Nadia Carlesso, MD, PhD Associate Professor, Department of Pediatrics
Associate Professor: Department of Pediatrics
Clinical Section: Neonatal-Perinatal Medicine
Basic Science Joint Appointment: Medical and Molecular Genetics
Director: Student Research Program in Academic Medicine
Assistant Professor: Department of Pediatrics, Indiana School of Medicine, Indianapolis, IN
Assistant Professor: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Postdoctoral Fellowship: Massachusetts General Hospital, Harvard Medical School, Boston, MA
PhD: University of Genoa, Genoa, Italy / Dana Farber Cancer Institute, Boston, MA, 1995
Fellowship: Division of Hematology/Oncology, University of Torino School of Medicine, Torino, Italy
MD: University of Torino School of Medicine, Torino, Italy, 1989
Current Research Interests:
Our research is focused on identifying the molecular mechanisms involved in the regulation of hematopoietic stem cells (HCS) self-renewal and differentiation with the ultimate goal to develop novel approaches for treating bone marrow (BM) failures and leukemias.
Specifically, our research is focused on identifying pathways and networks linking microenvironmental cues with the cell cycle and cell fate of HSC in inflammation and cancer. We are particularly interested in Notch signaling and how the Notch pathway regulates HSCs cell fate in hematopoietic development and disease. Activation of Notch receptors upon binding to their ligands on a neighboring cell triggers downstream events that culminate with transcription of genes involved in development and differentiation. Notch signaling plays an essential role in the development of normal hematopoiesis and is involved in leukemogenesis. In the past few years, we developed a framework that allows us to integrate the molecular aspects of Notch signaling with cellular and physiologic processes in the hematopoietic system. Furthermore, we have been exploring the role of non cell-autonomous mechanisms in controlling the hematopoietic cell intrinsic transcriptional program. Increasing evidence indicates that normal hematopoiesis is dependent on, and regulated by, distinct microenvironmental cues in the bone marrow, which include specialized cellular niches modulating critical functions of the hematopoietic stem cells, such as self-renewal and cell-fate decisions.
To address these questions, we are using genetically engineered mice lacking components of critical signaling pathways, sepsis and leukemias animal models and intravital imaging of the bone marrow to study stem cell and niche interactions in normal and pathologic conditions.
Current areas of research include:
- Notch signaling
- Oncogenic transformation
- Cell cycle regulation
- Cancer and inflammation
- Intravital microscopy
- 1. Defining the role of the Notch/SKP2/CKIs pathway in HSC homeostasis and regeneration in SKP2 null mice.
- 2. Evaluating the impact of Notch signaling in the hematopoietic stem cell niche, by using genetic models of Notch loss-of-function.
- 3. Investigating the molecular mechanisms (role of signaling pathways and microRNAs) leading to dysfunctional expansion of HSC and their block of differentiation during bacterial sepsis and inflammation.
- 4. Defining the bone marrow HSC niche and the interactions between “stromal” cells and the hematopoietic cells in normal HSC and leukemias by intravital multiphoton, microscopy currently in use in our laboratory.
Sonia Rodriguez, Ph.D., University of Barcelona, Spain
Lin Wang, Ph.D., Peking University, China
Huajia Wang, PhD candidate, IBMG Program –Genetics- IUSM
Christy Mumaw, Lab manager and Co-coordinator
Amy Zollman, Imaging Technologist
Declan McGuigan, 3rd year Undergraduate, University of Ulster, Coleraine, Ireland
Ann Collier, 3rd year Undergraduate, DePauw University, Indiana
James Godzik, 2nd year IUSM Medical Student