About

Scott Summers, PhD, is a Distinguished Professor and Department Chair of Nutrition and Integrative Physiology at the University of Utah. As a principal investigator in the Summers and Holland Investigational Team, his research focuses on nutrition and physiology, contributing to the understanding of these fields through his leadership and scholarly work. His role involves guiding research initiatives, mentoring students and staff, and advancing knowledge in nutrition and integrative physiology.

Research topics

• Endocrinology
• Medicine
• Internal medicine
• Biology
• Sociology
• Biochemistry
• Bioinformatics
• Data Mining
• Psychology
• Demography
• Nursing
• Chemistry
• Cell biology
• Clinical psychology
• Gerontology
• Genetics
• Oncology
• Psychotherapist
• Cardiology

Selected publications

• Lipidomic Analysis of Plasma Extracellular Vesicles from Adiponectin Deficient Mice or Metabolic Syndrome Patients Reveals Pro‐Oxidative and Pro‐Inflammatory Lipid Signatures Correlating with Metabolic Dysfunction

  Journal of Extracellular Vesicles · 2026-02-01 · 2 citations

  articleOpen access

  Extracellular vesicles (EV) are emerging regulators of metabolic homeostasis through their bioactive cargo. This study first investigated the lipidomic profile and functional effects of plasma EV derived from adiponectin-knockout (KO) mice to identify EV-associated lipid signatures linked to metabolic dysfunction. Lipidomic profiling revealed that KO EV were enriched in sphingolipids and polyunsaturated phospholipids compared to wild-type (WT) EV. To evaluate functional consequences, recipient cell assays were conducted using macrophages, skeletal muscle cells, and pancreatic beta cells. KO EV showed an increased uptake in RAW 264.7 macrophages and induced elevated reactive oxygen species (ROS) and activation of NF-κB and IRF inflammatory pathways. In L6 skeletal muscle cells, WT EV increased ATP production, while KO EV failed to elicit this effect. Furthermore, KO EV impaired glucose-stimulated insulin secretion in INS-1 pancreatic beta cells. These findings suggested that altered lipid composition in EV from KO mice contributes to oxidative stress, inflammation, and impaired metabolic regulation in recipient cells. Next, translational relevance was established by documenting that plasma EV from patients with metabolic syndrome exhibited lipidomic remodeling features in parallel to the murine KO phenotype, in particular enriched PUFA-containing lipids. Together, these findings identify a conserved adiponectin-EV lipid composition axis regulating oxidative stress, inflammation, and impaired metabolic regulation. The new knowledge presented in this study has implications for biomarker discovery and therapeutic targeting in metabolic disease.

  PublisherOA PDFDOI

• Integrative Clinical–Molecular Modeling Identifies <i>LRRN4CL</i> as a Determinant of Structural and Functional Myocardial Improvement

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-26

  articleOpen access

  ABSTRACT Background Mechanical ventricular unloading and systemic circulatory support with left ventricular assist devices (LVADs) enable myocardial recovery in a subset of advanced heart failure (HF) patients, but predictors and mechanisms of recovery are not well understood. Integrating clinical and molecular data may improve identification of patients most likely to recover and uncover biologically relevant targets in HF. Methods We collected and analyzed left ventricular apical myocardial tissue and clinical data from 208 patients undergoing LVAD implantation across five centers. Pre-implant transcriptomic profiles (22,373 mRNA transcripts) were integrated with 59 clinical variables using supervised machine learning with repeated cross-validation to identify and prioritize features associated with myocardial recovery, defined as a binary outcome based on improvement in left ventricular ejection fraction (LVEF ≥40%) and left ventricular end-diastolic diameter (LVEDD ≤5.9 cm). We also modeled functional (LVEF) and structural (LVEDD) improvement as a continuous outcome without any predefined LVEF and LVEDD pathological thresholds. Feature prioritization was followed by validation in human myocardial tissue and mechanistic interrogation in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Results Integrative models achieved modest discrimination for myocardial recovery as a binary categorical outcome (maximum mean cross-validated area under the curve 0.73±0.15), identifying clinical features such as HF duration, LVEDD, HF pharmacologic therapy, and device configuration. Leucine-rich repeat neuronal 4C-like ( LRRN4CL ), measured in human myocardium, consistently emerged as a top transcriptomic predictor across both binary and continuous metric models (functional and structural). Higher pre-LVAD LRRN4CL expression was associated with reduced likelihood of myocardial recovery and localized primarily to cardiomyocytes. In iPSC-CMs, LRRN4CL overexpression localized to the sarcoplasmic reticulum, induced transcriptional remodeling characterized by suppression of contractile pathways and activation of stress programs, impaired calcium handling, impaired contraction–relaxation kinetics, and diminished mitochondrial respiratory reserve capacity. Conclusions Integration of clinical and myocardial transcriptomic data identifies LRRN4CL as a novel marker associated with impaired myocardial recovery following LVAD-mediated ventricular unloading and systemic circulatory support. These findings move beyond predictive modeling, linking integrative computational discovery to cardiomyocyte dysfunction and providing a translational framework for biologically informed risk stratification and therapeutic targeting for myocardial recovery. CLINICAL PERSPECTIVE What Is New? Integrative clinical and myocardial transcriptomic modeling identifies LRRN4CL as a novel molecular determinant of structural and functional changes after LVAD-mediated ventricular unloading and enhanced systemic circulatory support. Elevated LRRN4CL expression is associated with adverse remodeling signatures, impaired calcium handling, and stress responses in human iPSC-derived cardiomyocytes. Experimental overexpression of LRRN4CL directly disrupts calcium cycling, contractile performance, and mitochondrial respiration linking molecular signature to functional phenotype. What Are the Clinical Implications? Identification of LRRN4CL as a marker associated with impaired myocardial recovery supports future efforts toward biologically informed risk stratification for patients undergoing LVAD therapy. LRRN4CL as a marker of cardiac improvement potential may extend beyond advanced HF to earlier stage disease patients and inform prognosis, risk stratification, and response to medical therapies. These findings highlight LRRN4CL -associated pathways as potential therapeutic targets and demonstrate how integrative clinical–transcriptomic approaches can move beyond clinical prediction toward identification of new biologically precise therapeutic targets in HF following a bedside to bench and back approach.

  PublisherOA PDFDOI

• Abstract 3628: Obesity, metabolic dysfunction, and cancer risk: Uncovering the metabolic landscape

  Cancer Research · 2026-04-03

  article

  Abstract As smoking rates decline, obesity has emerged as the leading modifiable risk factor for cancer in the United States. With obesity rates rising, especially in younger populations, its association with increased cancer risk is becoming more evident. There is an urgent need to understand the mechanisms underlying the relationship between obesity related metabolic dysregulation and cancer risk. This session highlights transdisciplinary research from the NCI-sponsored Metabolic Dysregulation and Obesity Cancer Risk (MeDOC) Consortium, which applies integrative methods across basic science, translational models, and clinical research. The MeDOC Consortium aims to discover mechanisms linking obesity and cancer to define markers that will enhance cancer risk prediction and identify targets for intervention. Metabolic alterations include immune dysfunction, metabolite signaling, hormonal imbalance, gut microbiome and adipocyte metabolism which can disrupt several downstream signaling pathways related to cancer initiation and progression. In our novel triangulation approach, we synthesize evidence from randomized controlled trials, mechanistic animal studies, and large-scale secondary data analyses establishing population-level patterns with clinical relevance to build a comprehensive metabolic atlas of cancer risk factors. Our research topics include the gut microbiome, lipid signaling, circulating metabolites, and local and systemic immune landscape, with a focus on how these processes influence the development of colorectal, breast, and liver cancers. We will highlight complementary research projects that bridge animal studies, human cohorts, and data science across diet, inflammation, microbiome, immunity, and obesity and weight loss. We will review current evidence and describe novel applications of systems biology with big data analytics featured as tools to integrate mechanistic insights and population-level patterns to establish robust causal frameworks. Early-career investigators will participate in an open discussion on emerging challenges and opportunities in obesity and cancer research. Specifically, we will report on the role of fatty acid binding protein, ceramides, bile acids, hormones, inflammation, and gut microbiome metabolites in cancers of the colon, breast, and liver, Through a translational lens, the session will emphasize how combining data science, bench studies, and interventional trials can accelerate the discovery of biomarkers, risk stratification tools, and actionable targets for cancer prevention or interception. Citation Format: Liza Makowski, Mary Playdon, Bing Li, Sonia L. Sugg, Scott A. Summers, Cornelia M. Ulrich, Deirdre Tobias, Edward L. Giovannucci, Xuehong Zhang, James R. Hébert, E. Angela Murphy, Joeseph F. Pierre, Loretta DiPietro, Lorne J. Hofseth, Marinella Temprosa. Obesity, metabolic dysfunction, and cancer risk: Uncovering the metabolic landscape [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 3628.

  PublisherDOI

• Detergents without a drain: the evolutionary logic (and liability) of sphingolipids

  Journal of Lipid Research · 2026-02-13

  articleOpen access1st authorCorresponding

  Sphingolipids are evolutionarily conserved lipids that, I contend, emerged as a solution to a fundamental biochemical problem: cells require fatty acids, yet these molecules are potent detergents. In higher metazoans, a metabolic asymmetry amplifies this physical threat: unlike most macronutrients, fatty acids cannot be readily converted into nonlipid forms of biomass. Thus, when their supply exceeds energetic demand, they remain chemically committed lipids with the capacity to destabilize membranes and disrupt cellular organization. The emergence of sphingolipid metabolism offered an elegant solution to this challenge. By incorporating fatty acids into sphingolipids, cells both stabilize membranes to combat detergent stress and generate ceramide-dependent signaling programs that coordinate metabolic adaptation, remodeling, and, when necessary, cell elimination in response to lipid overload. In modern settings of chronic lipid surplus, most prominently obesity, this otherwise adaptive system becomes pathological. Across liver, adipose tissue, skeletal muscle, heart, pancreas, and kidney, excessive sphingolipid accumulation enforces metabolic inflexibility, impairs mitochondrial efficiency, and promotes cell dysfunction or loss, contributing to diabetes, steatohepatitis, heart failure, and kidney disease. Human studies consistently associate circulating ceramide species with cardiometabolic risk, while interventional studies in rodents demonstrate their causal roles in disease progression. Together, these findings position sphingolipids-much like cholesterol-as both early biomarkers and modifiable drivers of chronic disease, highlighting how an evolutionary solution becomes pathogenic in the setting of prolonged nutrient excess.

  PublisherOA PDFDOI

• Excessive Ca ²⁺ -dependent ER-mitochondrial contact stabilization by EFHD1 drives liver injury

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-16

  articleOpen access

  ABSTRACT Metabolic-associated steatohepatitis (MASH) involves hepatocyte damage that cannot be explained solely by lipid accumulation. Here, to discover injury-specific pathways, we focused on a gene of uncertain function, EF-Hand Domain Family Member D1 (EFHD1), identified in human genome-wide association studies of liver injury but not liver fat. We show that EFHD1, a Ca 2+ -dependent actin crosslinker, stabilizes endoplasmic reticulum–mitochondria contact sites (ERMCS), detecting spatiotemporal coincidence of inter-organellar proximity and ER Ca 2+ release. During MASH, EFHD1 upregulation drives pathological mitochondrial fragmentation via excessive contact persistence. This structural failure promotes mitochondrial double-stranded RNA escape and activation of a maladaptive antiviral PKR-dependent stress response, a causal relationship also supported by Mendelian randomization in humans. Consequently, inhibiting EFHD1 in human and mouse models blunts hepatocyte damage. These findings identify EFHD1 as a Ca 2+ -dependent ERMCS stabilizer, reveal a hepatocyte-intrinsic injury pathway, and suggest EFHD1 inhibition as a therapeutic strategy.

  PublisherOA PDFDOI

• Reduced Cardiolipin Drives Defects in ATP Production and May Contribute to Reduced GFR and CKD Progression

  Journal of the American Society of Nephrology · 2025-10-01

  article
  PublisherDOI

• Supplemental Table 7 from New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative

  2025-11-26

  articleOpen access

  &lt;p&gt;Supplemental Table 7 provides results for the 6 months lag analysis.&lt;/p&gt;

  PublisherDOI

• Cardiolipin deficiency disrupts electron transport chain to drive steatohepatitis

  eLife · 2025-06-18 · 1 citations

  preprintOpen access

  Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder marked by lipid accumulation, leading to metabolic dysfunction-associated steatohepatitis (MASH). A key feature of the transition to MASH involves oxidative stress resulting from defects in mitochondrial oxidative phosphorylation (OXPHOS). Here, we show that pathological alterations in the lipid composition of the inner mitochondrial membrane (IMM) directly instigate electron transfer inefficiency to promote oxidative stress. Specifically, mitochondrial cardiolipin (CL) was downregulated with MASLD/MASH in humans and in mice. Hepatocyte-specific CL synthase knockout (CLS-LKO) led to spontaneous and robust MASH with extensive steatotic and fibrotic phenotype. Loss of CL paradoxically increased mitochondrial respiratory capacity but also reduced the formation of I+III2+IV respiratory supercomplex, promoted electron leak primarily at sites IIIQO and IIF of the electron transport chain, and disrupted the propensity of coenzyme Q (CoQ) to become reduced. Thus, low mitochondrial CL disrupts electron transport chain to promote oxidative stress and contributes to pathogenesis of MASH.

  PublisherDOI

• Therapeutic remodeling of the ceramide backbone prevents kidney injury

  Cell Metabolism · 2025-11-12 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Supplemental Table 3 from New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative

  2025-11-26

  articleOpen access

  &lt;p&gt;Supplemental Table 3 provides effect estimates for the association of incident diabetes and all-cause mortality among obesity-related cancer survivors and cancer-free individuals, stratified by covariates that did not meet PH assumptions.&lt;/p&gt;

  PublisherDOI

Recent grants

• NIH Grant R56DK058784

  NIH · $50k · 2006

• Interdisciplinary Training Program in Metabolism

  NIH · $4.5M · 2011–2026

• The Role of Ceramides in Skeletal Muscle

  NIH · $2.6M · 2018–2022

• NIH Grant R21DK073181

  NIH · $482k · 2008

• NIH Grant F32DK009475

  NIH · $91k

Frequent coauthors

• William L. Holland

  University of Utah

  82 shared

• Olga Ilkayeva

  40 shared

• Mary C. Playdon

  Huntsman Cancer Institute

  37 shared

• Jianhong Ching

  KK Women's and Children's Hospital

  33 shared

• Morris J. Birnbaum

  Pfizer (United States)

  33 shared

• Leonardo Pinto de Carvalho

  Universidade de São Paulo

  33 shared

• Monowarul Mobin Siddique

  University of Utah

  30 shared

• Prasoona Karra

  Dartmouth College

  29 shared

Labs

• Summers and Holland Investigational TeamPI

Education

• Postdoctoral, Medicine

  University of Pennsylvania

  1999

• Ph.D., Physiology

  Southern Illinois University

  1995

• BS, Biochemistry

  Indiana University

  1989