About

Judith Klein-Seetharaman is a professor in the School of Molecular Sciences and College of Health Solutions at Arizona State University. She obtained her PhD at the Massachusetts Institute of Technology under the supervision of Nobel Laureate Har Gobind Khorana, focusing on conformational changes and folding in the G protein-coupled receptor rhodopsin. She holds dual undergraduate degrees in Biology and Chemistry from the University of Cologne, Germany. Her research combines computational and experimental studies of protein structure, dynamics, and function, with a particular emphasis on membrane proteins. Professor Klein-Seetharaman has published over 150 papers and has received numerous awards, including the Marie Curie International Incoming Fellowship, the Sofya Kovalevskaya Award from the Humboldt Foundation, a Bill and Melinda Gates Foundation Grand Challenges Award, the NSF CAREER Award, and the Margaret Oakley Dayhoff Award of the Biophysical Society. Her work is recognized for its integration of computational biology with experimental biophysics, especially in the context of membrane receptor signaling and protein interactions.

Selected publications

• Three Unrelated Children With Childhood Apraxia of Speech: Exome Sequencing and Functional Gene Analysis Imply a Role of Laminin‐511 in Early Neurodevelopment

  Case Reports in Genetics · 2026-01-01

  articleOpen access

  Childhood apraxia of speech (CAS) is characterized by motor discoordination in the speech domain and also in fine and gross motor systems, implicating the early developing cerebellum. Comorbidity with autism spectrum disorder (ASD) and other neurodevelopmental conditions has been observed. The genetic etiology is highly heterogeneous. Here, we present three unrelated individuals with CAS and concomitant fine and gross motor involvement but different genetic variants of interest. The DNA of the cases and their parents underwent exome sequencing and variant filtering. Using publicly available data, the genes of interest derived from the variants were investigated for expression rates in the early developing brain. Known and putative protein–protein interactions among the genes of highest confidence were identified. Of 28 variants in 28 different genes, variants with highest confidence were situated in FOXN4 , LAMA5 , LAMB1 , LRRK2 , and USP17L2 . High gene expression rates in the developing cerebellum were observed for LAMA5 and LAMB1 . These genes encode the α5 and β1 subunits, respectively, of the heterotrimeric extracellular laminin‐511 complex, a major component of the basal membrane in many tissues. Network analysis of the five high‐confidence genes required expansion with only one additional gene, CDK6 , to arrive at a fully connected network. The addition of four genes and inclusion of transcriptional regulation as an additional edge type allowed connecting all 28 genes of interest to arrive at a dense connectome with 32 nodes and 73 edges, representing a network enrichment with p value of < 0.001, suggesting that our network has significantly more interactions than expected under random conditions. We conclude that high levels of genetic heterogeneity converge on a functional gene network governed by stimulation of cells through laminin‐511 with shared direct or regulatory expression in the developing cerebellum and phenotypic overlaps of CAS, ASD, and other neurodevelopmental disorders.

  PublisherDOI

• Decoding the Functional Interactome of Non-model Organisms with PHILHARMONIC

  Lecture notes in computer science · 2025-01-01

  book-chapter
  PublisherDOI

• Allostery-Driven Substrate Gating in the Chlorothalonil Dehalogenase from Pseudomonas sp. CTN-3

  Biology · 2025-12-22

  articleOpen access

  The catalytic mechanism of the Zn(II)-dependent chlorothalonil dehalogenase from Pseudomonas sp. CTN-3 (Chd) was examined using molecular dynamics (MD) simulations, Bayesian network analysis, and Markov state model analysis to quantify its motions. Chd selectively substitutes an aromatic chlorine-carbon bond in chlorothalonil (TPN; 2,4,5,6-tetrachloroisophtalonitrile) with an aromatic alcohol (4-hydroxytrichloro-isophthalonitrile; 4-OH-TPN). It is a homodimer with two solvent-accessible channels in each monomer, which are proposed to provide different routes for substrate and products to access/leave the catalytic Zn(II) site. Based on MD simulations, Chd exhibits allosteric behavior wherein a “Y”-shaped substrate channel exhibits a “flip flop” mechanism, where the “right” substrate channel opens to allow TPN to enter, after which it closes, followed by the “left” channel opening. The “right” channel then reopens, likely to allow the product, 4-OH-TPN, to leave the active site, but this reopening of the right channel drives the “left” channel to close. Coupled with the substrate channels alternately opening and closing, a corresponding possible Cl− channel opens and closes. Although the dynamics of this process are fast, Chd needs to overcome a 5 kT free-energy barrier for this transition and to relax after opening. Additionally, exposed “wing” residues, hydrophilic residues at the ends of protruding α-helices, act as allosteric indicators, signaling the complex allosteric motions required to open the substrate channel. We propose, for the first time, a dynamic mechanism that drives substrate binding and product release, providing new insight into Chd’s catalytic mechanism.

  PublisherOA PDFDOI

• Current State of Artificial Intelligence Model Development in Obstetrics

  Obstetrics and Gynecology · 2025-06-05 · 6 citations

  reviewSenior author

  Publications on artificial intelligence (AI) applications have dramatically increased for most medical specialties, including obstetrics. Here, we review the most recent pertinent publications on AI programs in obstetrics, describe trends in AI applications for specific obstetric problems, and assess AI's possible effects on obstetric care. Searches were performed in PubMed (MeSH), MEDLINE, Ovid, ClinicalTrials.gov , Google Scholar, and Web of Science using a combination of keywords and text words related to "obstetrics," "pregnancy," "artificial intelligence," "machine learning," "deep learning," and "neural networks," for articles published between June 1, 2019, and May 31, 2024. A total of 1,768 articles met at least one search criterion. After eliminating reviews, duplicates, retractions, inactive research protocols, unspecified AI programs, and non-English-language articles, 207 publications remained for further review. Most studies were conducted outside of the United States, were published in nonobstetric journals, and focused on risk prediction. Study population sizes ranged widely from 10 to 953,909, and model performance abilities also varied widely. Evidence quality was assessed by the description of model construction, predictive accuracy, and whether validation had been performed. Most studies had patient groups differing considerably from U.S. populations, rendering their generalizability to U.S. patients uncertain. Artificial intelligence ultrasound applications focused on imaging issues are those most likely to influence current obstetric care. Other promising AI models include early risk screening for spontaneous preterm birth, preeclampsia, and gestational diabetes mellitus. The rate at which AI studies are being performed virtually guarantees that numerous applications will eventually be introduced into future U.S. obstetric practice. Very few of the models have been deployed in obstetric practice, and more high-quality studies are needed with high predictive accuracy and generalizability. Assuming these conditions are met, there will be an urgent need to educate medical students, postgraduate trainees and practicing physicians to understand how to effectively and safely implement this technology.

  PublisherDOI

• Speech and Language Development of Two Brothers With Bainbridge‐Ropers Syndrome: Phenotypic and Bioinformatic Support for a Cerebellar <scp> <i>ASXL3</i> </scp> Hypothesis

  American Journal of Medical Genetics Part A · 2025-09-02 · 3 citations

  articleSenior author

  Bainbridge-Ropers syndrome (BRPS) is a rare neurodevelopmental disorder caused by variants in the ASXL3 gene. Nearly all cases are de novo, representing widely varying ASXL3 genotypes. Commonly observed traits include feeding difficulties, global motor delays, hypotonia, intellectual disability, autism, seizures, and craniofacial and skeletal changes. Difficulty with verbal communication is present in all cases, yet speech and language characteristics have not been described closely. Here, we present two brothers with BRPS due to suspected parental germline mosaicism. Clinical histories were based on chart review, interviews with a parent, and direct observations. Despite identical genotypes, phenotypic expression varies in severity. Both children have developmental coordination disorder, consistent with cerebellar dysfunction. Child 1, age 11 years, has childhood apraxia of speech (CAS) and largely intact cognitive skills. He received specialized therapy focused on motor learning and communicates verbally. Child 2, age 8, has oral apraxia, intellectual disability, autism, and language disorder. He communicates using non-speaking means. Bioinformatic analyses show that ASXL3 belongs to a regulatory network with highest cerebellar expression up to postconception Week 24. This study contributes speech and language descriptions, illustrates phenotypic variability likely resulting from the transcriptional regulatory network interacting with environmental influences, and underscores the importance of therapies that take motor discoordination into account.

  PublisherDOI

• Understanding metabolic resilience by unraveling temporal dynamics of cellular responses

  Trends in Endocrinology and Metabolism · 2025-05-26 · 8 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Abstract 1955 Insulin Signaling Pathways in Corals

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  Coral reefs cover 0.3% of the ocean and are vital marine ecosystems.Corals live in symbiosis with photosynthetic algae, which provide essential nutrients.Coral bleaching, triggered by environmental stress, is defined by a drastic drop in algae in the coral tissue, often leading to coral death.Between 2009 and 2018, 14% of coral reefs experienced mortality.From 2023 to mid-May 2024, widespread bleaching was documented in over 62 countries, marking the fourth global bleaching event.If current trends continue, 90% of reefs could be at risk by 2030.Understanding the molecular mechanisms behind bleaching is essential for coral resilience.Glucose is a critical metabolite that maintains homeostasis between coral cells and their endosymbionts.Previous coral transcriptome data reveal a glucose regulation systems similar to human energy metabolism.Our studies on Pocillopora damicornis (P.dam) identified 151 GPCR candidates with similarities to human signal transduction pathways.Using remote homology detection, we found insulin (INS), the insulin receptor (INSR), and 67 of 75 human INS signaling proteins likely conserved in P.dam.Based on this finding we hypothesized that INS signaling is present in corals and aberrant signaling, as it occurs in human diabetes, may play a role in coral bleaching.To test this hypothesis, we developed an experimental platform to validate predictions from remote homology modeling.To explore the role of INS signaling in coral physiology, we analyzed downstream protein effects using cell culture, bioinformatics, western blot, and mass spectrometry.Live cells (P.acuta) were dissociated from the coral skeleton using calcium-magnesium-free artificial seawater.Proteins were extracted and analyzed via SDS-PAGE, western blot, and mass spectrometry.Results support the remote homology finding as P.acuta cells stained positive for INSR, phosphorylated and non-phosphorylated ERK1/2 using the respective human antibodies.This research offers new insights into coral molecular mechanisms in resilience, with potential applications in coral pharmacology and conservation.

  PublisherOA PDFDOI

• PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance

  Molecular Cell · 2025-08-14 · 2 citations

  erratumOpen access
  PublisherDOI

• Microbiome association with coral growth and survival

  Nature Microbiology · 2025-05-20 · 2 citations

  articleSenior author
  PublisherDOI

• Benchmarking a large-scale protein-ligand docking workflow on an HPC cluster

  2025-07-18

  articleSenior author
  PublisherDOI

Education

• PhD, Chemistry

  Massachusetts Institute of Technolog

  2000

Awards & honors

• Howard Hughes Predoctoral Fellowship
• Gordon Research Conference Young Investigator Award
• Merck Award, Merck Frosst Center for Therapeutic Research
• Sofya Kovalevskaya Prize, Alexander von Humboldt-Foundation,…
• NSF CAREER Award "Evolution of Signaling Mechanisms in Membr…