- Pregnancy and Medication Impact
- Reproductive System and Pregnancy
- COVID-19 Impact on Reproduction
- NF-κB Signaling Pathways
- Complement system in diseases
- Immunotherapy and Immune Responses
- Malaria Research and Control
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Vector-borne infectious diseases
- Peripheral Neuropathies and Disorders
- Viral Infections and Vectors
- Rheumatoid Arthritis Research and Therapies
- Mosquito-borne diseases and control
- Toxin Mechanisms and Immunotoxins
Ragon Institute of MGH, MIT and Harvard
2019-2024
Health and Human Development (2HD) Research Network
2022
Tufts University
2019-2020
Walter Reed Army Institute of Research
2013
ABSTRACT Background Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide decision-making are lacking. We sought evaluate the immunogenicity reactogenicity of mRNA vaccination in pregnant women. Methods 131 reproductive-age recipients (84 pregnant, 31 lactating, 16 non-pregnant) enrolled a prospective cohort study at two academic medical centers. Titers SARS-CoV-2 Spike RBD IgG, IgA IgM quantified participant sera (N=131), umbilical cord (N=10),...
Substantial immunological changes occur throughout pregnancy to render the mother immunologically tolerant fetus and allow fetal growth. However, additional local systemic adaptations also occur, allowing maternal immune system continue protect dyad against pathogens both during after birth through lactation. This fine balance of tolerance immunity, along with physiological hormonal changes, contributes increased susceptibility particular infections in pregnancy, including more severe...
BackgroundAlthough emerging data during the SARS-CoV-2 pandemic have demonstrated robust messenger RNA vaccine–induced immunogenicity across populations, including pregnant and lactating individuals, rapid waning of vaccine-induced immunity emergence variants concern motivated use vaccine booster doses. Whether all will mount a comparable response to dose is not known.ObjectiveThis study aimed profile humoral immune COVID-19 in cohort pregnant, lactating, nonpregnant age-matched women.Study...
Significant immunological changes occur throughout pregnancy to tolerize the mother and allow growth of fetal graft. However, additional local systemic adaptations also occur, allowing maternal immune system continue protect dyad against foreign invaders both during after birth through lactation. This fine balance tolerance immunity, along with physiological hormonal changes, contribute increased susceptibility particular infections in pregnancy, including more severe COVID-19 disease....
Studies have demonstrated the protective role of antibodies against malaria. Young children are known to be particularly vulnerable malaria, pointing evolution naturally acquired clinical immunity over time. However, whether changes in antibody functionality track with acquisition malaria remains incompletely understood.
Genetically inactivated, Gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting approach. Antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting cells but also provide strong danger signal thus circumventing the requirement for potent extraneous adjuvants. E. coli expressing malarial antigens resulted in induction of either Th1 or Th2 biased responses were dependent both antigen and sub-cellular...
Lyme arthritis, caused by the spirochete
Abstract BACKGROUND While emerging data during the SARS-CoV-2 pandemic have demonstrated robust mRNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, rapid waning of immunity emergence variants concern motivated use vaccine booster doses. Whether all will mount a comparable response to dose is not known. OBJECTIVE We sought profile humoral immune COVID-19 in cohort pregnant, lactating, age-matched nonpregnant women. STUDY DESIGN characterized...
Abstract The IκB kinase (IKK) complex mediates the activation of canonical NFκB isoforms following T cell receptor (TCR) ligation. This consists kinases IKKα and IKKβ an essential adaptor subunit, modulator protein (NEMO). Most models suggest that IKK is activated within oligomeric Carma1/Bcl10/Malt1 (CBM) signalosomes. However, we observed NEMO enters TCR microclusters before CBM complexes are assembled, ~70 seconds engagement. also entered mobile vesicles in larger membrane-bounded...
Abstract Background Lyme disease, caused by the spirochete Borrelia burgdorferi, is most common vector-borne disease in United States. It drives a multisystem disorder, of which arthritis feature late disseminated seen approximately 60% untreated individuals. While resolves with oral or IV antibiotics, termed “antibiotic-responsive” arthritis, small percentage individuals develop progressive synovitis despite both and antibiotic therapy, called “antibiotic refractory” (LA), requiring...
Abstract The NF-κB essential modulator protein (NEMO) is required for activation of canonical by the T cell antigen receptor (TCR). However, subcellular localization NEMO during this process not well understood. By dynamically imaging fluorescent chimeras in live human cells, we demonstrate that rapidly recruited into TCR microclusters via domains previously implicated recognition linear and K63-linked polyubiquitin. recruitment requires activities tyrosine kinases Lck ZAP-70, but adaptor...
Abstract The IkB kinase (IKK) complex coordinates inflammatory responses by activating canonical NFkB downstream of immune receptors. This consists the kinases IKKa/β and dimeric adaptor subunit NEMO (NFkB essential modulator protein). mutations cause immunodeficiencies impair antigen receptor function. Canonical activation immunoreceptors, such as T cell (TCR), requires assembly Carma1/Bcl10/Malt1 (CBM) signalosome. While, functional studies in vitro interactions, place IKK CBM signalosome,...