Dr. Lalitha Nagarajan
The University of Texas MD Anderson Cancer Center
Department of Hematology and Genetics
- Genetic regulation
- Chromosomal alterations
- Malignant Transformation
- Hematopoietic stem cell
- Mouse Models
Molecular mechanisms underlying normal growth and differentiation are altered in cancer. Activation of growth promoting genes and inactivation of differentiation/ growth arrest genes represent important steps in the evolution of a malignant clone. Acute myelogenous leukemia (AML) is an excellent paradigm to study the genetic basis of malignant transformation. AML represents clonal, abnormal proliferation of hematopoietic stem cells (HSC). The clinical outcome of AML patients is tightly correlated with the chromosomal abnormalities. Specifically, deletions of chromosomes 5, 7 and 17 signify dismal outcome. Our goal is to establish how the normal pathways of hematopoietic stem cell differentiation are perturbed during malignant transformation by loss of critical genes in these chromosomes.
The research in my laboratory focuses on two major areas:
(1) Deletions and translocations of chromosome 5q: The SSBP2 gene was positionally cloned in our laboratory as a candidate leukemia suppressor gene. SSBP2 encodes a component of a multi-protein transcriptional complex required for differentiation of normal hematopoietic stem cells. Current studies focus on understanding on the mechanistic basis of SSDP2 mediated regulation of HSCs and the consequence of loss of SSDP2 expression in AML.
(2) The MIXL gene pathway in hematopoiesis and leukemia: The MIXL gene, a transcriptional co-activator which mediates signals from the BMP family of peptides to drive hematopoietic differentiation in amphibians. Very little is known about the function of MIXL in humans. Our preliminary studies shows MIXL expression is restricted to hematopoietic stem cells and some leukemia cells. We are interested in identifying factors that regulate MIXL expression as well as target genes that are regulated by MIXL.
Xu Z, Meng X, Cai Y, Liang H, Nagarajan L, Brandt SJ (2007) Single-stranded DNA-binding proteins regulate the abundance of LIM domain and LIM domain-binding proteins. Genes and Development 21:942-955.
Fleisig H, Orazio N, Liang H, Tyler AF, Adams HP, Weitzman MA, Nagarajan L (2007) Adenoviral Oncoprotein E1b55k binds and sequesters leukemia candidate suppressor SSBP2 in aggresomes. Oncogene 26:4797-4805.
Drakos E, Rassidakis GZ, Leventaki V, Guo W, Medeiros LJ, Nagarajan L (2007) Differential expression of the Human MIXL1 gene product in Non-Hodgkin’s and Hodgkin’s lymphoma. Human Pathology 38: 500-507.
Guo W, Nagarajan L (2006) Amino terminal phosphorylation of MIXL1. J. Mol. Signaling 1:6-15.
Office: MDA BSRB S13.833 (Unit 1006)
Title: Associate Professor
Ph.D. - University of Madras Cancer Institute - 1977