Our Science – Tessarollo Website

Lino Tessarollo, Ph.D.

Mouse Cancer Genetics Program Head, Neural Development Section Deputy Director Building 560, Room 32-31D NCI-Frederick Frederick, MD 21702-1201 Phone:   301-846-1202 Fax:   301-846-7017 E-Mail:   tessarol@ncifcrf.gov

Biography

Dr. Tessarollo received his Ph.D. in biological sciences from the University of Padua, Italy, in 1987. He carried out postdoctoral training in the laboratory of Dr. Chieco-Bianchi at the Institute of Oncology, Padua, and Dr. Parada at the ABL-Basic Research Program, NCI-Frederick. In 1994, Dr. Tessarollo established the Special Program in Germline Mutation and, in 1996, he formed the Neural Development Group. In 1997, while continuing his research effort, Dr. Tessarollo established a mouse gene targeting program for the National Cancer Institute. In 1999, he joined the Center for Cancer Research, NCI where he continues to direct the Neural Development Section and the Gene Targeting Facility. In 2006, Dr. Tessarollo was appointed Deputy Director of the Mouse Cancer Genetics Program.

Research

Neurotrophins are a highly homologous family of secreted growth factors that have been extensively studied for their roles in the proliferation, survival, and differentiation of various cell populations in the mammalian nervous system. Each neurotrophin interacts with the p75 receptor and a specific member of the trk tyrosine kinase receptor family. Trk receptors, in addition to the tyrosine kinase isoforms, include receptors which lack kinase activity.
Over the last two decades many laboratories have contributed to the dissection of signaling pathways and the biological responses activated by neurotrophins in a variety of cell types. Most of this information was generated with the use of in vitro systems. Thus, many of these activities were caused by pharmacological rather than physiological activation of neurotrophin signaling. My laboratory is using the mouse as a genetically amenable in vivo tool to address some of the many still unresolved issues in neurotrophin biology. Specifically, we are interested in the role of neurotrophins in the mature nervous system and in non-neuronal organs such as the immune system. Furthermore, we are interested in the contribution of specific receptor isoforms and signaling pathways in mediating defined neurotrophin activities. In this respect we have generated a variety of mouse models that have helped us to dissect specific roles of neurotrophins in mouse development. For example, to investigate the significance of NT-3 interactions with its non-preferred receptor TrkB we have generated a mutant mouse in which NT-3 has been replaced by BDNF. With this strategy we eliminated TrkC and TrkA activation by the product of the NT-3 locus while preserving only the spatio-temporal activation of the TrkB receptor. Analysis of this mouse model led to two major observations on neurotrophin functions in vivo. First, the dynamics of neuronal numbers in the dorsal root ganglia (DRG) during neurogenesis and target tissue innervation demonstrate for the first time a physiological role of TrkA and TrkB activation by NT-3. Second, we have provided in vivo genetic evidence that neurotrophins in the ear exert both survival and axon guidance roles.
Other recent accomplishments of our laboratory include the identification of proteins that interacts with a phylogenetically conserved intracellular domain of truncated TrkC receptors. Thus, our finding may provide one of the long sought direct link between neurotrophins and signaling of truncated Trk receptors.
A more general role of neurotrophins in lymphoid organs is further suggested by our study of trkA in the immune system. Using a novel approach of 'reverse conditional gene targeting' we have demonstrated for the first time a direct role of the NGF receptor TrkA in the development of a specific class of B lymphocytes and immunoglobulin production. However, the results also show that TrkA is not required for the basic development of lymphoid organs. Instead it may play a modulatory role in immunological functions since the phenotypes so far identified in this mutant mouse are very selective.
In summary, we are generating data that shed light on the role of specific Trk isoforms and of specific Trk signaling pathways in vivo. We have also uncovered some of the functions of neurotrophins in the mature nervous system and in the immune system. These data contribute to our understanding of the complex nature of ligand-receptor family interactions in the maintenance of higher organisms, and may lead to a better understanding of pharmacological neurotrophin activities in vivo.

Our collaborators include Bernd Fritzsch, Creighton University, Omaha; Colin Fletcher and Lisa Tarantino, Novartis Genomics Institute, San Diego, CA; Antonio Contestabile, University of Bologna, Bologna, Italy; Paul Randazzo, NCI, CCR.

This page was last updated on 6/12/2008.