Teams
João Barata’s Lab | Instituto de Medicina Molecular João Lobo Antunes (iMM)
João Taborda Barata is internationally recognized for his work on leukemia development mechanisms, with particular emphasis on IL-7R (Nature Immunology, 2019). He conducted groundbreaking work demonstrating that nondeletional postranslational inactivation of PTEN plays a critical pro-leukemia role (The Journal of Clinical Investigation, 2008). He also revealed that the ‘tumor suppressor’ CHK1 has an oncogenic role by preventing excessive replication stress (Oncogene, 2015).
João Barata´s lab aims to understand the mechanisms by which malignant T-cells acquire a selective advantage over their healthy counterparts, we are also interested in studying particular features of normal T-cell biology (e.g. how developing thymocytes respond to certain extracellular cues, most notably interleukin 7).
In order to understand whether the oncogenic mechanisms we identify in T-ALL extend to other cancers, we study other leukemias, especially B-cell ALL. Finally, we recently initiated new research avenues on brain tumors and on lung cancer.
Overall, our research aims to illuminate the role that cell-intrinsic aberrations and microenvironmental factors might play during tumor initiation and progression, metastization, and response to treatment. Our goal is to characterize the cellular and molecular mechanisms underpinning these processes, identifying genes and signaling pathways that are implicated in cancer maintenance and expansion at different stages.
University Hospital 12 Octubre (H12O)
The Alvarez-Vallina’s Lab has pre-clinically developed and validated novel cancer immunotherapy strategies based on the adoptive transfer of genetically engineered cells secreting bispecific T cellengagers (BiTEs) both in hematological and solid tumor. The group is actively working on transferring these strategies to the clinic in collaboration with hematologists and medical oncologists from Madrid, Barcelona and Copenhagen. The Alvarez-Vallina’s group is internationally recognized by its contributions on the generation of next-generation antibody formats. LAV is inventor of the trimerbody technology platform and is co-founder of Ledartis SL, a starp-up company based in Madrid aiming to generate more effective immunostimulatory antibodies. LAV´s lab is actively working in the generation of the nextgeneration T cell-engagers, such as the ATTACK (Asymmetric Tandem Trimerbody for T cell Activation and Cancer Killing), a novel T cell-recruiting bispecific antibody which combines three EGFR binding single-domain antibodies (VHH) with a single CD3-binding single-chain variable fragment (scFv) in an intermediate molecular weight package. LAV has a strong experience in the design of novel guided selection strategies for the generation of fully-human recombinant antibodies in vivo in tumor-bearing mice (in vivo phage antibody display) and in vitro on complex antigen mixtures expressed on tumor cell surfaces (T lymphocyte display), in the context of chimeric antigen receptor (CAR).
The collaboration in the context of this Project with Dr. João Barata (JB), an internationally recognized scientist for his contributions on IL-7R biology and cancer development and progression, and Dr. Jon Zugazagoitia (JZ) leading a renowned Lab in biomarker discovery associated with PD-1 checkpoint blockade in non-small cell lung cancer would allow to build-up a highly competitive consortium able to dissect how IL7R is subverted by lung cancer cells to promote tumor development, metastasis and resistance to immunotherapy, and to develop innovative breakthrough therapies.
Centro Nacional de Investigaciones Oncológicas (CNIO)
Jon Zugazagoitia (PI): I am a physician scientist (MD, PhD) in thoracic oncology (Juan Rodes contract). I treat patients with lung cancer, and my clinical research is mostly focused on the early phases of clinical development of novel immunotherapy drugs for lung cancer. From a scientific perspective, I have expertise in molecular taxonomy of lung cancer, immune profiling, biomarker science, and immunobiology. My research experience includes a 2-year postdoc in the prestigious laboratory of Dr. Rimm at Yale. I believe that my demonstrated scientific record, commitment, and hard work, has prepared me to be the PI of this joint scientific project. Irene Ferrer is a senior post-doctoral scientist (PhD) with extensive experience in basic and translational research. She is an expert in lung cancer animal models for the discovery of novel targets for lung cancer.
She developed the PDX platform in our group, and she currently leads the h-PDX development. Gorka Ruiz De Garibay is an immunologist and post-doctoral scientist (PhD) with strong expertise in molecular biology, genetics, and oncology. He has worked in several national and international high-level research centers, including ICO-IdiBELL and the University of Bergen. He is a highly experienced researcher with animal models as well as multiple techniques related to immunology and molecular cell biology. Magdalena Abraham is a post-doctoral scientist (PhD) with expertise in immune profiling and expert operator of the Digital Spatial Profiling system. Teresa Muñoz is a post-doctoral research pathologist (MD, PhD) with long-standing experience in lung cancer pathology and biomarkers. She has full-time research dedication. Vera Adradas is a research technician with more than 5-year experience working in the biobank service of the 12 de Octubre Hospital. She has advanced operator abilities with immunohistochemistry and Digital Spatial Profiling sample preparation protocols. Finally, Patricia Cozar is a research technician specialized in animal models. She is the research technician leading and setting up the humanization protocol of our PDX collection.
