Daniel G. Tenen
Department of Medicine, Harvard Medical School
Hematology/Oncology Division, BIDMC
Center for Life Sciences Room 437
3 Blackfan Circle
Boston, MA 02115
Lab Members: 5 Instructors, 9 postdoctoral fellows, 3 technicians
Dr. Tenen's laboratory focuses on transcription factors and gene regulation, and their relationship to differentiation. The laboratory has characterized transcription factors which play a role in the differentiation of hematopoietic stem cells into different specific lineages, with particular focus on myeloid (granulocyte and monocyte) differentiation in normal and leukemic cells. The laboratory has isolated and characterized regulatory elements of master transcription factors expressed at different stages of differentiation, including stem and progenitor cells. Our studies have demonstrated a role for these transcription factors in the regulation of expression of important myeloid genes, and knockout studies demonstrated that they play a major role in hematopoietic development. In addition, we have identified mutations and specific abnormalities in expression of these factors in specific subtypes of myeloid leukemias. Part of the current efforts in the laboratory focus on understanding regulation, signal transduction pathways, and interacting partners of these factors, and their role in stem cells in normal hematopoiesis. In addition, a major effort in our laboratory is focused on further characterization of these factors in leukemogenesis, including developing drugs and other therapies specifically aimed at these factors. A related project in the lab is studying the role of transcription factors in normal lung differentiation, as well as in lung cancer. Other basic studies are investigating the role of long noncoding RNAs in gene regulation and chromatin structure. Techniques in the laboratory include analysis of regulation, function, and signaling of transcription factors, transgenic and knockout studies, and gene therapy applications.
Levantini E, Lee S, Radomska HS, Hetherington CJ, Alberich-Jorda M, Amabile G, Zhang P, Gonzalez DA, Zhang J, Basseres DS, Wilson NK, Koschmieder S, Huang G, Zhang DE, Ebralidze AK, Bonifer C, Okuno Y, Gottgens B, Tenen DG. RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interaction with a distal regulatory element. 2011 EMBO J 30:4059-4070.
Guibal FC, Alberich-Jorda M, Hirai H, Ebralidze A, Levantini E, Diruscio A, Zhang P, Santana-Lemos BA, Neuberg D, Wagers AJ, Rego EM, Tenen DG. Identification of a myeloid committed progenitor as the cancer initiating cell in acute promyelocytic leukemia. 2009. Blood 114:5415-5425. PMID: 19797526.
Huang G, Zhang P, Hirai H, Elf S, Yan X, Chen Z, Koschmieder S, Okuno Y, Dayaram T, Growney JD, Shivdasani RA, Gilliland DG, Speck NA, Nimer SD, Tenen DG. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. 2008: Nature Genet 40:51-60.
Ebralidze AK, Guibal FC, Steidl U, Zhang P, Lee S, Bartholdy B, Alberich Jorda M, Petkova V, Rosenbauer F, Huang G, Dayaram T, Klupp J, O’Brien K, Will B, Hoogenkamp M, Borden K, Bonifer C, Tenen DG. PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. 2008. Genes Dev 22:2085-2092.
Zhang P, Iwasaki-Arai J, Iwasaki H, Fenyus ML, Dayaram T, Owens BM, Shigematsu H, Levantini E, Huettner CS, Lekstrom-Himes JA, Akashi K, Tenen DG. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor CCAAT Enhancer Binding Protein α. 2004: Immunity 21:853-863. PMID: 15589173.
Last Update: 1/6/2014