Linda Bockenstedt, MD
Harold W. Jockers Professor of MedicineCards
Appointments
Contact Info
About
Titles
Harold W. Jockers Professor of Medicine
Biography
Dr. Linda Bockenstedt is the Harold W. Jockers Professor of Medicine, Section of Rheumatology, and Deputy Dean for Faculty Affairs at Yale School of Medicine. She received her undergraduate degree in chemistry and physics from Harvard College and is a graduate of the Ohio State University School of Medicine. After completing residency training in medicine and serving as Chief Resident in Medicine at Yale, Dr. Bockenstedt obtained rheumatology clinical and research fellowship training at the University of California, San Francisco. She has been a faculty member at Yale School of Medicine since 1989, where she directs a research program devoted toward understanding the pathogenesis of Lyme disease, an infection-related rheumatic disease. Her research has been continually supported by the National Institutes of Health since 1990, and she is internationally recognized for her studies of the host immune response to spirochetal infection. As a physician-scientist, she also is an active clinician and educator for medical trainees.
Dr. Bockenstedt is a Master of the American College of Rheumatology, and an elected member of the Kunkel Society and the Interurban Clinical Club. She is a former standing member of the Immunity and Host Defense Study Section at NIH and former member of the Board of Directors for the American College of Rheumatology Research & Education Foundation. She currently serves on the NIH NIAID Council and the DOD Tick-Borne Disease Research Program Programmatic Panel. Since 2006 she has been active in faculty affairs at Yale School of Medicine and in 2017, was appointed YSM Deputy Dean for Academic Affairs.
Appointments
Rheumatology
Professor Phased RetirementPrimary
Other Departments & Organizations
- Internal Medicine
- MORE
- Rheumatic Diseases Research Core
- Rheumatology
- Rheumatology, Allergy, & Immunology
- Yale Medicine
- Yale Ventures
Education & Training
- Fellow
- University of California, San Francisco (1989)
- Chief Resident
- Yale-New Haven Hospital (1985)
- Resident
- Yale-New Haven Hospital (1984)
- MD
- The Ohio State University College of Medicine (1981)
- AB
- Harvard College, Chemistry & Physics (1977)
Board Certifications
Rheumatology
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1988
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1985
Research
Overview
Lyme borreliosis is an infectious disease caused by the
tick-transmitted spirochete Borrelia burgdorferi. Since its recognition in the United States in the early
1970’s, it has emerged as the most common vector-borne disease in North America
and a significant health care concern, with nearly 30,000 confirmed new cases
in 2009. The infection can present
with a localized skin rash at the site of tick bite or with involvement of
other organ systems, especially the heart, joints and nervous system. Although the infection is highly
responsive to antibiotic therapy when detected early, the time to symptom
resolution may be protracted. A
delay in diagnosis can result in disease manifestations, such as arthritis,
that persist despite antibiotics effective at earlier stages of the illness.
My laboratory used the murine model of Lyme borreliosis to
study the host immune response to B. burgdorferi in an effort to understand factors
that influence clearance of the organism and disease expression. Our published work has demonstrated the
importance of innate immunity, especially phagocytes and T cell independent antibody,
in control of pathogen burden and the role of IgG subtypes and Fc receptors in
severity of arthritis. Through
imaging modalities, we have begun to dissect the role of spirochete motility
and fluidity of its outer membrane in evasion of the innate and adaptive immune
responses. In collaboration with
Dr. Eric Dufresne (Yale Department of Engineering), we are using optical
tweezers and speckle microscopy to measure the mobility of proteins in the
spirochete outer membrane and the consequences of membrane fluidity on the
ability of phagocytes to capture and ingest B. burgdorferi. In vivo, we are using multiphoton
microscopy to measure in real time the speed and motility patterns of
spirochetes as they move between the tick and the mammal, and the requirement
for select B. burgdorferi proteins in this process. Using this system, we have also shown that the vast majority
of spirochetes are eliminated within the first few days of antibiotic therapy
for disseminated Lyme borreliosis, but antigenic debris can persist in tissue
adjacent to cartilaginous structures.
Our current studies are designed to investigate the duration of
persistence of this debris and the potential for it to incite inflammation,
which may contribute to persistent symptoms after treatment for Lyme disease.
In addition to pathogenesis studies, we are also working in
conjunction with L2 Diagnostics, Inc., to improve the diagnosis of Lyme
disease. We have identified panels
of B. burgdorferi antigens expressed at early and late stages of infection that
are underrepresented in lysates of cultured spirochetes, which are the
substrates of current serologic tests for Lyme disease. These antigens are being evaluated for use
as new antigens for diagnosing Lyme disease and for evaluating response to
therapy.
1. Real-time intravital microscopy of Borrelia burgdorferi infection in mice
This project is using multiphoton microscopy to define in real-time spirochete interactions between the feeding tick and the mammalian host, including modes of spirochete dissemination from the skin and evolving host immune responses.
2. Biophysical properties of Borrelia burgdorferi outer surface membrane
This collaborative project with Dr. Eric Dufresne (Yale Dept. of Engineering) employs optical tweezer technology and speckle microscopy to measure Borrelia burgdorferi outer membrane protein mobility and the relationship to directional forces exerted by spirochetes when trapped at one end.
3. Cutaneous host immune response to Borrelia burgdorferi.
This project seeks to understand the skin immune response to tick feeding and tick-introduced pathogens.
4. Development of improved diagnostic tests for Lyme disease
These projects, performed in collaboration with L2 Diagnostics, seek to develop improved diagnostic tests for Lyme disease based on in vivo expressed Borrelia burgdorferi proteins.
5. Innate immune pathways in elderly and immunosuppressed populations
This contract with Drs. Fikrig and Montgomery will analyze human
innate immune cell function in aging and medication-induced immunosuppression
and identify critical pathways and mechanisms that mediate impaired/dysregulated
immune responses in the elderly and immunosuppressed populations.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Alexia Belperron, PhD
Ruth R Montgomery, PhD
Durland Fish, PhD
Erol Fikrig, MD
Insoo Kang, MD
Albert C Shaw, MD, PhD
Lyme Disease
Immunity, Innate
Publications
2024
Combining short- and long-read sequencing unveils geographically structured diversity in Borrelia miyamotoi
Hoornstra D, Kuleshov K, Fingerle V, Hepner S, Wagemakers A, Strube C, Castillo-Ramírez S, Bockenstedt L, Telford S, Sprong H, Platonov A, Margos G, Hovius J. Combining short- and long-read sequencing unveils geographically structured diversity in Borrelia miyamotoi. IScience 2024, 27: 110616. DOI: 10.1016/j.isci.2024.110616.Peer-Reviewed Original ResearchConceptsComparative whole-genome sequencingCombination of IlluminaLong-read sequencingGenetically distinct populationsGenome assemblyPacBio platformPlasmid typesCore plasmidHuman pathogensGenetic basisDistinct populationsExpression sitesPlasmidGeographical originIxodes speciesGenomeIsolatesTick-borne human pathogenVector competenceStructural diversityNorth AmericaBorrelia miyamotoiPacBioIlluminaVirulenceInsights From Omics in Lyme Disease
Bockenstedt L, Belperron A. Insights From Omics in Lyme Disease. The Journal Of Infectious Diseases 2024, 230: s18-s26. PMID: 39140719, DOI: 10.1093/infdis/jiae250.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and Concepts491 Novel characteristics of memory B cells identified by single-cell immunophenotyping of erythema migrans skin lesions
Jiang R, Kleinstein S, Bockenstedt L. 491 Novel characteristics of memory B cells identified by single-cell immunophenotyping of erythema migrans skin lesions. Journal Of Investigative Dermatology 2024, 144: s85. DOI: 10.1016/j.jid.2024.06.507.Peer-Reviewed Original Research
2023
Proteome Analysis for Inflammation Related to Acute and Convalescent Infection
Sigdel T, Sur S, Boada P, McDermott S, Arlehamn C, Murray K, Bockenstedt L, Kerwin M, Reed E, Harris E, Stuart K, Peters B, Sesma A, Montgomery R, Sarwal M. Proteome Analysis for Inflammation Related to Acute and Convalescent Infection. Inflammation 2023, 47: 346-362. PMID: 37831367, PMCID: PMC10799112, DOI: 10.1007/s10753-023-01913-3.Peer-Reviewed Original ResearchCitationsAltmetricConceptsC motif chemokine ligand 1C motif chemokine receptor 7Human Immunology Project ConsortiumWest Nile virusDengue virusLyme diseaseKidney transplant patientsChemokine ligand 1Chemokine receptor 7Common therapeutic interventionTumor necrosis factor receptorHost defense mechanismsNecrosis factor receptorCell surface markersConvalescent infectionTransplant patientsConvalescent phaseImmune signaturesAcute phaseConvalescent stageReceptor 7Common biological pathwaysHealthy donorsPolyomavirus infectionImmune response
2022
Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection
Boada P, Fatou B, Belperron A, Sigdel T, Smolen K, Wurie Z, Levy O, Ronca S, Murray K, Liberto J, Rashmi P, Kerwin M, Montgomery R, Bockenstedt L, Steen H, Sarwal M. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection. Frontiers In Immunology 2022, 13: 1012824. PMID: 36569838, PMCID: PMC9784464, DOI: 10.3389/fimmu.2022.1012824.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsWest Nile virus infectionLyme diseaseVirus infectionWNV infectionSerum proteomeSymptomatic WNV infectionTime of diagnosisHealthy control seraDisseminated Lyme diseaseHost response pathwaysExtracellular bacterial infectionsSerum proteomic analysisIntracellular viral infectionsViral infectionHost responseBacterial infectionsControl seraStudy participantsInfectionDiseaseDisease biomarkersEarly diagnosticsLC/MSMolecular mechanismsRecovery phase
2021
Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes
Bockenstedt L, Wooten R, Baumgarth N. Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes. 2021 DOI: 10.21775/9781913652616.18.ChaptersCitations
2017
Chapter 110 Lyme Disease
Bockenstedt L. Chapter 110 Lyme Disease. 2017, 1891-1904.e4. DOI: 10.1016/b978-0-323-31696-5.00110-8.ChaptersCitations
2016
A Tribute to James N. Miller
Bockenstedt L. A Tribute to James N. Miller. Onco Therapeutics 2016, 7: 163-164. DOI: 10.1615/forumimmundisther.2017020474.Peer-Reviewed Original Research
2013
In Memoriam: Stephen E. Malawista, MD, 1934–2013
Montgomery R, Bucala R, Bockenstedt L. In Memoriam: Stephen E. Malawista, MD, 1934–2013. Arthritis & Rheumatology 2013, 66: 1-1. DOI: 10.1002/art.38233.Commentaries, Editorials and Letters110 Lyme Disease
Bockenstedt L. 110 Lyme Disease. 2013, 1815-1828.e3. DOI: 10.1016/b978-1-4377-1738-9.00110-9.ChaptersCitations
Clinical Trials
Current Trials
Yale Rheumatology Program Patient Registry and Bio-Repository
HIC ID2000026608REGRoleSub InvestigatorPrimary Completion Date06/01/2030Recruiting ParticipantsGenderBothAge18 years - 99 years
Academic Achievements & Community Involvement
activity ICLB2013
ResearchDetails01/01/2013 - PresentUnited StatesAbstract/SynopsisCo-Chair, Internatlonal Conference on Lyme Borreliosis and Other Tick-Borne Diseases August 18-21, Boston, Massachusetts
honor Elected Member, CT Academy for Science & Engineering
UnknownCT Academy for Science & EngineeringDetails05/01/2012United Stateshonor Best Doctors in America
UnknownBest DoctorsDetails07/01/2010United Stateshonor Top Doctors, Internal Medicine & Rheumatology
UnknownConnecticut MagazineDetails07/01/2009United Stateshonor Member
UnknownThe Interurban Clinical ClubDetails07/01/2007United States
News & Links
News
- May 14, 2024
Ball Is Named Deputy Dean for Academic Affairs
- April 13, 2023
Discoveries & Impact (April 2023)
- February 27, 2023
Rheumatology Faculty Recognized at American College of Rheumatology Convergence
- October 27, 2022
Dr. Linda Bockenstedt and Dr. Richard Bucala Named ACR Masters
Get In Touch
Contacts
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Locations
The Anlyan Center
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300 Cedar Street, Ste Suite S520
New Haven, CT 06519
General Information
203.785.7665Yale Rheumatology
Academic Office
The Anlyan Center
300 Cedar Street, Fl 5, Rm S525C
New Haven, CT 06519