Nadia Carlesso, M.D., Ph.D.

Research Focus :

Mechanisms of hematopoietic cell clonal dominance and transformation
Role of Notch signaling in the regulation of inflammation
Contribution of inflammation to leukemia and bone marrow failure
Microenvironment – Leukemia crosstalk
In vivo-visualization of normal and malignant bone marrow niches

Nadia Carlesso M.D., Ph.D., joined the Beckman Research Institute of City of Hope as Associate Director of Basic Research in the Gehr Family Center for Leukemia Research, Professor in the Department of Hematologic Malignancies Translational Science and Professor at the Gehr Family Center for Leukemia Research.

Dr. Carlesso and her team will lead efforts to identify novel therapeutic approaches targeting simultaneously the leukemia cells and the leukemic microenvironment, in particular in relapse and refractory disease, and strategies to improve hematopoietic cell engraftment following transplant.

Dr. Carlesso received her M.D. from the University of Torino (Italy) and her Ph.D. from the University of Genova (Italy). She performed her Ph.D. work at the Dana-Farber Cancer Institute and received the postdoctoral training at the Massachusetts General Hospital, Harvard Medical School.

Dr. Carlesso has been continuously funded by the NIH since 2001. Her work has been supported by NHLBI and NIDDK and by several external grants including the MPN/Leukemia Lymphoma Foundation. She serves on the editorial boards of the Journal of Experimental Hematology and of Trends in Cancer, she is a member of peer review panels for NIH, the Department of Defense and the NY State Stem Cell Science.

Professional Experience

2016 - Present, Professor, Department of Hematologic Malignancies Translational Science, Beckman Research Institute of City of Hope, Duarte, CA
2016 - Present, Professor, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope, Duarte, CA
2016, Professor of Pediatrics and Medical & Molecular Genetics, University School of Medicine, Indiana University
2010 - 2015, Associate Professor of Pediatrics and Medical & Molecular Genetics, University School of Medicine, Indiana University
2010 - 2016, Co-Director, Core Center of Excellence in Hematology (CCEH) Intravital Imaging Core, University School of Medicine, Indiana University
2008 - 2016, Director, Medical Student Research Program in Academic Medicine, University School of Medicine, Indiana University
2007 - 2009, Assistant Professor of Pediatrics and Medical & Molecular Genetics, University School of Medicine, Indiana University
2002 - 2006, Assistant Professor of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
1997 - 2002, Instructor of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
1995 - 1997, Postdoctoral Fellow, Massachusetts General Hospital, Harvard Medical School, Boston,, MA

Education

Degrees

1995, University of Genoa School of Medicine, Italy, Ph.D.
1989, University of Turin School of Medicine, Italy, M.D.

Fellowship

1995 - 1997, Postdoctoral Fellow, Division of Experimental Hematology, Massachusetts General Hospital, Harvard Medical School. David Scadden-Mentor
1990 - 1992, Clinical Fellow, Hematology/Oncology, Department of Medicine and Experimental Oncology, Molinette Hospital, University of Turin, Turin, Italy, M.D.

Residency

1989 - 1990, Resident in Hematology, Division of Hematology, Department of Medicine and Experimental Oncology, Molinette Hospital, University of Turin, Turin, Italy, M.D.

Laboratory

Our laboratory studies the molecular mechanisms driving normal stem cell differentiation and malignant transformation in the hematopoietic system. More specifically we are investigating how the interactions between the bone marrow microenvironment and the hematopoietic stem and progenitor cells shape their cell fate decisions. We are interested in defining: a) how Notch signaling guides and affects the reciprocal interactions between normal or malignant stem cells and their niches; b) Notch signaling and its interplay with the Toll receptors and NF-kB pathways; and c) how this crosstalk is involved in the link between inflammation, aging and leukemia development. To address these questions, we are using complementary approaches including in vivo models of sepsis and leukemia, xenograft models and in vivo multi-model imaging.

The long-term goal of our research is to exploit basic insights in hematopoietic stem cell biology to identify therapeutic targets and test drugs that will target leukemia cells and the inflamed microenvironment.

An Expert's Voice

Publications

Selected publications:

Zhang H, Rodriguez S, Wang L, Wang S, Serezani H, Kapur R, Cardoso AA, Carlesso, N. Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88. Stem Cell Reports. 2016 Jun 14;6(6):940-56. doi: 10.1016/j.stemcr.2016.05.002. Epub 2016 Jun 2. PMID: 27264973
Pengpeng Bi, Tizhong Shan, Xin Yang, Weiyi Liu, Xin-Rong Liang, Jinghua Wang, Jie Li, Carlesso N., Xiaoqi Liu, Shihuan Kuang. Notch signaling regulates adipose browning and energy metabolism. Nature Medicine, 2014 Jul 20. doi: 10.1038/nm.3615. [Epub ahead of print].
Wang L, Rodriguez S, Zhang H, Cao L, Parish J, Mumaw C, Zollman A, Kamoka G, Mu J., Chen D.Z., Srour E, Chitteti B, Hoegenesh H, Boswell S., Manshouri T., Verstovsek S., Yoder M., Kapur R, Cardoso A and Carlesso N. Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in a NF-κB dependent manner. Cell Stem Cell. 2014 Jul 3;15(1):51-65. PMID: 24996169.
Rodriguez S., Wang L, Mumaw C, Srour EF, Lo Celso C, Nakayama K, Carlesso N. The SKP2 E3 ligase regulates basal homeostasis and stress-induced regeneration of HSCs. Blood. June 2011, 16;117(24):6509-19, 2011. PMCID: PMC312021.
Carlesso N. When IFN interferes with cell fate. Blood. 2012 Feb 9;119(6):1327-9. PMID: 22323406
Batista A., Barata J., Raderschall E., Sallan SE, Nadler LM., Carlesso N., Cardoso AA. Targeting of activated mTOR inhibits leukemia T-cells and synergizes with cytotoxic Drugs and Signaling Inhibitors. Exp Hematol. Apr 2011;39(4):457-472.e3, 2011. PMID: 21277936.
Cheng YH, Chitteti BR, Streicher DA, Morgan, JA, Rodriguez-Rodriguez, Carlesso N, Srour EF, Kacena MA. Impact of maturational status on the ability of osteoblasts to enhance the hematopoietic function of stem and progenitor cells. J Bone Miner Res. May 2011;26(5):1111-21. PMID: 21542011.
Carlesso N., Cardoso AA. Stem cell regulatory niches and their role in normal and malignant hematopoiesis. Curr Opin Hematol. July 2010;17(4):281-6. PMID: 20473160.
Rodriguez S., Chora A., Goumnerov B., Goebel S., Mumaw C., Fernandez F., Baldini R., HogenEsh H., Doumbousky D., Rice S., Rahme L.G., and Carlesso N. Dysfunctional Expansion of Hematopoietic Stem Cells and Block of Myeloid Differentiation in Lethal Sepsis. Blood. Nov 2009;114(19):4064-76. PMCID: PMC2774548.
Fernandez L., Rodríguez S., Huang H., Chora A., Mumaw C., Cruz E., Pollok K, Cristina F., Price J.E., Ferkowitz M.J., Scadden D.T., Clauss M., Cardoso A.A, Carlesso N. TNFα and Endothelial Cells Modulate Notch Signaling in the Bone Marrow Microenvironment during Inflammation. Exp. Hematology. 2008, May; 36(5):545-558. PMID: 18439488.
Sarmento L., Huang H., Limon A., Gordon W., Fernandes J., Tavares M.J., Miele L., Cardoso A.A., Classon M., Carlesso N. Notch1 Modulates Timing of G1-S Progression by Inducing SKP2 Transcription and p27Kip1 Degradation. J Exp Med., 2005, 202(1):157-168.
Ellisen L.W. #, Carlesso N. #, Scadden, D.T., Haber, D.A. Regulation of Hematopoiesis by the Tumor Suppressor WT1. Embo J., 20 (8): 1897-1909, 2001. # Equal contribution.
Lewin M.#, Carlesso N.#, Tung C., Tang X., Cory D., Scadden D., Weissleder R. HIV-TAT Derivatized Magnetic Nanoparticles allow in vivo tracking and recovery of progenitor cells. Nature Biotech., 18(4):410-414, 2000. # Equal contribution.
Carlesso N., Aster J., Sklar J., Scadden D. Notch1-Induced Delay of Human Hematopoietic Progenitor Cell Differentiation is Associated with Altered Cell Cycle Kinetics. Blood, 93(3): 838-848, 1999.
Bazzoni G.F., Carlesso N. #, Griffin J.D., Hemler M.E. Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. J. Clin. Invest., 98(2): 521-528, 1996. #Equal contribution.
Carlesso N., Frank D.A., Griffin J.D. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J. Exp. Med., 183(3): 811-820, 1996
Inhorn R.C., Carlesso N., Durstin M., Frank D.A., Griffin J.D. Identification of a viability domain in the granulocyte/macrophage colony--chain involving tyrosine-750 and SHC. Proc. Natl. Acad. Sci. USA, 92(19): 8665-8669, 1995
Carlesso N., Griffin J.D., Druker B.J. Use of a temperature-sensitive mutant to define the biological effects of the p210BCR-ABL tyrosine kinase on proliferation of a factor-dependent murine myeloid cell line. Oncogene, 9(1):149-156, 1994
Carlesso N., Pregno P., Bresso P., Gallo E., Pileri A., Zsebo K.M., Ferrero D. Human recombinant stem cell factor stimulates in vitro proliferation of acute myeloid leukemia cells and expands the clonogenic cell pool. Leukemia, 6(7):642-648, 1992
Ferrero D., Carlesso N., Pregno P., Gallo E., Pileri A. Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation. Leukemia, 6(2):100-106, 1992

Awards

1995, Sandoz Drug Discovery Program Award
1998, American Medical Association Education, F.A. Carter Fellowship in Leukemia Award
1999, Nesson Investigator Award (Massachusetts General Hospital)
1999-2001, Claflin Distinguished Scholar Award-Harvard Medical School 50th Anniversary
2004, Harvard Medical School Leadership Development for Physicians and Scientist
2006, Milton Fund Scholar Award (Harvard University)
2007, Showalter Research Trust Funding Award
2010, IUPUI Women’s Leadership Award
2012, “Exceptional Physician Mentor” recognition. AMA Women Physician Congress - Physician Mentor Recognition Program