The NIAID Training office is celebrating the amazing contributions of our postdoctoral, visiting, and research fellows during National Postdoc Appreciation Week from Monday, September 21 through Friday, September 25, 2020. Read what NIAID postdocs have to say about their research and what they like most about working at NIAID.
Billur Akkaya, M.D., DPhil
Research Fellow in the Cellular Immunology Section of the Laboratory of Immune System Biology
“I truly enjoy the resources that NIAID provides me to pursue my ideal in research. NIAID intramural research program is where the sky is the limit for creative minds.” Billur Akkaya, M.D., DPhil
Autoimmunity is a leading cause of chronic illness that encompasses more than 100 individual diseases. Regulatory T cells (Tregs) are body’s safeguard against autoimmunity, therefore constitute a desirable target for therapies. My research at NIAID unraveled a new working principle for Tregs whereby they modulate the immune response and prevent autoimmunity via stealing antigen from antigen presenting cells (1), (2). In the near future, the biological processes leading up to this phenomenon will be under spotlight for designing new generation antigen-targeted therapies to defeat not only autoimmune diseases but also cancer. Stay tuned! NIAID New Innovators Awardee (DP2).
- Akkaya, Billur et al. “Regulatory T cells mediate specific suppression by depleting peptide-MHC class II from dendritic cells.” Nature immunology vol. 20,2 (2019): 218-231. doi:10.1038/s41590-018-0280-2
- Akkaya, Billur, and Ethan M Shevach. “Regulatory T cells: Master thieves of the immune system.” Cellular immunology vol. 355 (2020): 104160. doi:10.1016/j.cellimm.2020.104160
Allison Bucsan, Ph.D.
Postdoctoral Fellow in the Cellular Immunology Section of the Immunology Laboratory, Vaccine Research Center
“I like that my research program supports the development of vaccines to prevent tuberculosis, as well as therapeutics and vaccines for other diseases like malaria and cancer.” – Allison Bucsan, Ph.D.
I work in the Vaccine Research Center on the characterization of host immune responses that will protect against Mycobacterium tuberculosis (Mtb) infection. Recently our research has sought to investigate mechanisms by which the BCG vaccine protects against Mtb infection and found that changing the route of vaccination improved protection. Our goal is to identify correlates of immunity that can be used to evaluate immunity.
Foreman, Taylor W et al. “Isoniazid and Rifapentine Treatment Eradicates Persistent Mycobacterium tuberculosis in Macaques.” American journal of respiratory and critical care medicine vol. 201,4 (2020): 469-477. doi:10.1164/rccm.201903-0646OC
Bucşan, Allison N et al. “Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection.” The Journal of clinical investigation vol. 129,12 (2019): 5254-5260. doi:10.1172/JCI125810
Pedro H Gazzinelli-Guimaraes MSc., Ph.D.
Research Fellow in the Helminth Immunology Section of the Laboratory of Parasitic Diseases
“Completing my postdoc at NIAID has allowed me to contribute meaningfully to my field of research, and to influence a number of global health goals.” - Pedro Guimaraes-Gazzinelli, MSc., Ph.D.
Under the supervision of Thomas Nutman, M.D., my project has been focused on evaluating the relationship between helminth infections and allergies. We have demonstrated that house-dust mite (HDM)-allergic sensitization coincident with filarial infection induces an augmented parasite-specific Th2-dominated immune response in humans. Using a murine model of HDM-induced allergic inflammation followed by infection with the Ascaris roundworm, we have shown that environmental allergens drive a lung-specific eosinophil-rich type-2-immunity that leads to 70% reduction in parasite burden. We are now exploring the function, plasticity and specificity of the effector Th2 cell subsets at the single cell level and through systems immunology to understand their implication in the pathogenesis of helminth-allergy reactivity.
Gazzinelli-Guimaraes, Pedro H et al. “Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development.” The Journal of clinical investigation vol. 129,9 3686-3701. 5 Aug. 2019, doi:10.1172/JCI127963
Gazzinelli-Guimaraes, Pedro H, and Thomas B Nutman. “Helminth parasites and immune regulation.” F1000Research vol. 7 F1000 Faculty Rev-1685. 23 Oct. 2018, doi:10.12688/f1000research.15596.1
Jeffrey Grabowski, Ph.D.
Postdoctoral Fellow in the Biology of Vector-Borne Viruses Section in the Laboratory of Virology
“It is exciting to see that my basic research can be used in a translational pipeline leading towards designing countermeasures to combat tick-borne virus infections and possibly other tick-borne diseases.” - Jeffrey Grabowski, Ph.D.
My research intersects vector biology, arbovirology, and microbiology. The interdisciplinary projects I've spearheaded with virus-tick interactions and virus-tick model development provide novel findings in a neglected research area. Little is known regarding the mechanisms of virus infection and dissemination from tick organs. Currently, my research aims at dissecting macromolecular interactions between viruses and ticks, especially within salivary glands (SGs). Much of this has led to identification of tick-specific transcripts that are functionally involved in virus infection of SGs. Ongoing and future research continues to characterize the potential roles of these select transcripts and corresponding proteins in the virus lifecycle and in tick physiology.
Grabowski, Jeffrey M et al. “Dissecting Flavivirus Biology in Salivary Gland Cultures from Fed and Unfed Ixodes scapularis (Black-Legged Tick).” mBio vol. 10,1 e02628-18. 29 Jan. 2019, doi:10.1128/mBio.02628-18
Grabowski, Jeffrey M et al. “The Use of Ex Vivo Organ Cultures in Tick-Borne Virus Research.” ACS infectious diseases vol. 4,3 (2018): 247-256. doi:10.1021/acsinfecdis.7b00274
Jessica C. Hargarten, Ph.D.
Postdoctoral Fellow in the Translational Mycology Section of the Laboratory of Clinical Immunology and Microbiology
“Being a postdoc at NIAID allows me the uniquely rewarding opportunity to meet the patients most impacted by the scientific discoveries our team makes in the lab. Patient stories are my daily inspiration.” – Jessica C. Hargarten, Ph.D.
As a postdoc in the Translational Mycology Section in the Laboratory of Clinical Immunology and Microbiology at the NIAID, my research project focuses on understanding how rare genetic mutations increase the susceptibility of previously healthy people to fungal infections, particularly those caused by the neurotropic pathogen Cryptococcus. Globally, cryptococcal meningoencephalitis (CM) is responsible for ~11% of AIDS-related deaths and carries a mortality rate upwards of 30-50% in HIV-uninfected individuals, including the previously healthy with no apparent underlying predispositions at a rate of ~1:500,000 in the United States. Little is known about the immune defects underlying disease in the previously healthy. Through whole exome sequencing analysis, we identified rare alleles predicted to have deleterious functional consequences. Ongoing experiments will further determine the role of these genes in immunity and susceptibility to CM in order to facilitate development of personalized therapeutic interventions.
Hargarten, Jessica C, and Peter R Williamson. “Epigenetic Regulation of Autophagy: A Path to the Control of Autoimmunity.” Frontiers in immunology vol. 9 1864. 14 Aug. 2018, doi:10.3389/fimmu.2018.01864
Xu, Jintao et al. “Chemokine receptor CXCR3 is required for lethal brain pathology but not pathogen clearance during cryptococcal meningoencephalitis.” Science advances vol. 6,25 eaba2502. 17 Jun. 2020, doi:10.1126/sciadv.aba2502
Julia Lederhofer, MSc., Ph.D.
Postdoctoral Fellow in the Viral Pathogenesis Laboratory of the Vaccine Research Center
“I like that the scientific resources and research opportunities at the Vaccine Research Center are endless.” – Julia Lederhofer, Msc., Ph.D.
Despite immense efforts in the past several decades and the availability of commercial vaccines influenza remains a major public health burden worldwide. Although currently only two subtypes of influenza A and two lineages of influenza B viruses cause seasonal epidemic in humans, there are a number of influenza viruses in zoonotic reservoirs that pose a pandemic threat to humans. Current influenza vaccines consist of predicted circulating strains of influenza A H1N1, H3N2, and one or two lineages of influenza B viruses. These vaccines induce protective immunity to vaccine-matched strains but are not effective when the circulating virus(es) is not matched to the vaccines. In our laboratories, significant effort is being invested to develop universal influenza vaccines that are efficacious regardless of antigenic match.
Boyoglu-Barnum S, Hutchinson GB, Boyington JC, et al. Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses. Nat Commun. 2020;11(1):791. Published 2020 Feb 7. doi:10.1038/s41467-020-14579-4
Leanne Low, Ph.D.
Postdoctoral Fellow in the Malaria Cell Biology Section of the Laboratory of Malaria and Vector Research
“I enjoy the range of opportunities available, both in and out of the lab, that allow me to develop as a scientist.” – Leanne Low, Ph.D.
My research currently centers on the investigation of the role of the Plasmodium falciparum rhoptry neck protein 3 (PfRON3) towards intracellular development of the malaria parasite. Additionally, I am also involved in a study dissecting serum factors that influence the binding of PfEMP1 variants associated with cerebral malaria to brain endothelial cells.
Low, Leanne M et al. “Deletion of Plasmodium falciparum Protein RON3 Affects the Functional Translocation of Exported Proteins and Glucose Uptake.” mBio vol. 10,4 e01460-19. 9 Jul. 2019, doi:10.1128/mBio.01460-19
Gaurav Shrivastava, Ph.D.
Postdoctoral Fellow in the Molecular Entomology Unit of the Laboratory of Malaria and Vector Research
“I enjoy highly collaborative and extensive scientific expert interactions in NIAID along with excellent professional training opportunities." – Gaurav Shrivastava, Ph.D.
My work is focused on the role of mosquito saliva on the host innate immune response during arbovirus infection. My main objective is to identify proteins of the salivary gland that can facilitate the viral transmission and further modulates the host innate immune response. Under the supervision of Eric Calvo, Ph.D., I am currently working with Aedes aegypti mosquito salivary gland extract as well as several female specific salivary gland protein candidates that may play a crucial role in modulating the host innate immune response due to arboviruses infection.
Shrivastava G, Carolina Valenzuela PC, Calvo Eric. Inflammasome fuels dengue severity. Front. Cell. Infect. Microbiol. Sep 2020 doi: 10.3389/fcimb.2020.00489
Shrivastava, Gaurav et al. “Dengue Virus Serotype 2 and Its Non-Structural Proteins 2A and 2B Activate NLRP3 Inflammasome.” Frontiers in immunology vol. 11 352. 10 Mar. 2020, doi:10.3389/fimmu.2020.00352
Malcolm Sim, Ph.D.
Postdoctoral Fellow in the Structural Immunology Section of the Laboratory of Immunogenetics
“I enjoy the freedom to pursue my ideas in a supportive and intellectually stimulating environment.” - Malcolm Sim, Ph.D.
My research is focused on receptors of the innate and adaptive immune system that recognize human class I MHC molecules. I use molecular, cellular and structural techniques to understand how these interactions regulate immune responses to a variety of human diseases including cancer, bacterial infections and malaria. Last year, we described the first functional ligands for the natural killer cell receptor KIR2DS4 to include a conserved bacterial epitope presented by HLA-C (1). In addition, earlier this year we published a biochemical and structural characterization of therapeutic T cell receptors specific for the oncogenic hotspot mutation KRAS-G12D (2).
- Sim MJW, Rajagopalan S, Altmann DM, Boyton RJ, Sun PD, Long EO. Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C. Proc Natl Acad Sci U S A. 2019;116(26):12964-12973.
- Sim MJW, Lu J, Spencer M, et al. High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D. Proc Natl Acad Sci U S A. 2020;117(23):12826-12835.
Jenny Wachter, MSc., Ph.D.
Postdoctoral Fellow in the Molecular Genetics Section of the Laboratory of Bacteriology
"I am honored to be able to study the important human pathogen, Borrelia burgdorferi, under one of the most renowned scientists in the field at the facility it was discovered.” - Jenny Wachter, MSc., Ph.D.
Borrelia burgdorferi is the causative agent of Lyme disease, the most common vector-borne illness in the United States. B. burgdorferi persists in nature in an infectious cycle between a tick vector and a vertebrate host. In order to successfully survive and transition between these disparate environments, B. burgdorferi must tightly regulate gene expression. Many genes transcribed by the sigma factor RpoS are necessary for successful infection and survival of this spirochete within the mammalian host. Our lab originally described and characterized BBD18 as a negative regulator of RpoS. In the absence of bbd18 it appears that endogenous, transducing phage cause cell lysis in vitro. Investigation into the contribution of BBD18 during the infectious cycle found that bbd18 expression is diminished during tick feeding, preceding transmission to the host, but is critical for spirochete survival after the bloodmeal. We hypothesize that transducing phage are a natural component of the RpoS-dependent host-adaptive response, thereby facilitating horizontal gene transfer between spirochetes in infected ticks prior to transmission, and that BBD18 modulates RpoS activity to circumvent uncontrolled activation of lytic phage.
Hillman, Chadwick et al. “Visualization of Spirochetes by Labeling Membrane Proteins With Fluorescent Biarsenical Dyes.” Frontiers in cellular and infection microbiology vol. 9 287. 20 Aug. 2019, doi:10.3389/fcimb.2019.00287
Marissa Zarakas, D.D.S., M.D.
Postdoctoral Fellow in the Fungal Pathogenesis Section of the Laboratory of Clinical Immunology and Microbiology
“What I enjoy most about my experience as a postdoc is the opportunity to acquire diverse clinical and research skills to better understand the complex, yet fascinating mechanisms of innate host immunity.” - Marissa Zarakas
Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase (BTK), which is a critical component of B-cell receptor signaling and regulates B-cell proliferation and survival. Ibrutinib is successfully used in treatment of various B-cell malignancies (1), however, its use has been associated with increased risk for invasive aspergillosis (2), indicating a critical protective role of BTK in innate antifungal immunity. My work has been focused on determining the BTK-dependent regulation of antifungal effector functions in human phagocytes from healthy donors and lymphoma patients in order to comprehensively characterize the mechanistic basis of susceptibility to invasive fungal disease.
- Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma. Cancer Cell. 2017;31(6):833-843.e5.
- Chamilos G, Lionakis MS, Kontoyiannis DP. Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways. Clin Infect Dis. 2018;66(1):140-148.