About

Dr. Gregg B. Wells received his B.A. with distinction in chemistry from Northwestern University in 1981. He earned his Ph.D. in biophysical and theoretical biology from the University of Chicago Pritzker School of Medicine in 1987 and his M.D. from the same institution in 1989. He completed his residency in anatomic pathology and fellowship in neuropathology at the Hospital of the University of Pennsylvania from 1989 to 1996. Certified in anatomic pathology with special certification in neuropathology by the American Board of Pathology, he joined the faculty at Texas A&M University Naresh K. Vashisht College of Medicine in 1999. His research focuses on the role of protein structure in disease, particularly neurological diseases. His laboratory investigates the structure and function of neurotransmitter-gated ion channels, including nicotinic acetylcholine, serotonin 5HT3, glycine, and GABAA receptors, which are involved in drug addiction, neurodegenerative diseases such as Alzheimer's and Parkinson's, genetic epilepsy, and neuropsychiatric disorders like schizophrenia and depression. The lab develops approaches to elucidate the molecular structures of these ion channels from animals and bacteria. Other research areas include cyclic nucleotide gated channels, cochlear hair cell electrophysiology, and the genomics of electrogenic animals, aiming to reveal new insights into ion channel lifecycles. His work links neuroscience with neuropathology, emphasizing the importance of protein structure in understanding neurological diseases.

Research topics

• Computer Science
• Materials science
• Condensed matter physics
• Organic chemistry
• Nuclear magnetic resonance
• Metallurgy
• Chemistry
• Mathematics
• Physics
• Psychology
• Medical education
• Chemical physics
• Medicine

Selected publications

• A transdisciplinary dual degree curriculum yields novel and successful learning outcomes: early lessons from training physicianeers

  Frontiers in Medicine · 2025-02-28 · 4 citations

  articleOpen access1st authorCorresponding

  The evolving needs in healthcare education and delivery have led to diverse MD-based dual degree programs offering trainees broader experiences and credential-based credibility after graduation. Medical schools typically implement multidisciplinary or interdisciplinary dual degree training with designs that separate the contributing disciplines chronologically and experientially. As a result, these designs fail to maximize the cohesive learning environment and outcomes possible with a transdisciplinary dual degree design, which integrates the contributing disciplines chronologically, experientially, and conceptually. Though rare, transdisciplinary dual degrees promise transformative educational outcomes and discipline convergence by dissolving traditional discipline boundaries and fostering a new learning environment and professional identity. Therefore, we hypothesize that a transdisciplinary dual degree curriculum yields novel-and potentially better-learning outcomes. ENMED, a transdisciplinary dual degree program collaboratively developed, sponsored, and implemented by Texas A&M University and Houston Methodist Hospital, is testing this hypothesis by training "physicianeers." This new type of healthcare professional trains simultaneously for the MD and Master of Engineering degrees, thereby integrating medical and engineering expertise to advance health system innovations. Supporting the hypothesis, ENMED's early experiences suggest its transdisciplinary dual-degree model leads physicianeer trainees to novel perspectives with the potential to transform healthcare systemically.

  PublisherOA PDFDOI

• Application of EPR Saturation Methods to Paramagnetic Metal Ions in Proteins

  CRC Press eBooks · 2024 · 2 citations

  Senior authorCorresponding
  • Materials science
  • Nuclear magnetic resonance
  • Chemistry

  Saturation of a paramagnetic spin system with incident microwave power has been widely applied in electron paramagnetic resonance (EPR) studies to evaluate both electronic and structural properties of spin systems. The method essentially consists of irradiating the spin system with high levels of microwave power and observing the response of the system to reestablish thermal equilibrium of the spins with the lattice, and can be employed with both continuous wave (cw) and pulse saturation and recovery techniques. In the former, the spin system is progressively irradiated with increasingly higher levels of incident microwave power during which time the spectrum is collected to monitor the change in signal intensity; in the latter, the system is subjected to an intense pulse of microwave power of short duration after which the kinetic response of the system to reestablish thermal equilibrium is followed. Application of either method requires thorough familiarity with the physical principles and theory underlying relaxation processes as well as with the limitations of the technique with respect to instrumentation. Therefore, in this chapter we first discuss the salient features of magnetic relaxation theory that are necessary to describe and interpret results from experiments using saturation techniques in EPR studies, and we briefly outline the basic requirements for instrumentation, particularly with a view on limitations in data collection. Because this chapter is directed to structural analysis of paramagnetic metal ion sites in proteins, the discussion is restricted to relaxation theory of transition metal ions in ionic solids. Furthermore, for all of the transition metal ions discussed in this review, we need concern ourselves only with magnetic resonance theory applied to Kramers ions. Readers are directed to reviews and monographs on EPR spectroscopy and relaxation phenomena [1–6] for more detailed or specialized discussions of the concepts outlined here.

  PublisherDOI

• Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3

  Arteriosclerosis Thrombosis and Vascular Biology · 2024-03-14 · 5 citations

  articleOpen access

  BACKGROUND: New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. METHODS: Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from noninvading cells. We used this model to perform multiple transcriptomics analyses from independent donors to monitor endothelial gene expression changes. RESULTS: Single-cell population analyses, single-cell cluster analyses, and bulk RNA sequencing revealed common transcriptomic changes associated with invading cells. We also found that collagenase digestion used to isolate single cells upregulated the Fos proto-oncogene transcription factor. Exclusion of Fos proto-oncogene expressing cells revealed a gene signature consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis and included multiple tip cell markers. Upregulation of SNAI1 (snail family transcriptional repressor 1), PTGS2 (prostaglandin synthase 2), and JUNB (JunB proto-oncogene) protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated rounding 3, also known as RhoE, which has not yet been implicated in angiogenesis. Silencing rounding 3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for rounding 3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared with wild-type littermates. CONCLUSIONS: Validation of multiple genes, including rounding 3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation.

  PublisherOA PDFDOI

• Short-Term Training with Basic Science Research Literature Advances Medical Students’ Skills for Adaptive Expertise

  Journal of Medical Education and Curricular Development · 2024 · 3 citations

  • Computer Science
  • Medical education
  • Psychology

  Physicians must adapt their learning and expertise to the rapid evolution of healthcare. To train for the innovation-efficient demands of adaptive expertise, medical students need to acquire the skill of adaptive self-regulated learning, which includes accessing, interpreting, and synthesizing emerging basic and translational research to support patient care. In response, we developed the course Medical Student Grand Rounds (MSGR). It engages all pre-clerkship students at our institution with self-regulated learning from translational basic research literature. In this report, we describe MSGR's methodology and important outcomes. Students found, interpreted, critically assessed, and presented basic research literature about self-selected clinically relevant topics. In less than one semester and mentored by basic science researchers, they completed eight milestones: (a) search research literature databases; (b) choose a clinical topic using searching skills; (c) outline the topic's background; (d) outline a presentation based on the topic's mechanistic research literature; (e) attend translational research-oriented grand rounds by faculty; (f) learn to prepare oral presentations; (g) write an abstract; and (h) present at Grand Rounds Day, emphasizing their topic's research literature. Graded milestones and end-of-course self-assessments indicated students became proficient in interpreting research articles, preparing and delivering presentations, understanding links among basic and translational research and clinical applications, and pursuing self-regulated learning. Qualitative analysis of self-assessment surveys found most students thought they progressed toward the learning objectives: find scientific information about a research topic (56% positive responses), interpret and critically assess scientific information (64%), and prepare and deliver a scientific presentation (50%). Milestones improve time management and provide a scaffolded method for presenting focused research topics. MSGR equips students with critical thinking skills for lifelong, adaptive, self-regulated learning-a foundation for adaptive expertise. The master adaptive learner cycle of planning, learning, assessing, and adjusting is a conceptual framework for understanding students' MSGR learning experiences.

  PublisherOA PDFDOI

• Identification of new markers of angiogenic sprouting using transcriptomics: New role for RND3

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-10-19 · 1 citations

  preprint

  Background: New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. Approach and Results: Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from non-invading cells. We used this model to perform multiple transcriptomics analyses from multiple donors to monitor endothelial gene expression changes. Single-cell Population Analyses, single-cell Cluster Analyses, and bulk RNA sequencing were used to delineate transcriptomic changes in invading cells. The results revealed a 39 gene signature that was consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis, and include multiple tip cell markers. Upregulation of SNAI1, PTGS2, and JUNB protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated Rounding 3 (RND3), also known as RhoE, which has not yet been implicated in angiogenesis. Silencing RND3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for RND3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared to wild type littermates. Conclusion: Validation of multiple genes, including RND3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes that are associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation.

  PublisherDOI

• A tail of two voltages: Proteomic comparison of the three electric organs of the electric eel

  Science Advances · 2017-07-06 · 25 citations

  articleOpen access

  ) is unusual among electric fishes because it has three pairs of electric organs that serve multiple biological functions: For navigation and communication, it emits continuous pulses of weak electric discharge (<1 V), but for predation and defense, it intermittently emits lethal strong electric discharges (10 to 600 V). We hypothesized that these two electrogenic outputs have different energetic demands reflected by differences in their proteome and phosphoproteome. We report the use of isotope-assisted quantitative mass spectrometry to test this hypothesis. We observed novel phosphorylation sites in sodium transporters and identified a potassium channel with unique differences in protein concentration among the electric organs. In addition, we found transcription factors and protein kinases that show differential abundance in the strong versus weak electric organs. Our findings support the hypothesis that proteomic differences among electric organs underlie differences in energetic needs, reflecting a trade-off between generating weak voltages continuously and strong voltages intermittently.

  PublisherOA PDFDOI

• Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus)

  BMC Genomics · 2015-03-25 · 28 citations

  articleOpen access

  BACKGROUND: With its unique ability to produce high-voltage electric discharges in excess of 600 volts, the South American strong voltage electric eel (Electrophorus electricus) has played an important role in the history of science. Remarkably little is understood about the molecular nature of its electric organs. RESULTS: We present an in-depth analysis of the genome of E. electricus, including the transcriptomes of eight mature tissues: brain, spinal cord, kidney, heart, skeletal muscle, Sachs' electric organ, main electric organ, and Hunter's electric organ. A gene set enrichment analysis based on gene ontology reveals enriched functions in all three electric organs related to transmembrane transport, androgen binding, and signaling. This study also represents the first analysis of miRNA in electric fish. It identified a number of miRNAs displaying electric organ-specific expression patterns, including one novel miRNA highly over-expressed in all three electric organs of E. electricus. All three electric organ tissues also express three conserved miRNAs that have been reported to inhibit muscle development in mammals, suggesting that miRNA-dependent regulation of gene expression might play an important role in specifying an electric organ identity from its muscle precursor. These miRNA data were supported using another complete miRNA profile from muscle and electric organ tissues of a second gymnotiform species. CONCLUSIONS: Our work on the E. electricus genome and eight tissue-specific gene expression profiles will greatly facilitate future research on determining the coding and regulatory sequences that specify the function, development, and evolution of electric organs. Moreover, these data and future studies will be informed by the first comprehensive analysis of miRNA expression in an electric fish presented here.

  PublisherOA PDFDOI

• Genomic basis for the convergent evolution of electric organs

  Science · 2014-06-26 · 214 citations

  articleOpen access

  Little is known about the genetic basis of convergent traits that originate repeatedly over broad taxonomic scales. The myogenic electric organ has evolved six times in fishes to produce electric fields used in communication, navigation, predation, or defense. We have examined the genomic basis of the convergent anatomical and physiological origins of these organs by assembling the genome of the electric eel (Electrophorus electricus) and sequencing electric organ and skeletal muscle transcriptomes from three lineages that have independently evolved electric organs. Our results indicate that, despite millions of years of evolution and large differences in the morphology of electric organ cells, independent lineages have leveraged similar transcription factors and developmental and cellular pathways in the evolution of electric organs.

  PublisherOA PDFDOI

• Fatal Strikes

  Scientific American Mind · 2013-12-19 · 1 citations

  articleSenior author
  PublisherDOI

• A Highly Conserved Cytoplasmic Cysteine Residue in the α4 Nicotinic Acetylcholine Receptor Is Palmitoylated and Regulates Protein Expression

  Journal of Biological Chemistry · 2012-05-17 · 20 citations

  articleOpen access

  Nicotinic acetylcholine receptor (nAChR) cell surface expression levels are modulated during nicotine dependence and multiple disorders of the nervous system, but the mechanisms underlying nAChR trafficking remain unclear. To determine the role of cysteine residues, including their palmitoylation, on neuronal α4 nAChR subunit maturation and cell surface trafficking, the cysteines in the two intracellular regions of the receptor were replaced with serines using site-directed mutagenesis. Palmitoylation is a post-translational modification that regulates membrane receptor trafficking and function. Metabolic labeling with [(3)H]palmitate determined that the cysteine in the cytoplasmic loop between transmembrane domains 1 and 2 (M1-M2) is palmitoylated. When this cysteine is mutated to a serine, producing a depalmitoylated α4 nAChR, total protein expression decreases, but surface expression increases compared with wild-type α4 levels, as determined by Western blotting and enzyme-linked immunoassays, respectively. The cysteines in the M3-M4 cytoplasmic loop do not appear to be palmitoylated, but replacing all of the cysteines in the loop with serines increases total and cell surface expression. When all of the intracellular cysteines in both loops are mutated to serines, there is no change in total expression, but there is an increase in surface expression. Calcium accumulation assays and high affinity binding for [(3)H]epibatidine determined that all mutants retain functional activity. Thus, our results identify a novel palmitoylation site on cysteine 273 in the M1-M2 loop of the α4 nAChR and determine that cysteines in both intracellular loops are regulatory factors in total and cell surface protein expression of the α4β2 nAChR.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F32NS009642

  NIH · $69k

• NIH Grant K08NS001903

  NIH · $514k · 2002

Frequent coauthors

• Jon Lindstrom

  University of Pennsylvania

  21 shared

• Alexander Kuryatov

  University of Pennsylvania

  14 shared

• René Anand

  The Ohio State University Wexner Medical Center

  12 shared

• Marvin W. Makinen

  University of Chicago

  12 shared

• Bianca M. Conti‐Fine

  7 shared

• James F. Howard

  University of North Carolina at Chapel Hill

  7 shared

• David P. Huston

  Bryan College

  7 shared

• Robin Fuchs‐Young

  Texas A&M University

  7 shared

Labs

• Gregg B. Wells LaboratoryPI