About

Erik R. Nelson, Ph.D., is a professor of Molecular and Integrative Physiology at the University of Illinois, with additional professorships in Animal Sciences and Nutritional Sciences. He is also affiliated with the Beckman Institute for Advanced Science and Technology and the Carl R. Woese Institute for Genomic Biology, where he contributes to the Personalized Nutrition Initiative and the Anticancer Discovery from Pets to People research theme. Dr. Nelson serves as a Program Leader at the Cancer Center at Illinois and is recognized as the Keith W. and Sara M. Kelley Professor. His academic background includes a B.Sc. in Zoology and a Ph.D. in Comparative Endocrinology from the University of Calgary, followed by postdoctoral training at Duke University School of Medicine. Dr. Nelson's research focuses on the endocrine and metabolic control of breast and ovarian cancer pathophysiology, aiming to understand how the endocrine system and metabolism influence cancer initiation and progression. His lab integrates expertise in physiology, endocrinology, immunology, and in vivo models to pursue translational research. A significant aspect of his work involves studying cholesterol metabolism and its critical roles in tumors and tumor-infiltrating immune cells. His research goals include using cholesterol biology to reprogram tumor-associated immune cells, defining mechanisms by which cholesterol metabolites impact tumor progression and metastasis, investigating nuclear receptor signaling within the tumor microenvironment, and determining the regulation of extracellular vesicles. Dr. Nelson has been recognized for his contributions to cancer research, including being named the 2025-2026 Dean’s Distinguished Professorial Scholar by the College of Liberal Arts and Sciences for his work on cholesterol metabolism and cancer. His honors also include the Era of Hope Scholar Award from the Department of Defense Breast Cancer Research Program and the I.C. Gunsalus Scholar at the University of Illinois. His research advances the understanding of metabolic regulation in cancer and aims to develop novel therapeutic approaches to treat breast and ovarian cancers.

Research topics

• Internal medicine
• Cancer research
• Medicine
• Biochemistry
• Biology
• Chemistry
• Immunology
• Oncology
• Endocrinology
• Optics
• Materials science
• Biophysics

Selected publications

• Reciprocal macrophage-MSC crosstalk drives immunomodulatory and regenerative phenotypes in a mineralized collagen scaffold

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-12

  articleOpen access

  ABSTRACT Critical sized craniomaxillofacial bone defects do not heal naturally and often exhibit chronic inflammatory responses that restrict regeneration. It is increasingly apparent that biomaterials must facilitate dynamic crosstalk between immune cells, such as macrophages, and osteoprogenitors to resolve inflammation and accelerate regeneration. Here, we evaluate interactions between macrophages in a neutral (M0) or pro-inflammatory (M1) state with mesenchymal stem cells (MSCs) in a basal or licensed state within a mineralized collagen scaffold. We reveal that MSC-macrophage crosstalk influences significant changes in osteoprogenitor cell differentiation and immune cell polarization. Notably, crosstalk between MSCs and macrophages drives an early-stage inflammatory response, which enhances the immunomodulatory activity of MSCs via secretion of IL-6, an effect that is heightened for already licensed MSCs. The presence of macrophages in the co-cultures upregulated osteogenic ( ALPL , BMP2 , COL1A2 , and RUNX2 ) and angiogenic genes ( ANGPT1 ) in basal MSC groups. Further, MSC-macrophage interactions subsequently drive increased M2-like macrophage polarization as early as 7 days of culture, as indicated by surface marker expression. These findings show that biomaterial scaffolds can be leveraged as mediators of MSC-mediated immunomodulation with an emphasis on achieving early-stage pro-inflammatory phenotypes that drive subsequent macrophage polarization and markers of increased regenerative potency.

  PublisherOA PDFDOI

• LncRNA-splicing factor condensates regulate hypoxia-responsive pre-mRNA processing near nuclear speckles

  Molecular Cell · 2026-03-01 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• CASM potentiates STING-driven NFκB signaling in immune cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-24

  articleOpen access

  Abstract Stimulator of Interferon Gene (STING), a key player of antimicrobial immune responses, has emerged as a promising target to mitigate inflammation and cancer. Following STING activation, proinflammatory molecules and type I Interferons (IFN) are released thus favoring the establishment of effective immune responses and adaptive immunity. Autophagy has been proposed to negatively regulate STING signaling. While STING activation drives microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) lipidation, the underlying mechanisms and functional consequences remain however incompletely defined. Especially, the consequences of STING-associated Conjugation of autophagy related (ATG) 8 to Single Membranes (CASM) in the control of immune responses remain elusive. Using innate and adaptive cells specifically inactivated for autophagy or CASM, we found that STING agonists primarily trigger CASM over autophagy. While STING-associated autophagy exerts negative feedback on the STING pathway and downstream type I IFN and pro-inflammatory responses, with different underlying molecular mechanisms between immune cells, STING-driven CASM potentiates NFκB-associated TNF production. These results overall uncover a new function of CASM and underscore the relevance of both CASM and autophagy in shaping STING signaling

  PublisherOA PDFDOI

• Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells

  Science Advances · 2026-01-01 · 1 citations

  articleOpen accessSenior author

  Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages and angiogenic potential, VEGFA , and CD8 T cell abundance and activity. The culmination of these activities was demonstrated through increased tumor growth and metastasis in mice lacking MC-expressed ABCA1. Tumors grown in these mice were also more resistant to immune therapy. Therefore, modulating ABCA1 activity within MCs may represent a previously unidentified approach to immune therapy.

  PublisherDOI

• Abstract 5012: Multiomic profiling reveals ligand and cell specific regulatory programs of LXR selective modulation in myeloid immune cells

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Selective modulation of steroid nuclear receptors such as estrogen (ER), glucocorticoid (GR), and androgen receptors (AR) has advanced cancer therapy by enabling precise control of receptor signaling. However, selective modulation of other nuclear receptors remains underexplored. Liver X receptors (LXRs) are key regulators of cholesterol homeostasis, inflammation, and immune responses. LXR ligands have shown antiproliferative and immunomodulatory effects across multiple cancers, including prostate, breast, and colorectal cancers, as well as hematologic tumors. Certain LXR ligands also attenuate immunosuppressive cell populations in the tumor microenvironment, making LXR a promising therapeutic target.However, many synthetic LXR agonists have shown adverse metabolic and neurologic effects and their impact on tumor progression is often inconsistent, suggesting potential ligand- and cell-specific modulation. Understanding the mechanisms underlying such selective LXR modulation, inspired by established selective modulation strategies for ER and AR related cancers, may enable the development of safer and more effective LXR-directed cancer therapies.To elucidate the mechanism of selective LXR modulation in myeloid cells, we performed multi-omics profiling (RNA-seq, ATAC-seq, and RIME proteomics) on murine bone marrow derived macrophages and dendritic cells treated with seven LXR ligands. We observed both shared and ligand- or cell-specific transcriptional and chromatin accessibility patterns. Notably, 27-hydroxycholesterol (27HC) suppressed interferon/STAT1 programs in macrophages and induced a MYC/E2F associated immunosuppressive state, whereas dendritic cells exhibited suppression of interferon stimulated genes and MYC/E2F program.T cell proliferation can be suppressed by 27HC treated macrophages. Preliminary functional assays suggested that this effect could be reversed by inhibiting E2F pathway (CDK4/6 blockade) or by targeting NF-κB, STAT3, or HDAC2 signaling in macrophages. These findings delineate cell-specific mechanisms of LXR selective modulation and suggest that targeting LXR may fine-tune E2F, NF-κB, STAT3, and HDAC2 dependent signaling that impacting macrophage-T cell crosstalk and thereby enhance T cell antitumor function. Citation Format: Yifan Fei, Rajendra K C, Mark Flory, Natalia Julianna Krawczynska, Yu Wang, Kevin T. VanBortle, Hisham Mohammed, Erik R. Nelson. Multiomic profiling reveals ligand and cell specific regulatory programs of LXR selective modulation in myeloid immune cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5012.

  PublisherDOI

• Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-15

  articleOpen accessSenior authorCorresponding

  ABSTRACT Breast cancer recurrence remains a clinical challenge. The period after the treatment of the primary tumor while cancer cells that evaded initial treatment lay dormant, provides a unique window of opportunity for interventions to prevent recurrence. Specific modifiable factors such as consumption of high fat diets or elevated circulating cholesterol are associated with decreased time to recurrence. Mechanistically, oxidized cholesterol and lipid species have been implicated in the regulation of the tumor microenvironment. This suggests that consumption of food prepared under oxidizing conditions such as pan-frying, may be an underappreciated risk. Using murine models of mammary cancer dormancy, we found that a diet enriched with fat from fried, cured bacon (cfBF) decreased dormancy latency times. Resulting lesions had fewer mast cells (MCs). Loss of MCs alone resulted in reemergence from dormancy. Elevated expression of a MC gene signature in breast tumors was associated with improved progression free and overall survival, highlighting the human relevance of these findings. MCs are a major source of tissue histamine, and lesions from mice fed cfBF had decreased concentrations. Importantly, antagonists of the histamine receptor 2 (H 2 R) sparked reemergence from dormancy. H 2 R antagonists are over-the-counter drugs are taken to alleviate gastroesophageal reflux disease. Chronic treatment of mice with H 2 R-antagonists sensitized platelets towards activation and crosstalk with neutrophils, and subsequent formation of neutrophil extracellular traps (NETs). The loss of platelet or NETosis activity mitigated the H 2 R-antagonist stimulated reemergence from dormancy. Therefore, we establish a novel metastatic axis which links diet to recurrence via MCs, histaminergic signaling and NETosis: Diet -- MC -- H 2 R -- ( decreased ) Platelet Activity -- ( decreased ) Neutrophil-NETosis -- ( decreased ) Reemergence from Dormancy. Our data reveal several potential intervention strategies: lifestyle, MC stabilization, histaminergic signaling, and neutrophil and platelet activity.

  PublisherDOI

• Abstract 1365: Histamine from mast cells protects against breast cancer recurrence

  Cancer Research · 2025-04-21

  articleSenior author

  Abstract One in eight women will develop breast cancer in their lifetime. 20-30% of these women develop recurrent metastatic disease, for which clinical treatments have limited efficacy. Metastasis is thought to be a stepwise process, terminating with extravasation into distal tissues. After this distal extravasation, cancer cells do not always immediately proliferate, but remain dormant. These dormant cells may awaken through yet-unknown mechanisms. There is therefore an urgent need to better understand dormancy and reawakening to mitigate the risk of metastatic recurrence. Previous work from our group has shown that elevated circulating cholesterol, and particularly an oxidized metabolite 27-hydroxycholesterol (27HC), has a pro-metastatic effect with breast cancer. Bacon is a high cholesterol food that is often prepared in a highly oxidative pan-frying process. Using mouse models, we demonstrate that consumption of cured, fried bacon promotes metastatic recurrence from dormancy. Assessment of metastatic tissues showed that consumption of cured fried bacon fat dramatically reduced mast cell (MC) numbers. MCs are granulocytic innate immune cells whose function in reemergence from dormancy is not well characterized. Interestingly, depletion of mast cells also stimulated reemergence, suggesting that mast cells might be protective against cancer progression. A major mediator of MC function is histamine. Therefore, we used small molecules to test the effects of histamine. Importantly, histamine 2 receptor antagonism stimulates recurrence. RNA-Sequencing data revealed that H2-receptor antagonism yields a unique transcriptional profile enriched with genes associated with platelet activation. Subsequent work indicates that H2 antagonism primes platelets towards activation which then increases neutrophil NETosis. Thus, we establish a novel metastatic axis: Diet - Mast cell - H2-receptor - Dormancy. The ultimate goal is to leverage this axis to develop novel therapeutic targets or lifestyle interventions to prevent recurrence. This work was supported by the American Institute for Cancer Research grant (713063), the National Cancer Institute (R01CA234025) and Department of Defense Breast Cancer Research Program Era of Hope Scholar Award (BC200206). Further support awarded to CPS from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number T32EB019944 and ATN from a National Institutes of Environment Health Sciences and Research Training in Toxicology and Environmental Health (T32) Fellowship (ES007326). Citation Format: Claire P. Schane, Adam T. Nelczyk, Cheng Chen, Shruti V. Bendre, Erin Weisser, Hashni E. Gamage, Mohammed Kadiri, Michael T. McHenry, Jiyoung Seo, Yu Wang, Natalia Krawczynska, Dhanya Pradeep, Lara I. Kockaya, Yifan Fei, Shin-Hsuan Hsiao, Nicki J. Engeseth, Michael K. Wendt, Timothy M. Fan, William G. Helferich, Erik R. Nelson. Histamine from mast cells protects against breast cancer recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1365.

  PublisherDOI

• Cholesterol-targeting Wnt–β-catenin signaling inhibitors for colorectal cancer

  Nature Chemical Biology · 2025-04-16 · 15 citations

  articleOpen access
  PublisherOA PDFDOI

• Supplementary Data from Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy–Induced Necrosis

  2025-11-24

  articleOpen access

  <p>Supplementary Movie 3</p>

  PublisherDOI

• Supplementary Data from Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy–Induced Necrosis

  2025-11-24

  articleOpen access

  <p>Supplementary Movie 2</p>

  PublisherDOI

Recent grants

• Impact of cholesterol and its metabolites on breast cancer progression

  NIH · $1.7M · 2019–2024

• NIH Grant K99CA172357

  NIH · $190k · 2014

• NIH Grant R00CA172357

  NIH · $727k · 2017

Frequent coauthors

• Donald P. McDonnell

  Duke University

  102 shared

• David J. Shapiro

  University of Illinois Urbana-Champaign

  67 shared

• Paul J. Hergenrother

  University of Illinois Urbana-Champaign

  59 shared

• Darjan Duraki

  McMaster University

  57 shared

• Ben Ho Park

  53 shared

• Matthew W. Boudreau

  University of Illinois Urbana-Champaign

  52 shared

• Chengjian Mao

  50 shared

• Liqian Ma

  Nanjing Tech University

  47 shared

Labs

• Nelson LabPI

Education

• Ph.D. Comparative Endocrinology, Biological Sciences

  University of Calgary

  2008

• B.Sc., Biological Sciences

  University of Calgary

  2002

Awards & honors

• Dean’s Distinguished Professorial Scholar (2025-2026)
• Richard E. Weitzman Outstanding Early Career Investigator La…
• List of Researchers to Know by the Illinois Science & Techno…
• Emerging Research Leader, University of Illinois (2023)
• James E. and Maxine S. Heath Award for Excellence in Teachin…