One person in 10 over the age of 70 will experience an explosive, clonal growth of abnormal blood cells, called clonal hematopoiesis of indeterminant potential or CHIP, that increases the risk of blood cancer and death from cardiovascular, lung and liver disease. 

The risk of blood cancer differs significantly, however, depending upon whether patients with CHIP also develop cytopenia (low blood cell count). 

An analysis of genetic sequencing data from more than 34,000 people over a 17-year period by researchers at Vanderbilt University Medical Center has found that persistent cytopenia appears to be a critical step in the progression of CHIP to blood cancer. 

For patients with CHIP who developed cytopenia, the risk of progression to blood cancer was 10 times higher than it was for patients without cytopenia — a 1-in-200 chance per year versus 1 in 2,000, the researchers report in the June 2025 issue of the Lancet journal, eClinicalMedicine.  

These findings suggest that checking blood counts regularly may be an effective way to monitor patients with CHIP for their risk of developing blood cancer, and cytopenia-free survival may be a valuable endpoint for clinical trials aimed at preventing blood cancer in these patients.

“This work is the largest longitudinal analysis of its kind and provides a roadmap for identifying high-risk CHIP patients who may benefit from closer monitoring or early intervention,” said the paper’s corresponding author, Alexander Bick, MD, PhD, associate professor of Medicine and director of the Division of Genetic Medicine at VUMC. 

“It also lays the groundwork for more feasible and targeted clinical trials in blood cancer prevention,” he said. 

Bick is internationally known for his research on the genetics of blood disorders. He and his colleagues have advanced the understanding of somatic (non-inherited) mutations in blood stem cells that can trigger a potentially life-threatening clonal growth of abnormal cells known as CHIP.  

Blood cancer (myeloid neoplasm) results from the abnormal growth of myeloid (blood) cells in the bone marrow. The current study compared blood cancer rates in patients with CHIP who did not develop cytopenia, to those with both CHIP and concurrent, clonal cytopenia of undetermined significance. 

Led by the paper’s first authors, James Brogan, MD, MS, a resident physician in the Department of Medicine, and Ashwin Kishtagari, MD, assistant professor of Medicine in the Division of Hematology and Oncology, the study required large numbers. 

The researchers pulled genetic sequencing data from three major population-level cohorts: the National Institutes of Health (NIH) All of Us Research Program, the UK (United Kingdom) Biobank and VUMC’s biobank, BioVU. 

With roughly 350,000 DNA samples collected to date, BioVU is the world’s largest repository of genetic material linked to de-identified electronic health records (EHRs) based at a single academic center.  

Access to whole genome sequences linked to EHRs for more than 107,000 adults enrolled in BioVU between 2006 and 2023 was provided through the Alliance for Genomic Discovery (AGD), a unique endeavor to accelerate the application of large-scale genomics to biomedical science and therapeutic development. 

Launched in 2022 by Nashville Biosciences LLC, a wholly owned VUMC subsidiary, and the global DNA sequencing giant Illumina Inc., AGD now includes eight major pharmaceutical companies that support the development and availability of whole genome sequences for research aimed at identifying disease associations and targets for intervention. 

The report in eClinicalMedicine “is one of the first papers to leverage data from the BioVU/Alliance for Genomic Discovery whole genome sequencing effort,” Bick said. “It also highlights how at VUMC medical trainees are doing cutting-edge research while developing as physicians.” 

Between the three biobanks, the researchers had access to 805,000 whole genome sequences. From this pool, they identified 8,114 individuals with CHIP who did not develop cytopenia and 1,260 who did. These 9,374 cases were matched with 24,749 controls who did not have CHIP. 

The annual blood cancer progression rate for participants with CHIP who did not develop cytopenia was nearly the same as the rate observed in the control population without CHIP (0.06% versus 0.04%), whereas the rate was 10 times higher for those with both CHIP and cytopenia (0.5% per year). 

Approximately 13% of participants with CHIP developed a cytopenia within five years. Men, smokers and older individuals (over 64) were at a higher risk of developing cytopenia, as were those who had two or more mutations or any high-risk mutations associated with CHIP. 

“Given the substantial risk of cytopenia, patients with multiple high-risk features may benefit from regular monitoring for cytopenia progression,” the researchers concluded. The good news is that this five-year window before the development of cytopenia and blood cancer “provides an opportunity for early intervention with potential disease-modifying therapies,” they wrote.  

Treatments for cytopenia range from drugs that stimulate the production of certain blood cell types to bone marrow or stem cell transplants. 

Co-authors from the Bick lab included rheumatology fellow Robert Corty, MD, PhD, Yash Pershad, an MD-PhD student, and Brian Sharber, MS. Other VUMC co-authors included faculty members Brett Heimlich, MD, PhD, Leo Luo, MD, Brent Ferrell Jr., MD, Michael Savona, MD, and Yaomin Xu, PhD. 

This research was supported by NIH grants DP5OD029586, R01AG088657, R01AG083736, and P30CA068485, the Burroughs Wellcome Fund Career Award for Medical Scientists, the Edward P. Evans Foundation, and the Pew Charitable Trusts and the Alexander and Margaret Stewart Trust. 

Savona holds the Beverly and George Rawlings Directorship. Bick is supported in part by a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research, and Brogan is supported in part by an American Society of Hematology HONORS Award.

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Cases of appendiceal cancer tripled for Americans born between 1976 to 1984 and quadrupled for those born between 1981 to 1989, according to a study published June 9 in the Annals of Internal Medicine. 

The study compared chronological data in five-year intervals from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program, using 1941 to 1949 as the baseline. The lead author, Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, said the findings reveal the need for increased awareness about appendiceal cancer from both clinicians and the public as well as more research to determine the reasons for the sharp spike in incidence.  

“When you take these alarming rates that we are seeing for appendiceal cancer across generations, together with the fact that 1 in every 3 patients diagnosed with appendiceal cancer is diagnosed under the age of 50, these point to a timely need for everyone to be aware of the signs and symptoms of appendix cancer.

“Albeit cancer of the appendix is rare, it is important for individuals who have these symptoms to see a health care professional. Ruling out the possibility of an appendix cancer diagnosis, or diagnosing it early, is important for this cancer as we continue to learn what factors may be contributing to this worrisome trend,” Holowatyj said.

Symptoms may include abdominal pain, bloating, changes in bowel habits, and loss of appetite. 

Appendiceal cancer is a rare cancer with about 3,000 new cases diagnosed every year in the United States, according to prior studies, but Holowatyj and colleagues took a closer look at statistics by combing through the SEER database. 

“As incidence rates in younger generations are often indicative of future disease burden, these results support the need for histology-specific investigations of appendiceal adenocarcinoma, as well as increased education and awareness of appendiceal adenocarcinomas among health care providers and the public,” the study stated. 

Appendiceal cancer has had no standardized screening guidelines, risk factors or tumor classifications — a lack of clinical evidence that has resulted in late diagnosis and poor prognosis. Up to 1 of every 2 patients is diagnosed with distant metastatic disease, and five-year survival rates vary between 10% and 63%.  

Earlier this year, Holowatyj and a team of experts identified six key research priority areas to deliver a fundamental understanding of appendiceal tumors and to improve treatments and outcomes for patients.  

The recommendations published Feb. 20 in Nature Reviews Cancer are the result of a concerted focus by the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation to better understand the disease that afflicts an estimated 3,000 new patients across all age groups each year. 

The recommendations arose from the inaugural ACPMP Research Foundation Scientific Think Tank, sponsored by ACPMP and chaired by Holowatyj at Vanderbilt-Ingram Cancer Center in December 2023. 

The current study in the Annals of Internal Medicine received support from ACPMP and the National Institutes of Health (grants K12HD043483 and P50CA236733). 

Other authors on the study are Mary Kay Washington, MD, PhD, professor of Pathology, Microbiology and Immunology at VUMC, Richard Goldberg, MD, of the West Virginia University School of Medicine, and Caitlin Murphy, PhD, MPH, of the UT Health Houston School of Public Health. 

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Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine, has been named to the 40 Under 40 In Cancer Class of 2025 by the Association for Value-Based Cancer Care.

This year’s class was selected from more than 3,000 nominations. The awards initiative identifies and recognizes contributions across the field of cancer by rising stars and emerging leaders under the age of 40. 

Holowatyj’s research is focused on early-onset cancers, including colorectal and appendiceal cancers. She has received the National Cancer Institute’s Method to Extend Research in Time (MERIT) Award to support her ongoing investigation into how early-onset colorectal cancer and its treatments impact reproductive health. MERIT Awards provide longer-term funding than is typical for most grants to early-stage investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. As part of this Award, Holowatyj established and leads the Preserving Fertility After Colorectal Cancer (PREFACE) clinical study, which is currently recruiting patients.  

She is focused on providing evidence-based guidance that will ultimately improve clinical care and outcomes for individuals ages 18 to 49 when diagnosed with cancer. Holowatyj and her team discovered that 1 in 2 young cancer patients report that a health care provider involved in their cancer care did not discuss options to preserve fertility prior to starting cancer treatment. 

Her research has been published in high-impact medical research journals and has led to clinical practice changes and revisions to consensus guidelines. She has also been invited to serve on several international committees, including the American Joint Committee on Cancer Lower Gastrointestinal Tract Expert Panel that updates clinical cancer staging systems, the Fight Colorectal Cancer Global Early-Onset Colorectal Cancer Think Tank, and as the inaugural chair of the Scientific Advisory Board for the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation. This year, with the support of the ACPMP Research Foundation, she led an expert recommendation report in the journal Nature Reviews Cancer that identified six key research priority areas to deliver a fundamental understanding of appendiceal tumors and to improve treatments and outcomes for patients with this rare cancer.

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Navigational bronchoscopy is as effective as the traditionally used transthoracic needle biopsy for diagnosing lung nodules, but with significantly fewer complications, per a new study published May 18 in the New England Journal of Medicine. This development may shift medical practice and reduce hospitalizations for patients undergoing lung nodule biopsies, said researchers.  

Each year, millions of lung nodules are detected during routine X-rays or CT scans. While most nodules are benign, some are cancerous and when found at this stage they are the earliest and most curable stage of lung cancer.   

Accurate biopsy of lung nodules is often required to tell benign nodules from malignant ones. To date, the most commonly used method, CT-guided transthoracic needle biopsy, carries a high complication rate — including pneumothorax, or partial lung collapse, affecting about 25% of patients. Treatment of the partially collapsed lung often requires a chest tube during a multiple day inpatient stay.  

This study is the first to directly compare these biopsy techniques and the results are compelling, said first author Robert Lentz, MD, associate professor of Medicine and Thoracic Surgery in the Division of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt University Medical Center. The study, conducted across seven centers in the United States, compared the two techniques in a multicenter, randomized trial involving 234 patients with lung nodules between 10-30 mm.  

Navigational bronchoscopy uses a sophisticated targeting system and 3D imaging to guide biopsy tools through small peripheral airways directly to a lung nodule.   

The comparison revealed a diagnostic accuracy of 79% using navigational technology, closely matching the 74% accuracy of transthoracic biopsy. More importantly, the risk of pneumothorax was significantly lower, occurring in only 3% of bronchoscopy patients compared to 35% in those undergoing transthoracic biopsy. Severe cases requiring hospital admission or chest tube insertion were less than 1% with bronchoscopy, as opposed to 14% with the traditional method.  

“With approximately 300,000 lung nodule biopsies performed annually in the U.S., shifting to navigational bronchoscopy could greatly reduce complications and hospital stays. This study confirms its diagnostic efficacy and superior safety profile, making it the preferred choice for lung nodule diagnosis,” said senior author Fabien Maldonado, MD, MSc, professor of Medicine and Thoracic Surgery and director of Interventional Pulmonology.  

The research team plans to continue exploring optimal biopsy techniques, comparing different navigational and robotic bronchoscopy systems, and studying novel biopsy tools, said Maldonado, Pierre Massion Director in Lung Cancer Research.  

They are also involved in research on bronchoscopic ablation of lung cancer, advancing the field of interventional pulmonology.  

“As a relatively new medical subspecialty, we are quite proud and excited to have matured our research infrastructure to the point of being able to produce high quality multicenter trials like this, and hope that publication of this trial will serve as an introduction of sorts for interventional pulmonology to the larger general medical audience,” said Lentz.   

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A grant from VoLo Foundation will augment federal funding for the Southern Environmental Health Study, an initiative to determine whether environmental exposures are contributing to cancer cases in the region.

The study received its initial funding from the National Cancer Institute and the Vanderbilt-Ingram Cancer Center. A grant from VoLo Foundation — a private nonprofit organization dedicated to accelerating global impact through science-based solutions, education enhancement, and health improvement initiatives — will allow investigators to recruit additional participants and conduct methylation- and proteomics-based biological aging assays to check for biomarkers of early disease risk.

On cancer incidence and mortality maps, some of the highest rates in the country appear in the southern U.S., but whether environmental exposures are a contributing factor has not been scientifically determined. The study is a long-term cohort investigation that will follow participants for at least 10 to 20 years. The participants are between the ages of 40 and 70 and live in Alabama, Arkansas, Delaware, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, South Carolina, Texas, Tennessee, Virginia, West Virginia or the District of Columbia.

“Humans are exposed to large numbers of chemicals and their mixtures with more than 80,000 chemicals having been registered by the Environmental Protection Agency,” said Wei Zheng, MD, PhD, MPH, the Anne Potter Wilson Professor of Medicine and the director of the Vanderbilt Epidemiology Center. “However, very few of them have been adequately investigated in relation to human cancers and other diseases in epidemiologic studies. There are considerable challenges in studying environmental exposures in epidemiologic studies.”

Participants will wear silicone wristbands designed to collect chemicals, which researchers will use to measure exposure to approximately 500 compounds. They will also analyze blood samples to assess the internal exposome using both liquid chromatography and gas chromatography with high-resolution mass spectrometry, allowing them to detect approximately 1,500 confirmed chemicals and endogenous metabolites. To identify potential environmental carcinogens, the researchers will use an innovative exposome-wide association study to link chemical exposures with disease biomarkers, including indicators of biological aging and inflammation.

“Supporting the Southern Environmental Health Study aligns with our mission to advance data-driven solutions that can lead to healthier, more resilient communities. This research has the potential to uncover possible links between environmental exposures and chronic diseases,” said David Vogel, co-founder and chief scientist of VoLo Foundation.

Vogel and his wife, Thais Lopez Vogel, formed the VoLo Foundation in 2014.

“We are very grateful for the support of the VoLo Foundation and believe that this study will generate significant amounts of novel data regarding potential impacts of environmental exposures on human health and pave the way for future studies in this important area,” Zheng said.

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The cellular therapy programs at Vanderbilt-Ingram Cancer Center, Monroe Carell Jr. Children’s Hospital at Vanderbilt, and the VA Tennessee Valley Healthcare System have received reaccreditation from the Foundation for the Accreditation of Cellular Therapy (FACT).

Founded in 1995, FACT establishes standards for high quality medical and laboratory practice in cellular therapies. FACT is a nonprofit corporation co-founded by the International Society for Cell and Gene Therapy and the American Society for Transplantation and Cellular Therapy for the purposes of voluntary inspection and accreditation in the field of cellular therapy.

“FACT is an internationally recognized accrediting body for hospitals that offer stem cell transplant and cellular therapy, and recognition by FACT indicates that the accredited institution has met the most rigorous standard in every aspect of cellular therapy,” said Adetola Kassim, MD, professor of Medicine and director of the Vanderbilt Stem Cell Transplant and Cellular Therapy Program. “This covers the entire spectrum of stem cell therapy from clinical care to donor management, cell collection, processing, storage, transplant, administration and cell release.”

The Vanderbilt and VA Tennessee Valley Healthcare System programs received accreditation notification on April 14 after on-site inspections in October 2024. The accreditation is effective for three years.

“Congratulations to the entire Vanderbilt University Medical Center and VA Tennessee Valley Healthcare System team on achieving FACT accreditation and providing quality care for the people we serve,” Kassim said.

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Kimberly Dahlman, PhD, associate professor of Medicine in the Division of Hematology and Oncology, has been elected to the board of directors of the International Association of Medical Science Educators (IAMSE). 

Dahlman, who is the assistant director of Cancer Research Training and Education at Vanderbilt-Ingram Cancer Center, will begin serving her three-year term upon the closing of the association’s annual conference on June 17. She serves as co-director of the third- and fourth-year undergraduate medical education curriculum at Vanderbilt University School of Medicine and as co-director of the Research Education Core of the Meharry-Vanderbilt-Tennessee State University Cancer Partnership.

She is also director of the VERTICAL post-baccalaureate program, the V-EXCEL undergraduate cancer research program and the VISTO medical student research program at Vanderbilt-Ingram. Nationally, she is president of the Association of Biochemistry Educators.  

With more than 2,000 members, the IAMSE’s mission is to advance health profession education through teacher development and to ensure that the teaching and learning of medical science continues to be firmly grounded in foundational sciences and the best practices of teaching. 

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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.

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.

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Some cancer patients experience durable remissions from immune checkpoint inhibitors that spur their T cells to attack cancer cells, but these immunotherapies can also cause reactions.

One of the adverse effects of these treatments is skin reactions known as cutaneous immune-related adverse events (cirAEs), although it is not known how often they morph into a chronic condition. Research led by investigators at Vanderbilt University Medical Center published in JAMA Dermatology provides insight into chronic cirAEs. They recommended long-term follow-up for patients by dermatologists familiar with cirAEs and consideration of corticosteroid-sparing treatment options.

“Understanding the potential for side effects to become long-lasting has been an important advance recently, and managing them more effectively is a key unmet need,” said the study’s corresponding author, Douglas Johnson, MD, MSCI, professor of Medicine, holder of the Susan and Luke Simons Directorship, and co-leader of the Translational Research and Interventional Oncology Research Program at Vanderbilt-Ingram Cancer Center.

The investigators reviewed the records of 318 patients from a previous study who had been treated with immune checkpoint inhibitors. Of that number, 100 or 31% developed cirAEs with the skin conditions becoming chronic for 24 of the patients — nearly 8% of the full cohort. The study looked at 21 of those patients who underwent detailed follow-up. Another 31 patients were added from Vanderbilt clinics who were treated for cirAEs.

The 52 patients had received either pembrolizumab, nivolumab, ipilimumab or anti-PD1 and CTLA4 combination therapy.

The types of skin reactions varied, with 15 experiencing pruritus or itchy skin, 12 experienced morbilliform eruptions or drug-induced skin rashes, 12 experienced dermatitis or inflamed and scaly rashes, eight experienced bullous pemphigoid-like eruptions (fluid-filled blisters that resemble a rare autoimmune skin disease), five experienced eczema, four experienced lichenoid (flat-topped, scaly lesions), two experienced psoriasiform (breakouts that resemble psoriasis), and one experienced acneiform or acne-like eruptions.

The median duration of cirAE from treatment cessation was 446 days. Rare cases lasted more than five years.

Other Vanderbilt authors on the study included the study’s lead author, Kylie Fletcher, BS, Rachel Goodman, MD, MBA, J. Randall Patrinely, MD, MBA, and Anna Dewan, MD, MHS.

The research received support from Medical Scholars at Vanderbilt University School of Medicine, the Susan and Luke Simons Directorship, the James C. Bradford Jr. Fund in Melanoma Cancer Research and the Van Stephenson Memorial Cancer Research Fund.

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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, 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).

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