Michael Jeltsch

Michael Jeltsch
University of Helsinki | HY · Translational Cancer Biology Program

Professor

About

111
Publications
23,845
Reads
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14,464
Citations
Introduction
I work on cancer drug target identification and validation focussing on anti-angiogenic and anti-lymphangiogenic compounds. http://lab.jeltsch.org
Additional affiliations
September 2013 - present
University of Helsinki
Position
  • Academy Research Fellow
Description
  • http://lab.jeltsch.org
January 2013 - present
Wihuri Research Institute
Description
  • postdoc (lymphangiogenesis research)
January 2003 - December 2011
Licentia Oy
Position
  • Vegenics Ltd./Circadian Technologies
Description
  • biotherapeutics' development

Publications

Publications (111)
Article
Blood vessels are thought to form either by de novo vasculogenesis or by angiogenesis from pre-existing blood vessels. Research now finds that anal fin blood vessels form by endothelial transdifferentiation from lymphatic vessels.
Article
Full-text available
In this focused review, we address the role of the kallikrein-related peptidase 3 (KLK3), also known as prostate-specific antigen (PSA), in the regulation of angiogenesis. Early studies suggest that KLK3 is able to inhibit angiogenic processes, which is most likely dependent on its proteolytic activity. However, more recent evidence suggests that K...
Article
In this issue of Science Signaling , Kataru et al. did two simple but powerful tweaks to the typical studies that aim to advance our understanding of proangiogenic interventions. They shifted the focus from the outside of the endothelial cell to the inside, and they chose not to deliver an angiogenic signal, but instead to release the brakes from a...
Article
Full-text available
Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptor...
Preprint
Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptor...
Article
Full-text available
The lymphatic system, fundamental for body fluid homeostasis and immune system functions, also participates in pathogenic processes including cancer, cardiovascular and neurodegenerative diseases. Many aspects of the lymphatic system are unclear, but great advancements have been made-e.g. the discovery of meningeal lymphatics and the lymphatic-like...
Article
Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) stem cell niche, which provides a vital source of HSC regulatory signals. Radiation and chemotherapy disrupt the HSC niche, including its sinusoidal vessels and perivascular cells, contributing to delayed hematopoietic recovery. Thus, identification of factors that can protect the HSC n...
Article
Full-text available
Background Milroy‐like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4 . In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF‐C variations found in a female proband born with congenital edema con...
Article
Full-text available
Vascular endothelial growth factor-C (VEGF-C) acts primarily on endothelial cells, but also on non-vascular targets, e.g. in the CNS and immune system. Here we describe a novel, unique VEGF-C form in the human reproductive system produced via cleavage by kallikrein-related peptidase 3 (KLK3), aka prostate-specific antigen (PSA). KLK3 activated VEGF...
Article
Full-text available
While both blood and lymphatic vessels transport fluids and thus share many similarities, they also show functional and structural differences, which can be used to differentiate them. Specific visualization of lymphatic vessels has historically been and still is a pivot point in lymphatic research. Many of the proteins that are investigated by mol...
Article
Full-text available
Because virtually all tissues contain blood vessels, the importance of hemevascularization has been long recognized in regenerative medicine and tissue engineering. However, the lymphatic vasculature has only recently become a subject of interest. Central to the task of growing a lymphatic network are lymphatic endothelial cells (LECs), which const...
Article
Full-text available
The collagen- and calcium-binding EGF domains 1 (CCBE1) protein is necessary for lymphangiogenesis. Its C-terminal collagen-like domain was shown to be required for the activation of the major lymphangiogenic growth factor VEGF-C (Vascular Endothelial Growth Factor-C) along with the ADAMTS3 (A Disintegrin And Metalloproteinase with Thrombospondin M...
Article
Cytosolic phospholipase A2 alpha (cPLA2α) plays a key role in signaling in mammalian cells by releasing arachidonic acid (AA) from glycerophospholipids (GPLs) but the factors determining the specificity of cPLA2α for AA-containing GPLs are not well understood. Accordingly, we investigated those factors by determining the activity of human cPLA2α to...
Article
Full-text available
Rationale: Lymphatic vessel growth is mediated by major pro-lymphangiogenic factors such as VEGF-C and -D, among other endothelial effectors. Heparan sulfate is a linear polysaccharide expressed on proteoglycan core proteins on cell-membranes and matrix, playing roles in angiogenesis, although little is known regarding any function(s) in lymphatic...
Article
The lymphatic system is involved in maintaining interstitial fluid homeostasis, fat absorption and immune surveillance. Dysfunction of lymphatic fluid uptake can lead to lymphedema. Worldwide up to 250 million people are estimated to suffer from this disfiguring and disabling disease, which places a strain on the healthcare system as well as on the...
Article
Organ damage and innate immunity during heart transplantation may evoke adaptive immunity with serious consequences. Because lymphatic vessels bridge innate and adaptive immunity, they are critical in immune surveillance; however, their role in ischemia-reperfusion injury (IRI) in allotransplantation remains unknown. We investigated whether the lym...
Article
Full-text available
The question "How does the lymphatic system develop?" may be a simple one, but it is fundamental to our understanding of lymphatic malformations in children and the regeneration of lymphatics in adults.The question is by no means new and was already explored in the early 20th century.This resulted in a long-lasting controversy, which until recently...
Article
CCBE1 is essential for lymphangiogenesis in vertebrates and has been associated with Hennekam Syndrome (HS). Recently, CCBE1 has emerged as a crucial regulator of VEGFC signaling. CCBE1 is a secreted protein characterized by two EGF domains and two collagen repeats. The functional role of the different CCBE1 protein domains is completely unknown. H...
Article
Full-text available
A-type phospholipases (PLAs) are key players in glycerophospholipid (GPL)homeostasis and in mammalian cells, Ca2(+-)independent PLA-beta (iPLAβ) in particular has been implicated in this essential process.However, the regulation of this enzyme,which is necessary to avoid futile competition between synthesis and degradation, is not understood. Recen...
Article
Full-text available
The endothelial TIE1 and TIE2 receptor tyrosine kinases form a distinct subfamily characterized by their unique extracellular domains. Together with the angiopoietin growth factors (ANGPT1, ANGPT2, ANGPT4, also abbreviated as ANG), the TIE receptors form an endothelial specific signaling pathway with important functions in the regulation of lymphat...
Chapter
Full-text available
Primary lymphedema is treatable but not curable. In addition, diagnosis is often not clear due to heterogeneous phenotypes. To address these problems, we need to know the underlying genetic lesions, diagnose them and develop targeted therapies. The necessary technologies for these tasks are provided by new developments in the field of molecular bio...
Article
BACKGROUND: Hennekam lymphangiectasia-lymphedema syndrome (Online Mendelian Inheritance in Man 235510) is a rare autosomal recessive disease, which is associated with mutations in the CCBE1 gene. Because of the striking phenotypic similarity of embryos lacking either the Ccbe1 gene or the lymphangiogenic growth factor Vegfc gene, we searched for co...
Article
Full-text available
VEGF-C and VEGF-D are the two central signaling molecules that govern the development and growth of the lymphatic system. The presence or absence of lymphangiogenesis plays a central and sometimes causative role in a variety of diseases. Therefore, the molecules that govern lymphangiogenesis – especially VEGF-C and VEG-FR-3 – offer the possibility...
Data
Full-text available
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key drivers of blood and lymph vessel formation in development, but also in several pathological processes. VEGF-C signaling through VEGFR-3 promotes lymphangiogenesis, which is a clinically relevant target for treating lymphatic insufficiency and for blocking tumor angiog...
Article
Full-text available
The endothelial cell is the essential cell type forming the inner layer of the vasculature. Two families of receptor tyrosine kinases (RTKs) are almost completely endothelial cell specific: the vascular endothelial growth factor (VEGF) receptors (VEGFR1-3) and the Tie receptors (Tie1 and Tie2). Both are key players governing the generation of blood...
Article
Full-text available
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key drivers of blood and lymph vessel formation in development, but also in several pathological processes. VEGF-C signaling through VEGFR-3 promotes lymphangiogenesis, which is a clinically relevant target for treating lymphatic insufficiency and for blocking tumor angiog...
Article
Full-text available
Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development through VEGF receptors (VEGFRs). The VEGFR immunoglobulin homology domain 2 (D2) is critical for ligand binding, and D3 provides additional interaction sites. VEGF-B and placenta growth factor (PlGF) bind to VEGFR-1 with high affinity, but only PlGF is angio...
Patent
Full-text available
The present invention provides materials and methods for preventing stenosis or restenosis of a blood vessel using Vascular Endothelial Growth Factor C (VEGF-C) and/or Vascular Endothelial Growth Factor D (VEGF-D) genes or proteins.
Article
Full-text available
VEGF-C and VEGF-D are the two central signaling molecules that stimulate the development and the growth of lymphatic system. Both belong to the VEGF protein family which plays important roles in the growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis). In mammals the VEGF family comprises five members: VEGF, PlGF, VEGF-B...
Article
Full-text available
VEGF-C and VEGF-D are the two central signaling molecules that stimulate the development and growth of the lymphatic system. Both belong to the vascular endothelial growth factor (VEGF) protein family, which plays important roles in the growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis). In mammals, the VEGF family com...
Article
Full-text available
Vascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized. Here, we identify a mutation in zebrafish vegfc that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic...
Article
Full-text available
There is an unmet need for proangiogenic therapeutic molecules for the treatment of tissue ischemia in cardiovascular diseases. However, major inducers of angiogenesis such as vascular endothelial growth factor (VEGF/VEGF-A) have side effects that limit their therapeutic utility in vivo, especially at high concentrations. Angiopoietin-1 has been co...
Article
Full-text available
VEGF-C and VEGF-D are the two central signaling molecules that stimulate the develop- ment and growth of the lymphatic system. Both belong to the vascular endothelial growth factor (VEGF) protein family, which plays important roles in the growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis). In mammals, the VEGF family c...
Article
Full-text available
VEGF-C and VEGF-D are the two central signaling molecules that stimulate the develop- ment and growth of the lymphatic system. Both belong to the vascular endothelial growth factor (VEGF) protein family, which plays important roles in the growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis). In mammals, the VEGF family c...
Article
Full-text available
Vascular endothelial growth factor C (VEGF-C) and VEGF-D are the two central signaling molecules that govern the development and growth of the lymphovascular system. The presence or absence of lymphangiogenesis plays a central and sometimes causative role in a variety of diseases. Therefore, molecules that govern lymphangiogenesis, especially VEGF-...
Article
Chronic inflammation, a hallmark of obliterative bronchiolitis, is known to induce lymphangiogenesis. We therefore studied the role of lymphangiogenic vascular endothelial growth factor C (VEGF-C), its receptor VEGFR-3, and lymphangiogenesis during development of experimental obliterative bronchiolitis [ie, obliterative airway disease (OAD)] in rat...
Article
Full-text available
Vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors (VEGFR-1-3) are central mediators of angiogenesis and lymphangiogenesis. VEGFR-3 ligands VEGF-C and VEGF-D are produced as precursor proteins with long N- and C-terminal propeptides and show enhanced VEGFR-2 and VEGFR-3 binding on proteolytic removal of the propeptides....
Article
Full-text available
Antibodies that block vascular endothelial growth factor (VEGF) have become an integral part of antiangiogenic tumor therapy, and antibodies targeting other VEGFs and receptors (VEGFRs) are in clinical trials. Typically receptor-blocking antibodies are targeted to the VEGFR ligand-binding site. Here we describe a monoclonal antibody that inhibits V...
Data
Analysis of the phenotypic consequence of VEGF-B expression in RIP1-Tag2 tumors. A) Evaluation of mFatp1-3, mBik and mBmf mRNA expression by quantitative PCR in total tumors of RIP1-Tag2 (n = 5) and RIP1-Tag2; RIP1-VEGFB (n = 5) mice. The mRNA expression profiles of the indicated genes are normalized to the expression of the internal control gene r...
Data
Characterization of the phenotype of tumors derived from Vegfb-deficient RIP1-Tag2 tumors. A) Quantification of the number of angiogenic islets in 12-weeks old RIP1-Tag2; Vegfb+/- (n = 14) and RIP1-Tag2; Vegfb-/- (n = 8) mice. B) Quantification of tumor cell proliferation in lesions from RIP1-Tag2; Vegfb+/- (n = 27) and RIP1-Tag2; Vegfb-/- (n = 26)...
Data
Analysis of the expression of VEGFB in RIP1-VEGFB mice. A) Quantitative RT-PCR determination of expression of mouse and human VEGF-B in tumors from RIP1-Tag2 and Rip1-Tag2; RIP1-VEGFB mice. B) Analysis of the abundance of human VEGF-B protein in serum and tumor tissue from RIP1-Tag2; RIP1-VEGFB mice using ELISA. (0.23 MB TIF)
Data
Comparison of the ability of mouse and human VEGF-B to activate VEGFR-1 downstream target gene transcription. Quantitative RT-PCR determination of the induction of FATP3 and FATP4 mRNA by mouse pancreatic islet endothelial cells (MS1) following 24h of stimulation by control, human VEGF-B167, or mouse VEGF-B167 and VEGF-B186. (0.13 MB TIF)
Data
Characterization of the phenotype of tumors derived from RIP1-Tag2; RIP1-VEGFB mice. A) Staging of tumors into normal/hyperplastic islets, adenoma or carcinoma in RIP1-Tag2 (N = 6) and RIP1-Tag2; RIP1-VEGFB (N = 6) mice. B, C, D) Quantification of tumor cell proliferation in RIP1-Tag2 (N = 5, n = 28) and RIP1-Tag2; RIP1-VEGFB (N = 5, n = 38) (B) mi...
Data
Characterization of the pancreatic islet architecture in RIP1-VEGFB mice. A) Pancreatic sections of control C57BL/6 (left) and of RIP1-VEGFB mice (right) stained for glucagon and insulin to examine islet architecture. Nuclei were counterstained with DAPI. Scale bar: 100 µm. B, C) Quantification of islet number (B, left), area (B, right) and Beta-ce...
Article
Full-text available
The family of vascular endothelial growth factors (VEGF) contains key regulators of blood and lymph vessel development, including VEGF-A, -B, -C, -D, and placental growth factor. The role of VEGF-B during physiological or pathological angiogenesis has not yet been conclusively delineated. Herein, we investigate the function of VEGF-B by the generat...
Article
Vascular endothelial growth factor-B (VEGF-B) binds to VEGF receptor-1 and neuropilin-1 and is abundantly expressed in the heart, skeletal muscle, and brown fat. The biological function of VEGF-B is incompletely understood. Unlike placenta growth factor, which binds to the same receptors, adeno-associated viral delivery of VEGF-B to mouse skeletal...