About

Jay T. Groves is a Professor of Chemistry at the University of California, Berkeley, affiliated with the College of Chemistry. He received his B.S. degree in Physics and Chemistry from Tufts University and completed his Ph.D. in Biophysics at Stanford University under Professors Steven Boxer and Harden McConnell. His early research included a visiting scholar position at Academia Sinica in Taipei, Taiwan, and a fellowship at Lawrence Berkeley National Laboratory in the Physical Biosciences Division. He joined UC Berkeley's Chemistry Department in 2001, progressing from Assistant Professor to full Professor by 2010, and was appointed as a Howard Hughes Medical Institute Investigator in 2008. Professor Groves' research focuses on physical chemistry in living systems, particularly the role of spatial organization in biochemical reaction systems. His work explores how spatial patterns influence signal transduction processes at the cell membrane, employing techniques in optical microscopy, spectroscopy, materials fabrication, and cell biology. His integrated approach enables the direct observation and physical manipulation of living reaction systems at the single-molecule level. His overarching goal is to develop a quantitative and mechanistic understanding of biochemical processes in living systems, rooted in physics and physical chemistry.

Research topics

• Chemistry
• Biology
• Biochemistry
• Thermodynamics
• Organic chemistry
• Materials science
• Cell biology
• Biophysics

Selected publications

• Disordered protein LAT encodes relative levels of signaling pathways in T cell activation

  Science · 2026-04-30

  article

  The disordered adapter protein linker for activation of T cells (LAT) propagates T cell receptor signaling. To interrogate how LAT coordinates multiple downstream pathways, we developed a single-cell screening approach, identifying widespread functional segments including protein interaction motifs and blocks of negative charge. Regardless of their position in LAT, individual segments generally conferred defects across all downstream signaling pathways. To understand the underlying mechanism, we used molecular biology, computational modeling, and imaging to demonstrate that disruption of LAT interaction with a single partner protein indirectly disrupts other partner interactions, likely through the dual roles of these proteins as effectors of downstream signaling and bridging factors between LAT molecules. Overall, we describe an extendable approach for interrogating sequence-function relationships for proteins with complex activities.

  PublisherDOI

• Supported membrane assay probes PLCγ1 activity in LAT condensates

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-25 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract Phospholipase C-γ1 (PLCγ1) plays a critical role linking T cell receptor activation with downstream signaling pathways including calcium. PLCγ1 activation in T Cells relies on phosphotyrosine-mediated recruitment to the membrane-bound scaffold LAT, which becomes crosslinked through a bond percolation network with Grb2 and other scaffold and signaling molecules to form a signaling condensate. PLCγ1 in these LAT condensates becomes activated, leading to induction of extracellular calcium influx. While PLCγ1-driven calcium signaling is clearly correlated with LAT condensation, it is less clear how—or if— the LAT condensation state facilitates PLCγ1 activity. Here we develop an image-based PLCγ1 activity assay in supported bilayers that enables simultaneous measurement of both PLCγ1 recruitment to phosphorylated LAT and PLCγ1-catalyzed hydrolysis of PIP 2 in the membrane. The condensation state of LAT is independently controlled by adjusting levels of co-condensation proteins such as Grb2, SOS, GADS, and SLP76. The hydrolysis product, diacylglycerol (DAG), remains in the membrane and is monitored as a readout of catalytic activity using a DAG sensor based on the C1b (DAG binding) domain of PKCθ. Assays are performed directly with mammalian cell lysate containing fluorescent PLCγ1 fusion constructs. The results reveal that PLCγ1 is highly active when recruited to dispersed LAT and that the condensed state does not promote activity. Overall, this assay platform reveals that despite the correlation between PLCγ1 signal gating and LAT condensation, the physical environment of the condensate itself is not a key regulator of PLCγ1 signaling. More broadly, this assay system offers a quantitative means of probing how PLCγ1 activity is controlled at the membrane.

  PublisherOA PDFDOI

• Abstract B001: eIF2B Selectively Anchors and Activates Mutant KRAS4B

  Cancer Research · 2026-03-05

  article

  Abstract Activating mutations in KRAS occur at high frequency in colorectal, lung, and pancreatic cancers, which together account for a substantial proportion of global cancer mortality. Mutant KRAS is constitutively biased toward the GTP-bound state, driving persistent proliferative signaling, but simultaneously imposes oncogenic stresses that threaten cellular homeostasis. To sustain transformation, KRAS-mutant cells engage adaptive stress-response mechanisms, many of which converge on translational control mediated by the eIF2-eIF2B axis. While eIF2B is classically known as a guanine nucleotide exchange factor (GEF) for eIF2 during translation initiation, its potential role in directly regulating oncogenic signaling pathways has remained unexplored. Here, we identify a non-canonical function of eIF2B as a direct activator of mutant KRAS signaling. We demonstrate that eIF2B forms a tripartite complex with SOS and mutant KRAS at the plasma membrane (PM), thereby enhancing KRAS activation and tumorigenic signaling. Biochemical assays and structural modeling support an interaction between the catalytic ε subunit of eIF2B and the allosteric Ras-binding site of SOS, stabilizing SOS in an active conformation. This interaction potentiates SOS-mediated GDP/GTP exchange on mutant KRAS and promotes KRAS nanoclustering at the PM. Importantly, eIF2B exhibits marked specificity for mutant KRAS4B, but not KRAS4A, HRAS, or NRAS. This selectivity arises from KRAS4B’s unique polybasic membrane-anchoring domain and from eIF2B-dependent remodeling of plasma membrane lipid composition. eIF2B enhances glycosphingolipid (GSL) biosynthesis, particularly GM3 and SM4, through translational upregulation of B4GALT5, generating a membrane environment that preferentially supports mutant KRAS4B anchoring and signaling. Disruption of GSL synthesis impairs formation of the eIF2B:SOS:KRAS complex and selectively reduces mutant KRAS activation. Notably, eIF2B’s stimulation of mutant KRAS signaling occurs independently of eIF2α phosphorylation, separating its translational stress-response function from its oncogenic signaling role. Functionally, eIF2B promotes tumor growth specifically in KRAS-mutant cancer models, including human xenografts and an autochthonous KRAS G12C-driven lung adenocarcinoma model. Clinically, high expression of eIF2Bε correlates with poorer outcomes in patients with KRAS-mutant tumors. Our findings identify eIF2B as a previously unrecognized regulator of mutant KRAS-driven tumorigenesis that links translational control, membrane lipid remodeling, and oncogenic signaling. By coordinating SOS activation, KRAS membrane nanoclustering, and selective translation, eIF2B emerges as a central modulator of KRAS oncogenic output and a potential therapeutic and prognostic target. In vivo targeting of eIF2B supports its use as a combinatorial strategy with KRAS inhibition to broaden the therapeutic window in KRAS-mutant cancers. This abstract was edited and refined with the assistance of generative artificial intelligence to improve clarity and conciseness. Citation Format: Hyungdong Kim, Shiqi Diao, Kwang-Jin Cho, Hyun-Ro Lee, Junchen Liu, Pascal Egea, Tatu Pantsar, Milla Kurki, Nour Ghaddar, Shuo Wang, Jia Yi Zou, Mehdi Amiri, Ritchel Gannaban, John F. Hancock, Kylie M. Rice, Atsuo Sasaki, John Asara, Brajendra Tripathi, Douglas Lowy, Rosalie Lawrence, Maria Hatzoglou, Carlos R. Azpilcueta-Nicolas, Jean-Philip Lumb, John Columbus, Thomas J. Turbyville, Christopher B. Marshall, Mitsuhiko Ikura, Jay T. Groves, Nahum Sonenberg, Peter Walter, Antonis E. Koromilas. eIF2B Selectively Anchors and Activates Mutant KRAS4B [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RAS Oncogenesis and Therapeutics; 2026 Mar 5-8; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_1):Abstract nr B001.

  PublisherDOI

• BPS2026 – Pre-assembly of a partial signaling unit primes T cell receptor signal transduction

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• BPS2026 – Signaling protein nucleation and condensation in the T-cell signaling pathway

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• BPS2026 – Kinetics of PLCG1 mutant lysates on a suppolipid bilayer

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Homogeneous image-based digital immunoassays with high error tolerance

  npj Imaging · 2026-05-04

  articleOpen accessSenior author

  There is a significant global health need to translate more in vitro diagnostic tests from clinical laboratories to field-based applications, including point-of-care and self-administered test formats. These applications typically require smaller sample sizes, limit sample processing and measurement capabilities, and introduce greater handling variability. Error tolerance is one of the most critical factors for successful field-based assay design. Here, we examine machine-learning (ML) strategies to enhance the error tolerance of image-based nanoparticle immunoassays. Random dispersions of nanoparticles were imaged in microliter sample volumes, and images were processed to determine analyte concentrations based on nanoparticle appearance. Assay performance was characterized using two common blood analytes: C-reactive protein and anti-SARS-CoV-2 IgG. We compare the results from conventional image analysis, a hybrid ML-conventional approach based on pixel segmentation, and end-to-end image regression using a targeted regularization strategy. Using serum samples from SARS-CoV-2 positive individuals, the segmentation-based approach enabled binary classification with 96% specificity and 90% sensitivity, matching seroconversion rates. The end-to-end regression model achieved superior quantitative performance (5.2 ng/mL), approaching ELISA-level detection range (0.01-10 ng/mL, depending on capture antibody affinity) in a single 30 min workflow without sample preprocessing. The limit of detection for digital molecular assays is not fixed, and we perform a theoretical analysis showing how adjusting particle counts and polydispersity can achieve arbitrary sensitivity down to the Poisson limit. Training images for the full image regression approach required only a single label-the analyte concentration-eliminating labor-intensive pixel-level labeling. Ultimately, the image-based readouts significantly improved dynamic range, sensitivity, and reproducibility over conventional readouts.

  PublisherOA PDFDOI

• BPS2026 – EGFR condensation in live cells is mediated by Grb2 and distinct from EGFR oligomerization

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-01

  articleSenior author

  Abstract T cells can respond to even a single molecular binding event of antigen to a TCR. A key step in the TCR signaling pathway that definitively exhibits this single molecule response is the initiation of calcium influx by activation of PLCγ1 in the LAT protein condensate. Here, we describe detailed kinetic measurements examining how protein condensation of LAT regulates activation of PLCγ1 using a reconstituted membrane system. The results reveal that membrane recruitment of PLCγ1 is tightly controlled by the LAT phosphorylation state, with no measurable independent recruitment to PIP 2 or PIP 3 lipids via the PLCγ1 PH domains. We further observe PLCγ1 is rapidly activated by membrane-associated kinase upon recruitment, irrespective of the LAT condensation state. These studies also revealed a crosstalk mechanism in which the TEC family kinases responsible for PLCγ1 activation also phosphorylate LAT. This interaction establishes a positive feedback loop in LAT phosphorylation, mediated through LAT condensation, which drives a bimodal LAT phosphorylation response to TCR activation. Kinetic modeling reveals how this LAT phosphorylation response can cooperatively gate PLCγ1 activation from a single TCR. These results suggest the LAT condensate facilitates both signal amplification and noise suppression in PLCγ1 activation through a bimodal switch affecting LAT phosphorylation. Significance Statement T cells are sensitive sensors capable of detecting and responding to trace amounts of foreign antigen. Understanding how they achieve such sensitivity while maintaining accurate antigen discrimination remains a key challenge. Here, through detailed kinetic measurements of PLCγ1 activation, we identify a cross reactivity in which kinases responsible for PLCγ1 phosphorylation also phosphorylate LAT. This creates a bimodal switch controlling LAT phosphorylation levels, which gates PLCγ1 activation from single TCR signals. We suggest this mechanism plays a key role in the signal amplification and noise suppression required for T cells to detect single antigen molecules.

  PublisherDOI

• Conditional requirement for dimerization of the membrane-binding module for BTK signaling in lymphocyte cell lines

  Science Signaling · 2025-01-14 · 5 citations

  articleOpen access

  Bruton's tyrosine kinase (BTK) is a major drug target in immune cells. The membrane-binding pleckstrin homology and tec homology (PH-TH) domains of BTK are required for signaling. Dimerization of the PH-TH module strongly stimulates the kinase activity of BTK in vitro. Here, we investigated whether BTK dimerizes in cells using the PH-TH module and whether this dimerization is necessary for signaling. To address this question, we developed high-throughput mutagenesis assays for BTK function in Ramos B cells and Jurkat T cells. We measured the fitness costs for thousands of point mutations in the PH-TH module and kinase domain to assess whether dimerization of the PH-TH module and BTK kinase activity were necessary for function. In Ramos cells, we found that neither PH-TH dimerization nor kinase activity was required for BTK signaling. Instead, in Ramos cells, BTK signaling was enhanced by PH-TH module mutations that increased membrane adsorption, even at the cost of reduced PH-TH dimerization. In contrast, in Jurkat cells, we found that BTK signaling depended on both PH-TH dimerization and kinase activity. Evolutionary analysis indicated that BTK proteins in organisms that evolved before the divergence of ray-finned fishes lacked PH-TH dimerization but had active kinase domains, similar to other Tec family kinases. Thus, PH-TH dimerization is a distinct feature of BTK that evolved to exert stricter regulatory control on kinase activity as adaptive immune systems gained increased complexity.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM064900

  NIH · $1.9M · 2008

• The role of positive and negative regulation on ligand discrimination by the TCR signaling pathway

  NIH · $54.2M · 2011–2027

• NIH Grant U01CA202241

  NIH · $3.3M · 2021

• CAREER: Mechanisms of Spatial Pattern Formation and Signal Transduction at Intercellular Junctions

  NSF · $547k · 2005–2010

Frequent coauthors

• John Kuriyan

  Vanderbilt University

  188 shared

• Wan‐Chen Lin

  Chang Gung Memorial Hospital

  85 shared

• Arup K. Chakraborty

  Massachusetts Institute of Technology

  64 shared

• Adam W. Smith

  Texas Tech University

  62 shared

• Rebecca S. Petit

  Howard Hughes Medical Institute

  54 shared

• Alexander A. Smoligovets

  University of California, Berkeley

  54 shared

• Il‐Hyung Lee

  Montclair State University

  51 shared

• Carolyn R. Bertozzi

  Stanford University

  49 shared

Awards & honors

• Burroughs Wellcome Career Award in the Biomedical Sciences (…
• Searle Scholars Award (2002)
• MIT TR100 (2003)
• Beckman Young Investigator Award (2004)
• NSF CAREER Award (2005)