About

Arup K. Chakraborty is an Institute Professor at MIT, holding the John M. Deutch Institute Professorship, and serves as a Professor of Chemical Engineering, Physics, and Chemistry. His central research focus is to understand the mechanistic underpinnings of the adaptive immune response to pathogens and to harness this understanding for the design of better vaccines and therapies. His work integrates approaches from statistical physics, immunology, and virology, and involves developing and applying theoretical and computational methods to study collective dynamic processes that span molecular to organismal scales. Chakraborty’s research includes investigating T cell signaling, T cell development in the thymus, the human immune response to HIV, and cell membrane biophysics. He has contributed significantly to the understanding of virus evolution, antibody responses, and vaccine design, and has recently explored the role of phase separation in gene regulation. Chakraborty is a member of all three branches of the US National Academies and is a Fellow of the American Academy of Arts & Sciences. He has received numerous honors, including the NIH Director’s Pioneer Award, the E. O. Lawrence Medal, a Guggenheim Fellowship, and the Max Delbruck Prize in Biological Physics. He is also recognized for his excellence in teaching and is a co-author of the book 'Viruses, Pandemics, & Immunity'.

Research topics

• Biology
• Computer Science
• Computational biology
• Physics
• Medicine
• Biophysics
• Genetics
• Virology
• Ecology
• Cell biology
• Immunology
• Internal medicine
• Evolutionary biology

Selected publications

• LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation

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

  article

  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

• Interplay between the immune response and the adaptation of metabolic pathways upon infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-02

  articleOpen accessSenior authorCorresponding

  Glucose is the principal metabolic fuel for the energy needs of most cell types. Upon infection, cytokines secreted by the immune system regulate redistribution of glucose to meet new metabolic needs associated with clearing the pathogen. We develop a mathematical model to describe the dynamics of such adaptation of metabolic pathways mediated by the immune response and its impact on the ability to clear pathogen and restore health. We find that cytokine-regulated redistribution of glucose resources in different tissues is critical for an effective immune response to pathogen as strictly clamping plasma glucose levels to homeostatic levels results in an ineffective immune response. By studying the effects of various parameters in our model, we describe how aberrant regulation of adaptation mechanisms affect outcomes of infection. Too high a glucose consumption rate by innate immune cells to mediate functions results in failure to clear pathogen. Pathogens with a very high replication rate can be controlled to low levels, but at a very high metabolic cost. Too low a pathogen replication rate allows the pathogen to hide from the immune system and rebound to high levels at later times. Finally, the strength of the innate immune response must be regulated to not be too high, not only to limit immunopathogenesis, but also for mediating an effective adaptive immune response.

  PublisherDOI

• Mechanism for evolution of diverse autologous antibodies upon broadly neutralizing antibody therapy of people with HIV

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-10 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Antiretroviral therapy (ART) inhibits Human Immunodeficiency Virus (HIV) replication to maintain undetectable viral loads in people living with HIV, but does not result in a cure. Due to the significant challenges of lifelong ART for many, there is strong interest in therapeutic strategies that result in cure. Recent clinical trials have shown that administration of broadly neutralizing antibodies (bnAbs) when there is some viremia can lead to ART-free viral control in some people; however, the underlying mechanisms are unclear. Our computational modeling shows that bnAbs administered in the presence of some viremia promote the evolution of autologous antibodies (aAbs) that target diverse epitopes of HIV spike proteins. This "net" of polyclonal aAbs could confer control since evasion of this response would require developing mutations in multiple epitopes. Our results provide a common mechanistic framework underlying recent clinical observations upon bnAb/ART therapy, and they should also motivate and inform new trials.

  PublisherOA PDFDOI

• Author response: Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses

  2025-08-26

  peer-reviewOpen access

  Vaccines are the most effective way to prevent many infectious diseases and millions of deaths worldwide every year. They work by training the immune system to react to a protein – the antigen – that is specific to a pathogen. In response, the body produces specific antibodies, large proteins that mark the invaders for destruction. This builds a memory of this particular pathogen, enabling them to fight future infections better. Some vaccines contain antigens, while others contain weakened or inactivated viruses or bacteria. Newer vaccines often contain a blueprint for producing antigens, such as DNA or RNA, instead of an antigen. Each year, the flu vaccine is updated to match the main flu strains in circulation. This is because the vaccine’s key component – the spike protein hemagglutinin (HA) – works best when it triggers antibodies that recognize and neutralize viruses with the same HA sequence. A major obstacle to creating a universal flu vaccine is that influenza viruses constantly mutate, weakening the match between the vaccine and the virus. The problem is made worse because vaccines tend to produce antibodies that target the very parts of HA that change most frequently. Repeated vaccination with the same flu shot (called vaccine boosting) was thought to strengthen the original immune response by increasing the number of antibodies targeting the same variable parts of HA. However, recent findings from studies on SARS-CoV-2 (the virus that causes COVID-19) suggest this is not always the case. Instead, repeated vaccination can both boost existing antibodies and generate new ones that target previously unrecognized regions of the antigen. This broader antibody response can help protect against variant viruses that share these newly recognized regions. Deng, Tang et al. tested whether this antibody broadening also occurs with repeated influenza vaccination. The researchers evaluated data from a group of people who received the same flu vaccine for four consecutive years between 2013 to 2016, which included the new 2009 pandemic strain that many had never encountered before. The analyses showed that over time, their antibody responses became more diverse and capable of recognizing flu viruses spanning almost a century of evolution. To understand how this happens, Deng, Tang et al. built a computational model to trace how a type of immune cell known as the B cells mature and diversify their antibody production after vaccination. The findings suggest that the broad antibody response during vaccination boosting is an inherent feature of the human immune system. The next step and challenge will be to harness the natural ability to broaden antibody responses for designing vaccines that can protect against strains that may emerge in the future. This could involve fine-tuning HA or other vaccine proteins to better guide the immune system toward producing a broadly protective set of antibodies. Importantly, this principle of immune broadening could apply to any vaccine antigen – not just influenza.

  PublisherDOI

• Designed mosaic nanoparticles enhance cross-reactive immune responses in mice

  Cell · 2025-01-23 · 22 citations

  articleOpen accessSenior author

  <h2>Summary</h2> Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2_COMs), five (mosaic-5_COM), or seven (mosaic-7_COM) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges. Naive and COVID-19 pre-vaccinated mice immunized with mosaic-7_COM elicited antibodies targeting conserved RBD epitopes, and their sera exhibited higher binding and neutralization titers against sarbecoviruses than mosaic-8b. Mosaic-2_COMs and mosaic-5_COM elicited higher antibody potencies against some SARS-CoV-2 variants than mosaic-7_COM. However, mosaic-7_COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons, supporting its use to protect against SARS-CoV-2 variants and zoonotic sarbecoviruses.

  PublisherDOI

• RNA gradients can guide condensates toward promoters: Implications for enhancer–promoter contacts and condensate-promoter kissing

  The Journal of Chemical Physics · 2025-09-09 · 4 citations

  articleOpen accessSenior author

  We study how protein condensates respond to a site of active RNA transcription (i.e., a gene promoter) due to electrostatic protein-RNA interactions. Our results indicate that condensates can show directed motion toward the promoter, driven by gradients in the RNA concentration. Analytical theory, consistent with simulations, predicts that the droplet velocity has a non-monotonic dependence on the distance to the promoter. We explore the consequences of this gradient-sensing mechanism for enhancer-promoter (E-P) communication using polymer simulations of the intervening chromatin chain. Directed motion of enhancer-bound condensates can, together with loop extrusion by cohesin, collaboratively increase the enhancer-promoter contact probability. Finally, we investigate under which conditions condensates can exhibit oscillations in their morphology and in the distance to the promoter. Oscillatory dynamics are caused by a delayed response of transcription to condensate-promoter contact and negative feedback from the accumulation of RNA at the promoter, which results in charge repulsion.

  PublisherOA PDFDOI

• Awareness of Post-exposure Prophylaxis after Accidental Contact with Body Fluids among Interns at Medical College, Kolkata: A Cross-Sectional Observational Study

  Amrita Journal of Medicine · 2025-10-01

  articleOpen access

  Abstract Introduction: Exposure to body fluids can lead to serious health concerns among healthcare workers. Proper and timely post-exposure prophylaxis (PEP) is thus necessary. This study thus assessed the level of awareness of PEP (for human immunodeficiency virus [HIV] and Hepatitis B) among interns in a tertiary care hospital in West Bengal. Materials and Methods: The study was conducted on 150 intern healthcare professionals between August and September 2023, at Medical College, Kolkata, in West Bengal, India. All participants completed a pre-tested, self-administered questionnaire with items relating to PEP for HIV and hepatitis B. Data entry was conducted using Microsoft Excel (2019), while statistical analysis was performed using SPSS software. Results: Among 150 participants (92 male and 58 female), the mean age was 23.78 ± 1.055 years. All participants, except one intern nurse, were aware of PEP. Formal training on PEP was received by 70.37% of intern nurses, while only 28.45% of intern doctors. 92.59% of intern nurses, and 56.1% of intern doctors were aware of the reporting and documentation procedures after potential exposure; 53.69% of intern doctors and 51.85% of intern nurses reported feeling “Somewhat confident” in guiding colleagues for effective PEP, and 72% of participants demonstrated adequate knowledge, with intern nurses slightly outperforming compared to intern doctors. The majority of the participants reported completing the recommended hepatitis B vaccination regimen, adhering to universal precautions during procedures, and having no history of accidental exposure. Conclusion: Urgent action is needed to enhance PEP awareness among interns, especially intern doctors, guiding targeted interventions for knowledge improvement.

  PublisherDOI

• BPS2025 - A model of the dynamics of LAT condensates in reconstitution experiments

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Repeated vaccination with homologous influenza hemagglutinin broadens human antibody responses to unmatched flu viruses

  eLife · 2025-09-04 · 1 citations

  articleOpen access

  The ongoing diversification of influenza virus necessitates annual vaccine updating. The vaccine antigen, the viral spike protein hemagglutinin (HA), tends to elicit strain-specific neutralizing activity, predicting that sequential immunization with the same HA strain will boost antibodies with narrow coverage. However, repeated vaccination with homologous SARS-CoV-2 vaccine eventually elicits neutralizing activity against highly unmatched variants, questioning this immunological premise. We evaluated a longitudinal influenza vaccine cohort, where each year the subjects received the same, novel H1N1 2009 pandemic vaccine strain. Repeated vaccination gradually enhanced receptor-blocking antibodies (HAI) to highly unmatched H1N1 strains within individuals with no initial memory recall against these historical viruses. An in silico model of affinity maturation in germinal centers (GCs) integrated with a model of differentiation and expansion of memory cells outside GCs during a recall response provides insight into the potential mechanisms underlying these results and shows how repeated exposure to the same immunogen can broaden the antibody response against diversified targets.

  PublisherDOI

• A unifying model of LAT condensates in reconstitution experiments

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-01

  preprintOpen accessSenior author

  The formation of condensates by the Linker for the Activation of T-cells (LAT) is a key signal gating and amplification step in the T-cell receptor signaling pathway. LAT condensation is challenging to study in-vivo and is therefore often investigated using reconstitution experiments. While these experiments recapitulate key aspects of LAT condensation, they also exhibit some puzzling features. Here, we describe the mechanisms underlying these observations using two complementary models. First, we employ a Smoluchowski aggregation model to show that the delay time before condensation is observed arises from a low effective binding probability between LAT monomers. Second, we propose a field-theoretic model that reproduces all condensate morphologies observed in experiments, showing that they can arise from common underlying dynamics modulated by variations in experimental conditions. This result unifies different experimental observations reported previously. While this article addresses open questions regarding the formation of LAT condensates, our results also provide a common framework for understanding condensation of other multivalent membrane proteins such as EGFR, FGFR2, and nephrin.

  PublisherOA PDFDOI

Recent grants

• Biophysics of Nuclear Condensates

  NSF · $5.0M · 2021–2027

• Balanced signaling cues to guide cell transitions in the blood lineage continuum

  NIH · $2.9M · 2015–2021

• RAISE: A Phase Separation Model for Transcriptional Control in Mammals

  NSF · $1.0M · 2017–2020

• Exploiting Biomimetic Recognition between Polymers & Surfaces to Design Nanoscale Separation Processes

  NSF · $250k · 2000–2004

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

  NIH · $54.2M · 2011–2027

Frequent coauthors

• Mehran Kardar

  Massachusetts Institute of Technology

  68 shared

• Jay T. Groves

  University of California, Berkeley

  64 shared

• Alexis T. Bell

  62 shared

• John P. Barton

  University of California, Riverside

  58 shared

• Arthur Weiss

  43 shared

• Jayajit Das

  The Ohio State University

  41 shared

• Karthik Shekhar

  University of California, Berkeley

  39 shared

• Dennis R. Burton

  Scripps Research Institute

  33 shared

Awards & honors

• NIH Director’s Pioneer Award
• E. O. Lawrence Medal (DOE)
• Guggenheim Fellowship
• Max Delbruck Prize in Biological Physics from the American P…
• Colburn, Professional Progress, Alpha Chi Sigma and Prausnit…