Hauke Stephan Busch

• Prof. Dr.
• Professor (Full) at University of Lübeck

Colorectal cancer (CRC) progression occurs through three stages: adenoma (pre-cancerous lesion), carcinoma in situ (CIS) and adenocarcinoma, with tumor stage playing a pivotal role in the prognosis and treatment outcomes. Despite therapeutic advancements, the lack of stage-specific biomarkers hinders the development of accurate diagnostic tools and...

Myelofibrosis (MF) in 50% of cases is driven by an activating JAK2 mutation, mostly V617F. Ruxolinitib is approved for the treatment of MF. Responses to ruxolitinib in MF are of limited duration. Unexpectedly, treatment of JAK2-V617F expressing cells with ruxolitinib causes paradoxical hyperphosphorylation of JAK2 at activation loop Tyr1007/Tyr1008...

Monomethyl fumarate (MMF) and its prodrug dimethyl fumarate (DMF) are currently the most widely used agents for the treatment of multiple sclerosis (MS). However, not all patients benefit from DMF. We hypothesized that the variable response of patients may be due to their diet. In support of this hypothesis, mice subjected to experimental autoimmun...

In classic Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with respon...

Desmoglein 1 (DSG1) and desmoglein 3 (DSG3) are adhesion molecules that maintain intercellular connections between epidermal, hair follicle, and mucosal keratinocytes. Autoantibodies (AAbs) targeting these molecules ultimately lead to the blister formation characteristic of pemphigus vulgaris (PV) or pemphigus foliaceus (PF). To investigate the mol...

Background The hypomorphic variant rs11209026-A in the IL23R gene provides significant protection against immune-related diseases in Europeans, notably inflammatory bowel diseases (IBD). Today, the A-allele occurs with an average frequency of 5% in Europe. Methods This study comprised 251 ancient genomes from Europe spanning over 14,000 years. In...

BACKGROUND Patient similarity is a fundamental concept in precision oncology, offering a pathway to personalized medicine by identifying patterns and shared characteristics among patients. This concept enables stratification into clinically meaningful subgroups, prediction of treatment responses, and the tailoring of therapeutic interventions to in...

Colorectal cancer (CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role...

Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role i...

Parkinson’s disease (PD) is a neurodegenerative disorder with a high variability of age at onset, disease severity, and progression. This suggests that other factors, including genetic, environmental, or biological factors, are at play in PD. The loss of PINK1 causes a recessive form of PD and is typically fully penetrant; however, it features a wi...

Background Secretory IgA (sIgA) is critical for the maintenance of the mucosal barrier function, preventing bacterial translocation and reducing the risk of chronic inflammation. Several decades of research have revealed a dysregulation of the B-cell compartment in inflammatory bowel disease (IBD) of yet unknown origin1,2. While increased serum lev...

Background Molecular tumor boards (MTBs) play a pivotal role in personalized oncology, leveraging complex data sets to tailor therapy for cancer patients. The integration of digital support and visualization tools is essential in this rapidly evolving field facing fast-growing data and changing clinical processes. This study addresses the gap in un...

Parkinson’s disease (PD) is a neurodegenerative disorder with a high variability of age at onset, disease severity, and progression. This suggests that other factors, including genetic, environ-mental, or biological factors, are at play in PD. Loss of PINK1 causes a recessive form of PD and is typically fully penetrant; however, it features a wide...

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient manage...

Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%) and the identification of several disease-linked genes, the etiology in most patients remains elusive. Moreover, understanding the correlations between clinical manifestation and gen...

The pemphigus family of skin blistering diseases represents a rare yet potentially life-threatening condition characterized by multiple known genetic loci associated with other autoimmune disorders. While several studies have empirically indicated an increased risk of developing additional autoimmune diseases in individuals with pemphigus, the scar...

BACKGROUND Complex and expanding data sets in clinical oncology applications require flexible and interactive visualization of patient data to provide physicians and other medical professionals with a maximum amount of information. In particular, interdisciplinary tumor conferences profit from customized tools to integrate, link, and visualize rele...

Background/Objectives: The prevalence of food allergy (FA) in children is increasing. Dysbiosis of the microbiome has been linked to FA but needs to be better understood. We aimed to characterize the gut and skin microbiome of young food-allergic children over time and within different types of immunoglobulin E (IgE)-mediated FA. Methods: We studie...

Introduction Treatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microbiota transfer (FMT) approach. Methods Seven week...

Introduction More than 80 percent of chronic neutrophilic leukemia (CNL) patients harbor the membrane proximal mutation T618I in the colony-stimulating factor 3 receptor (CSF3R), which leads to constitutive activation of the JAK1/STAT3-pathway. However, the molecular mechanisms of oncogenic transformation by CSF3R mutations in CNL are not well unde...

Background: Lenalidomide (Len), approved in 2017 as maintenance therapy for multiple myeloma (MM), is known to increase the cumulative incidence of secondary malignancies, including Len-associated B-cell precursor ALL (LenB-ALL). However, the molecular basis of LenB-ALL leukemogenesis is not yet fully understood. Methods: We present the results of...

CCAAT-enhancer-binding proteins (C/EBP) are important regulators of myeloid differentiation and cell cycle control. The C/EBP family member CEBPE has been implicated in B precursor acute lymphoblastic leukemia (BCP-ALL) through IGH locus gene fusions and rare germline single nucleotide variants. ‘ZEB2 (p.H1038R)/IGH::CEBPE‘ BCP-ALL is a provisional...

The immune system plays a critical role in inflammation by initiating responses to infections or tissue damage. The nuclear factor-κB (NF-κB) pathway plays a key role in inflammation and innate immunity, as well as other cellular activities. Dysregulation of this well-choreographed pathway has been implicated in various diseases, including cancer....

Zusammenfassung Das Verbundprojekt Personalisierte Medizin für die Onkologie (PM4Onco), das 2023 als Anwendungsfall der Medizininformatik-Initiative (MII) im Rahmen der Nationalen Dekade gegen Krebs (NDK) initiiert wurde, zielt darauf ab, eine nachhaltige Infrastruktur zur Integration und Nutzung von Daten aus der klinischen Routine und biomedizini...

Tenosynovial giant cell tumor (TGCT) is a rare type of tumor that originates from the synovium of joints and tendon sheaths. It is characterized by recurring genetic abnormalities, often involving the CSF1 gene. Common symptoms include pain and swelling, which are not specific to TGCT, so MRI and a pathological biopsy are needed for an accurate dia...

The integration of tumor-related diagnosis and therapy data is a key factor for cancer-related collaborative projects and research projects on-site. The Medical Data Integration Center (MeDIC) of the University Hospital Schleswig-Holstein, resulting from the Medical Informatics Initiative and Network University Medicine in Germany, has agreed on an...

Background The hypomorphic variant rs11209026-A in the IL23R gene provides significant protection against immune-related diseases in Europeans, notably inflammatory bowel disease (IBD). Today, the A-allele occurs with an average frequency of 5% in Europe. Methods This study comprised 251 ancient genomes from Europe spanning over 14,000 years. In t...

Primary renal manifestations of diffuse large B-cell lymphoma (PR-DLBCL) represent an exceptionally rare variant of the most common type of non-Hodgkin lymphoma (NHL). Insights into PR-DLBCL pathogenesis have been limited to small case series and methodologically limited approaches. The mechanisms driving lymphomagenesis within an organ lacking an...

We report a case of a long-term surviving patient with EML4/ALK translocated non–small cell adenocarcinoma of the lung in UICC8 stage IVA. During recurrence under continuous crizotinib therapy, a hitherto insufficiently characterized missense mutation in the ALK gene (Arg1181His) was identified through targeted sequencing. The aforementioned EML4/A...

The pemphigus family of skin blistering diseases represents a rare yet potentially life-threatening condition characterized by multiple known genetic loci associated with other autoimmune disorders. While several studies have empirically indicated an increased risk of developing additional autoimmune diseases in individuals with pemphigus, the scar...

BACKGROUND Understanding the similarities of cancer patients is essential to advancing personalized medicine, improving patient outcomes, and developing more effective and individualized treatments. It enables researchers to discover important patterns, biomarkers, and treatment strategies that can have a significant impact on cancer research and o...

Background Understanding the similarities of patients with cancer is essential to advancing personalized medicine, improving patient outcomes, and developing more effective and individualized treatments. It enables researchers to discover important patterns, biomarkers, and treatment strategies that can have a significant impact on cancer research...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients...

Editorial: This article is part of the Research Topic "Epigenetic and metabolic regulators of breast carcinogenesis"

Introduction: In classical Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in cont...

Dystonia due to pathogenic variants in the THAP1 gene (DYT-THAP1) shows variable expressivity and reduced penetrance of ~ 50%. Since THAP1 encodes a transcription factor, modifiers influencing this variability likely operate at the gene expression level. This study aimed to assess the transferability of differentially expressed genes (DEGs) in neur...

Background Complex and expanding data sets in clinical oncology applications require flexible and interactive visualization of patient data to provide the maximum amount of information to physicians and other medical practitioners. Interdisciplinary tumor conferences in particular profit from customized tools to integrate, link, and visualize relev...

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is characterized by high tumor cell plasticity and heterogeneity, contributing to poor prognosis and treatment failure. Epithelial–mesenchymal transition (EMT) and gain of cancer stem cell (CSC) properties are crucial processes determining tumor cell plasticity. Investigating CSC and non-CSC cl...

Background Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co‐occurring movement disorders such as Parkin...

Post-COVID syndrome (PCS) currently affects approximately 3-17% of people following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has the potential to become a significant global health burden. PCS presents with various symptoms, and methods for improved PCS assessment are presently developed to guide therapy. Neverthel...

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF...

Background In molecular tumor boards (MTBs), patients with rare or advanced cancers are discussed by a multidisciplinary team of health care professionals. Software support for MTBs is lacking; in particular, tools for preparing and documenting MTB therapy recommendations need to be developed. Objective We aimed to implement an extension to cBioPo...

Clonal hematopoiesis (CH) is characterized by the acquisition of defined somatic mutations in hematopoietic stem cells (HSC). It is well known that CH contributes to the development of hematological malignancies but also increases the risk of developing non-malignant conditions such as cardiovascular, pulmonary, and inflammatory liver disease. Howe...

Diabetes mellitus (DM) represents a major health problem in Egypt and worldwide, with increasing numbers of patients with prediabetes every year. Numerous factors, such as obesity, hyperlipidemia, and hypertension, which have recently become serious concerns, affect the complex pathophysiology of diabetes. These metabolic syndrome diseases are high...

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) p...

Background Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in h...

Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this...

Detlef Zillikens, MD, director and chair of the Department of Dermatology at the University of Lübeck, Lübeck, Germany, died in September 2022, aged only 64. He dedicated his professional life to autoimmune blistering diseases (AIBDs) and built his department into one of the world’s leading centers for these diseases. Herein, his professional life...

BACKGROUND Complex and expanding datasets in clinical oncology applications require flexible and interactive visualization of patient data to provide the maximum amount of information to physicians and other medical practitioners. Interdisciplinary tumor conferences in particular profit from customized tools to integrate, link and visualize relevan...

Growth Factor Independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of haematopoiesis. GFI1-36N is a germline variant causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10-15% among patients with acute myeloid leukemia (AML) and 5-7% among he...

Purpose Chemotherapy is pivotal in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC). Technical advances unveiled a high degree of inter- and intratumoral heterogeneity. We hypothesized that intratumoral heterogeneity (ITH) impacts response to gemcitabine treatment and demands specific targeting of resistant subclones. Methods Us...

Recent studies have linked proton pump inhibitor (PPI) treatment to increased complications of cirrhosis, such as bacterial infections and hepatic encephalopathy. However, the underlying pathophysiological mechanisms remain unclear. The present study investigated the hypothesis that PPI treatment may promote adverse effects in patients with advance...

Critical genetic and hormonal switches characterize fetal sex development in humans. They are decisive for gonadal sex determination and subsequent differentiation of the genital and somatic sex phenotype. Only at the first glace these switches seem to behave like the dual 0 and 1 system in computer sciences and lead invariably to either typically...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid/common dendritic cells (pDCs/cDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BP...

Introduction Primarily driven by autoreactive B cells, pemphigus foliaceus (PF) is an uncommon autoimmune blistering skin disease of sporadic occurrence worldwide. However, PF reaches a prevalence of 3% in the endemic areas of Brazil, the highest ever registered for any autoimmune disease, which indicates environmental factors influencing the immun...

Background: There is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard. Objective: The present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with...

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding euk...

(1) Background: Next-generation sequencing (NGS) of patients with advanced tumors is becoming an established method in Molecular Tumor Boards. However, somatic variant detection, interpretation, and report generation, require in-depth knowledge of both bioinformatics and oncology. (2) Methods: MIRACUM-Pipe combines many individual tools into a seam...

BACKGROUND In molecular tumor boards (MTBs), patients with rare or advanced cancers are discussed by a multidisciplinary team of health care professionals. Software support for MTBs is lacking; in particular, tools for preparing and documenting MTB therapy recommendations need to be developed. OBJECTIVE We aimed to implement an extension to cBioPo...

Introduction: Resistance in anti-cancer treatment is a result of clonal evolution and clonal selection. In chronic myeloid leukemia (CML), the hematopoietic neoplasm is predominantly caused by the formation of the BCR::ABL1 kinase. Evidently, treatment with tyrosine kinase inhibitors (TKIs) is tremendously successful. It has become the role model...

Background Autoantibodies (ab) against G protein-coupled receptors (GPCR), such as ab against angiotensin II receptor type 1 (AT1R), endothelin receptor type A (ETAR) or CXC chemokine receptor 3 and 4 (CXCR3/4) may contribute to the pathogenesis of systemic sclerosis (SSc) [1]. AT1R- and ETAR-ab are associated with SSc-related mortality and CXCR3/4...

Despite the availability of batch effect correcting algorithms (BECA), no comprehensive tool that combines batch correction and evaluation of the results exists for microbiome datasets. This work outlines the Microbiome Batch Effects Correction Suite development that integrates several BECAs and evaluation metrics into a software package for the st...

GFI1 is a transcriptional repressor and plays a pivotal role in regulating the differentiation of hematopoietic stem cells (HSCs) towards myeloid and lymphoid cells. Serial transplantation of Gfi1 deficient HSCs repopulated whole hematopoietic system but in a competitive setting involving wild-type HSCs, they lose this ability. The underlying mecha...

Schnitzler syndrome is a rare autoinflammatory disorder characterized by urticarial rash, joint pain, recurrent fever, leucocytosis, elevated C-reactive protein (CRP) and serum amyloid A (SAA), and monoclonal IgM or IgG gammopathy. According to the Strasbourg criteria, both urticarial rash and gammopathy are mandatorily required for the diagnosis o...

[This corrects the article DOI: 10.3389/fpsyt.2022.902433.].

Introduction Hematologic malignancies are currently underrepresented in multidisciplinary molecular-tumor-boards (MTB). This study assesses the potential of precision-oncology in primary-refractory plasmablastic-lymphoma (prPBL), a highly lethal blood cancer. Methods We evaluated clinicopathological and molecular-genetic data of 14 clinically anno...

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is exceedingly poor. Although surgical resection is the only curative treatment option, multimodal treatment is of the utmost importance, as only about 20% of tumors are primarily resectable at the time of diagnosis. The choice of chemotherapeutic treatment regimens involving gemcitabine and...

Introduction: Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as...

Objective: Congenital defects of androgen synthesis or action in 46, XY individuals can result in impaired virilisation, despite the apparent testicular development. In a recent case report of a young adult with complete androgen insensitivity syndrome (CAIS), tumorous gonadal tissue was shown to express HSD17B3 in Sertoli cells (SCs) and not in L...

Background Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to id...

Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role i...