Assistant Professor, Baylor College of Medicine
Ph.D., Nagoya University, Japan, 2005
Postdoc, University of Michigan, Ann Arbor, 2006-11
Molecular and genetic analysis of stem cell function and cancer
The main focus of our lab is to elucidate the molecular and cellular mechanisms that regulate stem cell function. The integrity of many adult tissues is maintained by stem cells that are capable of producing differentiated cells and generating more stem cells by self-renewal. Many important questions remain regarding the mechanism by which stem cells maintain their self-renewal capacity throughout life, and how stem cell functions are integrated in animal physiology. We study hematopoietic stem cells, which produce all blood cells, using genetic engineering and molecular, cellular biology techniques. By understanding how stem cells undergo self-renewal division, we not only get insight into how tissue integrity is maintained, but also how cancer cells acquire unlimited proliferative potential, because pathways that regulate stem cell self-renewal are often dysregulated to promote cancer cell proliferation.
We recently discovered that the Lkb1-AMPK pathway is critical to maintain hematopoietic stem cells by regulating energy metabolism and chromosome stability. By studying precisely the biology of stem cells, we found that even fundamental biological processes such as regulation of energy metabolism and chromosome segregation differ between stem cells and more differentiated progenies. We are currently investigating the molecular mechanisms by which Lkb1 regulates the unique metabolic and chromosomal regulation in hematopoietic stem cells. Since both regulation of energy metabolism and chromosome stability are involved in tumor suppression, we are also testing the hypothesis that the tumor suppressor gene Lkb1, mutated in Peutz-Jeghers syndrome, suppresses tumorigenesis by controlling energy metabolism or chromosome stability in immature cells.
By studying the mechanisms that regulate stem cells and tumor suppression in parallel, we hope to gain deep understanding of tissue homeostasis and yield new therapeutic strategies for cancer.
Nakada D, Shimomura T, Matsumoto K, Sugimoto K (2003) The ATM-related Tel1 protein of Saccharomyces cerevisiae controls a checkpoint response following phleomycin treatment. Nucleic Acids Research 31:1715-1724.
Nakada D, Matsumoto K, Sugimoto K (2003) ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism. Genes and Development 17:1957-1962.
Nakada D, Hirano Y, Sugimoto K (2004) Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway. Molecular and Cellular Biology 24:10016-10025.
Nakada D, Hirano Y, Tanaka Y, Sugimoto K (2005) Role of the C terminus of Mec1 checkpoint kinase in its localization to sites of DNA damage. Molecular Biology of the Cell 16:5227-5235.
He S, Nakada D, Morrison SJ (2009) Mechanisms of stem cell self-renewal. Annual Review of Cell and Developmental Biology 25:377-406.
Lee JY, Nakada D, Yilmaz OH, Tothova Z, Joseph NM, Lim MS, Gilliland DG, Morrison SJ (2010) mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion. Cell Stem Cell 7:593-605.
Nakada D, Saunders TL, Morrison SJ (2010) Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 468:653-658.
Nakada D, Levi BP, Morrison SJ (2011) Integrating physiological regulation with stem cell and tissue homeostasis. Neuron 70:703-718.
Daisuke Nakada, Ph.D.
Center for Cell and Gene Therapy
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030, U.S.A.
Tel: (713) 798-1175