About

Christopher Rhodes is an Emeritus/Emerita Professor at the University of Chicago in the Department of Medicine-Endocrinology. His research activities and funding have focused on pancreatic islet function, metabolic control of proinsulin biosynthesis, insulin exocytosis, and signal transduction in pancreatic beta-cells. He has led multiple NIH-funded projects, including studies on central control of pancreatic islet function and interdisciplinary molecular metabolism training. His work has contributed to understanding the metabolic regulation of insulin and proinsulin, as well as the cellular mechanisms underlying pancreatic beta-cell function. Rhodes has also been involved in research related to pulmonary arterial hypertension, pulmonary vascular disease, and the role of ferroptosis and inflammation in pulmonary hypertension. His publications include studies on pulmonary arterial hypertension, lung metabolism, and the genetic determinants of right ventricular structure and function, reflecting a broad focus on metabolic and vascular diseases.

Research topics

• Biology
• Medicine
• Genetics
• Internal medicine
• Cardiology
• Bioinformatics
• Pathology
• Computational biology

Selected publications

• From New World Order to War on Terror

  2026-01-02

  book-chapter1st authorCorresponding
  PublisherDOI

• Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series)

  Pulmonary Circulation · 2025-01-01 · 3 citations

  articleOpen access

  Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools. Nevertheless, challenges exist in implementing these tools to optimal effect. The 2023 Grover Conference Series reviewed the research landscape to summarize the current state of the art and provide a better understanding of the application of precision medicine to managing pulmonary vascular disease. In particular, the following aspects were discussed: (1) Clinical phenotypes, (2) genetics, (3) epigenetics, (4) biomarker discovery, (5) application of precision biology to clinical trials, (6) the right ventricle (RV), and (7) integrating precision medicine to clinical care. The present review summarizes the content of these discussions and the prospects for the future.

  PublisherOA PDFDOI

• Inflammation and obesity correlate in pulmonary hypertension but associate with diverging outcomes

  2025-09-27

  article

  <bold>Background:</bold> Inflammation is associated with all types of Pulmonary Hypertension (PH) both as a known cause and/or a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informed clinical endotyping. <bold>Methods:</bold> Time-series clustering of longitudinal CRP levels was employed. Clinical differences between clusters were validated in three independent UK/International cohorts (n=10,301; UK-cohort, ASPIRE and FDA cohort). Associations were analysed with functional and mortality outcomes by linear and Cox regression models including all-causes of PH (groups 1-5). Multi-omics were interrogated from associated previously published arrays. <bold>Results:</bold> Patients segregated into two stable CRP clusters, with strong associations with body mass index (BMI). Increased CRP and BMI associated with worse exercise capacity. Inflammation associated with worse survival, more comorbidities, higher pulmonary vascular resistance (PVR), and smoking status. No relationship was observed between CRP and circulating autoantibodies, but CRP and BMI were associated with differing inflammatory profiles in proteomic and transcriptomic analyses. Despite the relationship with CRP, higher BMI associated with improved survival and lower PVR and did not negatively affect treatment response. <bold>Conclusions:</bold> We establish a strong relationship between CRP and BMI across all cause PH. Despite this relationship, CRP and BMI associated with diverging clinical outcomes. Inflammation and obesity are relevant phenotypes for consideration in clinical trial design. Understanding their impacts on outcomes is important for clinical practice.

  PublisherDOI

• GLP-1 agonist, semaglutide use in acute pulmonary embolism recovery: a four-week proof-of-concept study including proteomic profiling

  European Heart Journal Open · 2025-12-16

  articleOpen access

  Abstract Aims Vasorelaxant and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) agonists support their investigation in aiding the recovery of patients with acute pulmonary embolism (PE) at risk of worse outcomes. Methods We undertook a four week non-randomized, controlled open-label study examining proteomic changes, markers of vascular inflammation and exploratory imaging endpoints in response to GLP-1 agonist, semaglutide (0.25 mg weekly) added to standard of care anticoagulation in patients with intermediate high-risk PE. Results 44 plasma proteins were downregulated in response to semaglutide that were significantly enriched for glycoproteins (false discovery rate q &amp;lt; 0.01). Glycopeptide analysis of highly abundant glycoproteins between diagnosis and follow-up demonstrated a reduction in glycopeptide abundance suggesting protein deglycosylation as a possible mechanism of glycoprotein down-regulation. Down-regulated proteins included regulators of metabolic stress and complement pathway intermediates, which were at higher abundance in PE patients at diagnosis compared to age and sex-matched controls without PE (all P &amp;lt; 0.001). Exploratory evaluation of radiological markers of right ventricular dysfunction improved from baseline to follow-up only in patients who received semaglutide (P &amp;lt; 0.01). Conclusions These findings suggest merit in wider investigation of immunometabolic changes in the plasma proteome during acute PE recovery and their potential relevance to modulation using GLP-1 agonists. Registration The study was registered under clinicaltrials.org (NCT06118203).

  PublisherOA PDFDOI

• Live Confocal Super Plankton

  2025-09-03 · 1 citations

  dataset
  PublisherDOI

• S146 Inflammation and obesity correlate in pulmonary hypertension but associate with diverging outcomes

  2025-11-01

  article

  <h3>Rationale and Objectives</h3> Inflammation is associated with all types of Pulmonary Hypertension (PH) both as a known cause and/or a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informed clinical endotyping and outcomes. <h3>Methods</h3> Time-series clustering of longitudinal CRP levels was employed. Clinical differences between clusters were validated in three independent UK/international cohorts using clinical cut off values (n=10,301; UK-cohort, ASPIRE and FDA cohort). Associations were analysed with functional and mortality outcomes by linear and Cox regression models including all-causes of PH (groups 1–5). To add mechanistic insight, multi-omics were interrogated from associated previously published arrays. <h3>Results</h3> Patients segregated into two stable CRP clusters (median CRP 2 versus 6.5 mg/l), with the high cluster exhibiting significantly higher BMI (difference between medians DBM=5.4 kg/m2), higher RAP (DBM=2 mmHg) and reduced 6-minute walk distance (6MWD (DBM=55m)). Inflammation was associated with worse survival, comorbidities, higher pulmonary vascular resistance (PVR), and smoking status. CRP and BMI were associated with differing inflammatory profiles in proteomic and transcriptomic analyses. Despite the relationship with CRP, higher BMI associated with improved survival, lower PVR and did not negatively affect 6MWD treatment-related functional responses. <h3>Conclusions</h3> We establish a relationship between CRP and BMI across all-cause PH, though CRP and BMI associate with diverging clinical outcomes. Inflammation and obesity are relevant phenotypes for consideration in clinical trial design. Understanding their impacts on outcomes is important for clinical practice.

  PublisherDOI

• Enrichment of Cysteine S-palmitoylated Peptides Using Sodium Deoxycholate Acid Precipitation

  Molecular & Cellular Proteomics · 2025-10-17

  articleOpen access

  S-palmitoylation is a poorly understood post-translational modification that is gaining more attention as an essential regulator of cellular processes. The reversible nature of S-palmitoylation may allow for fine-tuned control of cellular events and adaptation to stimuli. The detection of S-palmitoylated proteins and peptides includes the Acyl-Biotin Exchange (ABE) method, Acyl resin-assisted Capture (Acyl-RAC), metabolic labelling, and derivatives thereof. We present a novel method of enrichment of S-palmitoylated peptides termed SDC Acid Precipitation Enrichment (SDC-ACE). Here, S-palmitoylated peptides are enriched by taking advantage of their co-precipitation with Sodium deoxycholate (SDC) under acidic conditions, allowing easy and fast separation of lipidated peptides from the sample suspension. We initially applied our novel method for the characterization of the mouse brain, providing an in-depth analysis of S-palmitoylation events within the brain and comprehensive profile of the mouse brain S-palmitoylome. Further, we applied our method for mapping mouse tissue-specific S-palmitoylation, highlighting the extensive role of S-palmitoylation throughout various organs in the body. Finally, we applied our methods for studying the brain palmitoylome of diabetic db/db mouse, uncovering alterations in the palmitoylation of proteins associated with obesity and type 2 diabetes. The SDC-ACE method allows fast and easy enrichment of S-palmitoylated peptides, providing a valuable tool for exploring the dynamics and function of S-palmitoylation in diverse biological systems.

  PublisherOA PDFDOI

• S143 StratosPHere 1 study – a novel BMP target engagement biomarker panel for use in clinical trials demonstrates sotatercept alters gene expression in PAH

  2025-11-01

  article

  <h3></h3> Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease where imbalances in the TGFb superfamily pathways have causal roles in hereditary and idiopathic forms. These pathways are emerging attractive candidates for therapeutic intervention but there is an unmet need for clinically relevant and practical biomarkers that can measure target engagement. A major challenge has been the inaccessibility of lung tissue in disease for molecular profiling. Here we explore the surrogate capacity of peripheral blood BMP pathway-specific markers. Plasma proteomic analysis demonstrates widespread pleiotropic alterations of TGFß/BMP modulators. Downstream BMPR-II canonical and non-canonical signaling is altered and measurable in whole blood, and transcriptomic signatures cluster by discrete BMPR-II gene modules. We present discovery and international replication cohorts for the transcriptomic BMPR-II signaling signatures and derive a composite transcriptomic biomarker panel that is repeatable, reproducible, longitudinally stable and expressed in correlated gene modules in PAH which associate with clinical outcomes, most notably mortality. The assay performance characteristics of the biomarker panel make it feasible for early phase, target engagement clinical trials and we have utilised it in a pilot study of sotatercept-treated patients that suggests the therapy does not mechanistically rebalance/increase BMPR-II pathway signaling, but rather shows a reduction, likely due to depletion of circulating BMP9 and BMP10.

  PublisherDOI

• Small Molecule Compound BX-912 Reverses Increased Susceptibility to Pulmonary Hypertension in SOX17 Enhancer Knockout Mice

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract RATIONALE: Numerous genetic mutations are associated with an increased risk for developing pulmonary arterial hypertension (PAH), but there are no orally active treatments that target them. Genome-wide association studies have identified 2 independent risk variant-containing signals (SOX17-signal 1 and -signal 2) upstream of the SOX17 promoter. Fifty-nine percent of PAH patients are homozygous for the risk allele of both signals versus 46% of control subjects. In addition, rare deleterious variants in SOX17 are associated with severe PAH. Transgenic mice with deletion of signal 1 (Sox17eKO) develop more severe hypoxic pulmonary hypertension and are more susceptible to developing Sugen/hypoxia pulmonary hypertension (SuHx-PH) than wild-type mice. We hypothesize that SOX17 dysregulation leads to pulmonary endothelial dysfunction, that can be rescued by restoring SOX17 or its downstream targets. METHODS: We performed epigenomic, transcriptomic and proteomic analyses to identify novel genes and pathways regulated by SOX17. Our results were passed into the LINCS drug:gene expression database to predict therapeutic compounds that would rescue impaired SOX17 expression by enhancing SOX17 regulated genes and pathways. The effect of one compound, BX-912 on endothelial cell function and PH was assessed in vitro and in vivo. RESULTS: Seven therapeutic compounds were found that reinstate SOX17-regulated gene expression in human pulmonary artery endothelial cells (hPAEC). BX-912 increased SOX17 expression (figure) and restored SOX17 regulated gene expression in hPAEC. SOX17 knockdown by siRNA and enhancer-targeting CRISPR in hPAEC resulted in gene expression changes and increased proliferation, whereas treatment with BX-912 had the opposite effect. Sox17eKO mice given low dose Sugen (5 mg/kg) during exposure to mild hypoxia (12.5%) for 3 weeks developed severe PH compared to controls with increased right ventricular systolic pressure (RVSP) (48.4 ± 6.5 vs 18.2 ± 0.6 mmHg) and right ventricle to left ventricle plus septum weight (RV/(LV+S) (0.34 ± 0.02 vs 0.17 ± 0.02). BX-912 given orally by gavage (50 mg/kg) every other day for 6 treatments starting one week after Sugen/hypoxia completely ameliorated the increase in RVSP (17.7 ± 0.5 mmHg) and significantly reduced RV/LV+S (0.23 ± 0.02) (figure). CONCLUSIONS: BX-912 increases SOX17 expression, reverses impaired SOX17 signaling and prevents the increased susceptibility to PH phenotype in Sox17eKO mice. Considering the large number of patients with SOX17 enhancer risk alleles, and the importance of SOX17 in endothelial biology, targeting SOX17 through BX-912 may be an effective strategy for treating PAH. Additional studies in the SuHx-PH rat model are ongoing and will be presented.

  PublisherDOI

• Roles for Prlhr/GPR10 and Npffr2/GPR74 in feeding responses to PrRP

  Molecular Metabolism · 2025-01-05 · 1 citations

  articleOpen access

  Several groups of neurons in the NTS suppress food intake, including Prlh -expressing neurons (NTS Prlh cells). Not only does the artificial activation of NTS Prlh cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS Prlh neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We used animals lacking PrRP receptors GPR10 and/or GRP74 (encoded by Prlhr and Npffr2 , respectively) to determine roles for each in the restraint of food intake and body weight by the increased expression of Prlh in NTS Prlh neurons (NTS PrlhOX mice) and in response to the anorectic PrRP analog, p52. Although Prlhr played a crucial role in the restraint of food intake and body weight in HFD-fed control animals, the combined absence of Prlhr and Npffr2 was required to abrogate the restraint of food intake in NTS PrlhOX mice. p52 suppressed feeding independently of both receptors, however. Hence, each receptor can participate in the NTS Prlh -mediated suppression of food intake and body weight gain, while PrRP analog treatment can mediate its effects via distinct systems. While Prlhr plays a crucial role in the physiologic restraint of weight gain, the action of either receptor is capable of ameliorating obesity in response to enhanced NTS Prlh signaling. • Prlhr but not Npffr2 restrains food intake and body weight in normal HFD-fed animals. • Either Prlhr or Npffr2 suffices to can restrain obesity in response to increased NTS PrRP. • PrRP analog can decreases feeding independently of Prlhr and Npffr2 • There exists an additional pharmacologically relevant PrRP receptor

  PublisherDOI

Recent grants

• NIH Grant R56DK050610

  NIH · $380k · 2010

• NIH Grant R01DK047919

  NIH · $3.0M · 2007

• NIH Grant R01DK099359

  NIH · $1.9M · 2019

• NIH Grant T32DK087703

  NIH · $709k · 2016

• NIH Grant R01DK055267

  NIH · $4.9M · 2015

Frequent coauthors

• Martin R. Wilkins

  Imperial College London

  333 shared

• John Wharton

  Imperial College London

  266 shared

• Nicholas W. Morrell

  220 shared

• Luke Howard

  Imperial College Healthcare NHS Trust

  139 shared

• Timothy J. Aitman

  134 shared

• Almaz Aldashev

  123 shared

• Baktybek Kojonazarov

  University of Giessen

  122 shared

• Michael A. Marletta

  University of California, Berkeley

  121 shared

Labs

• Christopher Rhodes LabPI

Education

• PhD, Pharmacology & Therapeutics, Medicine

  Imperial College London

  2011

• BA, Natural Sciences: Pharmacology

  University of Cambridge

  2007