatic Cancer. She leads a team of certified genetic counselors at the Vanderbilt Hereditary Cancer Clinic.

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A multidisciplinary team led by investigators at Vanderbilt University Medical Center has received a $4.2 million grant from the National Cancer Institute (NCI) to probe the genetics of colorectal adenomas — polyps that can develop into colon cancer — and to identify drug candidates that could reduce adenoma recurrence. 

Colorectal cancer is the second most common cause of cancer-related death in the United States, according to the NCI, part of the National Institutes of Health. Removing precancerous polyps during colonoscopy procedures significantly reduces the burden of colorectal cancer, but about 30% of patients who have a colorectal adenoma removed will develop recurrent adenomas. 

“Patients who have recurrent adenomas are at higher risk for developing cancer,” said Xingyi Guo, PhD, associate professor of Medicine in the Division of Epidemiology and lead principal investigator for the project. “We will integrate cutting-edge genomic research with real-world patient data from electronic health records, with the goal of translating genetic discoveries into actionable strategies to prevent colorectal cancer.” 

Zhijun Yin, PhD, MS, associate professor of Biomedical Informatics, is co-principal investigator for the four-year project. 

The team previously conducted genome-wide association studies (GWAS) of about 8,000 colorectal adenoma cases from European American and African American participants included in BioVU, VUMC’s de-identified DNA biobank and linked electronic health records. Using a large-scale analysis of electronic health records and pathology reports, the investigators also established the Vanderbilt Colonoscopy Cohort of colorectal adenoma cases after polyp removal, which includes 76,664 cases. 

With the new funding support, the team will extend its efforts to establish the largest-ever genetic study of colorectal adenoma, drawing on BioVU, the Mass General Brigham Biobank, and the NIH All of Us Research Program to include over 25,000 cases in European Americans and 6,500 cases in African Americans, with thousands of recurrences. African Americans are about 20% more likely to have colorectal cancer and about 40% more likely to die from it compared to other racial groups, according to the American Cancer Society. 

“Our approach will allow us to examine racial differences in adenoma recurrence and colorectal cancer risk,” Guo said. 

In addition to GWAS, the team will conduct transcriptome-wide, methylome-wide, and proteome-wide association studies to identify genes and proteins associated with colorectal adenomas and their recurrence. The investigators will integrate findings from these “omics” studies with electronic health record data from the Vanderbilt Colonoscopy Cohort and the Mass General Brigham Colonoscopy Cohort and use machine learning frameworks to identify candidate drugs that could prevent colorectal adenoma recurrence. They will test the most promising drug candidates in colorectal adenoma and cancer cells, patient-derived organoids, and animal models. 

“This project is an innovative integration of multiomics analyses with electronic health record-based real-world clinical evidence,” Yin said. “We anticipate that our findings will inform personalized colorectal polyp surveillance, guide therapeutic prevention strategies, and ultimately reduce the burden of colorectal cancer nationwide.” 

Guo holds a secondary appointment in the Department of Biomedical Informatics at VUMC, and Yin holds secondary appointments in the Department of Computer Science and the Department of Electrical and Computer Engineering at Vanderbilt University. Guo and Yin have both received NCI R37 MERIT Awards, which provide long-term grant support to outstanding investigators. 

Other collaborators for the new NCI grant (R01CA297582) include VUMC Department of Medicine investigators Wei Zheng, MD, PhD, MPH, Qiuyin Cai, MD, PhD, and Wanqing Wen, MD, MPH, Division of Epidemiology; Bhuminder Singh, PhD, Division of Gastroenterology, Hepatology and Nutrition; and Kristen Ciombor, MD, MSCI, Division of Hematology and Oncology; and Harvard T.H. Chan School of Public Health investigator Mingyang Song, ScD, Departments of Epidemiology and Nutrition.

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Researchers from Vanderbilt University Medical Center have demonstrated in a precision-based clinical trial that a magnesium supplement increases gut bacteria in humans that have been shown to synthesize vitamin D and inhibit colorectal cancer carcinogenesis.

However, the effect was observed primarily in females — an outcome that the researchers surmised may be attributable to the role that estrogen plays in shifting magnesium from circulation into cellular uptake.

Intestinal microbiome data and colonoscopy results were analyzed from participants who were randomized by whether they had the TRPM7 genotype, which plays a crucial role in regulating magnesium and calcium uptake.

Previously, the investigators showed in the same randomized trial that magnesium enhances the synthesis of vitamin D and increases the blood levels of vitamin D. The findings from the current study suggest that magnesium also increases the gut synthesis of vitamin D, which does not go to the blood and takes effect locally.

These results from the Personalized Prevention of Colorectal Cancer Trial were published Sept. 12 inThe American Journal of Clinical Nutrition. 

“Our previous study showed magnesium supplementation increased blood levels of vitamin D when vitamin D levels were low,” said Qi Dai, MD, PhD, professor of Medicine. “The current study reveals that magnesium supplementation also increases the gut microbes which have been shown to synthesize vitamin D in the gut without sunlight and locally inhibit colorectal cancer development.”

The participants were divided into two arms, one that received the magnesium supplement and another that received a placebo. Their gut microbiome was analyzed from stools, rectal swabs and rectal tissues. Among participants with adequate TRPM7 function, the magnesium supplement increased Carnobacterium maltaromaticumand Faecalibacterium prausnitzii, which were previously found to work synergistically to increase vitamin D and decrease colorectal carcinogenesis. Among those with inadequate TRPM7function, the magnesium supplement reduced the abundance of F. prausnitziiin rectal mucosa.

Among 236 participants who all had a history of colorectal polyps, 124 underwent colonoscopies after completing the trial with a 3.5-year median follow-up time. A higher abundance of F. prausnitzii in rectal mucosa was associated with an almost threefold increase in developing additional polyps.

The findings suggest that magnesium supplementation treatment may decrease colorectal cancer risk in individuals with inadequate TRPM7function. All together, these findings provide new insights into the interplays between nutrition and gut microbiome contributing to colorectal carcinogenesis and establish the foundation for a precision-based strategy for prevention of colorectal cancer in high-risk populations.

The researchers received support from the National Cancer Institute (R01 DK110166, R01 CA149633 and R03 CA 189455) and the Vanderbilt-Ingram Cancer Center Endowment Fund. Dai and Martha Shrubsole, PhD, Ingram Professor of Cancer Research and research professor of Medicine, are principal investigators of the grant that funded the microbiome research from the National Institute of Diabetes and Digestive and Kidney Diseases (DK110116).

Other major Vanderbilt authors on the study include Elizabeth Sun, Xiangzhu Zhu, MD, MPH, Reid Ness, MD, MPH, Harvey Murff, MD, MPH, and Lei Fan, MD, PhD. The first author, Elizabeth Sun, a medical student at Vanderbilt University School of Medicine, was elected for an Early Investigator Travel Award, a young investigator lightning talk, and an in-person poster presentation at the Precision Nutrition Forum and PREDIMED Omics Symposium 2025 held by Harvard University.

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Four researchers at Vanderbilt-Ingram Cancer Center have assumed new leadership roles. 

Shared resources at Vanderbilt-Ingram are designed to support and enhance cancer-relevant research and scientific interaction by providing access to cutting-edge technologies and services, as well as scientific expertise.

Scott Hiebert, PhD, emeritus professor of Biochemistry and the Hortense B. Ingram Chair in Cancer Researchat Vanderbilt University, led these shared resources in the Cancer Center from 2010 to 2025. With his retirement from Vanderbilt University, Ben Ho Park, MD, PhD, director of Vanderbilt-Ingram, has appointed William Tansey, PhD, Ingram Professor of Cancer Research and professor of Cell and Developmental Biology, as the next associate director for Shared Resources for Vanderbilt-Ingram.  

As associate director for Shared Resources, Tansey will oversee 10 resources, including animal and human imaging, bioanalytics and proteomics, chemical synthesis and high-throughput analytics, cell imaging, data science, flow cytometry, genome editing, genomic sciences, survey and biospecimen, and translational pathology. In addition to his leadership roles at Vanderbilt-Ingram, Tansey has an active research lab that focuses on transcriptional dysregulation in cancer cells. 

“Shared resources provide Vanderbilt-Ingram Cancer Center investigators access to technologies, expertise, and a collaborative infrastructure that would be impractical to have in their own laboratories. Our shared resources are world-class in every respect, and each of them are backed by experienced teams of professionals dedicated to advancing and accelerating cancer discovery. I am honored and excited to oversee this vital and vibrant part of the Vanderbilt-Ingram Cancer Center mission,” said Tansey, who also serves as co-leader of the Genome Maintenance Research Program at Vanderbilt-Ingram. 

Translational Research, which is an essential component of Vanderbilt-Ingram and how findings in the lab are “translated” to clinical practice, was previously led by Park. With an ever-increasing number of opportunities to perform translational cancer research at Vanderbilt-Ingram, Douglas Johnson, MD, MSCI, professor of Medicine and the holder of the Susan and Luke Simons Directorship, has been named the next associate director for Translational Research.  

Johnson will oversee the implementation of emerging treatments and therapy advancements, such as cellular therapies, immunotherapies and targeted therapies. Johnson, who is clinical director of melanoma at Vanderbilt-Ingram, has expertise in this realm, having been an investigator on early clinical trials for immunotherapies and having recently implemented a tumor-infiltrating lymphocyte therapy service line for patients. 

“Vanderbilt-Ingram Cancer Center has incredible strengths in translating observations in the lab to the clinic, and from the clinic to the lab. I look forward to continuing to work with so many talented scientists and physicians in this role,” Johnson said. 

Douglas Kojetin, PhD, Ingram Associate Professor of Cancer Research and associate professor of Biochemistry, will join two other experts as co-leader of the Genome Maintenance Research Program. He joins Tansey and David Cortez, PhD, the Richard N. Armstrong PhD Professor of Innovation in Biochemistry, at the helm. The Genome Maintenance Research Program is focused on understanding how DNA is damaged, repaired, packaged, expressed and replicated. These are the processes that take place in carcinogenesis. 

“Dr. Kojetin will be an outstanding leader of the Genome Maintenance Program,” Cortez said. “His own research program is creative, rigorous and impactful. His thoughtfulness, enthusiasm and dedication to service will help our entire research community to make discoveries that reduce the suffering caused by cancer. I look forward to working with him.”  

Kristen Ciombor, MD, MSCI, has been named co-leader of the Gastrointestinal (GI) Cancer Research Program. She brings a wealth of knowledge to this role, having previously been co-leader of the Translational Research and Interventional Oncology Research Program. She is nationally and internationally recognized for her clinical research program and clinical expertise in colon cancer.

Ciombor also serves as the principal investigator for the NCI-funded National Clinical Trials Network (NCTN) Lead Academic Participating Site (LAPS) grant at Vanderbilt-Ingram. Ciombor will join Cathy Eng, MD, who has led the GI Research Program for seven years, as she transitions away from this role over the next six months to focus more on her role as associate director of Strategic Relations and Research Partnerships and the Young Adult Cancers Program at Vanderbilt-Ingram.  

Park said the four researchers have established track records that make them the perfect choice for their new respective leadership roles. 

“Drs. Tansey, Johnson, Kojetin and Ciombor are all highly respected cancer researchers with the leadership skills to effectively lead these areas at Vanderbilt-Ingram,” Park said. “Cancer encompasses a myriad of complicated diseases, and our investigators are approaching it from many fronts. The research areas these scientists lead, and their ability to cultivate interactions across and between programs, are integral to our mission of advancing treatments and improving outcomes for people with cancer.” 

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A colorectal cancer research team led by Robert Coffey, MD, has received a prestigious Specialized Programs of Research Excellence (SPORE) grant renewal totaling $12.6 million from the National Cancer Institute (NCI) for a five-year period.

The grant marks ongoing funding of the GI SPORE awarded to Coffey’s team, which dates back to its inception at the Vanderbilt-Ingram Cancer Center in 2002. Currently, Vanderbilt-Ingram is one of only four cancer centers in the United States with GI Cancer SPORE funding. The team has made numerous discoveries over the past 23 years, and it plans to build upon those achievements with the goal of “drugging the undruggable.”

Applications for SPORE funding are intensely competitive. SPORE grants are highly sought after because they show that a cancer center demonstrates scientific excellence, promotes collaboration, maintains robust research programs and merits substantial funding — factors that are key determinants for an NCI designation as a Comprehensive Cancer Center.

“Our success is built upon clinical and basic investigators working closely together with patient advocates,” said Coffey, Ingram Professor of Cancer Research, professor of Medicine and of Cell and Developmental Biology, and co-director of the Epithelial Biology Center.

Coffey, the grant’s principal investigator, is joined by clinical co-leaders, basic science co-leaders, and patient advocates in pursuing three projects that are aimed at targeting three mechanisms of colorectal cancer progression: immune exclusion, MYC activation, and Wnt pathway activation. Each project has an embedded patient advocate to ensure that each project is focused on its translational goal.

“Securing SPORE funding is an achievement to be recognized, but having a program funded for 23 years is truly outstanding,” said Ben Ho Park, MD, PhD, the Benjamin F. Byrd Jr. Professor of Oncology and director of Vanderbilt-Ingram. “Congratulations go to Dr. Coffey, the principal investigator, and to the entire research team for a job well done. With this grant renewal, they are building upon years of rigorous and innovative research and are making great progress towards developing new therapies for gastrointestinal cancers that are recalcitrant to current treatment modalities.”

The team dedicated to the project of overcoming immune exclusion in microsatellite stable colorectal cancer includes clinical co-leader, Jordan Berlin, MD, associate director for Clinical Research at Vanderbilt-Ingram, Cornelius Abernathy Craig Professor of Medicine and director of the Division of Hematology and Oncology, along with basic science co-leaders Coffey and Ken Lau, PhD, professor of Cell and Developmental Biology and of Surgery and director of the Center for Computational Systems Biology.

Immunotherapies such as immune checkpoint blockade inhibitors have proven effective for a number of cancers, including a subset of colorectal cancer, but not for the 85% to 90% of colorectal cancers that are deemed microsatellite stable. The team will launch a clinical trial to see if an investigational drug can spur response in microsatellite stable colorectal cancers when combined with the immunotherapy drug pembrolizumab.

The investigators will also determine whether response can be tracked by monitoring proteins associated with plasma supermeres, novel nanoparticles discovered by the Coffey lab.

The team dedicated to targeting MYC is led by clinical co-leader, Kristin Ciombor, MD, MSCI, co-leader of the Gastrointestinal Cancer Research Program at Vanderbilt-Ingram, Ingram Associate Professor of Cancer Research and associate professor of Medicine. The basic science co-leader is William Tansey, PhD, associate director for Shared Resources and co-leader of the Genome Maintenance Research Program at Vanderbilt-Ingram, Ingram Professor of Cancer Research and professor of Cell and Developmental Biology.

Overexpression of the MYC gene is common in colorectal cancer, and the team will delve into whether a site on the protein WDR5 that plays a role inMYC action can be targeted for therapeutic benefit for patients with unresectable colorectal cancer. The investigators will lead a clinical trial to investigate the tolerability and antitumor efficacy of an experimental therapy developed by Stephen Fesik and Tansey in the last cycle of the SPORE award.

The team developing an inhibitor drug for the Wnt pathway is led by clinical co-leader, Cathy Eng, MD, co-leader of the Gastrointestinal Cancer Research Program at Vanderbilt-Ingram, David H. Johnson Professor of Surgical and Medical Oncology and professor of Medicine, along with basic science co-leaders Stephen Fesik, PhD, the Orrin H. Ingram II Professor of Cancer Research and professor of Biochemistry, Pharmacology and Chemistry, and Ethan Lee, MD, PhD, professor of Cell and Developmental Biology and of Pharmacology.

Activation of the Wntpathway is a characteristic of colorectal cancer and has been notoriously hard to target without adverse toxicities. The Wnt-focused team will be developing a first-in-class inhibitor that could revolutionize the landscape of treatment for colorectal cancer due to its dependence on Wnt activation for establishment and progression.

The GI SPORE grant also cultivates future scientific advancement through the Career Enhancement Program at Vanderbilt-Ingram, which recruits young investigators and helps them develop into independent researchers. Participants can apply for seed funding — small grants that help them establish the basis for research achievements that merit additional funding.

These programs are led by Karen Winkfield, MD, PhD, associate director for Community Outreach and Engagement at Vanderbilt-Ingram, Ingram Professor of Cancer Research and professor of Radiation Oncology, and Richard Peek, MD, the Mina Cobb Wallace Professor of Immunology and professor of Medicine and Pathology, Microbiology and Immunology.

Overall, this grant is a large accomplishment that shows the importance of team science and collaboration of basic and clinical leaders together with patient advocates to propel advances in the diagnosis and treatment of GI malignancies.

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Vanderbilt-Ingram Cancer Center, a leader in research to better understand early-onset cancers and to address the unique challenges faced by younger patients, will be holding the VICC 2025 Young Adult Cancer Symposium on Nov. 15.

The symposium, which is a CME-accredited event, offers clinicians, patients, caregivers and advocates the opportunity to learn from internationally known experts focused on early-onset cancers.

The inaugural event will begin with a 7 a.m. breakfast and end at 3 p.m. at Listening Room Cafe, 618 4^th Ave. South, in Nashville. There will be a meet-and-greet the evening before the symposium, on Nov. 14, from 6 to 8 p.m. at The Printing House Hotel, 501 3^rd Ave. South, in Nashville.

The symposium will focus on breast cancer, colorectal cancer and stem cell therapies, as well as discussions on other topics.

“The Vanderbilt-Ingram Young Adults Cancer Program is one of the first in the country.” said Cathy Eng, MD, the David H. Johnson Endowed Professor of Surgical and Medical Oncology, professor of Medicine and executive director of the VICC Young Adult Cancers Program. “Early-onset cancer is a global matter of concern.

“By 2040, early-onset cancer cases are projected to increase by approximately 14%, resulting in 1.15 million deaths. Colorectal cancer is expected to become the leading cause of cancer death by 2030, with about 49new cases daily. Breast cancer continues to rise, with approximately 35 new cases daily. Bloodborne cancers may result in the range of 50 to 75 new cases per day.”

To meet this challenge and to better serve younger patients, Vanderbilt-Ingram established the Young Adults Cancer Program in 2019.

“Since the program’s inception, referrals have increased by about 80%, leading to 1,250 individual, new patient visits in 2024,” Eng said. “Our goals are to empower young adult patients with the latest research and treatment updates; foster a community among patients, caregivers, and advocates; and address the unique psychosocial challenges faced by young adults navigating cancer care. We hope this event will inspire support for young adult cancer research and become an annual event.”

Guest speakers include:

• Ann Partridge, MD, MPH, interim chair of the Department of Medical Oncology and the co-founder and director of the Program for Young Adults with Breast Cancer at Dana-Farber Cancer Institute, will speak on breast cancer.
• Terri Woodard, MD, professor of Gynecologic Oncology and Reproductive Medicine at MD Anderson Cancer Center, will speak on fertility preservation.
• Neel Bhatt, MBBS, MPH, associate professor in the Clinical Research Division at Fred Hutchinson Cancer Center and a hematologist-oncologist specializing in treating young adults with blood cancers, will speak about financial toxicity and the economic challenges that younger patients encounter.

Vanderbilt-Ingram cancer experts will address breast and colorectal cancer, hematologic malignancies, early-onset cancers, survivorship, and sexual health/sexual dysfunction/body image. The symposium will also feature patients and advocates who will share their perspectives.

Go here to register on Eventbrite.

Registration fees:

• Survivors, advocates and patients:
  • $55 (early registration) or $70 (as of 10/1).
  • Registration fees will be waived for the first 100 survivors/patients.
• Other healthcare providers:
  • $65 (early registration) or $77 (as of 10/1).
• Physicians:
  • $85 (early registration) or $100 (as of 10/1).

A $10 discount is available to Vanderbilt University Medical Center/VICC employees.

For additional information, please contact Hasani Bland, hasani.l.bland@vumc.org.

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A study led by researchers from Vanderbilt University Medical Center has discovered genetic susceptibilities that may shed light on why people of African ancestry are disproportionately affected by lung cancer.  

Prior research has shown that Americans of African ancestry have a higher risk of lung cancer compared to white Americans despite smoking fewer cigarettes, but the reasons for this difference are not fully understood, and studies that delve into genetic susceptibilities for lung cancer among this population group have been limited. New research published Aug. 18 in the American Journal of Human Genetics revealed a total of 10 genomic regions — four of which had never been previously reported — associated with lung cancer. 

The researchers performed genome-wide association studies on 6,490 people of African ancestry that included 2,390 with a diagnosis of lung cancer and a control group of 4,100 for comparison. 

The authors confirmed that a well-known genetic region on chromosome 15 plays a major role in lung cancer risk across populations. The authors also discovered four additional genetic regions (on chromosomes 3, 8, 14 and 18) that had not been linked to lung cancer before. When their findings were combined with results from European and Asian populations, a total of 17 genetic regions were associated with lung cancer risk. Several genes in these regions are involved in biological processes such as lung function, cell growth and DNA repair.  

“Our work provides a critical advance in lung cancer by improving our limited understanding of genetic susceptibility in African ancestry populations and offers insights that may guide future treatment efforts,” said the study’s corresponding author, Melinda Aldrich, PhD, MPH, professor of Medicine, Thoracic Surgery and Biomedical Informatics at Vanderbilt.  

Aldrich and Jacklyn Hellwege, PhD, research assistant professor of Medicine, are the study’s senior authors. 

“This work was uniquely positioned to make use of advances in statistical modeling and genetic ancestry information to ultimately make new insights into the genetic architecture of lung cancer in this at-risk population,” said Hellwege. 

VUMC researchers received support from National Institutes of Health grants (U01CA253560, U01CA202979, R01CA141769, R01ES006717, P30CA022453 and P30CA068485) for the study. 

Other VUMC authors on the study are Michael Betti, PhD, James Jaworski, MPH, Shilin Zhao, PhD, and Eric Gamazon, PhD, MS. 

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Plant-based diets have become popular for their health and environmental benefits. 

However, these benefits may vary based on the quality of the plant foods and other foods that make up the diet. A recent study at VUMC analyzed the association of plant-based diet patterns with mortality in over 77,000 mostly Black and low-income participants in the Southern Community Cohort Study, which started in 2002.  

Dietary intakes were assessed using a validated, 89-item food frequency questionnaire. The investigators generated three measures to assess the association of diet and risk of premature death: an overall plant-based diet index (PDI) that included both healthy plant foods (such as whole grains, fruits and vegetables) and unhealthy plant foods (such as fruit juices, refined grains and potatoes); a healthy plant-based diet index (hPDI); and an unhealthy plant-based diet index (uPDI).  

The study follow-up was through 2022 with a median duration of almost 17 years. The investigators identified over 26,000 deaths during the duration of the study. The highest PDI and hPDI scores were associated with reduced mortality; while the highest uPDI scores were associated with elevated mortality. 

The findings were reported in the The American Journal of Clinical Nutrition, a journal of the American Society for Nutrition. They show a strong association between high quality plant-based diets and reduced mortality rate among low-income populations, suggesting that efforts to promote diets high in healthy plant foods and low in animal foods could improve health outcomes. 

Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and director of the Vanderbilt Epidemiology Center, is the corresponding author of the study. Fangcheng Yuan, a graduate student in the PhD Program in Epidemiology, is the first author. 

This work was supported by the National Cancer Institute, part of the National Institutes of Health (grant U01CA202979).

Guillermo Sanchez, PhD, is a staff scientist in the lab of Nick Zachos, PhD, associate professor of Surgery and Cell and Developmental Biology at Vanderbilt University.

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