Linden T Hu
Tufts University, MA·Microbiology & Immunology
Most people treated for Lyme disease, a tick-borne bacterial infection, get better after antibiotics. A minority do not: for more than six months they live with fatigue, pain, muscle weakness and memory problems, a condition called post-treatment Lyme disease syndrome (PTLDS).
- Fields
Microbiology & Immunology
Medicine & Clinical Research
- Topics
Lyme disease
Borrelia burgdorferi
tick-borne disease
- Grants
- 5 known grants, through Jun 2029
What they work on
- Follow patients from acute Lyme disease diagnosis until they recover or develop PTLDS, comparing co-infections, inflammation, immune cell types, autoantibodies and bacterial traits, and build a large shared specimen bank.
- Compare immune responses in PTLDS and recovered patients over time, using high-dimensional flow cytometry (counting many immune cell types at once) with bulk RNA sequencing and high-throughput protein measurements.
- Search for antibodies against Borrelia or the patient's own proteins that track with PTLDS, using PhIP-seq, a screen of antibodies against huge libraries of protein fragments, and peptide microarrays; then test whether patient antibodies bind nerve tissue.
- Find links between PTLDS and HLA-DR immune variants, then identify the bacterial or self protein fragments these molecules show to T cells, using nano-liquid chromatography with tandem mass spectrometry.
- Sequence genomes of B. burgdorferi strains from PTLDS and recovered patients, testing whether variation in about 80 surface lipoproteins or 14 cell-wall (peptidoglycan) genes distinguishes strains linked to PTLDS.
- Compare PTLDS and recovered-patient strains for antibiotic tolerance, persister cell formation, cell-wall shedding, complement resistance and cell binding, and test their inflammation and spread in tick-infected mice.
- Measure antibodies against host phospholipids, membrane fats the bacterium steals from its host, across Lyme disease stages, and test whether they bind human tissues or form immune complexes.
- Test whether serum from PTLDS, recovered Lyme and fibromyalgia patients causes pain sensitivity and movement changes when injected into mice, as a new animal model of PTLDS.
- Determine how the tlr1-1805GG variant, which keeps the bacterial sensor TLR1 off the cell surface, changes signaling, macrophage metabolism and cell death, and whether it disrupts the immune tolerance that normally limits inflammation.
More about the research
There is no diagnostic test for PTLDS, no agreed treatment, and no consensus on its cause. The working idea behind these grants is that several factors combine to produce it: traits of the infecting bacterium, Borrelia burgdorferi; how the patient's immune system responds; and prior or simultaneous exposures to other microbes. The projects look at each of these factors, using patients followed from diagnosis, human immune cells, and mice.
Why it matters
Patients with post-treatment Lyme disease syndrome currently have no diagnostic test and no agreed treatment. Finding the bacterial strain traits, immune patterns, autoantibodies and genetic variants that set these patients apart from those who recover could lead to tests that predict who will develop lasting symptoms. It may also point to ways to prevent or treat the condition. The shared specimen bank will give other researchers well-documented samples to study persistent Lyme symptoms.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Timothy Casselli
University of South Alabama, AL·Microbiology & Immunology
Determine whether the blood-cerebrospinal fluid barrier, the cell layer separating blood from the fluid around the brain, is where Borrelia burgdorferi and immune cells enter the central nervous system in infected mice.
Karen Cyndari
University of Iowa, IA·Microbiology & Immunology·Early-career
Measure whether Borrelia burgdorferi infection breaks down the tight-junction barrier formed by resident synovial macrophages, using infected human synovial explants imaged by confocal microscopy and histomorphometry.
Janakiram Seshu
University of Texas at San Antonio, TX·Microbiology & Immunology
Determine the correlates of protection from Purified Borrelial Lipoproteins by comparing antibody levels and bacteria-killing (borrelicidal) activity after oral versus injected dosing in C3H/HeN laboratory mice and white-footed mice (Peromyscus leucopus).
The school
Tufts University: 19 labs on PI Pages, $278M a year on research, 144 research doctorates a year.
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