KGCRF Poster Competition Winners 2025

KGCRF Rising Young Scientist Award – up to & including G3s

ALANIS CARMONA | G3
Biological Sciences in Public Health
Jessalyn Ubellacker Lab

Characterizing and targeting extracellular matrix proteins that contribute to breast survival in the lymph node
Breast cancer is the most prevalent cancer among women in the United States, representing approximately 30% of all new female cancer cases annually. This year alone it is anticipated that over 310,000 new cases of invasive breast cancer will arise and result in over 42,000 deaths.  Most cancer-related deaths result from metastasis, for which there is no treatment. Metastatic spread can occur through the circulatory and/or the lymphatic system. Prior work from our laboratory has shown that the lymph node tumor microenvironment protects metastasizing cancer cells from ferroptosis, which is a mode of cell death caused by unchecked lipid oxidation. Within the context of the lymph node microenvironment, in this project we sought to understand the contribution of cancer associated fibroblasts (CAFs) in the lymph node in secreting extracellular matrix (ECM) factors that could also contribute to differences in lipid oxidation levels of cancer cells in lymph nodes. The ECM is comprised of an intricate mixture of proteins including proteoglycans and adhesive glycoproteins, such as collagens and laminins. Here, we discovered that specific ECM components in lymph nodes provide protection from lipid oxidation and ferroptosis-inducing agents in vitro. We next tested conditioned media from human CAFs generated from patients with and without breast cancer detected in the lymph nodes to determine the extent to which the CAF-conditioned media, as well as CAF-derived ECM components, protect against lipid oxidation. We found that CAF-conditioned media from patients with, but not without, breast cancer cells in the lymph nodes protected breast cancer cells from ferroptosis in vitro.
 

OLIVIA LAVIDOR | G2
Chemical Biology
Brian Liau Lab

Targeting the Regulatory Domains of DNMT3A to Rescue Loss of Function Phenotypes in AML
DNA methyltransferase 3A (DNMT3A) is an epigenetic writer protein responsible for deposition of suppressive methylation marks on cytosine nucleobases in DNA. Because of its genome-wide, essential function, DNMT3A is often mutated in developmental and hematological disorders. The most common mutation is the dominant-negative R882H, which accounts for about two thirds of DNMT3A mutations in AML. DNMT3A is active as a tetramer, and ongoing debate in the field has left two hypotheses of the mechanism of R882H loss of function; Either it breaks a central protein-protein interface to form dimers, or it strengthens this interface resulting in macro-oligomers. Using techniques such as sucrose gradient ultracentrifugation, hydrogen deuterium exchange mass spectrometry, and DNA-encoded library screens, we aim to (1) lend evidence toward the oligomerization hypothesis, (2) explore the role of understudied regulatory domains of DNMT3A, and (3) potentiate the rescue this phenotype with a first-in-class small molecule activator for DNMT3A.

KGCRF Early Career Investigator Award – G4s & up

ALICE BERTOCCHI | G5
Immunology
Stephanie Dougan and Judith Agudo Labs

Eosinophils alter metastatic spread in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the US with a 13% 5-year survival rate. A key contributor of this dismal prognosis is early and frequent metastatic spread with limited treatment options for patients. In the primary tumor reactive stroma, we found increased eosinophils in both human and mouse PDAC compared to the normal pancreas. We used the ddGata mice, which lack eosinophils, to study their role during metastatic spread using a mouse model of resectable metastatic PDAC. We found that mice lacking eosinophils have increased metastasis to the lung in our spontaneous model, but no difference is seen in establishment of IV injected tumor cells, suggesting eosinophil control at the primary tumor site. Single cell sequencing of tumor cells and staining find alterations in their EMT state. When we investigated the anti-metastatic role of eosinophils, we observed production of IL-4 in human and mouse PDAC tissues. We showed that IL-4 treatment correlates with decreased metastasis to distal organs and increased epithelial state of the cancer cells in our spontaneous model of resectable PDAC, independently of IL-4 signaling in immune cells. We conclude that eosinophils in PDAC inhibit the metastatic process, in part, through control of tumor cell state through secretion IL-4.

RACHEL HONGO | G4
Biological and Biomedical Sciences
Leonard Zon Lab

Investigating extracellular factors driving neural crest state reactivation in melanoma initiation
Melanoma is the deadliest form of skin cancer, but it is curable with surgical resection if diagnosed early, making improved strategies for early detection and prevention critical. In a zebrafish melanoma model where melanocytes express human BRAFV600E in a p53 null background, we observe single melanocytes reactivating an embryonic neural crest program (crestin:EGFP+) that expand to form melanomas. This neural crest state reactivation marks a key transformative step in melanoma initiation. To understand what drives this transition, we are investigating the role of the local extracellular microenvironment. We performed proteomics on crestin:EGFP+ regions versus cancerized field skin and identified 498 upregulated proteins, including 13 ligands and matrisome components. Genetic overexpression of candidate ligands, such as midkine, in zebrafish melanocytes accelerated neural crest reactivation in vivo, suggesting that secreted factors in the microenvironment can promote melanoma initiation. Ongoing studies using zebrafish knockouts, single cell RNA-sequencing, and spatial transcriptomics aim to define ligand-receptor interactions and their cellular sources. These findings support a model in which local microenvironmental factors cooperate with oncogenes to trigger melanoma, providing insights into how tissue context influences cancer initiation