About

Paula Kavathas, PhD, is a Professor of Laboratory Medicine, of Immunobiology, and of Molecular, Cellular, and Developmental Biology at Yale School of Medicine. She studies the T cell co-receptor CD8ab and the functional significance of four isoforms of the human CD8b protein that exist in humans and great apes but not mice. Her recent research focuses on understanding the basis for acquired resistance to immunotherapy of human lung cancer tumors. Dr. Kavathas holds the position of Vice Chair for Collaborative Excellence in both the Departments of Laboratory Medicine and Immunobiology. She is also an institutional leader within the CIRTL Network. Her professional activities include serving on the board of SWIM (Status of Women in Medicine) and the Women’s Faculty Forum, where she served as Chair from 2013 to 2017. She has contributed to diversifying portraits at Yale, including commissioning a portrait of the first women PhDs located in the nave of Sterling Library. Her efforts extend to co-organizing conferences, publishing demographic analyses of women and underrepresented minorities at Yale, and advocating for institutional changes such as expanding childcare facilities and modifying parental leave policies.

Research topics

• Biology
• Genetics
• Immunology
• Medicine
• Internal medicine
• Computational biology
• Cancer research
• Evolutionary biology
• Biochemistry
• Endocrinology
• Pathology
• Bioinformatics

Selected publications

• Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-01 · 7 citations

  preprintOpen access

  To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. Also, we identified individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlated across body sites, suggesting systemic coordination influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals showed altered microbial stability and associations between microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease. Study Highlights: The stability of the human microbiome varies among individuals and body sites.Highly individualized microbial genera are more stable over time.At each of the four body sites, systematic interactions between the environment, the host and bacteria can be detected.Individuals with insulin resistance have lower microbiome stability, a more diversified skin microbiome, and significantly altered host-microbiome interactions.

  PublisherOA PDFDOI

• Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease

  Cell Host & Microbe · 2024 · 131 citations

  • Biology
  • Computational biology
  • Evolutionary biology

  To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.

  PublisherDOI

• Table S3 from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  2023-04-03

  preprintOpen access

  <p>Interferon pathway mutation and copy number alterations</p>

  PublisherDOI

• Supplementary Figure Legends from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  2023-04-03

  preprintOpen access

  <p>Legends for Figures S1-S8</p>

  PublisherDOI

• Supplementary Data from Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer

  2023-03-31

  preprintOpen access

  <p>Supplementary figures and tables.</p>

  PublisherDOI

• Data from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  2023-04-03

  preprintOpen access

  <div>Abstract<p>Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy-number changes were not detected in our cohort. In one case, we found acquired homozygous loss of <i>B2M</i> that caused lack of cell-surface HLA Class I expression in the tumor and a matched patient-derived xenograft (PDX). Downregulation of B2M was also found in two additional PDXs established from ICI-resistant tumors. CRISPR-mediated knockout of <i>B2m</i> in an immunocompetent lung cancer mouse model conferred resistance to PD-1 blockade <i>in vivo</i>, proving its role in resistance to ICIs. These results indicate that HLA Class I APM disruption can mediate escape from ICIs in lung cancer.</p><p><b>Significance:</b> As programmed death 1 axis inhibitors are becoming more established in standard treatment algorithms for diverse malignancies, acquired resistance to these therapies is increasingly being encountered. Here, we found that defective antigen processing and presentation can serve as a mechanism of such resistance in lung cancer. <i>Cancer Discov; 7(12); 1420–35. ©2017 AACR.</i></p><p><i>This article is highlighted in the In This Issue feature, p. 1355</i></p></div>

  PublisherDOI

• Supplementary Methods from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  2023-04-03

  preprintOpen access

  <p>Methods for quantitative immunofluorescence and IFN gamma treatment of PDXs</p>

  PublisherDOI

• Supplementary Figures from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  2023-04-03

  preprintOpen access

  <p>Supplementary Figures S1-S8</p>

  PublisherDOI

• A Perfect Fit: 3D-Printed Kit to Teach Students Principles of Antigen-Antibody Recognition and Herd Immunity

  The Journal of Immunology · 2023-05-01

  articleOpen accessSenior author

  Abstract The immunological principles underlying vaccines are a critical part of understanding human health and disease, but are typically not included in general K-12 education curriculum. The COVID-19 pandemic has underscored both the power of science and the importance of science literacy for our country. Though multifactorial, vaccine hesitancy is associated with patients’ lack of information surrounding vaccine biology. Recognizing this gap, we aimed to develop innovative learning activities that would distill the complex concepts of adaptive immunity and herd immunity to make them accessible to middle and high school students. Herein, we present one such learning activity intended to help students visualize the structural features of an antibody and the specificity of antibody-antigen interactions. Each student is provided with a base 3D-printed antibody, along with three sets of exchangeable variable domains and three model pathogens. Students explore the ability of their antibody combinations to recognize different pathogens, learning the structure and specificity of the antibody and the role they play in fighting pathogens. The set of kits for a classroom are distinct, with kits sharing some, but not all, variable regions. This feature allows for modeling of herd immunity and how different infections spread through a community depending on vaccination rates. This tangible model therefore can convey to students how vaccines elicit protection against pathogens at both an individual and population level. Inclusion of this learning activity during STEM outreach events or integration into classroom curriculum provides an opportunity for early educational intervention that would promote vaccine literacy in our communities.

  PublisherOA PDFDOI

• Supplementary Figure Legends from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer

  2023-04-03

  preprintOpen access

  <p>Legends for Figures S1-S8</p>

  PublisherDOI

Recent grants

• NIH Grant R01CA048115

  NIH · $6.3M · 2014

• NIH Grant R01AI049571

  NIH · $1.8M · 2010

• NIH Grant R01AI035417

  NIH · $2.5M · 2003

• NIH Grant R01AI023396

  NIH · $368k · 1990

Frequent coauthors

• Kurt A. Schalper

  Yale University

  30 shared

• David L. Rimm

  30 shared

• Ila Datar

  27 shared

• Soldano Ferrone

  26 shared

• Katerina Politi

  25 shared

• Sarah B. Goldberg

  25 shared

• Roy S. Herbst

  Yale Cancer Center

  25 shared

• Scott Gettinger

  Moffitt Cancer Center

  25 shared

Labs

• Kavathas LabPI