About

Emile R. Mohler III, M.D., is an attending physician at the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, and the Philadelphia Veteran's Administration Medical Center. He serves as the Director of the Non-Invasive Vascular Imaging Laboratory at Penn Presbyterian Medical Center and is a member of the Institute for Diabetes, Obesity and Metabolism, the Cardiovascular Institute, and the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania School of Medicine. Dr. Mohler is also the Co-Director of the Noninvasive Vascular Imaging Laboratory at the Perelman Center for Advanced Medicine and the Director of Vascular Medicine within the University of Pennsylvania Health System. His roles include directing research activities and contributing to clinical care in vascular medicine, with a focus on non-invasive vascular imaging and cardiovascular health.

Research topics

• Medicine
• Internal medicine
• Cardiology
• Surgery
• Endocrinology

Selected publications

• Vasculitis

  2023-03-17

  book-chapter1st authorCorresponding

  The term vasculitis describes pathologic inflammation and necrosis of blood vessels. Vasculitis can occur from an unknown cause (idiopathic) or be associated with an established disease (secondary). The etiology of the majority of vasculitides is thought to be either humoral or cellular immune-related injury. The hypersensitivity vasculitides are vasculitic diseases that were reported under a variety of names including cutaneous necrotizing vasculitis, allergic vasculitis, and leukocytoclastic vasculitis. These diseases characteristically have inflammation of small vessels (especially venules) with leukocytoclasis (nuclear debris) and cutaneous skin involvement. The etiology of this vasculitis is unknown and characteristically involves a necrotizing granulomatous process of the respiratory tract along with glomerulonephritis. This disease occurs primarily in young and middle-aged persons, with a slight male predominance. Behcet syndrome is a rare multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions.

  PublisherDOI

• Metabolite patterns associated with individual response to supervised exercise therapy in patients with intermittent claudication

  JVS Vascular Science · 2022-01-01

  articleOpen access

  Objective: Supervised exercise therapy (SET) is the first line treatment for intermittent claudication owing to peripheral arterial disease. Despite multiple randomized controlled trials proving the efficacy of SET, there are large differences in individual patient's responses. We used plasma metabolomics to identify potential metabolic influences on the individual response to SET. Methods: Primary metabolites, complex lipids, and lipid mediators were measured on plasma samples taken at before and after Gardner graded treadmill walking tests that were administered before and after 12 weeks of SET. We used an ensemble modeling approach to identify metabolites or changes in metabolites at specific time points that associated with interindividual variability in the functional response to SET. Specific time points analyzed included baseline metabolite levels before SET, dynamic metabolomics changes before SET, the difference in pre- and post-SET baseline metabolomics, and the difference (pre- and post-SET) of the dynamic (pre- and post-treadmill). Results: High levels of baseline anandamide levels pre- and post-SET were associated with a worse response to SET. Increased arachidonic acid (AA) and decreased levels of the AA precursor dihomo-γ-linolenic acid across SET were associated with a worse response to SET. Participants who were able to tolerate large increases in AA during acute exercise had longer, or better, walking times both before and after SET. Conclusions: We identified two pathways of relevance to individual response to SET that warrant further study: anandamide synthesis may activate endocannabinoid receptors, resulting in worse treadmill test performance. SET may train patients to withstand higher levels of AA, and inflammatory signaling, resulting in longer walking times. Clinical Relevance: This manuscript describes the use of metabolomic techniques to measure the interindividual effects of SET in patients with peripheral artery disease (PAD). We identified high levels of AEA are linked to CB1 signaling and activation of inflammatory pathways. This alters energy expenditure in myoblasts by decreasing glucose uptake and may induce an acquired skeletal muscle myopathy. SET may also help participants tolerate increased levels of AA and inflammation produced during exercise, resulting in longer walking times. This data will enhance understanding of the pathophysiology of PAD and the mechanism by which SET improves walking intolerance.

  PublisherDOI

• Impact of supervised exercise on skeletal muscle blood flow and vascular function measured with MRI in patients with peripheral artery disease

  American Journal of Physiology-Heart and Circulatory Physiology · 2022-07-08 · 12 citations

  articleOpen accessSenior author

  Supervised exercise interventions can improve symptomatology in patients with peripheral artery disease, but the underlying mechanism remains unclear. Here, MRI was used to evaluate perfusion, relative tissue oxygenation, and venous oxygen saturation in response to cuff-induced ischemia. Reactive hyperemia responses were measured before and after 3 mo of randomized supervised exercise therapy or standard medical care. Those participants who were adherent to the exercise regimen had a significant improvement in peak perfusion.

  PublisherOA PDFDOI

• Metabolite patterns of patients with peripheral arterial disease in response to exercise

  medRxiv · 2021-07-27

  preprintOpen access

  ABSTRACT Supervised exercise therapy (SET) is an effective intervention for symptomatic peripheral artery disease. Its effect on metabolism, measured by the circulating metabolome is not well understood. Participants underwent the Gardner graded treadmill test before and after SET and blood was sampled before and after each treadmill test. We tested the average association of metabolite levels with timing of blood draws. We used five models to identify metabolites or changes in metabolites at specific time points that associate with treadmill test performance or inter-individual variability in functional performance after SET. When analyzing individual time points, high levels of anandamide (AEA) before any exercise interventions were associated with shorter, or worse, walking time. Increased arachidonic acid (AA) and decreased levels of AA precursors (dihomo-γ-linolenic acid and diacylglycerol) before any exercise was associated with shorter walking times. Participants who tolerated large increases in AA during acute exercise had longer, or better, walking times before and after SET. We identified two pathways of relevance to individual response to SET: AEA synthesis may increase the activity at endocannabinoid receptors, resulting in worse treadmill test performance. SET may help train patients withstand higher levels of AA and inflammatory signaling, resulting in longer walking times.

  PublisherOA PDFDOI

• A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans

  UNC Libraries · 2020-11-07

  articleOpen access

  Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10−8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10−9), 7q11 (rs13236689, CD36, p = 2.8×10−9), 10q21 (rs7896518, JMJD1C, p = 2.3×10−12), 11q13 (rs477895, BAD, p = 4.9×10−8), and 20q13 (rs151361, SLMO2, p = 9.4×10−9). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10−8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.

  PublisherDOI

• Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)

  UNC Libraries · 2020-11-07

  articleOpen access

  Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.

  PublisherDOI

• Testosterone and Cardiovascular Disease

  UNC Libraries · 2020-04-18

  articleOpen access

  Abstract Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety.

  PublisherDOI

• Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

  UNC Libraries · 2020-11-01

  articleOpen access

  Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

  PublisherDOI

• Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans

  UNC Libraries · 2020-11-03

  articleOpen access

  Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P < 2.0 × 10−13, T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P = 3.0 × 10−7 in Caucasians; P = 3.0 × 10−7 in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P < 7 × 10−8, A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences.

  PublisherDOI

• Incentivizing physical activity through activity monitoring interventions in PAD – a pilot study

  VASA · 2020-11-05 · 14 citations

  articleSenior author

  Summary: Background: There is ample evidence to show that supervised exercise is efficacious and cost effective for improving claudication symptoms in patients with peripheral artery disease (PAD). Home based exercise therapy can be an effective alternative to supervised exercise however, the results of this is variable depending on the level of motivation and engagement of the patient. Patients and methods: We performed a pilot study in 41 patients to determine whether a home based exercise program with the use of an activity tracking device with personalized feedback and financial incentives can increase daily activity, improve walking and sustain engagement in the exercise regimen in patients with PAD. In this randomized pilot study, the patients in the study group were fitted with an activity monitoring device and given behavioral monitoring, motivational updates and feedback regarding their exercise program. This study group was further divided in to two groups. One half of these patients in the study group were also given financial incentives if they reached their set targets. The control group wore the device with no feedback or ability to see their number of steps walked. Results: Results showed that at the end of the 12 week period, patients in the study groups walked more compared to the controls and the financial incentive structure resulted in an additional 38–63% increase in average daily steps. Conclusions: This pilot study revealed that a home-based exercise program with activity monitoring, feedback and financial incentives resulted increased daily steps, 6-minute walking distance and overall compliance with the program in PAD patients with claudication.

  PublisherDOI

Recent grants

• NIH Grant K08HL003974

  NIH · $657k · 2004

• Research career training in vascular medicine

  NIH · $3.1M · 2007–2015

• The Microcirculation in Claudication and Exercise Rehabilitation

  NIH · $5.0M · 2003–2016

• NIH Grant M01RR000040

  NIH · $7.2M · 2007

• NIH Grant RC1HL099528

  NIH · $933k · 2012

Frequent coauthors

• Raymond R. Townsend

  184 shared

• Harold I. Feldman

  University of Illinois Chicago

  171 shared

• Bernard G. Jaar

  Johns Hopkins University

  165 shared

• Stephen M. Sozio

  Johns Hopkins University

  165 shared

• Scott E. Kasner

  Hospital of the University of Pennsylvania

  125 shared

• Steven R. Messé

  Hospital of the University of Pennsylvania

  115 shared

• Sanjay Rajagopalan

  University Hospitals of Cleveland

  107 shared

• Henrik Rasmussen

  105 shared

Labs

• Non-Invasive Vascular Imaging LaboratoryPI