The Wnt signaling pathway is involved in virtually every aspect of human development, as well as in adult homeostasis. Hyperactivation of this pathway has been linked to a wide range of cancers and especially colorectal cancer. Our aim is to understand the molecular events underlying Wnt signal transduction, as well as develop novel therapeutic strategies to fight colorectal cancer.

Current projects in the lab include:

1. Identifying and characterizing new Wnt signaling components.
2. Developing new anti-colorectal cancer treatment strategies.

The research activity addresses the following lines of research:

• Absorption and uptake of nanoparticles by cells in relation to drug delivery and toxicity
• Enhancement of uptake by electrical and chemical means 
• Treatment of cancer by electrochemical based approach
• Assessment of genetic and epigenetic risks following in-vitro exposure to electromagnetic fields associated with cell phone communication.
• Physiological regulation and underlying mechanism of cell membrane-cortical skeleton nanoscale mechanical fluctuations.

Research methods used include routine cell biology and biochemical methodologies with emphasis on special cutting edge light microscopies possessing nanometric resolution such as Digital Holographic Microscopy.

We focus on patient-driven basic research into the pathogenesis of childhood leukemia and cancer. We harness advanced molecular and cellular biology technologies utilizing in-vitro and in-vivo models with the ultimate goal of improving the care of children with cancer.

Our research is divided into two major topics:

1. Basic, translational and clinical research of leukemia.
2. The role of SIL (STIL) protein in mitosis, centrosomal biology and cancer.

Cancer is the deadliest disease of children and leukemia is the most common childhood cancer. We are interested in the fundamental question how normal blood development is diverted into leukemia. What are the genetic and biochemical abnormalities that block cell differentiation, enhance proliferation and survival and confer the unique stem cell properties of self renewal to leukemia stem cells? We focus on chromosome 21 because of the mysterious association of leukemia with Down Syndrome. We utilize advanced genomic technologies, cell based assays of transformation of primary human and mouse stem cells, mouse models including transgenic, transplantation and explants of human leukemia. Our recent discoveries of the major involvement of the TSLP-IL7R-JAK2 pathway in leukemogenesis have lead to clinical trials with novel inhibitors of this pathway for high-risk leukemias in children and adults. The spread of leukemia to the brain is a major clinical problem as preventive therapy to the brain consistingof chemotherapy or irradiation causes long term side effects. We are therefore studying how leukemia cells spread to the central nervous system and developing mouse models to study this challenging problem.

We have discovered that SIL, a gene cloned from childhood leukemia, is required for centrosomal biogenesis and for survival of cancer cells. Targeting SIL by siRNA cause cancer cell death at mitotic entry in-vitro and in-vivo. Current research focuses on the fundamental role of the SIL protein in centrosome generation in normal and malignant cells and on developing approaches for its targeting for cancer therapy. 

The long-term goal of our research is to develop a novel treatment for immune resistant cancers. Our research includes characterization of the mechanism of complement dependent cytotoxicity and of the basis for elevated resistance of cancer cells to cell death, and design of novel reagents that sensitize cancer cells to cell death. Research methods used include analyses of cell growth and death and mitochondrial activity, western blotting, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, confocal fluorescence microscopy, Fluorescence-activated Cell Sorting (FACS), peptide analysis by mass spectrometry, electon microscopy, and analysis of cancer growth in animal models.