DECIDE Collaborators

Professor Michael Danilenko
http://fohs.bgu.ac.il/research/PersonalWebSite1main.aspx?id=VusuidtuV  
Anti-cancer activity of plant antioxidants and their combinations with differentiation-inducing agents

The major research focus of Dr. Danilenko’s group is on the cooperation of various plant polyphenolic antioxidants and differentiation-inducing agents against acute myeloid leukemia (AML) in various preclinical models. 

This group, in collaboration with Dr. G.P. Studzinski (UMD-New Jersey Medical School), has demonstrated that certain plant polyphenols synergistically potentiate the differentiation and antiproliferative effects induced by physiological concentrations of active forms of vitamin D or retinoic acid on AML cells. Furthermore, the combination treatment with low-calcemic vitamin D analogs and plant polyphenols substantially inhibits the development of leukemic tumors and systemic AML in mice.

The molecular mechanism of this synergy involves cooperative modulation of (a) intracellular antioxidant systems and overall cell redox status; (b) cell cycle machinery; (c) nuclear receptors for vitamin D and retinoic acid, (d) mitogen-activated protein kinase cascades, and (e) redox- and extracellular signal-regulated transcription factors, such as Nrf2, AP-1, and EGR-1.

Most recently, Dr. Danilenko’s team has reported that in the absence of differentiation agents some polyphenols can strongly synergize with one another in the induction of growth arrest and apoptotic cell death in leukemic cells. These effects are selective towards malignant cells and are not observed in normal cells.

The long-term goal of the above research is to develop combinatorial approaches for the treatment of leukemias and, possibly, of other cancers using phytochemicals and differentiation inducers.

Dr Eustace Johnson
http://www1.aston.ac.uk/lhs/staff/az-index/dr-eustace-johnson/  

Research activity:

• Cell and molecular biology of neural and connective tissue, particularly re: the spine. 
• Developing cell-based therapies in regenerative medicine. This is currently targeted toward the use of autologous adult stem cells to promote functional recovery following spinal cord injury, and for bone and cartilaginous tissue repair.

The research converges on trying to develop a deeper understanding of how intercellular and cell-matrix interactions regulate stem cells and cell function, but the research is also driven towards clinical intervention. For example, initial in vitro studies conducted on the regulation of nerve growth by extracellular proteoglycans were adapted using co-culture systems to examine how human mesenchymal stem cell isolated from patients with spinal cord injury (SCI) may promote axonal regeneration following transplantation.

Current PhD projects include:

• Htoo Wai - mesenchymal stem cells in the zebrafish model of development/wound healing. 
• Jonathan Sheard - high content/high throughput screening for adult cell therapies in orthopaedics. 
• Nupur Kohli - comparative bone marrow transplants for osteoarthritis.

Htoo Aung Wai

Professor Daniela Finke 
http://biomedizin.unibas.ch/nc/about-us/people/profil/profile/person/finke/

Development of innate lymphoid cells, in particular lymphoid tissue inducer cells

The crosstalk between hematopoietic and stromal cells is fundamental for the development of the immune system, but also for generating protective host defense.

Research by Daniela Finke is shedding light on how innate lymphoid cells and mesenchymal stromal cells orchestrate the generation and function of secondary lymphoid organs. Daniela Finke and her colleagues at the Department of Biomedicine, Basel University (CH), did pioneer work on identifying a subset of innate lymphoid cells named lymphoid tissue inducer (LTI) cells.

Without LTi cells, the body can’t develop lymph nodes and Peyer’s patches. Daniela Finke’s laboratory could identify cytokine-driven pathways involved in the life cycle and differentiation of LTi cells and in their function to control lympho-organogenesis. More recently, other subtypes of innate lymphoid cells in the intestinal mucosa were discovered, but their relationship to LTi cells and their function during immune responses is poorly understood.

Daniela Finke, working as full professor at the Basel University since 2010, is now focusing on the origin, development and the immune function of LTi cells and related cell subsets using various genetic models. Moreover, cell dynamics such as growth, differentiation and survival are evaluated comparing fetal and adult LTi cells.

The understanding of how the growing family of innate lymphoid cells regulates innate and adaptive immunity will be substantial for the discovery of new biomedical targets of inflammation and autoimmunity.