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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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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