Facundo Martin Fernandez

• PhD
• Professor (Full) at Georgia Institute of Technology

We present a comprehensive map of the metabolomics research landscape, synthesizing insights from over 80,000 publications. Using PubMedBERT, we transformed abstracts into 768-dimensional embeddings that capture the nuanced thematic structure of the field. Dimensionality reduction with t-SNE revealed distinct clusters corresponding to key domains s...

Newborn screening (NBS) is one of the United States’ largest, most successful preventative public health initiatives, improving outcomes for newborns with inborn errors of metabolism. Most disorders on the Recommended Uniform Screening Panel are screened using triple-quadrupole mass spectrometry and flow injection analysis. While these methods are...

Specificity, sensitivity, and high metabolite coverage make mass spectrometry (MS) one of the most valuable tools in metabolomics and lipidomics. However, translation of metabolomics MS methods to multiyear studies conducted across multiple batches is limited by variability in electrospray ionization response, making batch-to-batch comparisons chal...

Background: Ovarian cancer (OC) remains one of the most lethal cancers among women due to most cases going undiagnosed until later stages. The early detection and treatment of this malignancy provides the best prognosis, but the lack of an accurate and sensitive screening tool combined with ambiguous symptoms hinders these diagnoses. In contrast, s...

Endurance exercise training (ExT) induces metabolic, structural, and functional adaptations via lipidomic modifications, yet the systematic elucidation of lipidome alterations in response to ExT remains incomplete. As a part of the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we leveraged non-targeted and targeted lipidomics for...

Lipidomics focuses on investigating alterations in a wide variety of lipids that harness important information on metabolic processes and disease pathology. However, the vast structural diversity of lipids and the presence of isobaric and isomeric species creates serious challenges in feature identification, particularly in mass spectrometry imagin...

Traumatic brain injury (TBI) is a global public health problem with 50–60 million incidents per year, most of which are considered mild (mTBI) and many of these repetitive (rmTBI). Despite their massive implications, the pathologies of mTBI and rmTBI are not fully understood, with a paucity of information on brain lipid dysregulation following mild...

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood 1–3 . Here, the Molecular Transducers of Physical Activity Consortium ⁴ profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome...

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical...

Triboelectric nanogenerators (TENG) are useful devices for converting mechanical motion into electric current using readily available materials. Though the applications for these devices span across many fields, TENG can be leveraged for mass spectrometry (MS) as inexpensive and effective power supplies for pulsed nanoelectrospray ionization (nESI)...

Background Distinguishing ovarian cancer from other gynecological malignancies is crucial for patient survival yet hindered by non-specific symptoms and limited understanding of ovarian cancer pathogenesis. Accumulating evidence suggests a link between ovarian cancer and deregulated lipid metabolism. Most studies have small sample sizes, especially...

Traumatic brain injury (TBI) is a significant source of disability in the United States and around the world and may lead to long-lasting cognitive deficits and a decreased quality of life for patients across injury severities. Following the primary injury phase, TBI is characterized by complex secondary cascades that involve altered homeostasis an...

Liquid chromatography–high-resolution mass spectrometry (LC-HRMS), as applied to untargeted metabolomics, enables the simultaneous detection of thousands of small molecules, generating complex datasets. Alignment is a crucial step in data processing pipelines, whereby LC-MS features derived from common ions are assembled into a unified matrix amena...

Background: Traumatic brain injury (TBI) is a global public health problem, with 50-60 million incidents per year, most of which are considered mild (mTBI). Despite its massive impact, the pathology of TBI is not fully understood, and there is a paucity of information on brain lipid dysregulation following mTBI. To gain more insight on mTBI patholo...

Many grants from US funding agencies are restricted to US citizens or permanent residents which negatively impacts the career options for foreign scientists working in the USA. [Image: see text]

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we pr...

Traumatic brain injury (TBI) is a major health concern in the United States and globally, contributing to disability and long-term neurological problems. Lipid dysregulation after TBI is underexplored, and a better understanding of lipid turnover and degradation could point to novel biomarker candidates and therapeutic targets. Here, we investigate...

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights on how metabolic and signaling alterations accompany its development. Herein, we present a...

We investigated the link between enhancement of SI (by hyperinsulinemic–euglycemic clamp) and muscle metabolites after 12 weeks of aerobic (high-intensity interval training [HIIT]), resistance training (RT), or combined training (CT) exercise in 52 lean healthy individuals. Muscle RNA sequencing revealed a significant association between SI after b...

Mesenchymal stromal cells (MSCs) have shown promise in regenerative medicine applications due in part to their ability to modulate immune cells. However, MSCs demonstrate significant functional heterogeneity in terms of their immunomodulatory function because of differences in MSC donor/tissue source, as well as non-standardized manufacturing appro...

Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic...

Induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine; however, few algorithms of quality control at the earliest stages of differentiation have been established. Despite lipids having known functions in cell signaling, their role in pluripotency maintenance and lineage specification is underexplored. We investigated th...

Mesenchymal stromal cells (MSCs) have shown promise in regenerative medicine applications due in part to their ability to modulate immune cells. However, MSCs demonstrate significant functional heterogeneity in terms of their immunomodulatory function because of differences in MSC donor/tissue source, as well as non-standardized manufacturing appro...

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training and sex on its molecular landscape has not been fully established. Utilizing an integrative multi-omics approach with data generated by the Molecular Transducers of Physical Activity C...

Untargeted lipidomics allows analysis of a broader range of lipids than targeted methods and permits discovery of unknown compounds. Previous ring trials have evaluated the reproducibility of targeted lipidomics methods, but inter-laboratory comparison of compound identification and unknown feature detection in untargeted lipidomics has not been at...

Mitochondria are adaptable organelles with diverse cellular functions critical to whole-body metabolic homeostasis. While chronic endurance exercise training is known to alter mitochondrial activity, these adaptations have not yet been systematically characterized. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) mapped the...

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds promise; however, these hi...

Ion mobility (IM) spectrometry provides semiorthogonal data to mass spectrometry (MS), showing promise for identifying unknown metabolites in complex non-targeted metabolomics data sets. While current literature has showcased IM-MS for identifying unknowns under near ideal circumstances, less work has been conducted to evaluate the performance of t...

Metabolite annotation continues to be the widely accepted bottleneck in nontargeted metabolomics workflows. Annotation of metabolites typically relies on a combination of high-resolution mass spectrometry (MS) with parent and tandem measurements, isotope cluster evaluations, and Kendrick mass defect (KMD) analysis. Chromatographic retention time ma...

Untargeted metabolomics studies are unbiased but identifying the same feature across studies is complicated by environmental variation, batch effects, and instrument variability. Ideally, several studies that assay the same set of metabolic features would be used to select recurring features to pursue for identification. Here, we developed an ancho...

Regular exercise promotes whole-body health and prevents disease, yet the underlying molecular mechanisms throughout a whole organism are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylpr...

Induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine; however, few algorithms of quality control at the earliest stages of differentiation have been established. Despite lipids having known functions in cell signaling, their role in pluripotency maintenance and lineage specification is underexplored. We investigated ch...

Invited for the cover of this issue are the groups of César Menor‐Salván, Facundo Fernández and Nicholas V. Hud at the University of Alcala and the Georgia Institute of Technology. The image depicts the authors contemplating the origin of pterins and guanosine nucleosides from a common precursor, with the art‐gallery setting embodying their feeling...

The lack of effective screening strategies for high-grade serous carcinoma (HGSC), a subtype of ovarian cancer (OC) responsible for 70–80% of OC related deaths, emphasizes the need for new diagnostic markers and a better understanding of disease pathogenesis. Capillary electrophoresis (CE) coupled with high-resolution mass spectrometry (HRMS) offer...

The identification of xenobiotics in nontargeted metabolomic analyses is a vital step in understanding human exposure. Xenobiotic metabolism, transformation, excretion, and coexistence with other endogenous molecules, however, greatly complicate the interpretation of features detected in nontargeted studies. While mass spectrometry (MS)-based platf...

Guanosine and pterins are depicted as the constellation Gemini. Guanine nucleosides are one of the immortal survivors of prebiotic chemistry, becoming the focus of many prebiotic reactions. However, like Pollux from Greek mythology, guanosine would not have been born alone—pterins would have been formed in equal (or, in this case, even in major) pa...

The prebiotic origins of biopolymers and metabolic co‐factors are key questions in Origins of Life studies. In a simple warm‐little‐pond model, using a drying phase to produce a urea‐enriched solution, we present a prebiotic synthetic path for the simultaneous formation of neopterins and tetrahydroneopterins, along with purine nucleosides. We show...

It is widely assumed that the condensation of building blocks into oligomers and polymers was important in the origins of life. High activation energies, unfavorable thermodynamics and side reactions are bottlenecks for abiotic peptide formation. All abiotic reactions reported thus far for peptide bond formation via thioester intermediates have rel...

The dismally low survival rate of ovarian cancer patients diagnosed with high-grade serous carcinoma (HGSC) emphasizes the lack of effective screening strategies. One major obstacle is the limited knowledge of the underlying mechanisms of HGSC pathogenesis at very early stages. Here, we present the first 10-month time-resolved serum metabolic profi...

The interpretation of ion mobility coupled to mass spectrometry (IM-MS) data to predict unknown structures is challenging and depends on accurate theoretical estimates of the molecular ion collision cross section (CCS) against a buffer gas in a low or atmospheric pressure drift chamber. The sensitivity and reliability of computational prediction of...

Large-scale untargeted metabolomics studies suffer from individual variation, batch effects and instrument variability, making comparisons of common spectral features across studies difficult. One solution is to compare studies after compound identification. However, compound identification is expensive and time consuming. We successfully identify...

Point-of-care screening tools are essential to expedite patient care and decrease reliance on slow diagnostic tools (e.g., microbial cultures) to identify pathogens and their associated antibiotic resistance. Analysis of volatile organic compounds (VOC) emitted from biological media has seen increased attention in recent years as a potential non-in...

Traumatic brain injury (TBI) poses a major health challenge, with tens of millions of new cases reported globally every year. Brain damage resulting from TBI can vary significantly due to factors including injury severity, injury mechanism and exposure to repeated injury events. Therefore, there is need for robust blood biomarkers. Serum from Sprag...

Urine metabolomics profiling has potential for non-invasive RCC staging, in addition to providing metabolic insights into disease progression. In this study, we utilized liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and machine learning (ML) for the discovery of urine metabolites associated with RCC progression....

The identification of xenobiotics in nontargeted metabolomic analyses is a vital step in understanding human exposure. Xenobiotic metabolism, excretion, and co-existence with other endogenous molecules however greatly complicate nontargeted studies. While mass spectrometry (MS)-based platforms are commonly used in metabolomic measurements, deconvol...

Background aims Mesenchymal stromal cells (MSCs) have shown great promise in the field of regenerative medicine, as many studies have shown that MSCs possess immunomodulatory function. Despite this promise, no MSC therapies have been licensed by the Food and Drug Administration. This lack of successful clinical translation is due in part to MSC het...

Background Post-market surveillance is a key regulatory function to prevent substandard and falsified (SF) medicines from being consumed by patients. Field deployable technologies offer the potential for rapid objective screening for SF medicines. Methods and findings We evaluated twelve devices: three near infrared spectrometers (MicroPHAZIR RX,...

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducin...

Background Medicine quality screening devices hold great promise for post-market surveillance (PMS). However, there is little independent evidence on their field utility and usability to inform policy decisions. This pilot study in the Lao PDR tested six devices’ utility and usability in detecting substandard and falsified (SF) medicines. Methodol...

Céline Caillet and co-authors discuss a Collection on use of portable devices for the evaluation of medicine quality and legitimacy.

An increased focus on characterizing the structural heterogeneity of carbohydrates has been driven by their many significant roles in extant life and potential roles in chemical evolution and the origin of life. In this work, multiplexed drift tube ion mobility-Orbitrap mass spectrometry methods were developed to analyze mixtures of disaccharides m...

Background Mesenchymal stromal cells (MSCs) have shown great promise in the field of regenerative medicine as many studies have shown that MSCs possess immunomodulatory function. Despite this promise, no MSC therapies have been granted licensure from the FDA. This lack of successful clinical translation is due in part to MSC heterogeneity and a lac...

This Communication describes a new thermal desorption/pyrolysis vacuum-assisted plasma ionization (pyro-VaPI) ion source coupled to ion mobility-mass spectrometry (IM-MS) for insoluble polymer analysis. Pyro-VaPI combines a pyrolysis device, soft ambient plasma ionization, IM, and MS into a single platform for polymer analysis with minimal sample p...

Lipids play a critical role in cell membrane integrity, signaling, and energy storage. However, in-depth structural characterization of lipids is still challenging and not routinely possible in lipidomics experiments. Techniques such as collision-induced dissociation (CID) tandem mass spectrometry (MS/MS), ion mobility (IM) spectrometry, and ultrah...

The condensation of building blocks into oligomers and polymers was an early and important stage in the origins of life. High activation energies, unfavorable thermodynamics and side reactions are bottlenecks for abiotic formation of peptides. Thioesters are hypothesized to have played key roles in prebiotic chemistry on early Earth, serving as ene...

Significance Why women carrying a pathogenic germline BRCA1 mutation are predisposed to ovarian and breast cancer remains elusive. This study points to ovarian progesterone as a culprit. Generally, BRCA1 -mutation carriers exhibit high yet individually varying levels of progesterone during the menstrual cycle. Although not all BRCA1 -mutation carri...

The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample volumes. The approach consists...

Carbohydrates are the most abundant class of biomolecules on Earth with a diverse array of biological functions. It is hypothesized that they likely had an important role in the development of life on the primoridal Earth as well. Since sugars have a variety of possible isobaric structures, it is necessary to characterize oligosaccharides beyond th...

Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to for...

Medulloblastoma (MB), the most common malignant pediatric brain tumor, has high propensity to metastasize. Currently, the standard treatment for MB patients includes radiation therapy administered to the entire brain and spine for the purpose of treating or preventing against metastasis. Due to this aggressive treatment, the majority of long-term s...

The amino acid proline plays critical roles in polypeptide structure and function. However, the influence of proline residues on proto-peptide evolution is unknown. In order to begin exploring this question, we formed mixtures of model prebiotic peptides by wet-dry cycling and compared proline incorporation to that of glycine, alanine, and valine....

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 a...

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that...

Multi-modal mass spectrometry imaging (MSI) data presents unique big data challenges in handling and analysis. Here, we present a pipeline for co-registering matrix-assisted laser desorption/ionization (MALDI) MSI and confocal immunofluorescence imaging data for extracting single cell metabolite signatures. We further describe methods and introduce...

Efficient ionization is a necessary condition for mass spectrometric analysis, but many compounds fail to ionize well enough to yield sufficient detection limits. Triboelectric nanogenerators (TENG) coupled to nanoelectrospray ionization (nanoESI) mass spectrometry (MS) are a highly effective approach to high sensitivity MS analysis. Here, we repor...

The prebiotic origin of polysaccharides, the largest class of biopolymers by mass in extant biology, has seldom been investigated experimentally. Herein, we report on the acid-catalyzed condensation of aqueous solutions of glucose, a model monosaccharide, under plausible prebiotic conditions employing a wet-dry (night-day) protocol with 0.01 M HCl...

Oligosaccharides serve many roles in extant life and may have had a significant role in prebiotic chemistry in early Earth. In both these contexts, the structural and isomeric diversity among carbohydrates presents analytical challenges necessitating improved separations. Here, we showcase a chemical derivatization approach, where 3-carboxy-5-nitro...

A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantita-tive metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using a common ex-perimental protocol provided with Biocrates AbsoluteIDQ p400HR kit, to quantify up to 408 metabolites. The specimen...

The most common cause of death in cystic fibrosis (CF) patients is progressive lung function decline, which is punctuated by acute pulmonary exacerbations (APEs). A major challenge is to discover biomarkers for detecting an oncoming APE and allow for preemptive clinical interventions. Metabolic profiling of exhaled breath condensate (EBC) samples c...

High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer (OC) type, accounting for 70–80% of OC deaths. This high mortality is largely due to late diagnosis. Early detection is thus crucial to reduce mortality. Yet tumor pathogenesis of HGSC remains poorly understood, making early detection difficult. Faithfully and reliab...

Metabolomics is the study of the metabolome, the collection of small molecules in living organisms, cells, tissues, and biofluids. Technological advances in mass spectrometry, liquid- and gas-phase separations, nuclear magnetic resonance spectroscopy, and big data analytics have now made it possible to study metabolism at an omics or systems level....

Mass spectrometry (MS) plays an important role in seeking biomarkers for disease detection. High-quality quantitative data is needed for accurate analysis of metabolic perturbations in patients. This article describes recent developments in MS-based non-targeted metabolomics research with applications to the detection of several major common human...

Rationale Understanding of the molecular processes that led to the first biomolecules on Earth is one of the key aspects of origins‐of‐life research. Depsipeptides, or polymers with mixed amide and ester backbones, have been proposed as plausible prebiotic precursors for peptide formation. Chemical characterization of depsipeptides in complex prebi...

Treatment for medulloblastoma (MB) — the most common malignant pediatric brain tumor — includes prophylactic radiation administered to the entire brain and spine due to the high incidence of metastasis to the central nervous system. However, the majority of long-term survivors are left with permanent and debilitating neurocognitive impairments as a...

Technological advances in mass spectrometry (MS), liquid chromatography (LC) separations, nuclear magnetic resonance (NMR) spectroscopy, and big data analytics have made possible studying metabolism at an “omics” or systems level. Here, we applied a multi-platform (NMR+LC-MS) metabolomics approach to the study of preoperative metabolic alterations...

Various portable screening technologies have been developed to assess the quality and authenticity of medicines and thereby combat the growing global problem of substandard and falsified (SF) medicines. However, the capabilities and limitations of many technologies are not well characterized, particularly when used outside the laboratory, for examp...

Laser-induced acoustic desorption coupled to microplasma-based atmospheric pressure photoionization (LIAD-APPI) using a nebulized sweep jet to aid in dopant introduction and ion transmission has been applied to the analysis of model, apolar lipid compounds. Specifically, several sterols, sterol esters, and triacylglycerols were detected using dopan...

Multimodal chemical imaging simultaneously offers high resolution chemical and physical information with nanoscale, and in select cases atomic resolution. By coupling modalities that collect physical and chemical information, we can address scientific problems in biological systems, battery and fuel cell research, catalysis, pharmaceuticals, photov...

Flow injection-traveling wave ion mobility-mass spectrometry (FI-TWIM-MS) was applied to the non-targeted metabolic profiling of serum extracts from 61 prostate cancer (PCa) patients and 42 controls with an analysis speed of 6 minutes per sample, including a wash run. Comprehensive data mining of the mobility-mass domain was used to discriminate sp...

Supplemental Figure 1: Positive ion mode background spectra generated via TENG wooden‐tip MS with three separate toothpick tips. Supplemental Figure 2: Negative ion mode background spectra generated via TENG wooden‐tip MS with three separate toothpick tips. Supplemental Figure 3: Negative ion mode spectra generated via TENG wooden‐tip MS for meth...

Background Poor quality medicines have devastating consequences. A plethora of innovative portable devices to screen for poor quality medicines has become available, leading to hope that they could empower medicine inspectors and enhance surveillance. However, information comparing these new technologies is woefully scarce. Methods We undertook a...

Rationale An epidemic of low quality medicines continues to endanger patients worldwide. Detection of such “medicines” requires low cost, ambient ionization sources coupled to fieldable mass spectrometers for optimum sensitivity and specificity. With the use of triboelectric nanogenerators (TENGs), the charge required to produce gas‐phase ions for...

The formation, propagation, and maintenance of harmful algal blooms are of interest due to their negative effects on marine life and human health. Some bloom-forming algae utilize allelopathy, the release of compounds that inhibit competitors, to exclude other species dependent on a common pool of limiting resources. Allelopathy is hypothesized to...

Traumatic brain injury (TBI) can occur across wide segments of the population, presenting in a heterogeneous manner that makes diagnosis inconsistent and management challenging. Biomarkers offer the potential to objectively identify injury status, severity, and phenotype by measuring the relative concentrations of endogenous molecules in readily ac...

Many technologies currently exist that are capable of analyzing the surface of solid samples under ambient or vacuum conditions, but they are typically limited to smooth, planar surfaces. Those few that can be applied to non-planar surfaces, however, require manual sampling and a high degree of human intervention. Herein, we describe a new platform...

In this communication, we report on the real-time analysis of organic aerosol particles by Vacuum-assisted Plasma Ionization-Mass Spectrometry (Aero-VaPI-MS) using a home-built VaPI ion source coupled to a Synapt G2-S HDMS ion mobility-mass spectrometry (IM-MS) system. Standards of organic molecules of interest in prebiotic chemistry were used to g...