Lothar at the Ride for the Roses   Lothar-2  
Lothar Hennighausen
Dr. Lothar Hennighausen is a Senior Investigator and Chief of the Laboratory of Genetics and Physiology. He received his Ph.D. from the Institute of Genetics of the University of Cologne, Germany in 1982 where he cloned genes expressed specifically in the mouse mammary gland and studied their regulation. Lothar carried out his post-doctoral research in Phil Leder's laboratory at Harvard Medical School in Boston where he focused his research efforts on a mammalian transcription factor, nuclear factor 1 (NF1). Lothar joined the National Institutes of Health in 1985 where he established a research group within the Max-Planck-Institute in Goettingen where he established with Dr. Priscilla Furth and in collaboration with Dr. Hermann Bujard the tetracycline inducible gene switch in mice (publication). This work culminated in the finding that tumors over time become independent of the initial oncogenic lesion.

Lothar's current research focuses on how mammals turned generic tools and components (the tyrosine kinase Jak2 and the transcription factor Stat5) into cell-specific signaling machineries (research program). This systems biology approach focuses on the mammary gland, pancreas, erythropoiesis and liver metabolism. Through the use of functional mouse genetics and contemporary molecular techniques, Lothar and his group have defined the significance for several genes in the development, proliferation, specification and differentiation of mammary epithelial cells.

Lothar is an avid cyclist and he recently rode with Lance Armstrong and Tyler Hamilton a century in the Ride for the Roses" (an event organized by the Lance Armstrong Foundation). More pictures from the event.

Lothar and Tyler Hamilton
Tyler Hamilton and Lothar at the 2003 "Ride for the Roses". Tyler is a world-renowned cyclist who won fourth place in the 2003 Tour de France.

Dr. Hennighausen has been awarded a number of honors, including the 2002 Presidential Lecture from the Society of Reproduction and the 2003 Olof Pearson Lecture from Case Western Reserve University. In recognition of his outstanding scientific contributions and mentorship, Lothar received the Alexander von Humboldt Research Award in 2001. He was recently presented with this award at a ceremony in Bamberg, Germany. Lothar also has met with congresswoman JoAnn Emerman to discuss research on breast cancer.

As a result of the Humboldt award, Lothar did spent a research sabbatical in 2002/2003 with Dr. Axel Ullrich at the Max-Planck-Institute of Biochemistry in Martinsried, Munich, to explore new frontiers. During this time he was introduced by Laure Bally-Cuif into the beauty and scientific power of zebrafish as a genetic system to decipher signaling pathways in development, physiology and disease. While on sabbatical in Munich, Lothar also pursued his interest in competitive mountain cycling with his son Zach in the Dolomites. Whenever time permits, Lothar, his wife Priscilla and the kids (Hannah, Molly and Zach) go to their family retreat in the Austrian Alps to enjoy the outdoors.

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Selected Publications

Shillingford, J.M., Miyoshi, K., Robinson, G.W., Bierie, B., Cao, Y., Karin, M. and Hennighausen, L. (2003) Proteotyping of mammary tissue from transgenic and gene knockout mice with immunohistochemical markers: a tool to define developmental lesions. J. Histochem. Cytochem., 51, 555-565.

Shillingford, J.M., Miyoshi, K., Robinson, G.W., Grimm, S.L., Rosen, J.M.., Neubauer, H., Pfeffer, K. and Hennighausen, L. (2002) Jak2 is an essential tyrosine kinase involved in pregnancy-mediated development of mammary secretory epithelium. Mol. Endo. 16, 563-570.

Miyoshi, K., Shillingford, J.M., Le Provost, F., Gounari, F., Bronson, R., von Boehmer, H., Taketo, M.M., Cardiff, R.D., Khazaie, K. and Hennighausen, L. (2002) Activation of -catenin signaling in differentiated mammary secretory epithelium induces transdifferentiation into epidermis. Proc. Natl. Acad. Sci. U.S.A., 99, 219-224.

Riedlinger, G., Okagaki, R., Wagner, K.U., Rucker, E.B., Oka, T., Miyoshi, K., Flaws, J.A. and Hennighausen, L. (2002) Bcl-x is not required for the maintenance of follicles and the corpus luteum in the postnatal mouse ovary. Biology of Reproduction, 66, 438-444.

Miyoshi, K., Shillingford, J.M., Smith, G.H., Grimm, S.L., Wagner, K.U., Oka, T., Rosen, J.M., Robinson, G.W. and Hennighausen, L. (2001) Signal transducer and activator of transcription 5 (Stat5) controls the specification and proliferation of mammary alveolar epithelium. J. Cell Biol., 155, 531-542.

Gallego, M. I., Binart, N., Robinson, G.W., Okagaki, R., Coschigano, K., Perry, J., Kopchick, J., Oka, T., Kelly, P.A. and Hennighausen, L. (2001) Prolactin, growth hormone and epidermal growth factor activate Stat5 in different cell types of the mammary gland and exert overlapping but distinct developmental effects. Developmental Biology, 229, 163-175.

Wagner K-U., Estefania C., Rucker, E., Riedlinger, G, Broussard, C., Schwartzberg, P.L., Siebenlist, U., Hennighausen, L. (2000) Conditional deletion of the bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly. Development, 127, 4949-4958.

Rucker, E., Dierisseau, P., Wagner, K.-U., Garrett, L., Wynshaw-Boris, A., Flaws, J. and Hennighausen, L., (2000). Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol. Endo., 7, 1038-1052.

Wagner, K.-U., Wall, R.J., St-Onge, L., Gruss, P., Garrett, L., Wynshaw-Boris, A., Li, M., Furth, P.A. and Hennighausen, L. (1997) Cre mediated gene deletion in the mammary gland. Nucleic Acids. Res. 25, 4323-4330.

Robinson, G.W. and Hennighausen, L. (1997) Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Development 124, 2701 2708.

Liu, X., Robinson, G.W., Wagner, K.-U., Garrett, L., Wynshaw-Boris, A. and Hennighausen, L. (1997) Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes and Dev. 11, 179-186.

Ewald, D., Li, M., Efrat, S., Auer, G., Wall, R.J., Furth, P.A. and Hennighausen, L.(1996) Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen. Science 273, 1384-1386.

Liu, X.-W., Goulliaux, F., Robinson, G.W., Groner, B. and Hennighausen, L. (1995) Identification and characterization of STAT5 and a novel homologue (STAT5b) involved in prolactin mediated signal transduction in mouse mammary tissue. Proc. Natl. Acad. Sci.U.S.A. 92, 8831-8835.

Robinson, G.W., McKnight, R.A., Smith, G.H. and Hennighausen, L. (1995) Mammary epithelial cells undergo differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation. Development 121, 2079-2090.

Furth, P.A., St. Onge, L., Boger, H., Gruss, P., Gossen, M., Kistner, A., Bujard, H. and Hennighausen, L. (1994) Temporal control of gene expression in transgenic mice by a tetracycline responsive promoter. Proc. Natl. Acad. Sci. U.S.A. 91, 9302-9306.

McKnight, R.A., Shamay, A., Sankaran, L., Wall, R.J. and Hennighausen, L. (1992) Matrix attachment regions impart position independent regulation of a tissue specific gene in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 89, 6943-6947.

Burdon, T., Sankaran, L., Wall, R.J., Spencer, M., and Hennighausen, L. (1991). Expression of a whey acidic protein transgene during mammary development: Evidence for different mechanisms of regulation during pregnancy and lactation. J. Biol. Chem. 266, 6909-6914.

Wall, R.J., Pursel, V.G., Shamay, A., McKnight, R.A., Pittius, C.W., and Hennighausen, L. (1991). High-level synthesis of a heterologous milk protein in the mammary glands of transgenic swine. Proc. Natl. Acad. Sci. USA 88, 1696-1700.

Pittius, C.W., Sankaran, L., Topper, Y.J. and Hennighausen. (1988). Comparison of the regulation of the whey acidic protein gene to a hybrid gene containing the whey acidic protein gene promoter in transgenic mice. Mol. Endocrinology 2, 1027-1032.

Pittius, C., Hennighausen, L., Lee, E., Westphal, H., Nicols, E., Vitale, J. and Gordon, K. (1988). A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 85, 5874-5878.

Gordon, K., Lee, E., Vitale, J.A., Smith, A.E., Westphal, H. and Hennighausen, L. (1987). Production of human tissue plasminogen activator in transgenic mouse milk. BIO/TECHNOLOGY 5, 1183-1187.

Ghazal, P., Lubon, H., Fleckenstein, B. and Hennighausen, L. (1987). Binding of transcription factors and the creation of a large nucleoprotein complex on the human cytomegalovirus enhancer. Proc. Natl. Acad. Sci. U.S.A. 84, 3658-3662.

Lubon, H. and Hennighausen, L. (1987). Nuclear proteins from lactating mammary glands bind to the promoter of a milk protein gene. Nucleic Acids Res. 15, 2103-2121.

Hennighausen, L. and Fleckenstein, B. (1986). Nuclear Factor 1 interacts with five DNA elements in the promoter region of the human cytomegalovirus major immediate early gene. EMBO J. 5, 1367-1371.

Hennighausen, L., Siebenlist, U., Danner, D., Leder, P., Rawlins, D., Rosenfeld, P. and Kelly, T. (1985). High affinity binding site for a specific nuclear protein in the human IgM gene. Nature 314, 289-292.

Hennighausen, L.G. and Sippel, A.E. (1982). Characterization and cloning of the mRNAs specific for the lactating mouse mammary gland. Eur. J. Biochem. 125, 131-141.

Hennighausen, L.G. and Sippel, A.E. (1982). The mouse whey acidic protein is a novel member of the family of 'four-disulfide-core' proteins. Nucleic Acids Res. 10, 2677-2684.

Reviews

Hennighausen, L. and Robinson, G.W. (2001) Signaling pathways in the mammary gland. Developmental Cell, 1, 467-475.

Hennighausen, L. and Robinson, G.W. (1998) Think globally, act locally: the making of a mammary gland. Genes and Development 12, 449-455.

Hennighausen, L. and Lubon, H. (1987). Protein-DNA interaction in vitro. Methods Enzymol. 152, 721-735.