Dr. Ste­fanie Bader

Phone.: 56–311091

stefanie.bader(at)uni-heidelberg.de

Our research focus­es on how viral infec­tions alter host sig­nalling net­works and immune respons­es, dri­ving sus­tained inflam­ma­tion and post-viral pathol­o­gy. We aim to uncov­er the mol­e­c­u­lar and cel­lu­lar mech­a­nisms that under­lie post-viral syn­dromes, with a par­tic­u­lar focus on long COVID.

Long COVID, or post-acute seque­lae of SARS-CoV­‑2 infec­tion (PASC), has emerged as a major glob­al health chal­lenge, affect­ing mil­lions of peo­ple long after the ini­tial infec­tion. Despite its preva­lence, the bio­log­i­cal caus­es of these per­sis­tent symp­toms remain poor­ly under­stood, and no diag­nos­tic mark­ers or tar­get­ed ther­a­pies cur­rent­ly exist. Many patients expe­ri­ence fatigue, cog­ni­tive impair­ment and organ dys­func­tion months to years after infec­tion, under­scor­ing the urgent need for mech­a­nis­tic insight and nov­el treat­ment strategies.

Dys­reg­u­lat­ed immune and inflam­ma­to­ry path­ways con­tribute to long COVID, yet the host fac­tors that trans­form an acute infec­tion into a chron­ic, mul­ti-organ inflam­ma­to­ry state remain elu­sive. To address this com­plex­i­ty, we take a mul­ti­dis­ci­pli­nary approach that bridges virol­o­gy, immunol­o­gy, and trans­la­tion­al med­i­cine. Our lab devel­ops and applies inno­v­a­tive exper­i­men­tal plat­forms – includ­ing advanced imag­ing, mul­ti-omics pro­fil­ing, and RNA-based ther­a­peu­tic deliv­ery sys­tems – to uncov­er dis­ease mech­a­nisms and eval­u­ate poten­tial interventions.

Defining the Molecular Drivers of Long-Term Pathology

Pro­grammed cell death is crit­i­cal for con­trol­ling infec­tion and restor­ing tis­sue integri­ty, but when these process­es are dys­reg­u­lat­ed, they can sus­tain per­sis­tent inflam­ma­tion. Many virus­es exploit cell death path­ways to their advan­tage, shift­ing the bal­ance from host defence toward viral per­sis­tence. We study how cell death and inflam­ma­to­ry path­ways are rewired fol­low­ing infec­tion and how this dys­reg­u­la­tion dri­ves the shift from an effec­tive acute response to chron­ic disease.

Dur­ing acute SARS-CoV­‑2 infec­tion, we have shown that the cell death pro­tein caspase‑8 is divert­ed from its canon­i­cal apop­tot­ic func­tion to instead prop­a­gate inflam­ma­to­ry sig­nalling. Caspase‑8 accu­mu­lates in the lung dur­ing infec­tion and remains dys­reg­u­lat­ed for months after viral clear­ance (Fig­ure 1). Our cur­rent work aims to uncov­er the mol­e­c­u­lar mech­a­nisms under­ly­ing this sus­tained imbal­ance by iden­ti­fy­ing the sig­nalling nodes that remain aber­rant­ly acti­vat­ed and con­tribute to long-term dis­ease. Using inte­grat­ed tran­scrip­tom­ic, pro­teom­ic, and high-res­o­lu­tion imag­ing approach­es in vivo, we map the net­works that main­tain chron­ic inflam­ma­tion and inves­ti­gate how they may be pre­cise­ly mod­u­lat­ed to restore immune bal­ance and pro­mote tis­sue repair.

Fig­ure 1: Immuno­his­to­chem­i­cal stain­ing of lung sec­tions high­light­ing caspase‑8 expres­sion. Mice with pri­or SARS-CoV­‑2 infec­tion exhib­it marked­ly increased caspase‑8 lev­els com­pared to naïve con­trols, and this ele­vat­ed expres­sion per­sists for months fol­low­ing viral clearance.

Linking Viral Infection to Neurodegenerative Disease

Epi­demi­o­log­i­cal stud­ies show that indi­vid­u­als recov­er­ing from COVID-19 have a high­er risk of devel­op­ing neu­rode­gen­er­a­tive dis­eases, includ­ing Alzheimer’s and Parkinson’s, but the bio­log­i­cal mech­a­nisms link­ing infec­tion to neu­ro­log­i­cal decline remain unclear. We inves­ti­gate how pri­or viral infec­tion alters neu­ronal and glial func­tion, pro­motes inflam­ma­to­ry sig­nalling, and affects brain health (Fig­ure 2). Using behav­iour­al test­ing plat­forms, tran­scrip­tomics, and sin­gle-cell approach­es, we aim to uncov­er how per­sis­tent immune dys­reg­u­la­tion con­tributes to long-term neu­ro­log­i­cal changes.

Fig­ure 2: Immuno­his­to­chem­i­cal stain­ing of microglia. Long COVID leads to acti­va­tion and changes in microglial morphology.

Translating Disease Mechanisms into Therapies

By inte­grat­ing exper­i­men­tal pre­clin­i­cal data with clin­i­cal col­lab­o­ra­tions, we con­nect mol­e­c­u­lar sig­na­tures of immune dys­reg­u­la­tion to patient out­comes, enabling the iden­ti­fi­ca­tion of bio­mark­ers and ther­a­peu­tic tar­gets for post-viral dis­eases. Our work also explores host-direct­ed and RNA-based strate­gies to pre­cise­ly mod­u­late key path­ways involved in chron­ic inflam­ma­tion, while main­tain­ing essen­tial immune func­tions. This includes both the repur­pos­ing of clin­i­cal-stage com­pounds and the devel­op­ment of lipid nanopar­ti­cle (LNP)-mediated RNA deliv­ery sys­tems for tar­get­ed ther­a­peu­tic intervention.

Through this mul­ti­dis­ci­pli­nary research pro­gramme, the Bad­er Lab aims to unrav­el how viral infec­tions dis­rupt immune home­osta­sis and to trans­late mech­a­nis­tic dis­cov­er­ies into pre­ci­sion ther­a­pies (Fig­ure 4). By link­ing fun­da­men­tal biol­o­gy with clin­i­cal appli­ca­tion, we seek to pre­vent and reverse the long-term con­se­quences of infec­tion — ulti­mate­ly improv­ing out­comes for peo­ple affect­ed by long COVID and relat­ed post-infec­tious disorders.

We are an ambi­tious, col­lab­o­ra­tive, and inter­na­tion­al team, and we wel­come appli­ca­tions from moti­vat­ed stu­dents and tech­ni­cal assis­tants who are excit­ed to con­tribute to cut­ting-edge research at the inter­sec­tion of immunol­o­gy, virol­o­gy, and trans­la­tion­al medicine.

Fig­ure 3: Overview of our objectives.