1. National Natural Science Foundation of China (31371425) 2013
2. Liaoning Provincial Natural Science Foundation of China (2013023056) 2013
3. EPIG grant University of Florida, Department of Pathology 2010
4. Training Award - Association for Cancer Research 2010
5. Membership - American Society for Investigative Pathology2010 - present
6. Membership - American Association for Cancer Research 2009-present.

Radiotherapy; Apoptotic signal pathway; Molecular and cellular biology; Chemotherapy; Hepatocellular/Pancreatic carcinoma; Cell proliferation and death; Interventional therapy; Cancer biology.

The goal of my research is to understand the epigenetic and transcriptional regulation of cancer and develop novel therapies for cancer. Currently, my research focus is on neuroblastoma and leukemia in particular identification of genome-wide chromatin state of Ikaros and HDAC1 targets in primary human leukemia cells. We found that targeting casein kinase II restores Ikaros tumor suppressor activity and demonstrated therapeutic efficacy in High-Risk leukemia cases. In collaboration with other researchers, I also identified miR-215 as a bio-marker in human glioma, Ikaros, c-MYC, LEF1, WDR5 and CRLF2 in human leukemia. I am very interested in the study on microbiome (infection) and cancers, and developing novel next generation sequencing panels for diagnosis of clinical diseases.

1. Fundamental science: Published data revealed the novel regulatory mechanism for Ikaros anti-tumor functions by epigenetic regulation through CK2/HDAC1/Ikaros axis in leukemia. We also identified several key molecules on oncogenesis of neuroblastoma and liver cancer, and also the association of hepatitis infection with liver cancers.
2. Translational science: The strong therapeutic efficacy of CK2 inhibitor was demonstrated in high-risk leukemia through restoring Ikaros function; also the potential combined therapy of CK2 inhibitor with the inhibitor of Ikaros gene targets on multioncogenic pathways for childhood leukemia. We also explore the effect of several extracts from nature products including herbs in treatment of cancers and other human diseases. We also developed diagnosis methods and next-generation sequencing panels for human cancers.
3. Clinical science: The identification of the oncogenic effects of key genes’ expression and mutations in leukemia and other cancers, their correlation with clinical feature, and Ikaros dysfunctions. This study will help me to identify more biomarkers for diagnosis of high-risk leukemia and other human cancers, and also the therapeutic targets in ALL and other childhood malignancies.
4. Thus far, my contributions include transcriptional and epigenetic regulations in Leukemia and CK2 inhibitors for leukemia therapy, identification of novel poly A polymerase regulated by phospholipid (Star-PAP), discovery of a novel phospholipase C (PLCepsilon) regulated by Ras, identification of biomarkers in cancer, anti-tumor effects of potential new drugs, and work on ion channels, metabolism and hepatitis infection.

1. 1992 Sasakawa Fellowship, Japan-China Medical Association, Japan;
2. 1998 Visiting Scholarship, Ministry of Education, China;
3. 1999 Visiting professorship, Ministry of Education, Japan
4. 2003 Postdoctoral fellowship, American Heart Association;
5. 2014 Young investigator award, Department of Pediatrics, PSU, USA
6. 2016 Co-instructor and co-director, International Cooperative Leukemia Group and International
7. Cooperative Laboratory of Hematology, Zhongda Hospital, Medical School of Southeast University, China

1. Genetic characterization and multiparameter flow cytometry analysis of leukemia stem cells associated with clonal evolution and disease progression.
2. Validation of genetic biomarkers in AML/APL as potential therapeutic targets.
3. Clonal evolution in APL patients resistant to arsenic trioxide.
4. Evaluation of FLT3-ITD leukemia-associated CD34/CD123/CD25/CD99-positive immunophenotype in patients with APL.
5. Characterization of the mutational landscape of t(11;17)-positive AML and APL-like leukemias.
6. Genetic characterization therapy-related AML.

TECHNICAL SKILLS AND COMPETENCES

Molecular Biology Isolation and cryopreservation of high-quality RNA and DNA, PCR, RT-PCR, Q-RT-PCR, Q-LAMP, SNPs analysis, DHPLC, DNA sequencing, cloning and bacterial transformation, NGS technology, droplet digital PCR, site-directed mutagenesis, Western blotting.

Cellular Biology Culture of leukemia cell lines, protein extraction, ELISA, immunofluorescence, FISH, immunoprecipitation, affinity chromatography.

AWARDS

1. Winner of a research fellowship by Fondazione Umberto Veronesi "Role of DNMT3A R882H mutation as a prognostic factor in acute myeloid leukemia" (2016).
2. Winner of a 3-year research fellowship by AIRC "Investigation on the mechanisms underlying the chromosomal translocations in secondary acute myeloid leukemias" (2009).

April 2009-May 2010: Clinical fellow, Hematology and stem cell Transplant program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada.

• January 2014 to current: Adjunct Professor, Division of Oncology, College of Graduate Studies and Research, University of Saskatchewan, SK, Canada
• June 2010 to current: Clinical Associate Professor, University of Saskatchewan, Saskatoon, SK, Canada.
• B-Saskatchewan Health Region/ Saskatchewan Cancer Agency:
• October 2014 to current: Medical Director of Blood and Marrow Transplant Program, Saskatoon Cancer Center.
• June 2010 to current: Transplant Hematologist, Provincial Hematology / Blood and Marrow Transplant Program, Saskatchewan Cancer Agency and Royal University Hospital.

In 1985 Dr.ssa de Totero Daniela developed novel techniques allowing generation of alloreactive T cell clones to identify new HLA specificity and then she participated to the X° International HLA Workshop in the T cell clone Section. During her training in USA ( from 1989 to 1991: Memorial Sloan Kettering New York, NY, Hystocompatibility Lab directed by Prof. Bo Dupont) she generated T cell clones specific for flu virus peptides for vaccination studies. She was further involved in studying the expansion of the malignant clone in lymphoproliferative diseases (LGL, HCL ,CLL) with particular regard to the expression of the CD8 antigen and of the IL2 receptor complex. She then analysed the use of immunotoxins in lymphomas therapy and in GVHD in transplants. She described a specific T cytotoxic2 subset CD3+/CD8+/CD30+ in Chronic Lymphocytic Leukemia (CLL) producing IL-4 and enhancing leukemic B cell survival. She further studied mechanisms regulating apoptosis in CLL cells induced by drug or by cytokines and the possibility of blocking anti-apoptotic molecules through targeted therapies. She has evidenced the expression of IL-21R and IL-15R on CLL cells and studied anti-apoptic effect of IL-21, and surviving effect of IL-15 on CLL cells. She has been recently involved in researchs aiming to define the interactions between mesenchymal stem cells and leukemic B cells . She described the expression of the HGF receptor c-MET in chronic lymphocytic leukemic B cells and the interactions with its ligand, HGF, abundantly produced by certain types of mesenchymal cells within bone marrow. Moreover she also described how Nurse-like cells, a particular type of cells of the CLL microenvironment , may support CLL expansion through the production of HGF and of SDF. She is currently an Assistant Director at the Molecular Pathology Unit (San Martino Hospital –IRCCS, Genoa , Italy) and she has been recently involved in studying the interactions between CLL cells and bone tissue. She is currently investigating how CLL cells, through production of soluble factors, modify differentiation of osteoblasts and of osteoclasts thus creating particular conditions in the tumor microenvironment that may favor expansion and proliferation of the leukemic B cell clone.

1. National Natural Science Foundation of China (3095476) 2012
2. National Natural Science Foundation of China (30600567) 2013
3. National Natural Science Foundation of China (30972685) 2010
4. Membership- China Society for Immunology 2007-present
5. Membership- American Society for Immunology 2008-present

Immunetherapy; T cell function; Macrophage development and function; Neutrophils development and function; Molecular and cellular biology; Chemotherapy; Cell proliferation and death; Cancer biology; Inflammation