Yves Albert Declerck, MD

Yves DeClerck MD is a Pediatrician-Scientist at Children’s Hospital Los Angeles and USC. He is leading a cancer biology research program focused on the tumor microenvironment. He is the co-leader of the Tumor Microenvironment Program at the USC-Norris Comprehensive Cancer Center and the Director for Research Education at the Children’s Center for Cancer and Blood Disease.
Research Focus of the Laboratory: The main focus of investigation in our laboratory is on the Tumor Microenvironment (TME) and its contribution to cancer progression and metastasis (Borriello et al., Cancer Lett. 2016). The main objective of the laboratory is to understand fundamental mechanisms of communication between tumor cells and stromal cells in the TME in order to identify targets for therapeutic intervention that can be tested in relevant pre-clinical models. These data are then used to design early phase clinical trials in children with cancer through collaboration with clinical investigators at the USC-Norris Comprehensive Cancer Center and Children’s Hospital Los Angeles (CHLA). A major focus is on Neuroblastoma (NB), the second most common solid tumor in children and a cancer that is highly metastatic. Our research approach combines cell and molecular biology with pre-clinical animal models in mice. Our research program has 3 major directions:
1. Contribution of cancer-associated fibroblasts (CAF) to neuroblastoma progression: Our laboratory has recently identified in neuroblastoma tumors, CAFs that share phenotypic and functional properties of bone marrow mesenchymal stromal cells (MSC). These cells are educated by NB cells toward a pro-tumorigenic function that enhance NB cell proliferation, survival and drug-resistance through the production of several pro-tumorigenic cytokines and chemokines such as IL-6, IL-8, VEGF, SDF1 and MCP1 (Borriello et al., Cancer Res. 2017, in press). Downstream of these cytokines is the activation of STAT3 and ERK1/2 in NB cells. Ongoing work investigates the effect of blocking STAT3 and ERK1/2 in combination with chemotherapy and immunotherapy to enhance therapeutic response and prevent resistance.
2. Contribution of exosomes and extracellular vesicles to the education of CAFs, MSCs and macrophages by tumor cells: Stromal cells in the TME are educated by tumor cells and polarized toward a pro-tumorigenic function (these cells from being foes learn to become friends of the tumor cells). Extracellular vesicles and in particular exosomes released by tumor cells are captured by stromal cells and contribute to their education not only in primary tumors but also in the pre-metastatic niche. Our laboratory has recently shown (Nakata et al., Journal of Extracellular Vesicles 2017, in press) that exosomes released by NB cells are captured by MSCs and macrophages and contribute to the production of pro-tumorigenic cytokines by these cells. Ongoing work is studying the mechanism involved in the capture of tumor-derived exosomes by MSCs and macrophages with a focus on galectin-3 binding protein and integrins in collaboration with Dr. Lyden at Cornell (NYU) and on identifying ways to inhibit the production of exosomes by tumor cells and its effect on tumor progression and metastasis in pre-clinical mouse models.
3. Role of plasminogen activator inhibitor-1 (PAI-1) in cancer progression: PAI-1 is a serine protease inhibitor which has been shown to have a paradoxically positive effect in cancer progression by promoting angiogenesis and protecting tumor cells from drug-induced apoptosis (Placencio et al., Cancer Res, 2016). More recent work in our laboratory shows that PAI-1 contributes to inflammation in cancer by promoting the recruitment of macrophages into tumors and their polarization (or education) toward a pro-tumorigenic (M2) phenotype.
Funding of the Laboratory: Our laboratory has been funded by the NIH without interruption since 1986. Current funding incudes 2 R01 grants (work on exosomes described under #2, and work on PAI-1 described under #3), and a project in a larger multi-institutional program project grant on neuroblastoma (work under #1).
Environment: Our laboratory is located on the 5th floor of the Smith Research Tower at The Saban Research Institute (TSRI) of Children’s Hospital Los Angeles (CHLA). Our research program is part of the Tumor Microenvironment Program of the USC Norris Comprehensive Cancer Center (USC-Norris) and the neuroblastoma research group of the Children’s Center for Cancer and Blood Diseases at CHLA. Both TSRI and USC-Norris provide a rich and interactive environment for the conduct of innovative research in the area of the TME. We have collaborations with faculty at USC, Cornell, City of Hope, Harvard and Children’s Hospital of Philadelphia. The laboratory has trained 10 graduate students and 25 postdoctoral fellows, many presently working at academic institutions and in industry. Career development of highly motivated and dedicated students is an integral part of the research experience in the laboratory.
The Principal Investigator: Dr. DeClerck is a Tenured Professor of Pediatrics and Biochemistry & Molecular Medicine at USC. He started his career as a physician-scientist in the early 1980s and has established an independent research program that has been funded by the NIH without interruption since 1986. He has organized multiple meetings and conferences in the field of metastasis and the tumor microenvironment. He has served and is still serving on multiple study sections at the NIH, was the co-chair of the NCI Tumor Microenvironment Network and is a senior editor for Cancer Research for the Tumor Microenvironment-Immunology section. He has a solid record of accomplishment in education, mentoring and career development, being the PI on a longstanding (1991-present) NCI-funded T32 Program grant, and the chair of multiple mentoring committees of junior faculty members and postdoctoral trainees at USC and CHLA. He is the recipient of the 1991 H. Russell Smith Award for Innovation in Pediatric Biomedical Research, the USC Associates Award for Creativity in Research (2013) and the Richard Call Family Endowed Chair in Pediatric Research Innovation (2010).

• Catholic University of Louvain: SPECIA prize, 1973
• American Cancer Society: Junior Faculty Career Development Award, 1982
   – 1985
• Children’s Hospital Los Angeles: Morris & Mary Press Humanism Award, 1987
• Fogarty: Senior International Fellowship, 1991
   – 1992
• Children’s Hospital Los Angeles: H.Russell Smith Award for Innovation in Biomedical Research, 1991
• Children’s Hospital Los Angeles: Associates & Affiliates Endowed Chair in Cancer Biology, 1994
   – pres
• Children’s Hospital Los Angeles: Richard Call Family Endowed Chair in Pediatric Research Innovation, 2010
   – pres
• USC: Associates Award for Creativity in Research, 2013

• Notre Dame University , Namur, Belgium — BS — 06/1969 — Biology/Pre-Med
• Catholic University of Louvain, Louvain, Belgium — MD — 07/1973 — Medicine
• Catholic University of Louvain, Belgium — 06/1975 — Pediatric Residency
• University of Montreal, Quebec, Canada — 06/1977 — Pediatric Residency
• Children's Hospital Los Angeles, California, USC — 06/1979 — Pediatric Hematology-Oncology Fellowship

• Discovering and Exploiting Mechanisms of Neuroblastoma Therapy Resistance
  NIH/NCI · 1P01-CA217959-01 · Sep 1, 2017 – Aug 30, 2022 · Role: PI on Project 3: Targeting the Pro-Tumorigenic Microenvironment
• Tumor-derived extracellular vesicles in the pre-metastatic niche.
  NIH · R01CA207983 · Aug 1, 2017 – Aug 31, 2029 · Role: Principal Investigator
• Exosomes in Tumor Cell-Mesenchymal Stromal Cells Interaction
  NIH/NCI · R01 CA207983-01A1 · Jul 1, 2017 – Jun 30, 2022 · Role: Principal Investigator
• Children’s Hospital Los Angeles Child Health Research Career Development Award
  NIH/NICHD · K12 HD529954-10 · Dec 1, 2011 – Nov 30, 2017 · Role: Program Director
• AACR Special Conference on Tumor Microenvironment Complexity: Emerging Roles in C
  NIH · R13CA165612 · Nov 1, 2011 – Oct 31, 2012 · Role: Principal Investigator
• Center for Environment-Mediated Drug Resistance in Pediatric Cancer
  NIH · U54CA163117 · Sep 20, 2011 – Jul 31, 2017 · Role: Principal Investigator
• Fifth International Conference on Tumor Microenvironment: Progression, Therapy a
  NIH · R13CA144431 · Sep 1, 2009 – Feb 28, 2010 · Role: Principal Investigator
• Plasminogen activator inhibitor-1 in tumor progression and metastasis
  NIH · R01CA129377 · Apr 1, 2008 – Apr 30, 2019 · Role: Principal Investigator
• Developing And Improving Institutional Animal Resources
  NIH · G20RR024015 · May 15, 2007 – May 14, 2009 · Role: Principal Investigator
• Tumor Microenvironment: Progression, Therapy and Prevention
  NIH · R13CA128588 · Mar 1, 2007 – Feb 29, 2008 · Role: Principal Investigator
• Cancer, Proteases and the Microenvironment
  NIH · R13CA119825 · Sep 15, 2005 – Sep 14, 2006 · Role: Principal Investigator
• MOLECULAR MECHANISMS AND IMAGING OF BONE INVASION
  NIH · R21AR051247 · Sep 17, 2003 – Jun 30, 2007 · Role: Principal Investigator
• DEVELOPING AND IMPROVING ANIMAL RESOURCES
  NIH · G20RR017067 · Jun 1, 2003 – May 31, 2004 · Role: Principal Investigator
• ECM MATRIX, PROTEASE AND MELANOMA PROLIFERATION
  NIH · R01CA098469 · Jan 10, 2003 – Dec 31, 2009 · Role: Principal Investigator
• Conference on Proteases, Extracellular Matrix, &Cancer
  NIH · R13CA099296 · Aug 1, 2002 – Jul 31, 2003 · Role: Principal Investigator
• EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION
  NIH · C06RR011246 · Sep 30, 1995 – Sep 29, 1998 · Role: Principal Investigator
• FUNC. AND REG. STUDIES OF METALLOPROTEINASE INHIBITOR
  NIH · F06TW001736 · Jul 11, 1992 · Role: Principal Investigator
• Training Physician Scientists in Pediatric Oncology
  NIH · T32CA009659 · Sep 15, 1991 – Jul 31, 2021 · Role: Principal Investigator
• TWO STEP INHIBITION OF INVASION AND METASTASIS
  NIH · R03CA054861 · Aug 1, 1991 – Jul 31, 1994 · Role: Principal Investigator
• METALLOPROTEINASE INHIBITORS IN TUMOR PROGRESSION
  NIH · R01CA042919 · May 1, 1987 – Feb 28, 2010 · Role: Principal Investigator

• Tumor Microenvironment
• Cancer Biology
• Neuroblastoma
• Metastasis
• Pediatric Cancer

• Asgharzadeh, Shahab
• Lenz, Heinz-Josef
• Marachelian, Araz
• Villablanca, Judith
• Pawel, Bruce
• Chai, Yang