Post Doctoral Fellow -Center for Vascular and Inflammatory Diseases ( Bromberg Lab)

Job Description - Post Doctoral Fellow -Center for Vascular and Inflammatory Diseases ( Bromberg Lab) (260000OM)

Job Description

Post Doctoral Fellow -Center for Vascular and Inflammatory Diseases ( Bromberg Lab) - (260000OM)

I. CELLULAR AND MOLECULAR IMMUNOLOGY OF MIGRATION AND LYMPH NODE STRUCTURE

Regulatory T Cells and Lymphatic Endothelial Cells: Regulatory Interactions for Migration and Function

Our investigations unraveled the key signaling pathways controlling Treg migration. Thymus derived (nTreg) and peripherally induced Treg (iTreg) express high cell surface levels of lymphotoxin ab (LTab). Treg, but not Tconv, use LTab to migrate from grafts across afferent lymphatic endothelial cells (LEC) and into dLN. Treg LTab binds the LEC LTb-receptor (LTbR) to stimulate non-canonical NFkB-inducing kinase (NIK). NIK signaling facilitates Treg transendothelial migration (TEM) by inducing LEC responses, including increased CCL21 expression, VCAM-1 rearrangement, and increases in basal lamellipodia that engage Treg. Our new preliminary studies now show that Treg-LEC interactions: 1.) use LTab-LTbR to condition LEC for permissiveness for TEM; 2.) determine the transition of Treg to become exTreg; and 3.) rely on Treg PD-1 and LEC PD-L1 TEM. Our data demonstrate novel Treg-LEC interactions that serve essential roles for Treg suppression and identify unique therapeutic opportunities for modulating immunity.

Treg-LEC are a regulatory nidus for suppression and tolerance. 1.) LTab-LTbR interactions condition the permissiveness of LEC for gating TEM of other leukocyte subsets. 2.) Treg-LEC interactions determine if Treg maintain suppressive functions or become exTreg. 3.) TEM relies on a novel role for PD-1-PD-L1.

Lymph Node Structure and Function in Tolerance: Role of Fibroblastic Reticular Cells (FRC)

Our recent studies now show three novel mechanisms by which FRC regulate tolerance and immunity. First, the FRC Lama4 conditional KO mice have markedly expanded Foxp3+CD8+ Tregs after transplant. Importantly, Lama5 directly stimulates the induction of CD8+ Treg subset. CD8 regulatory T cells (Tregs) are an extremely exciting subset of T cells that are increasingly being recognized; however, little is known about their formation. Second, our previous studies showed FRC CD40 regulates bidirectional FRC-T cell immune interactions, while studies using our newly made FRC CD40 KO mice show that FRC CD40 also regulates tolerogenic LN structure and function. FRC CD40 KO mice have reduced CD4+ Tregs, inflamed stromal structure, and are resistant to anti-CD40L induced tolerance. Third, Given the high plasticity of FRCs, they can readily adopt an 'immunologic scarring' phenotype in response to inflammation, contributing to a pro-inflammatory LN microenvironment that impairs transplant tolerance. Together, these new data support the specific hypothesis that FRC integrate immune cues to regulate LN niche structure and function and control immune fate toward inflammation and immunity or toward suppression and tolerance.

Immunological and Functional Consequences Triggered by the Gut Microbiota Regulate Alloimmunity and Cardiac Transplant Outcome

Many aspects of the innate and adaptive immunity are critically regulated by the microbiota. Microbial cells, their metabolites and nucleic acids engage various immune cells, resulting in pro- or anti-inflammatory signals that differ based on chemical structures, cellular receptors, and physiological context. The microbiota not only influences local immunity, but also has distant effects on systemic immunity. Local microbiota stimulation of innate and adaptive immune cells results in those cells or their products to migrate or traffic through lymphatics or blood, and influence diseases. Our results show that both pro-inflammatory and anti-inflammatory microbiota populations, as well as single bacteria, can be defined by their effects on the long-term outcome of the grafts. We hypothesize that the microbiota directly regulates innate immunity, which in turn regulates systemic inflammation and adaptive immunity, thereby determining the occurrence and progression of graft fibrosis, inflammation and graft survival. The definition of pro-inflammatory and anti-inflammatory microbiota and strains may provide a precise platform to define the most important upstream influences that initiate organ inflammation and scarring and could serve as potent diagnostic markers for allograft management.

Lymph Nodes at the Crossroads of Allo-Immunity and Regulation

Organ transplantation remains a mainstay therapeutic strategy for patients with end organ diseases. One of the highest unmet needs to improve long-term transplant outcomes is devising more effective immune modulation. This requires innovative mechanistic studies of transplant alloimmunity. The lymph node (LN) is the quintessential organ of alloimmunity. Our overarching hypothesis is that manipulating the microenvironment of LNs will provide a unique opportunity to direct the alloimmune reaction towards an anti-inflammatory tolerance response. Our major goals are to understand the cellular and molecular mechanisms that govern the microanatomical adaptation of the LN during immune activation or tolerance induction, and to develop highly innovative therapeutic strategies that promote a regulatory LN microenvironment and result in immune tolerance. This PPG sets forth a platform for connecting two teams (Drs. Abdi and Bromberg) with complementary skills and expertise in LN alloimmune-biology. Project 1 will test the hypothesis that sustained activation of fibroblastic reticular cells (FRCs) of the LN during alloimmunity will result in FRC transformation to proinflammatory myofibroblasts creating an inflammatory milieu within the LN, which would further promote alloimmunity. Our corollary hypothesis is that restoration of the function of FRCs and microanatomy of the LNs will enhance their immunoregulatory function and promote tolerance. Project 2 will test the hypothesis that FRCs regulate the LN laminin a4:a5 (LAMA4/LAMA5) ratio and control the fate of the immune response. The ultimate goal of these well-integrated and highly synergistic Projects and Cores is to generate transformative mechanistic data, which will lay the groundwork for developing highly targeted and innovative therapeutic strategies for transplantation.

II. BIOENGINEERING FOR THE MANIPULATION OF IMMUNITY

Programming Immune Function Through Modular Assembly of Polyionic Immune Signals

Therapeutic vaccines for autoimmune diseases could benefit from approaches which provide persistent delivery of drugs that can direct or modulate inflammatory or self-reactive effects of autoimmunity. In this proposal we present an approach for direct lymph node delivery of biodegradable particles loaded with antigens and tolerizing small molecules drugs. This strategy couples efficient, persistent delivery of bioactive cargo to key cells of the immune system that could induce anti-inflammatory or protective functions without significant side effects. Ultimately, this approach could contribute to new biomaterial-based approaches for therapeutic vaccines aimed at combating autoimmune disorders like multiple sclerosis.

Harnessing Biomaterials to Study the Link Between Local Lymph Node Function and Systemic Tolerance

This proposal combines the advantages of biomaterials (e.g., co-delivery of multiple signals, controlled release) with direct LN injection for the first time to study the link between local LN function and systemic tolerance. Our in vivo studies demonstrate that a single treatment with myelin antigen (MOG)/rapamycin immunosuppression (rapa) depots permanently reverses disease and paralysis in mouse models of multiple sclerosis (EAE), even when depots are administered at the peak of disease to non-draining LNs. Thus, a treatment given during the peak of inflammation and remote from the inflammatory site is curative. Our overarching goal is to dissect the role of signal location, combination, and kinetics on the structure and function of LNs, and reveal how these local changes bias the degree and specificity of tolerance in other lymphoid organs, at disease sites (i.e., CNS), and systemically.

Improving Multiple Sclerosis Patient Quality of Life Using Microneedle Patches to Simplify Delivery of MS Drugs

New findings indicate co-administration of regulatory signals with self-antigens can promote tolerogenic responses against antigens, instead of inflammation. We will develop a simple, modular system that mimics attractive features of biomaterials (e.g., co-delivery, tunable cargo loading), but built entirely from immune signals. These structures-termed immune polyelectrolyte multilayers (iPEMs)-are assembled by electrostatic interaction of self-peptides linked to cationic amino acids, and regulatory nucleic acid TLR ligands (anionic). iPEMs will be assembled on unique microneedle arrays that eliminate needles, stabilize cargo, and efficiently penetrate skin to deliver iPEMs to skin-resident dendritic cells (DCs). This idea offers transformative potential by addressing three key challenges: 1) intrinsic inflammatory features of biomaterials that could exacerbate disease, 2) poor control over the signals and context in which DCs encounter self-antigen, and 3) lack of specificity of current treatments that leave patients immunocompromised. The project will employ tools from nanotechnology and immunology, leveraging self assembly, transgenic animals, and testing in human multiple sclerosis patient samples and mouse models of multiple sclerosis and type 1 diabetes.

The University of Maryland is an equal opportunity , affirmative action employer. All qualified applicants will receive consideration for employment regardless of sex, gender identity, race, color, religion, national original, disability, protected veteran status, age, or any other characteristic protected by law or policy . We value diversity and how it enriches our academic and scientific community and strive towards cultivating an inclusive environment that supports all employees.

Qualifications

PhD in immunology, molecular biology, or related fields.

Job

: Postdoctoral Fellows

Organization

: School of Medicine - Centers/Programs/ORCs

Job Posting

: Jul 14, 2026