Molecular Medicine Fellows'
Research and Publications
Selected Research Work
Regulation of C. elegans
Ultimately I am interested in how biologic changes during aging are in part responsible for Geriatric syndromes, such as delirium and frailty, and influence the unique responses of Geriatric patients to illnesses and medications.
The orphan nuclear hormone receptor DAF-12 in C. elegans plays important roles in the determination of worm lifespan through the integration of both germline and daf-2 signaling. Additionally, daf-12 appears to act independently to alter longevity in response to changes in activity of the cytochrome P450 gene daf-9. While daf-9 mutants are long-lived compared to wild-type worms, the daf-9 mutation also results in essentially permanent dauer arrest and adult sterility resulting in the inability to maintain a homozygous daf-9 stock. This limits the opportunity to obtain sufficient homozygous adults to easily perform further analysis, such as microarray. To address this technical limitation, I explored the use of daf-c and daf-d daf-12 alleles as a means to study daf-12 signaling. These alleles were previously identified due their effects on dauer formation which is an alternate larval stage that worms enter under unfavorable environmental conditions, such as crowding, starvation, or elevated temperature. The designations daf-c and daf-d relate to whether the worm either enters dauer formation constitutively despite favorable conditions, daf-c, or is unable to enter dauer formation under any condition, daf-d. These mutants are viable as homozygotes and are significantly easier to maintain than daf-9 mutants.
I hypothesized that these daf-12 alleles could have opposing effects on lifespan. Indeed I found that these mutants have the predicted effects on adult longevity, with a 38% increase in lifespan between the alleles, and also have opposing effects on resistance to both oxidative and thermal stress. Importantly characterization of the daf-d mutant revealed that this mutation resulted in accelerated aging in young adulthood. I was able to exploit these daf-12 alleles to perform microarray analysis of gene expression differences and identify differentially expressed genes. This experiment is important as it provided the first look at the effects of daf-12 signaling on gene expression in the adult and contributes to the identification of genes that alter lifespan when activated or repressed. Comparison of the expression profiles with the profiles associated with dauer formation and long-lived daf-2 mutants revealed that while the profiles are largely different, there is significant overlap among the genes down-regulated, but not up-regulated, in all profiles. My results point to daf-12 signaling modulating aging and stress responses through the repression of gene expression. My conclusion is supported by the recent report of a co-repressor, DIN-1, that binds to DAF-12 and is required for the increased lifespan seen in daf-9 mutants. Experiments using RNAi have indeed demonstrated that the repressed genes have effects on worm longevity.
Andrei Goga, M.D., Ph.D.
Cyclin-Dependent Kinase Function in Murine Tumor Models:
The goal of the proposed research is to understand the function of cyclin-dependent kinases (Cdks) in developing tumors. Cdks are a conserved family of serine/threonine kinases that serve a central role in regulating the eukaryotic cell cycle. There are at least nine members of the Cdk family, though only Cdk1 and Cdk2 are felt to be essential for cell cycle progression in all mammalian cells. Cdk activity is regulated both by interaction with regulatory subunits and through phosphorylation events. Cdk activation requires binding to a cyclin subunit. Cyclin concentrations oscillate during the mammalian cell cycle and each Cdk can interact with only a subset of different cyclins. Cdks are activated in a cell-cycle-specific manner and regulate a precisely ordered transition to the next phase of the cell cycle. The essential role of Cdks in cell cycle progression makes them a target of great interest for the development of specific Cdk inhibitors as anti-cancer agents.
Tumor cells develop a deregulated cell cycle which may render their growth especially sensitive to Cdk inhibition. This raises the possibility that selective Cdk inhibition may be possible in an organism such that tumor cells are predominantly killed. Currently no murine model exists to validate the role of specific Cdk inhibition in developing tumors. Analysis of individual Cdk functions in vivo requires a highly specific, potent and reversible inhibitor. No such inhibitor exists which can distinguish between the highly related but functionally distinct Cdk1 and Cdk2 molecules. I am using a recently developed chemical-genetic approach to generate mutant forms of Cdks that can be selectively inhibited in vivo by a soluble small molecule inhibitor. This approach will allow the analysis of Cdk function in developing tumors and will help validate whether selective Cdk inhibition can provide anti-cancer therapy. Analysis of these tumor models may also reveal new genes that regulate Cdk function in vivo and may serve as targets for new cancer diagnostic and therapeutic agents. Christopher Haqq, M.D., Ph.D.
Development of amplification technologies for gene expression profiling
coming year, we plan to begin characterization of individualg genes marked Role of CD45 in a Mouse Model of Autoimmunity and Lymphoproliferation
CD45, a receptor-like protein tyrosine phosphatase (RPTP), is required for antigen receptor-mediated signaling on T and B cells by its ability to dephosphorylate the carboxy-terminal negative regulatory site of tyrosine phosphorylation in Src kinase. Previous studies from our lab, suggested that CD45 catalytic function is negatively regulated by dimerization of the CD45 cytoplasmic domain. The crystal structure of the membrane-proximal catalytic domain and the juxtamembrane domain of a related RPTP, RPTPa, suggested the presence of a wedge-like structure that could block the catalytic site of a partner phosphatase domain during dimerization. Modeling studies of CD45, based on that of RPTPa, and found that the CD45 model conformed well with the structure of RPTPa. Mutating a residue at the tip of the putative wedge in CD45 abolished the inhibitory effects of dimerization of a chimeric receptor in a transformed T cell line model (3). These results suggest that dimerization of CD45 inhibits its function via a wedge-like structure in its juxtamembrane domain.
Mutation of the homologous residue glutamic acid to arginine (E613R) in the murine CD45 gene by homologous recombination verified the physiologic role of this model. The lymphoid lineages of the resultant mice develop normally. However, at approximately 12-16 weeks of age, the homozygous mutant mice develop a lymphoproliferative and an autoimmunity syndrome typical of that seen in human lupus including anti-nuclear antibodies, anti-double stranded DNA antibodies and diffuse proliferative glomerulonephritis. These observations suggest that dimerization of CD45 plays a critical role in negatively regulating its function in vivo. This is the first in vivo evidence for such negative regulation by dimerization for any RPTP.
The goal of the current research is to define the molecular and cellular basis for the breakdown in tolerance and the development of autoimmunity in CD45 E613R mice. Current studies are focused on 1) defining the cell lineages responsible for and required for the disease, 2) defining the role of antigen in the development of autoimmunity in the CD45 E613R mutant mice; and 3) defining the molecular basis for the effects of the CD45 wedge mutant
Josina Reddy, M.D., Ph.D.
Bcl-XL expression or ARF deficiency abrogates Myc-induced islet involution and promotes pancreatic b-cell hyperplasia
The c-Myc oncoprotein is a transcription factor of the basic helix-loop-helix class encoded by the c-myc proto-oncogene that is frequently deregulated and/or over-expressed in human cancers. Although the best documented function of c-Myc is its ability to induce cell proliferation it is also a potent promoter of apoptosis, a property that is thought to act as an innate tumor suppressive mechanism that curbs expansion of cells harboring activated c-Myc. c-Myc can therefore act as both tumor promoter and tumor suppressor.
Prior attempts to determine the role of c-Myc in tumorigenesis have employed transgenic mice in which expression of activated c-Myc is targeted to various tissues with tissue-specific promoters. Unfortunately, interpretation of such classical transgenic studies is confounded by the fact that c-Myc is constitutively expressed in the tissue of choice, often throughout development of that tissue. Resulting tissues are therefore the net consequence of the protracted interplay between the various pro- and anti-proliferative activities of c-Myc in that tissue. In contrast, in naturally occurring cancers c-Myc is sporadically activated by somatic mutation in an established adult tissue. Therefore, to explore the immediate effects of acute c-Myc activation we have employed a fusion protein comprising Myc fused to a modified 4-hydroxytamoxifen (4-OHT)-dependent form of the estrogen receptor hormone binding domain. We have targeted this reversibly 4-OHT dependent c-MycERª to pancreatic § cells using the rat insulin promoter. Acute activation of physiological levels of c-Myc in § cells triggers dramatic and rapid involution of all pancreatic islets with concomitant development of diabetes mellitus. Morphological analysis indicates that islet involution occurs through massive § cell apoptosis. Subsequent c-MycERª deactivation, by withdrawal of daily 4-OHT, triggers rapid and synchronous islet regeneration over a period of weeks and affected mice become euglycemic. Thus, the oncogenic action of c-Myc in § cells is completely overwhelmed by the pro-apoptotic action of c-Myc.
We next examined the consequences for c-Myc oncogenesis of suppressing apoptosis, either through over-expression of the apoptosis suppressor Bcl-xL or through loss of the p19ARF tumor suppressor through which c-Myc activates the pro-apoptotic p53 protein. We find that apoptosis suppression by either mechanism curtails c-Myc induced § cell apoptosis and triggers immediate c-Myc-induced islet hyperplasias that progressively develop into malignant adenomas. Deletion of ARF results in a more aggressive, dysplastic, and angiogenic phenotype than does expression of Bcl-XL. We are currently using various markers of § cell differentiation, proliferation and apoptosis to define more accurately the molecular events precipitated by c-Myc activation.
Publications
Class of 2004
Laurence Cheng, 9/92 to 6/96 to University of California, Berkeley A.B. 9/96 to 6/04 University of Washington Ph.D. Immunology University of Washington M.D.
Francis Ka Ming Chan, Jianke Zhang, Laurence Cheng, David N. Shapiro, and Astar Winoto. (1995) Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16INK4. Molecular Cell Biology 15: 2682-2688.
John D. Woronicz, Andrea Lina, Barbara J. Calnan, Shannan Szychowski, Laurence Cheng, and Astar Winoto. (1995) Regulation of the Nur77 orphan steroid receptor in activation induced apoptosis. Molecular Cell Biology 15: 6364-6376.
Laurence E. Cheng, Francis Ka-Ming Chan, Dragana Cado, and Astar Winoto. (1997) Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T cell apoptosis by a Fas-independent pathway. EMBO J. 16: 1865-1875.
Laurence E. Cheng, Claes Öhlén Brad H. Nelson, Philip D. Greenberg. (2002) Enhanced signaling through the IL-2 receptor in CD8+ T cells following antigen recognition results in preferential proliferation and expansion of responding CD8+ T cells rather than promotion of cell death. PNAS. 99: 3001-3006.
C. Öhlén, M. Kalos, L. E. Cheng, A. C. Shur, D. J. Hong, B. D. Carson, C. G. Lerner, N. C. T. Kokot, E. S. Huseby, P. D. Greenberg. (2002) CD8+ T cell tolerance is maintained at the level of expansion rather than effector function. Journal of Experimental Medicine 195: 1407-1418.
Joseph N. Blattman, Laurence E. Cheng, and Philip D. Greenberg. (2002) CD8+ T cell responses: it's all downhill after their prime… Nature Immunology 3: 601-602.
Laurence E. Cheng and Philip D. Greenberg. (2002) Selective delivery of augmented IL-2R signals to responding CD8+ T cells increases the size of the acute anti-viral response and of the resulting memory T cell pool. Journal of Immunology 169: 4990-4997.
Greg Ku, 9/92 to 6/96 Harvard A.B. Biochemical Sciences 7/98 to 10/02 University of California San Francisco Ph.D. Immunology 9/96 – 6/04 University of California San Francisco M.D.
Ku, G.M., Yablonski, D., Manser, E., Lim, L., Weiss, A. (2001) A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp –76 and LAT. EMBO Journal 20: 457 – 65.
Kuhne, M.R., Ku, G. Weiss, A. (2000) A guanine nucleotide exchange factor-independent function of Vav1 in transcriptional activation. A Journal of Biological Chemistry 275: 2185 – 90.
McGinnis, K., Ku, G., Stern, A.M., Friedman, P.A. (1998) The five cysteine residues located in the active site region of bovine aspartyl beta-hydroxylse are not essential for catalysis. Biochemica et Biophysica Acta 1387: 454-56.
McGinnis, K., Ku, G., Van Dusen, W.J., Fu, J., Garsky, V., Stern, A.M., Friedman, P.A. (1996) Site-directed mutagenesis of residues in a conserved region of bovine aspartyl beta-hydroxylase: histadine 675 has as role in binding Fe2+. Biochemistry 35: 3957-62.
Doug Kwon, 9/89 to 6/93 Harvard A.B. Biochemistry 9/95 – 9/98 New York University School of Medicine M.S. Pathology 9/95 to 2/02 New York University School of Medicine Ph.D. Microbiology and Molecular Pathogenesis 9/95 – 6/04 New York University School of Medicine M.D.
Kwon, D.S., Greggario, G., Bitton, N., Littman, D.R. (2002) DC-SIGN mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 16: 135-144.
Geijtenbeek, T., Kwon, D.S., Torensma, R. van Vliet, S. J., van Duijnhoven, G.C., Middel, J., Cornelissen, I.L., Nottet, H.S., KewalRamani, V.N., Littman, D.R., Figdor, C.G., Kooyk, Y. (2000) DC-SIGN , a dendritic cell specific HIV-1 binding protein that enhances trans-infection of T cells. Cell 100: 587-597.
Chen, Z. Kwon, D.,S.,Jin, Z., Monard, S., Telfer, P., Jones, M.S., Lu, C. Y. Aguilar, R. F., Ho, D.D., Marx, P.A. (1998) Natural infection of homozygous delta24 CCR5 red-capped mangabey with an R2b-tropic simian immunodeficiency virus. Journal of Experimental Medicine 188:2057 – 2065.
Zhang, Y.J., Dragic, T. Cao, Y., Kostrikis, L., Kwon, D.R., KewalRamani, V.N., Moore, J. P. (1998) Use of co-receptors other than CCR5 by non-syncytium-inducing adult and pediatric isolates of human immunodeficiency virus type 1 is rare in vitro. Journal of Virology 72: 9337 – 9344.
Hill, C.M., Kwon, D. S., Jones, M., Davis, C. B., Marmon, S., Daugherty, B. L., DeMartino, J.A., Springer, M.S., Unutmaz, D., Littman, D. R. (1998) The amino terminus of human CCR5 is required for its function as a receptor for diverse human and simian immunodeficiency virus envelope glycoproteins. Virology 248: 357 – 371.
Kleckner, N., Chalmers, R. M., Kwon, D. S., Sakai, J., Bolland, S. (1996) Tn10 and IS10 transposition and chromosome rearrangements: Mechanism and regulation in vivo and in vitro. Current Topics in Immunology 204: 49 – 82.
Tim Lu, 8/92 to 6/96 Yale University B.S. Biology 6/96 to 6/04 University of Texas Southwestern Medical School at Dallas Ph.D. Cell Regulation 6/96 – 6/04 University of Texas Southwestern Medical School at Dallas M.D.
Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M. Haussler, M. R., Mangelsdorf, D. J. Vitamin D receptor as an intestinal bile acid sensor. Science 296: 1313 – 1316.
Repa, J. L., Makishima, M., Lu, T.T., Mangelsdorf, D. J. (2001) The Liver: Biology and Pathobiology, 4th edition, Arias, I. M., Boyer, J. L., Chisari, F.V., Fausto, N., Schachter, D. A. editors.
Lu, T.T., Repa, J. L., Mangelsdorf, D. J. (2001) Orphan nuclear receptors as elixirs and fixers of sterol metabolism. Journal of Biological Chemistry 276: 37735 – 37738.
Lu, T.T., Makishima, M., Repa, J. L., Schoonjans, T. A., Auwerx, J., Mangelsdorf, D. J. (2000) Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Molecular Cell 6: 507- 515.
Kanade Shinkai,9/91 to 12/94 Swarthmore College B. A. Biology 9/97 to 8/02 University of California San Francisco Ph.D. Biochemistry and Molecular Biology 9/95 – 6/04 University of California San Francisco M.D.
Shinkai, K., Mohrs, M, Locksley, R. M. (2002) Helper T cells regulate type 2 innate immunity in vivo. Nature 420: 825 – 829.
Baron, J. L., Gardiner, L., Nishimura, S., Shinkai, K., Bendelac, A., Kronenberg, M., Locksley, R.M., Ganem, D. (2002) Activation of a nonclassical NKT cell subset mediates liver injury in a transgenic mouse model of hepatitis B virus infection. Immunity 164: 583 – 594.
Mohrs, M., Blankespoor, C. M., Wang, Z-E, Afzal, V., Hadeiba, H., Shinkai, K., Rubin, E. M. Locksley, R. M. (2001) Deletion of a coordinate regulator of type 2 cytokine expression in mice. Nature Immunology 2(9): 842 – 847.
Mohrs, M., Shinkai, K., Mohrs, K., Locksley, R. M. (2001) Analysis of type 2 immunity in vivo using a bicistronic IL-4 reporter. Immunity 15: 303-311.
Shinkai, K., Locksley, R. M. (2000) CD1, tuberculosis and the evolution of MHC molecules. Journal of Experimental Medicine 191: 907 – 914.
Fowell, D. J., Shinkai, K., Liao, X. C., Beebe, A. M. Cofman, R. L., Littman, D. R., Locksley, R. M. (1999) impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells. Immunity : 11: 399 – 409.
Locksley, R. M., Fowell, D. J., Shinkai, K., Wakil, A. E., Lacy, D., Bix, M. Development of CD4+ effector T cells and susceptibility to infectious diseases. Advances in Experimental Medicine and Biology 452: 45 – 52.
Ed Thornborrow, 9/90 to 6/94 Wesleyan University B.A. Molecular Biology and Biochemistry 5/94 – 5/95 Wesleyan University M.A. Molecular Biology and Biochemistry 8/95 to 5/01 Mount Sinai School of Medicine of New York University Ph.D. Biomedical Sciences 8/95 – 5/03 Mount Sinai School of Medicine of New York University M.D.
Thornborrow, E. C., Maurer, M. Manfredi, J. J. (2003) Tumor suppressor Genes,Methods, and Protocols, Methods in Molecular medicine Series. Wafik, S. El-Deiry (ed) Humana Press, USA Electrophoretic Mobility Shift Analysis of the DNA binding of Tumor Supressor Gene Products.
Thornborrow, E. C., Patel, S., Mastropietro, A. E., Schwartzfard, E. M.,M. Manfredi, J. J. (2002) A conserved intronic response element mediates direct p53-dependent transcriptional activation of both the human and murine bax genes. Oncogene 21: 990–999.
Thornborrow, E. C., Manfredi, J. J. (2001) The tumor suppressor protein p53 requires a cofactor to activate transcriptionally the human bax promoter. The Journal of Biological Chemistry 276: 15598 – 15608.
Thornborrow, E. C., Manfredi, J. J. (1999) One mechanism for cell type-specific regulation of the bax promoter by the tumor suppressor p53 is dictated by the p53 response element. The Journal of Biological Chemistry 274: 33747 - 33756.
Class of 2003
Sarah Tuttleton Arron 9/92 to 6/96 Harvard University B.S. Biology 7/98 to 6/02 Rockefeller University Ph.D., Biology 8/96 to 5/03 Cornell University Medical School M.D
Zhang, L., Lewin, S.R., Markowitz, M., Lin, H.H., Skulsky, E., Karanicolas, R., He, Y. Jin, X. Tuttleton, S.T., Vesanen, M., Spiegel, H., Kost, R., Van Lunzen, J., Stellbrink, H.J., Wolinsky, S., Borkowsky, W., Palumbo, P., Kostrikis, L.G., Ho, D.D. (1999) Measuring recent thymic emigrants in blood of normal and HIV-1-individuals before and effective therapy. Journal of Experimental Medicine.190:725-743.
Jin, X., Bauer, D.E., Tuttleton, S.E., Lewin, S., Gettie, A., Blanchard, J., Irwin, C.R., Safrit, J.T., Mittler, J., Weinberger, L., Kostrikis, L.G., Zhang, L., Perelson, A.S., Ho, D.D. (1999) Dramatic rise in plasma virema after CD8+T cell depletion in simian immunodeficiency virus-infected macques. Journal of Experimental Medicine 189:991-998.
Zhang, L., Huang, Y., Yuan, H., Tuttleton, S., Ho, D.D. (1997) Genetic Characterization of vif,vpr,vpu sequences from long-term survivors ofhuman immunodeficiency virus type 1 infection. Virology 228:340-349.
Anil Bagri 8/91 to 5/95 University of Califronia B.A. Molecular and Cell Biology 6/97 to 8/01 UCSF Ph.D., Neuroscience 8/95 to 8/03 UCSF M.D.
Bagri, A., Marin, O., Plump, A., Mak, J. Pleasure, S.J., Rubenstein, J.L., Tessier-Lavigne, M. Neuron Slit proteins prevent midline crossing and determine dorsoventral position of major axonal pathways in the mammalian forebrain. 33:233-248.
Bagri, A., Gurney, T., HeX, Zou, Y.R., Littman, D.R., Tessier-Lavigne, M., Pleasure, S.J. (2002) The chemokine SDF1 regulates migration of dentate granule cells. Development 129:4240-4260.
Bagri, A. Tessier-Lavigne, M., Ed. D. Bagnard (2002) Neuropilin. "Neuropilin in the nervous system". Landes Press. Chapter 2.
Zhou, B., Bagri, A., Beckendorf, S.K. (2001) Salivary gland determination in Drosophila: A salivary-specific, fork head enhancer integrates spatial pattern and allows fork head autoregulation. Developmental Biology 237:54-67.
Marin, O., Yaron, A., Bagri, A., Tesier-Lavigne, M., Rubenstein, J.L. (2001) Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions. Science 293:872-875.
Cheng, H.J., Bagri, A., Yaron, A., Stein, E., Pleasure, S.J., Tessier-Lavigne, M. (2001) Plexin-A3 mediates semaphorin sign aling and regulates the development of hippocampal axonal projects Neuron 32:249-263.
Chen, H., Bagri, A., Zupicich, J., Zou, Y., Stoeckli, E., Pleasure, S., Lowenstein, D., Skarnes, W. Chedotal, A. and Tessier-Lavigne, M. (2000) Neuropolin-2 regulates the development of select cranial and sensory nerves and hippocampal mossy fiberprojections. Neuron 25:43-56.
Pleasure, S.J., Anderson, S., Hevner, R., Bagri, A., Marin, O., Lowenstein, D.H., Rubenstein, J.L. Neuron Cell migration from the ganglionic eminences is required forthe development of hippocampal GABAergic interneurons (2000) 28:727-40.
Chen, H., He, Z., Bagri, A., Tesier-Lavigne, M. (1998) Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphoris Neuron 21:1283-1290.
James Buxbaum, M.D., 9/95 to 6/99 Stanford University B.S. Chemistry 9/99 to 6/03 University of California San Francisco M.D.
Oghalai, J.S., Buxbaum, J.L., Pitts, L.H., Jackler, R.K. (2003) The effect of age on acoustic neuroma surgery outcomes. Otol Neurotol. 24: 473 – 477.
Oghalai, J.S., Buxbaum, J.L., Pitts, L.H., Jackler, R.K. The diagnois and treatment of chondrosarcoma of the skull base.
Brady Miller 9/92 to 11/97 University of Washington B.S. Biochemistry 9/98 to 12/03 University of Texas Southwestern Medical School M.D.
Pertsemlidis, A., Pande, A., Miller, B., Schilling, P., Wei, M.H., Lerman, M., Minna, J.D., Garner, H.R. (2000) Panorama: An integrated web-based sequence analysis tool and its role in gene discovery. Genomics 70:300-306.
Young, E., Sloan, J., Miller, B., Van Riper, K., Dombek, K. (2000) Evolution of a glucose-regulated ADH gene in the genus Saccharomyces Gene 245:299-30
Emin Maltepe 9/89 to 5/93 Yale University B.S. Biology 9/95 to 12/00 UCSF Ph.D., Genetics 9/93 to 6/02 UCSF M.D.
Adelman, D.M., Gertsenstein, M., Nagy, A., Simon, M.C. and Maltepe, E. (2000) Placental cell fates are regulated in vivo via HIF-mediated hypoxia responses. Genes Dev. 14, 3191-3203 .
Shiels, H., Li, X., Schumacker, P.T., Maltepe, E., Sperling, A., Thompson, C.B. and Lindsten, T. (2000) TRAF4 deficiency leads to tracheal malformation with resulting alterations in airflow to the lungs. Am. J. Pathol. 157, 679-688 .
Maltepe, E., Keith, B., Arsham, A.M., Brorson, J. and Simon, M.C. (2000) The role of ARNT2 in tumor angiogenesis and the neural responses to hypoxia. Bioch. Biophys. Res. Commun. 273, 231-238 .
Adelman, D.M., Maltepe, E. and Simon, M.C.(2000) HIF-1 is essential for multilineage hematopoiesis in the embryo. Adv. Exp. Med. Biol. 475, 275-284 .
Adelman, D.M., Maltepe, E. and Simon, M.C. (1999) Multilineage embryonic hematopoiesis requires hypoxic ARNT activity. Genes Dev. 19, 2478-83 .
Maltepe, E and Simon, M.C. (1999) The role of HIF-1a and ARNT proteins in blood vessel development. In: Angiogenesis in Health and Disease: Basic Mechanisms and Clinical Applications (Ed. G. Rubanyi).
Chandel, N.S., Maltepe, E., Goldwasser, E., Mathieu, C., Simon, M.C. and Schumacker, P.T. (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc. Natl. Acad. Sci. USA 95, 11715-11720 .
Maltepe, E and Simon, M.C. (1998) Oxygen, genes and development. An analysis of the role of hypoxic gene regulation during mammalian development. Journal of Molecular Medicine 76, 391-401 .
Jain, S., Maltepe, E., Lu, M.M., Simon, M.C. and Bradfield, C.A. (1998) Expression of ARNT, ARNT2, HIF1a, HIF2a and Ah receptor mRNAs in the developing mouse. Mechanisms of Development 73, 117-123 .
An, W.G., Kanekal, M., Simon, M.C., Maltepe, E., Blagosklonny, M.V. and Neckers, L. (1998) Stabilization of wild type p53 by hypoxia-inducible factor 1a. Nature 392, 405-408.
Maltepe, E., Schmidt, J.V., Baunoch, D., Bradfield, C.A. and Simon, M.C. (1997) Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 368, 403-407 .
Diaz MO., Pomykala, HM., Bohlander, SK., Maltepe, E., Malik, K., Brownstein, B., and Olopade, O. (1994) Structure of the human type-I interferon gene cluster determined from a YAC clone contig. Genomics 22, 540-542 .
Porterfield, BW., Pomykala, H., Maltepe, E., Bohlander, SK., Rowley, JD., and Diaz, MO. (1993) The use of methylthioadenosine phosphorylase activity to select for human chromosome 9 in interspecies and intraspecies hybrid cells. Somatic Cell and Molecular Genetics 19, 469-77 .
Olopade, OI., Bohlander, SK., Pomykala, H., Maltepe, E., Van Melle, E., Le Beau, MM. and Diaz, MO. (1992) Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia. Genomics 14, 437-43 .
Lisa Wilsbacher 9/89 to 5/93 Purdue University B.S. Biology 7/95 to 6/01 Northwestern University Ph.D., Neuroscience 9/93 to 5/03 Northwestern University M.D.
Wilsbacher, L.D., Yamazaki, S., Herzog, E.D., Song, E.J., Radcliffe, L.A., Abe, G., Block, E., Spitznagel, E., Menaker, M., Takahashi, J.S. (2002) Proceedings of the National Academy of Sciences U.S. A. Photic and circadian expression of luciferase in mPeriod1-luc transgenic mice in vivo. 99:489-494.
Wilsbacher, L.D., Sangoram, A. M., Antoch, M.P., and Takahashi, J.S. (2000) The mouse Clock locus: Sequence and comparative analysis of 204Kb from mouse chromosome 5. Genome Research 10:1928-1940.
Bunger, M.K., Wilsbacher, L.D., Moran, S. M., Clendenin, C., Radcliffe, L.A., Hogenesch, J.B., Simon, M.C., Takahashi,, J.S., and Bradfield, C.A.(2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103:1009-107.
Florez, J.C., Wilsbacher, L.D., and Takahashi, J.S. H.S. Friedman, ed. (1998) Encyclopedia of Mental Health. Body Rhythms/Body Clocks 1:267-284.
Gekakis, N.D., Staknis, D.,Nguyen, H.B., Davis, F.C., Wilsbacher, L.D., King, D. P. , Takahashi, J.S. and Weitz, C. J. (1998) Role of the CLOCK protein in the mammalian circadian mechanism. Science 280: 1564-1569.
Wilsbacher, L.D., Wisor, J.P. and Takahashi, J.S. Lydic, R. and Baghdoyan, H.A. (eds.) (1998) Handbook of Behavioral State Control: Cellular and Molecular Mechanisms Strategies for dissecting the molecular mechanisms of mammalian circadian rhythmicity. 78-84.
Wilsbacher, L.D., and Takahashi J.S. (1998) Circadian rhythms: Molecular basis of the clock. Current Opinion in Genetics and Development 8: 595-602.
King, D.P. Zhao, Y. Sangoram, L.D., Wilsbacher, M. Tanaka, M., Antoch, M.P., Steeves, T.D.L., Vitaterna, M.H., Kornahuser, J.M., Lowrey, P.L., Turek, F.W., and Takahashi, J.S. (1997) Positional cloning ofthe mouse circadian clock gene. Cell 89:641-653.
Antoch, M.P., Song, E.J., Chang, A.M., Vitaerna, Y., Zhao, Y., Wilsbacher, L.D., Sangoram, A.M., King, D. P., Pinto, L. H. (1997) Functional identifiction of the mouse circadian clock gene by transgencic BAC rescue. 89:655-667.
Watanabe, G., Pena, P., Albanese, C., Wilsbacher, L.D., Young, J.B., Pestell, R. G. (1997) Adrenocorticocotrpoin induction of stress-activated protein kinase inthe adrenal cortex in vivo. Journal of Biological Chemistry 272:2006-20069.
Class of 2002
Yee-Ming Chan 9/89 to 5/93 Yale University B.S. Biology 9/95 to 12/00 UCSF Ph.D., Genetics 9/93 to 6/02 UCSF M.D.
Abdeliah, S., Chan, Y-M., Zeng, C., Justice, N.J., Younger, S.H., Sharp, L.A., Barbel, S.A., Meadows, S., Jan, L.Y. (2000) A gain of function screen for genes that affect sensory organ development in Drosphila. Genetics. 155: 733-752.
Zeng, C., Justice, N.J., Abdelah, S., Chan, Y-M., Jan, Y.N. (1999) The Drosophila LIM-only gene, dLMO, is mutated in Beadex alleles and might represent an evolutionaryily conserved functiion in appendage development. Proceedings of the National Academy of Sciences USA. 95:10637-10642.
Chan, Y-M., Jan, Y.N. Conservation of neurogenic genes and mechanisms. (1999) Current Opinion in Neurobiology. 9: 582-588.
Chan, Y-M., Jan, Y.N. (1999) Presenilins, processing of beta-amyloid precursor protein, and Notch signaling. Neuron. 23: 201-204.
Chan, Y-M., Jan, Y.N. (1998) Roles for proteolysis and trafficking in Notch maturation and signal transduction. Cell. 94: 423-426.
Shen, C-P., Knoblich, J.A., Chan, Y-M., Jiang, M.M., Jan, L. Y., Jan, Y.N.. (1998) Miranda as a multidomain adapter linking apically localized Inscuteable and basally localized Staufen and Prospero during asymetric cell division in Drosophila. Genes and Development. 12: 1837-1846.
Ethan Corcoran 9/88 to 5/92 Cornell University B.A. Chemistry, 9/95 to 7/01 Duke University, Ph.D. Pharmacology and Cancer Biology, 8/93 to 5/02 Duke University, M.D.
Corcoran, E.E., and Means, A.R. (2001) Defining Ca2+/calmodulin-dependent protein kinase cascades in transcriptional regulation. Journal of Biological Chemistry. 276: 2975-2978.
Marvin, J.S., Corcoran, E.E., Hattangadi, N.A., Zhang, J.V., Gere, S. A. and Hellinga, H. W. (1997) The rational design of allosteric interactions in a monomeric protein and its applications to the construction of biosensors. Proceedings of the National Academy of Sciences USA. 94:4366-4371.
Pathirana, D., Fenical, W., corcoran, E., and Clardy, J.(1993) Erythrodiene - a new spirobicyclic sesquiterpene of a rare skeletal class from the Caribbean Gorgonaina coral Erythropodium-caribaeorum. Tetrahedron Letters. 34: 3371-3372.
Bernart, M.W., Gerwick, W.H., Corcoran, E.E., Lee, A. Y., and Clardy, J. (1992) Laurencione, a heterocycle from the red algae Laurencia Spectabilis. Phytochemistry. 31:1273-1276.
Venkateswarlu, Y., Faulkner, D.J., Rios, J.L., Corcoran, E. and Clardy, J. (1991) Smenochromenes, unusual macrocyclic sesquiterpene hydroquinone derivatives from a Seychelles sponge ofthe genus Smenospongia. Journal of Organic Chemistry. 56: 6271-6274.
Kevin Courtney 9/89 to 6/93 Dartmout University B.A., Chemistry 8/95 to 3/01 Duke University, Ph.D. Molecular Cancer Biology, 8/93 to 5/02 Duke University, M.D.
Stradal, T., Courtney, K.D., Rottner, K., Hahne, P., Small, J.V., Pendergast, A. M.. (2001) The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia. Current Biology. 11:891-895.
Courtney, K., Grove, M., Vandongen, A., LaManatia, A.-S., Pendergast, A.M. (2000) Localization and phosphorlylation of Abl-interactor proteins, Abi-1 and Abi-2, in the developing nervous system. Molecular and Cellular Neuroscience. 16: 244-257.
Quackenbush, R.C., Reuther, G. W., Miller, J.P. Courtney, K.D., Pear, W.S., Pendergast, A. M. (2000) Analysis of the biologic properties of p230 Bcr-Abl reveals unique and overlapping properties with the oncogenic p185 and p210 Bcr-Abl tyrosine kinases. Blood. 95: 2913-2921.
Ben Yeh et al., Eds, Courtney, K. Crashing the Boards: A Friendly Study Guide for the USMLE Step 1 Embryology (1999) 97-111.
Dai, Z., Quackenbush, R.C., Courtney, K.D., Grove, M., Cortez, D., Reuther, G.W., Pendergast, A. M. (1998) Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. Genes and Development. 12:1415-1424.
Wetterhahn, K.E., Stearns, D. M., Misra, M., Giangrande, P.H., Phieffer, L.S., Kennedy, L. J., Courtney, K.D. (1995) The role of ascorbate in metabolism and genotoxicity of chromium (VI). Genetic Response to Metals.
Stearns, D.M., Courntey, K.D., Giangrande, P.H., Phieffer, L.S., Wetterhahn, K.E. (1995) Reduction of chromium (VI) by abscorbate leads to chromium-DNA binding and DNA strand breaks in vitro. Biochemistry.34: 910-919.
Stearns, D.M., Courntey, K.D., Giangrande, P.H., Phieffer, L.S., Wetterhahn, K.E. (1994) Chromium (VI) reduction by ascorbate: role of reactive intermediates in DNA damage in vitro. Environmental Health Perspectives.102: 21-25.
Tamiko Katsumoto 9/89 to 6/94 University of California, Davis, B.S. Physiology,8/96 - 5/02 UCSF M.D.
Bruehl, R.E., Dasgupta, T.R., Katsumoto, Tan, J. H., Bertozzi, Cr. R., Spevak, W., Ahn, D. J., Rosen, S.D., Nagy, J. O. (2001) Polymerized liposome assemblies: bifunctional macromolecular selectin inhibitors mimicking physiological selectin ligands. Biochemistry. 40:5964-5974.
Giblin, P. A., Katsumoto, T. R., Hwang, S. T., Rosen, S. D. (1997) Ligation of L-selectin on T lymphocytes activates beta 1 integrins and promotes adhesion to fibronectin. Journal of Immunology.159:3498-3507.
Saunders, W. J., Katsumoto, T. R., Bertozzi, C. R., Rosen, S. D., Kiessling, L.L. L-selectin -carbohydrate interactions; relevant modifications of the Lewis x Trisaccharide. (1996) Biochemistry. 35:14862-14867.
Adam Lauring 9/90 to 5/94 Yale University B.S. Biology and History of Science, 6/94 to 12/2000 University of Washington, Ph.D. Molecular and Cellular Biology, 9/94 to 6/02 University of Washington, M.D
Anderson, M.M., Lauring, A. S., Robertson, S. R., Dirks, C., and Overbaugh, J. (2001) Feline Pit2 functions as a receptor for subgroup B feline leukemia viruses. Journal of Virology.
Lauring, A. S., Anderson, M.M., and OVerbaugh, J. (2001) Specificity in receptor usage by T-cell tropic feline leukemia viruses: implications for the in vivo tropism of immunodeficiency-inducing variants.Journal of Virology.75: 8888-8898.
Lauring, A.S. and Overbaugh, J. (2000) Evidence that an IRES within the Notch2 coding region can direct expression of a nuclear form of the protein. Molecular Cell. 6: 939-945.
Gwynn, S.R., Hankenson, F.C., Lauring, A.S., Rohn, J. L., and Overbaugh, J. (2000) Feline leukemia virus sequences that affect T-cell tropism and syncytia formaition are not part of known receptor-binding domains. Journal of Virology 74:5754-5761.
Anderson, M.M., Lauring, A. S., Burns, C. C., and Overbaugh, J. (2000) Identification of a cellular cofactor required for infection by fline leukemia virus. Science.287:1828-1830.
Collins, R. N., Brennwald, P., Garrett, M., Lauring, A. S., and Novick, P. (1997) Interactions of nucleotide release factor Dss4p with Sec4p in the post-Golgi secretory pathway of yeast. Journal of Biological Chemistry. 272:18281-18289.
Rohn, J. L., Gwynn, S. R., Lauring, A. S., Lineneberger, M. L., and Overbaugh, J. (1996) Viral genetic variation, AIDS, and the multistep nature of carcinogenesis: the feline leukemia virus model. Leukemia 10:1867-1869.
Rohn, J. L., Lauring, A. S., Lininberger, M. L., and Overbaugh, J. (1996) Transduction of Notch2 in feline leukemia virus induced thymic lymphoma. Journalof Virology. 70:8071-8080.
Class of 2001
Jonathan Alexander 9/87 to 6/91 Princeton University A.B. Molecular Biology 9/93 to 8/99 UCSF Ph.D. Biochemistry 9/91 to 6/01 UCSF M.D.
Haun, C., Alexander, J., Stainier, D.Y.R., and Okkema, P.G. (1998) Rescue of Caenorhabditis elegans pharyngeal development by a vertebrate heart specification gene. PNAS 95: 5072-5075.
Alexander, J., Stainier, D.Y.R., and Yelon, D. (1998) Screening mosaic F1 females for mutations affecting zebrafish heart induction and patterning. Dev. Gen. 22: 288-299.
Alexander, J., and Stainier, D.Y.R. (1999) Mutations affecting cardiac development in zebrafish. pp. 91-110. In Heart Development, ed. by R.P. Harvey and N. Rosenthal. Academic Press, San Diego.
Alexander, J., Rothenberg, M., Henry, G.L., and Stainier, D.Y.R. (1999) Casanova plays an early and essential role in endoderm formation in zebrafish. Dev. Biol. 215: 343-357.
Alexander, J., and Stainier, D.Y.R. (1999) A molecular pathway leading to endoderm formation in zebrafish. Curr. Biol. 9: 1147-1157.
Reiter, J.F., Alexander, J., Rodaway, A., Yelon, D., Patient, R., Holder, N., and Stainier, D.Y.R. (1999) Gata5 is required for the development of the heart and endoderm-derived organs in zebrafish. Genes Dev. 13: 2983-2995.
Kikuchi, Y., Trinh, L., Reiter, J. F., Alexander, J., Yelon, D., and Stainier, D. Y. R. (2000) The zebrafish bonnie and clyde gene encodes a mix family homeodomain protein that regulates the generation of endodermal precursors. Genes Dev 14: 1279-1289.
Kikuchi, Y., Agathon, A., Alexander, J., Thisse, C., Waldron, S., Yelon, D., Thisse, B., and Stainier, D Y. R. Casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish. Genes Dev. In press.
Jonathan Benjamin 9/86 to 6/90 Harvard College A.B. History and Literature 6/93 to 7/94 New York University M.S. Pathology 9/94 to 2/00 New York University Ph.D. Immunology 9/91 to 5/01 NYU School of Medicine M.D.
Fujimoto, J., Narayanan, C.S., Benjamin, J.E., Heinflink, M., Gershengorn, M.C. (1992) Mechanism of regulation of thyrotropin-releasing hormone receptor messenger ribonucleic acid in stably transfected rat pituitary cells. Endocrinology 130: 1879-84.
Fujimoto, J., Narayanan, C.S., Benjamin, J.E., Gershengorn, M.C. (1992) Posttranscrip- tional up-regulation of thyrotropin-releasing hormone (TRH) receptor messenger ribonucleic acid by TRH in COS-1 cells transfected with mouse pituitary TRH receptor complementary deoxyribonucleic acid. Endocrinology 131:1716-20.
Gu, C., Ma ,Y.C., Benjamin, J., Littman, D., Chao, M.V., Huang, X.Y. (2000) Apoptotic signaling through the b-adrenergic receptor: a new Gs coupled mechanism. Journal of Biological Chemistry 275:20726-33.
Rajiv Sahai Bhatnagar 9/85 to 6/89 University of California Berkeley Chemistry and Biophysics 9/90 to 5/00 Washington University School of Medicine M.D., Ph.D.
Leipala, J. A., Bhatnagar, R., Pineda, E., Najibi, S., Massoumi, K., and Packer, L. (1991) Protection of the reperfused heart by L-propionylcarnitine. Journal of Applied Physiology, 71 1518-1522.
Johnson, D. R., Bhatnagar, R. S., Knoll, L. J., and Gordon, J. I .(1994) Genetic and Biochemical Studies of Protein N-Myristoylation. Annual Review of Biochemistry, 63 869-914.
Bhatnagar, R. S., Jackson-Machelski, E., McWherter, C. A., and Gordon, J. I. (1994) Isothermal Titration Calorimetric Studies of Saccharomyces cerevisiae MyristoylCoA:Protein N-Myristoyltransferase. Journal of Biological Chemistry, 269 11045-11053.
Bhatnagar, R. S. and Gordon, J. I. (1995) Thermodynamic Studies of MyristoylCoA:Protein N-Myristoyltransferase Using Isothermal Titration Calorimetry. Methods in Enzymology, 250 467-86.
Bhatnagar, R. S. and Gordon, J. I. (1997) Understanding Covalent Modifications of Proteins by Lipids - Where Cell Biology and Biophysics Mingle. Trends in Cell Biology, 7 14-20.
Bhatnagar, R. S., Schall, O. F., Jackson-Machelski, E., Sikorski, J. A., Devadas, B., Gokel, G. W. and Gordon, J. I. (1997) Titration Calorimetric Analysis of AcylCoA Recognition by MyristoylCoA:Protein N-Myristoyltransferase. Biochemistry, 36 6700-6708.
Bhatnagar, R. S., FŸtterer, K., Farazi, T. A., Korolev, S., Murray, C. L., Jackson-Machelski, E., Gokel, G. W., Gordon, J. I., and Waksman, G. W. (1998) Structure of N-Myristoyltransferase with Bound MyristoylCoA and Peptide Substrate Analogs. Nature Structural Biology, 5 1091-1097.
Bhatnagar, R. S., FŸtterer, K., Waksman, G., and Gordon, J. I. (1999) The Structure of MyristoylCoA:Protein N-Myristoyltransferase. Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids, 1441 162-172.
Bhatnagar, R. S., Ashrafi, K., Fccctterer, K., Waksman, G., and Gordon, J. I. (2000) The Biology and Enzymology of Protein N-Myristoylation. In Lipid Modifications, F. Tamanoi and D. Sigman, eds., 241-290.
FŸtterer, K, Murray C. L., Bhatnagar, R. S., Gokel, G. W., and Waksman, G. (2001) Crystallographic phasing of myristoyl-CoA-protein N-myristoyltransferase using an iodinated analog of myristoyl-C oA. Acta Crystallogr. 57393-400.
Charles Chiu 8/89 to 5/93 UC Berkeley B.S. Electrical Engineering and Computer Science 5/96 to 6/99 UCLA Ph.D. Biomedical Physics 8/93 to 6/01 UCLA School of Medicine M.D.
Siegel, J.M., Nienhuis, R., Fahringer, H.M., Paul, R., Shiromani, P., Dement, W.C., and Chiu, C. Neuronal activity in narcolepsy: identification of cataplexy-related cells in the medial medulla. Science 252(5010):1315-1318.
Siegel, J.M., Nienhuis, R., Fahringer H.M., Chiu, C., Dement ,W.C., Mignot, E., and Lufkin R. (1992) Activity of medial mesopontine units during cataplexy and sleep-waking states in the narcoleptic dog. Journal of Neuroscience 12(5):1640-6.
Stewart, P.L., Chiu, C.Y., Huang, S., Muir, T., Zhao, Y., Chait ,B., Mathias, P., and Nemerow G.R. (1997) Cryo-EM visualization of an exposed RGD epitope on adenovirus that escapes antibody neutralization. The EMBO Journal 16(6):1189-1198.
Chiu, C.Y., Cary, R.B., Chen, D.J., Peterson, S.R., and Stewart, P.L. (1998) Cryo-EM imaging of the catalytic subunit of the DNA-dependent protein kinase. Journal of Molecular Biology 284:1075-1081.
Von Seggern, D., Chiu, C.Y., Fleck, S., Stewart, P.L., and Nemerow, G.R. (1999) A helper- independent adenovirus vector with E1, E3, and fiber deleted: structure and infectivity of fiberless particles. Journal of Virology 73:1601-1608.
Chiu, C.Y., Nemerow, G.R., Mathias, P., and Stewart, P.L. (1999) Structure of adenovirus complexed with its internalization receptor, avb5 integrin. Journal of Virology 73:6759-6768.
Stewart, P.L., Cary, R.B., Peterson, S.R., and Chiu, C.Y. (1999) Digitally collected cryo- electron micrographs for single particle reconstruction. Microscopy Research and Technique 49:224-232. Stewart, P.L., Chiu, C.Y., Haley, D.A., Kong, L.B., Schlessman, J.L. (1999) Review: Resolution issues in single-particle reconstruction. Journal of Structural Biolog 128:58-64.
Chiu, C.Y., Wu, E., Von Seggern, D., Nemerow, G.R., and Stewart, P.L. (2001) Structural analyses of a fiber-pseudotyped adenovirus with ocular tropism suggests differential modes of cell receptor interactions. Journal of Virology. In press.
Thakur, A., Chiu, C., Quiros-Tejeira, R.E., Reyen, L., Ament, M., Atkinson, J.B., and Fonkalsrud, E.R. (2001) Morbidity and mortality of short-bowel syndrome in infants with abdominal wall defects. The American Surgeon. In press.
Taylor Liu 9/88 to 6/92 Stanford University B.S. Biological Sciences 9/94 to 6/00 Stanford University Ph.D. Neuroscience 9/92 to 6/01 Stanford School of Medicine M.D.
Perri, M.A., Rosenthal, J.J.C., Liu, T.I., Gilly, W.F. (1994) Cloning and distribution of Kv1 type potassium channel sequences in the squid stellate ganglia. Biophysical Journal 66: A105.
Liu, T.I., Rosenthal, J.J.C., Gilly ,W.F. (1994) Subcellular localization and tissue distribution of sodium channel mRNA from the squid stellate ganglion. Molecular Biology of the Cell 5: 316A.Liu ,T.I., Gilly, W.F. (1995) Tissue distribution and subcellular localization of Na+ channel mRNA in the nervous system of the squid, Loligo opalescens. Receptors and Channels 3: 243-254.
Liu, T.I., and So, R. (1996) Knowledge, attitude, and preventive practice survey regarding AIDS comparing registered to freelance commercial sex workers in Iloilo City, Philippines. Southeast Asian Journal of Tropical Medicine and Public Health 27: 696-702.
Rosenthal, J.J.C., Liu, T.I., Gilly, W.F. (1997) A family of delayed rectifier Kv1 cDNAs showing cell type-specific expression in the squid stellate ganglion/giant fiber lobe complex. Journal of Neuroscience 17:5070-5079.
Liu ,T.I., Gilly ,W.F. (1998) Alteration of putative PKC-sites of the squid delayed rectifier modifies voltage-dependent gating. Biophysical Journal 74: A218.
Jerng, H.H., Liu, T.I., Gilly, W.F. (1999) C-type inactivation of a cloned quid K+ channel expressed in Xenopus oocytes. Biophysical Journal 76: A191.
Liu ,T.I., Lebaric, Z.N., Rosenthal, J.J.C., Gilly ,W.F. Natural deviations from highly conserved T1 domain residues in squid Kv1 a-subunits perturb channel processing and functional expression. Journal of Neurophysiology. In press.
Denise Marciano 9/89 to 6/93 Dartmouth College B.A. Chemistry 6/95 to 1/00 Rockerfeller University Ph.D. Cellular Biophysics 8/93 to 5/01 Cornell School of Medicine M.D.
Marciano DK, Russel M, Simon SM. (2001) Assembling filamentous phage occlude pIV channels. Proc Natl Acad Sci U S A.98(16):9359-64
Marciano, D. (2000) Filamentous phage are exported through phage-encoded pIV channels, Ph.D. Thesis, Rockefeller University.
Venkatesan,N., Lim, J., Bouch, C., Marciano, D., Davidson, M.B. (1996) Dexamethasone -induced imparitment in skeletal muscle glucose transport is not reversed by inhibition of freee fatty acid oxidization. Metabolism 45: 92-100.
Marciano, D.K., Russel, M. and Simon, S. M. (1999) An aqueous channel for finamentous phage export. Science, 284:1516.
Michael Shiloh 8/89 to 5/93 Pennsylavania State B.S. Chemistry 8/95 to 1/00 Cornell Graduate School Ph.D. Microbiology and Immunology 8/93 to 5/01 Cornell Medical College M.D.
Shiloh, M.U., Ruan, J., and Nathan,C. (1997) Evaluation of bacterial numbers and phagocyte function with a fluorescence-based microplate assay. Infect Immun. 65:3193-3197. Ehrt, S., Shiloh, M.U., Ruan, J., Choi, M., Gunzberg, S., Nathan, C., Xie, Q-w and Riley, L. (1997) An antioxidant gene from Mycobacterium tuberculosis. J. Exp. Med. 186:1885-1896.
De Groote, M.A., Ochsner, U.A.,. Shiloh, M.U , Nathan, C., McCord, J.M., Dinauer, M.C., Libby, S.J., Vasquez-Torres, A. ,Xu, Y. and Fang, F.C.. (1997) Periplasmic superoxide dismutase protects Salmonella from products of phagocyte oxidase and nitric oxide synthase. Proc. Natl. Acad. Sci USA 94:13997-14001.
Shiloh, M. U., MacMicking, J.D., Nicholson,S., Brause, J.E., Potter, S.,J., Marino, M., Dinauer, C.,and C. F. Nathan. (1999) Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. Immunity 10:29-38.
Nicholson, S. C., Grobmyer, S. R., Shiloh, M.U. , Brause, J. E. , Potter, S. , MacMicking, J. , Dinauer, M.C. and Nathan, C. F. (1999) Lethality of endotoxin in mice genetically deficient in the respiratory burst oxidase, inducible nitric oxide synthase, or both. Shock 11:253-258.
Shiloh, M. U., and Nathan, C. (2000) Reactive nitrogen intermediates and the pathogenesis of Salmonella and Mycobacteria. Curr. Opin. Micro. 3:35-42.
Grobmyer, S. R., Barie, P.S. , Nathan, C. F.,. Fuortes, M., Lin, E., Lowry, S. F. ,Wright, C. D. , Weyant, M. J. , Hydro, L. , Reeves, F. , Shiloh, M. U. and Ding, A.. (2000) Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia. Crit. CareMed. 28:1276-1282.
Nathan, C. and Shiloh, M. U. (2000) Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. USA. In press.
Shiloh, M. U. and Nathan, C. Antimicrobial mechanisms of macrophages. In Phagocytosis and Pathogens, (1999) S. Gordon (Greenwich, Conneticut:JAI Press, Inc.)
Class of 2000
Grant Barish 8/90 to 5/94 University of California, Berkeley B.A. Molecular and Cell Biology 8/94 to 6/00 University of Michigan Medical School M.D.
*Williams, B. O., *Barish, G. D., Klymkowsky, M. W., and Varmus, H. E. (2000). A Comparative Evaluation of b-catenin and plakoglobin signaling activity. Oncogene 19(50): 5720-5728. *Indicates authors contributed equally to the work. Barish, G. D. and Williams, B. O. (2000). The Wnt Signal Transuction Pathway. Signaling Networks and Cell Cycle Control; The Molecular Basis of Cancer and Other Diseases. Editor S. Gutkind. Totowa: Humana Press: 53-82.
Zorn, A. M., Barish, G. D., Williams, B. O., Lavender, P., Klymkowsky, M. W., and Varmus, H. E. (1999). Regulation of Wnt signaling by Sox proteins: XSox17a/b and XSox3 interact physically with b-catenin and repress b-catenin/TCF activity. Molecular Cell 4: 487-498.
Klymkowsky, M. W., Williams, B. O., Barish, G. D., Varmus, H. E., and Vourgourakis, Y. E. (1999). Membrane Anchored Plakoglobins have Multiple Mechanisms of Action in Wnt Signaling. Molecular Biology of the Cell 10(10): 3151-3169.
Hartt, J. K., Barish, G. D., Murphy, P. M., and Gao, J. L. (1999). N-formylpeptides Induce Two Distinct Concentration Optima for Mouse Neutrophil Chemotaxis by Differential Interaction with Two N-formylpeptide Receptor Subtypes: Molecular Characterization of FPR2, a Second Mouse Neutrophil N-formylpeptide Receptor. Journal of Experimental Medicine 190(5): 741-748.
Rameen Beroukim 8/87 to 5/91 University of California, Berkeley B.A. Physics and Philosophy9/91 to 8/92 University of Cambridge M.Phil.Biophysics 9/92 to 8/96 University of Cambridge, Ph.D. Biophysics 9/96 to 6/00 University of California, San Francisco M.D.
Beroukhim R, Unwin N. (1997). Distortion correction of tubular crystals: improvements in the nicotinic acetylcholine receptor structure. Ultramicroscopy, 70:57-81.
Beroukhim R. (1996). High-Resolution Electron Crystallographic Studies of Ion Channels. Ph.D. Thesis, University of Cambridge.
Beroukhim R, Unwin N. (1995 ). Three-dimensional location of the main immunogenic region of the nicotinic acetylcholine receptor. Neuron 15:323-331. 1995 Boess FG, Beroukhim R, Martin IL: Ultrastructure of the 5-hydroxytryptamine--3 receptor. J Neurochem 64:1401-1405.
Emily Garabedian 9/88 to 6/92 University of Michigan, Ann Arbor B.S. Cellular and Molecular Biology 9/92 to 5/00 Washington University M.D., Ph.D.
Garabedian, E. M., Roberts, L.J.J., McNevin, M.S. and and Gordon, J.I. (1997) Examining the role of Paneth cells in the small intestine by lineage ablation in tranagenic mice. J. Biol. Chem. 272(38): 23729-23740.
Garabedian, E. M., Humphrey, P.A. and Gordon, J.I. (1999) A transgenic mouse model of metastatic cancer originating from neuroendocrine cells. Proc. Natl. Acad. Sci. USA 95:15382-15387.
Abdulkadir, S. A., Qu, Z., Garabedian, E. M., Song, S. K., Peters, T. J., Svaren, J., Carbone, J. M., Naughton, C. K., Catalona, W. J., Ackerman, J. J. H., Gordon, J. I., Humphrey, P. A., and Milbrandt, J. Impaired prostate tumorigenesis in Egr-1 deficient mice. Nature Medicine, 2001 Jan 7(1)101-107.
Song, S-K., Qu, Z., Garabedian, E. M., Gordon, J. I., Milbrandt, J., and Ackerman, J. J. H. Improved MRI detection of prostate cancer in a transgenic mouse model, submitted.
Garabedian, E. M., Humphrey, P.A., Hu, H., Frye, S., Abdulkadir, S., Milbrandt, J. and Gordon, J.I. Cellular and molecular features of early invasion in a transgenic mouse model of neurendocrine cancer. (In preparation).
Agnieszka (Sheilha) Niewmierzycka 9/89 to 6/93 University of California, San Diego B.S. Biochemistry and Cell Biology 8/93 to 6/00 University of California, Los Angeles, School of Medicine Ph.D. Molecular Biology 2000 M.D.
Kalhor, H.R., Niewmierzycka, A. Faull, K.F., Yao, X., Grade, S. Clarke, S. and Rubenstein, P.A. (1999) A highly conserved 3-methylhistidine modification is absent in yeast actin. Arch. Biochem. Biophys. 370:105-111
Niewmierzycka, A. and Clarke, S. (1999) S-adenosylmethionine-dependent methylation in Saccharomyces cerevisiae: Identification of a novel protein arginine methyltransferase. Journal Biol. Chem. 279:814-824.
Niewmierzycka, A. and Clarke, S. (1999) Do damaged proteins accumulate in Caenorhabditis elegans L-isoaspartate methyltransferase (pcm-1) deletion mutants? Arch. Biochem. Biophys. 364:209-218.
Kagan, R. M., Niewmierzycka, A., Clarke, S. (1997) Targeted gene disruption of the Caenorhabditis elegans L-isoaspartyyl protein repair methyltransferase impairs survival of dauer stage nematodes. Arch. Biochem. Biophy. 348:320-328.
Robert Plenge 9/88 to 6/92 University of California, San Diego B.S. 7/95 to 8/98 Case Western Reserve University Ph.D. Genetics 8/92 to 5/00 Case Western Reserve University School of Medicine M.D.
Class of 1999
Alfred Fisher 8/87 to 5/91 Loyola Marymount University, L.A., B.S. Biochemistry and Biology 8/93 to 2/98 Cornell University Graduate School of Medical Sciences Ph.D. Cell Biology and Genetics 8/91 - 5/99 Cornell University Medical College M.D.
Koff, A., F. Cross, A. Fisher, J. Schumacher, K. Leguellec, M. Phillippe, and J.M. Roberts. 1991. Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell 66: 1217-1228.
Fisher, A.L., S. Ohsako, and M. Caudy. 1996. The WRPW motif of the Hairy-related basic helix-loop-helix repressor proteins acts as a four amino acid transcription repression and protein-protein interaction domain. Mol. Cell. Bio. 16: 2670-2677.
Aronson, A.D., A.L. Fisher, K. Blechman, M. Caudy, and J.P. Gergen. 1997. Groucho dependent and independent repression activities of Runt domain proteins. Mol. Cell. Bio. 17: 5581-5587.
A.L. Fisher and M. Caudy. 1998. The function of Hairy-related bHLH repressor proteins in cell fate decisions. BioEssays. 20:298-306. A.L. Fisher and M. Caudy. 1998. Groucho proteins: active transcriptional co-repressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates. Genes Dev. 12:1931-1940.
Robin Shaw 9/86 to 5/90 Brown University B.S. Bio-electrical Engineering 8/91 to 10/96 Case Western Reserve University School of Medicine Ph.D. Biomedical Engineering 8/91 to 5/99 Case Western Reserve University School of Medicine M.D.
Clarke LP, Cullom SJ, Shaw R, Reece C, Penney BC, King MA, Silbiger M. "Bremsstrahlung imaging using the gamma camera: Factors affecting attenuation" J Nuc Med 1992;33:161-6.
Shaw RM and Rudy Y. "The vulnerable window for unidirectional block in cardiac tissue: Characterization and dependence on membrane excitability and intercellular coupling" J Cardiovasc Electrophys 1995;6:115-31.
Shaw RM and Rudy Y. "Electrophysiological effects of acute myocardial ischemia: A mechanistic investigation of action potential conduction and conduction failure" Circ Res 1997;80:124-38.
Shaw RM and Rudy Y. "Electrophysiological effects of acute myocardial ischemia: A theoretical study of single cell excitability and action potential duration" Cardiovasc Res 1997;35:256-72.
Shaw RM and Rudy Y. "Ionic mechanisms of propagation in cardiac tissue: Roles of the sodium current and L-type calcium currents during reduced excitability and decreased gap junction coupling" Circ Res 1997;81:727-41.
Viswanathan PC, Shaw RM and Rudy Y. "Effects of IKr and IKs heterogeneity on action potential duration and its rate-dependence: A mechanistic study" Circulation 1999;99:2466-74.
Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. "VEGF gene delivery to myocardium: Deleterious effects of unregulated expression" Circulation 2000;102: 898-901.
CHAPTERS IN BOOKS AND REVIEWS
Shaw RM, Loomis AT, and Crisman E. "Input and Integration: Enabling tehcnologies for disabled users", In: "Extra-ordinary human-computer interaction: Interfaces for users with disabilities" Ed: A.D.N. Edwards, Cambridge University Press, New York, 1995.
Rudy Y and Shaw RM. "Membrane factors and gap-junction factors as determinants of ventricular conduction and reentry". In: "Discontinuous Conduction in the heart". Eds: P. Spooner, et al., Futura Publishing Company, Armonk, 1997.
Rudy Y and Shaw RM. "Cardiac excitation: An interactive process of ion channels and gap junctions" Adv Exp Med Bio 1997;430:269-79.
Shaw RM and Rudy Y. "Gap junctions and the spread of electrical current". In: "Heart cell communication in health and disease". Ed: W.C. De Mello and M. J. Janse, Kluwer Academic Publishers, Boston, 1998.
Class of 1998
Tony Gerber 9/86 to 6/90 Massachusettes Institute of Technology B.S. 9/92 to 6/97 University of Washington Ph.D. 9/90 to 5/98 University of Washington Medical School M.D.
Gerber A.N. and Tapcott S.J. 1996 Tumor cell complementation groups based on myogenic potential: evidence for inactivation of loci required for basic helix-loop-helix protein activity. Molecular and Cellular Biology, Jul 16; 7: 3901-8.
Gerber A.N., Klesert, T.R., Bergstrom, D.A., Tapscott, S.J. 1997. Two domains of MyoD mediate transcriptional activation of genes within repressive chromatin: a mechanism for lineage determination in myogenesis. Genes and Development, Feb 15; 11: 436-50.
Otten. A.D., Firpo, E.J., Gerber, A.N., Brody, L.L, Roberts, J.M., Tapscott, S.J. 1997. Inactivation of MyoD mediated expression of p21 in tumor lines. Cell Growth and Differentiation, Nov 8; 11: 1151-60.
Gredinger, E., Gerber, A.N., Tamir, Y., Tapscott, S.J., Bengal, E. 1998. Mitogen-activated protein kinase pathway is involved in the differentiation of muscle cells. Journal of Biological Chemistry, Apr 24; 273: 10436-10444.
Cook, D.L., Gerber, A.N., Tapscott, S.J. 1998. Modeling stochastic gene expression: Implications for haploinsufficiency. Procedings of the National Acadamy of Sciences, Dec 22; 26: 15641-6.
Feroz Papa 9/84 to 6/88 University of Illinois, Urbana B.S. Biochemistry 9/90 to 6/95 University of Chicago Ph.D. Biochemistry and Molecular Biology 9/96 to 5/90 University of Chicago, Pritzker School of Medicine M.D.
F.R. Papa, A. Y. Amerik, and M. Hochstrasser. 1999. Interaction of the Doa4 Deubiquitinating Enzyme with the Yeast 26S Proteasome. Mol. Bio. Cel. 10: 741-756.
T.E. Hansen-Hagge, J.W.G. Janssen, A. Jauch, H. Hameister, F.R. Papa, T. Seriu, M. Hochstrasser, and C.R. Bartram. 1998. An Evolutionarily Conserved Gene on Human Chromosome 5q33-34, UBH1, Encodes a Novel Deubiquitinating Enzyme. Genomics 49: 411-418.
M. Hochstrasser, F.R. Papa, P. Chen, S. Swaminathan, P. Johnson, L. Stillman, A. Amerik, and S. Li. 1996. The DOA pathway: Studies on the Functions and Mechanisms of Ubiquitin-Dependent Protein Degradation in the Yeast Saccharomyces cerevisiae. Cold Spring Harbor Symp. Quant. Biol. 60: 503-513.
Y. Zhu, M. Carroll, F.R. Papa, M. Hochstrasser, and A.D. DÕAndrea. 1996. DUB-1, a Deubiquitinating Enzyme with Growth-Suppressing Activity. Proc Natl Acad Sci USA 93: 3275-3279.
D.J. DeMarini, F.R. Papa, S. Swaminathan, D. Ursic, T.P. Rasmussen, M.R. Culbertson, and M. Hochstrasser. 1995. The Yeast SEN3 Gene Encodes a Regulatory Subunit of the 26S Proteasome Complex Required for Ubiquitin-Dependent Protein Degradation in vivo. Molecular and Cellular Biology 15: 6311-6321.
F.R. Papa *, H. Yu *, and V.P. Sukhatme. 1994. Bovine and Rodent Tamm-Horsfall Protein (THP) genes: Cloning, Structural Analysis, and Promoter Identification. Gene Expression 4: 63-75. *Equal contribution.
F.R. Papa and M. Hochstrasser. 1993. The Yeast DOA4 gene Encodes a Deubiquitinating Enzyme Related to the Human tre-2 Oncogene. Nature 366: 313-319.
Class of 1997
Andrei Goga 9/86 to 6/90 University of California, Los Angeles B.A. Biology 8/90 to 2/96 University of California, Los Angeles Molecular Biology Institute Ph.D. 8/90 to 5/97 University of California, Los Angeles, School of Medicine M.D.
Golub, T. R., Goga, A., Barker, G. F., Afar, D.E., McLaughlin, J., Bohlander, S. K., Rowley, J. D., Witte, O. N., and Gilliland, D. G. 1996. Oligomerization of the Abl tyrosine kinase by the Ets protein Tel in human leukemia. Mol. Cell Biol. 16: 4107-16.
Walkenhorst, J. Goga, A., Witte, O. N., and Superti-Furga, G. 1996. Analysis of human c-Abl tyrosine kinase activity and regulation in S. Pombe. Oncogene, 12: 1513-20.
Goga, A., McLaughlin, J., Afar, D.E.H., Saffran, D.C., and Witte, O.N. 1995. Alternative signals to Ras for hematopoietic transformation by the Bcr-Abl oncogene. Cell 82: 981-988.
Goga, A., Liu, X., Hambuch, T., Senechal, K., Major, E., Berk, A.J., Witte, O.N., and Sawyers, C.L. 1995. p53 dependent growth suppression by the c-ABL nuclear tyrosine kinase. Oncogene 11: 791-799.
Afar, D., Goga, A., McLaughlin, J., Witte, O.N., and Sawyers, C.S. 1994. Differential complementation of BCR/ABL point mutants with c-MYC. Science 264: 424-426.
Sawyers, C.L., McLaughlin, J., Goga, A., Havlik, M., and Witte, O.N. 1994. The nuclear tyrosine kinase c-ABL negatively regulates cell growth. Cell 77: 121-131.
Cohen, L., Mohr, R., Chen, Y.Y., Huang, M., Kato, R., Dorin, D., Tamanoi, F., Goga, A., Afar., D., Rosenberg, N., and Witte, O.N. 1994. Transcriptional activation of a novel ras-like gene (kir) by oncogenic tyrosine kinases. Proc. Nat. Acad. Sci. 91: 12448-12452.
Goga, A., McLaughlin, J., Pendergast, A.M., Parmar, K., Muller, A., Rosenberg, N., and Witte, O.N. 1993. Oncogenic activation of c-ABL by mutation within its last exon. Mol. Cell Biol. 13:4967-4975.
Mary Beth Humphrey 9/84 to 6/87 Austin College B.A. Baylor 9/89 to 6/94 College of Medicine Ph.D. 9/88 to 6/97 Baylor College of Medicine M.D.
Elrick, L. L., M. B. Humphrey, T. A. Cooper, and S. M. Berget. A short sequence within two purine-rich enhancers determines 5Õ splice site specificity. Molecular and Cellular Biology. 1998, 18: 343-352.
Humphrey, M. B., T. A. Cooper, J. Bryan, and S. M. Berget. A 32 nucleotide exon splicing enhancer regulates usage of competing 5' splice sites in a differential internal exon. Molecular and Cellular Biology. 1995, 15: 3977-3988.
Humphrey, M. B., H. Herrera-Sosa, G. Gonzales, R. Lee, and J. Bryan. Molecular cloning of human caldesmons. Gene. 1992, 112: 197-204.
Aguilar-Bryan, L., D. A. Nelson, Q. A. Vu, M. B. Humphrey, and A. E. Boyd III. Photoaffinity labeling and partial purification of the b cell sulfonylurea receptor using a novel, biologically active glyburide analog. J. Biological Chemistry. 1990, 265: 8218-8224.
Michelle Hermiston 9/84 to 6/88 University of Iowa B.S. Exercise Science 9/89 to 6/97 Washington University School of Medicine M.D., Ph.D.
Malone, R.E., Bullard, S., Hermiston, M.L., Rieger, R., Cool, M., and Galbraith, A. Isolation of mutants defected in early steps of meiotic recombination in the yeast Saccharomyces cerevisiae. Genetics, 128:79-88 (1991).
Roth, K.A., Hermiston, M.L., and Gordon, J.I. Use of transgenic mice to infer the biological properties of small intestinal stem cells and to examine the lineage relationships of their descendants. Proc. Natl. Acad. Sci. USA, 88:9407-9411 (1991).
Hermiston, M.L., Latham, C.B., Gordon, J.I., and Roth, K.A. Simultaneous localization of six antigens in sections of transgenic mouse intestine using a combination of light and fluorescence microscopy. J. Histochem. Cytochem., 40:1283-1290 (1992).
Hermiston, M.L., Green, R.P., and Gordon, J.I. Chimeric-transgenic mice represent a powerful tool for studying how the proliferation and differentiation programs of intestinal epithelial cell lineages are regulated. Proc. Natl. Acad. Sci. USA, 90:8866-8870 (1993).
Hermiston, M.L., and Gordon, J.I. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death. J. Cell Biol., 129:489-506 (1995).
Hermiston, M.L., and Gordon, J.I. Functional organization of the crypt-villus axis and evolution of its stem cell hierarchy during intestinal development. Amer. J. Physiol., 268 (Gastrointest. Liver Physiol. 31):G813-G822 (1995).
Hermiston, M.L., and Gordon, J.I. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science, 270:1203-1207 (1995).
Hermiston, M.L., Wong, M.H., and Gordon, J.I. Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for non-autonomous regulation of cell fate in a self-renewing system. Genes and Development, 10:985-996 (1996) (Selected for cover).
Wong, M.H., Hermiston, M.L., Snider, D., and Gordon, J.I. Forced expression of the tumor suppresser adeneomatosis polyposis coli protein induces disordered cell migration in the intestinal epithelium. Proc. Natl. Acad. Sci. USA, 93:9588-9593 (1996).
Fazeli, A., Dickinson, S.L., Hermiston, M.L., Tighe, R., Steen, R.G., Small, C.G., Stoeckli, E.T., Keino-Masu, K., Masu, M., Rayburn, H., Simons, J., Bronson, R.T., Gordon, J.I., Tessier-Lavigne, M., and Weinberg, R.A. Phenotype of mice lacking Deleted in colorectal cancer (DCC) gene. Nature, 386:796-804 (1997).
Invited Chapters and Reviews
Hermiston, M.L. and Gordon, J.I. Use of transgenic mice to characterize the multipotent intestinal stem cell and to analyze regulation of gene expression in various epithelial cell lineages as a function of their position along the cephalocaudal and crypt-to-villus (or crypt-to-surface epithelial cuff) axes of the gut. Seminars in Developmental Biology, 4:275-291 (1993).
Hermiston, M.L., Simon, T.C., Crossman, M.W., and Gordon, J.I. Model systems for studying cell fate specification and differentiation in the gut epithelium: From worms to flies to mice. In "Physiology of the Gastrointestinal Tract." Third ed. Johnson, L.R., 3rd edition, Raven Press, New York, New York (1994).
Gordon, J.I. and Hermiston, M.L. Differentiation and self-renewal in the mouse gastrointestinal epithelium. Current Opin. Cell Biol., 6:795-803 (1994).
Hermiston, M.L., Xu, Z, Majeti, R, and Weiss, A. Reciprocal regulation of tyrosine phosphorylation by protein tyrosine kinases and protein tyrosine phosphatases. J. Clin. Invest., in press 5. Hermiston, M.L. and Menzter, W.C. Approach to the Anemic Child. Pediatr. Clin. North Amer., in press.
Josina Reddy 9/84 to 6/88 Princeton University B.A. 8/88 to 5/97 Mount Sinai M.D., Ph.D.
Licht, J.D., Hanna-Rose, W., Reddy, J.C., English, M.A., Ro, M., Shaknovich, R., and Hansen, U. (1994) Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila KrŸppel protein. Mol. Cell. Biol. 14: 4057-4066.
Reddy, J.C., Morris, J.C., Wang, J., English, M.A., Haber, D.A., Shi, Y., and Licht, J.D. (1995) WT1-mediated transcriptional activation is inhibited by dominant negative mutant proteins. J. Biol. Chem. 270: 10878-10884.
Luo, X.N., Reddy, J.C., Yeyati, P.L., Idris, A.H., Hosono, S., Haber, D.A., Licht, J.D., and Atweh, G.F. (1995) The tumor suppressor gene WT1 inhibits ras-mediated transformation. Oncogene 11: 743-750.
Reddy, J.C., Hosono, S., and Licht, J.D. (1995) The transcriptional effect of WT1 is modulated by choice of expression vector. J. Biol. Chem. 270: 29976-29982.
Licht, J.D., Shaknovich, R., English, M.A., Melnick, A., Li, J.-Y., Reddy, J.C., Dong, S., Chen, S.-J., Zelent, A., and Waxman, S. (1996) Reduced and altered DNA-binding and transcriptional properties of the PLZF-retinoic acid receptor-a chimera generated in t(11:17)-associated acute promyelocytic leukemia. Oncogene 12: 323-336.
Reddy, J.C., and Licht, J.D. (1996) The WT1 Wilms' tumor suppressor gene: How much do we really know? (review) Biochim. Biophys. Acta 1287:1-28.
Hosono, S., Luo, X., Hyink, D.P., Schnapp, L.M., Wilson, P.D., Burrow, C.R., Reddy, J.C., Atweh, G.F., and Licht, J.D. (1999) WT1 expression induces features of renal epithelial differentiation in mesenchymal fibroblasts. Oncogene 18:417-27.
Reddy, J.C., Katz, P.P., Goldman, L., and Wachter, R.M. A pneumonia practice guideline and a hospitalist-based reorganization lead to equivalent efficacy gains. Am. J. Managed Care, in press (October 2001)
Class of 1996
Jody Baron 9/82 to 6/86 Rice University B.A. 9/85 to 5/93 Yale University School of Medicine M.D. 9/85 to 5/94 Yale University Ph.D.
Christopher Haqq 9/84 to 6/87 Stanford University B.S. 9/91 to 6/96 Harvard Graduate School of Arts and Sciences Ph.D. 9/87 to 9/96 Harvard Medical School M.D.
E Ukiyama, A Jancso-Radek, B Li, L Milos, W Zhang, N B Phillips, N Morikawa, C-Y King, G Chan, C M Haqq, J T Radek, F Poulat, P K Donahoe, M A Weiss (2001). SRY and architectural gene regulation: The kinetic stability of a bent protein-DNA complex can regulate its transcriptional potency. Molecular Endocrinology 15:363-377.
N Morikawa, T Clarke, C Novina, K Watanabe, C Haqq, M Weiss, A Roy, P K Donahoe (2000). Human Mullerian inhibiting substance promoter contains a functional TFII-I-binding initiator. Biology of Reproduction 63:1075-1083.
C Haqq, P Donahoe (1998). Regulation of sexual dimorphism in mammals. Physiological Reviews 78:1-33.
Haqq CM; King CY; Ukiyama E; Falsafi S; Haqq TN; Donahoe PK; Weiss MA (1994). Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY, Science, 266:1494
Haqq CM; King CY; Donahoe PK; Weiss MA(1993). SRY recognizes conserved DNA sites in sex-specific promoters. Proceedings of the National Academy of Sciences of the United States of America, 1993 Feb 1, 90(3):1097-101.
Haqq C; Lee MM; Tizard R; Wysk M; DeMarinis J; Donahoe PK; Cate RL(1992). Isolation of the rat gene for Mullerian inhibiting substance. Genomics, 1992 Apr, 12(4):665-9.
Kuroda T; Lee MM; Haqq CM; Powell DM; Manganaro TF; Donahoe PK(1990). Mullerian inhibiting substance ontogeny and its modulation by follicle-stimulating hormone in the rat testes. Endocrinology, 1990 Oct, 127(4):1825-32.
Dedhar S; Haqq C; Gray (1989). Specific overproduction of very late antigen 1 integrin in two human neuroblastoma cell lines selected for resistance to detachment by an Arg-Gly-Asp-containing synthetic peptide. Journal of Biological Chemistry, 1989 Mar 25, 264(9):4832-6.
Jancso, A; Ukiyama, E; Labeots, L; Morikawa, N; Chen, G; Haqq, C M; Radek, J; King, C-Y; Donahoe, P K; Weiss, M A. Structure-function relationships in SRY: Role of an architectural transcription factor in testis determination and "sex reversal". (Annual Meeting of the Association of American Physicians, the American Society...Journal of Investigative Medicine, v.44, n.3, (1996): 248A.
Haqq, C M; King, C Y; Ukiyama, E; Falsafi, S; Haqq, T N; Donahoe, P K; Weiss, M A. Molecular basis of mammalian sexual determination: Activation of Mullerian inhibiting substance gene expression by SRY. (Clinical Research Meeting, San Diego, California, USA, May 5-8, 1995. ) Journal of Investigative Medicine, v.43, n.SUPPL. 2, (1995): 257A.
Haqq, C M; Haqq, T N; Weiss, M A; Donahoe, P K. The testis determining factor, SRY, activates the Mullerian inhibiting substance promoter in a male rat urogenital ridge cell line. (Keystone Symposium on the Molecular Basis for Differences Between the Journal of Cellular Biochemistry Supplement, n.19B, (1995): 44.
Dedhar, S; Gary, V; Robertson, K; Haqq, C. Differential regulation of expression of specific integrin receptors by nerve growth factor and transforming growth factor beta-1 during differentiation of human neuroblastoma cells. Molecular and Cellular Differentiation, v.1, n.1, (1993): 1-20.
Mehrdad Matloubian 9/84 to 6/88 University of California, Los Angeles B.S. Biochemistry 9/90 to 6/94 University of California, Ph.D. Los Angeles 9/88 to 6/90, 9/94 to 6/96 University of California, Los Angeles, M.D.
Ahmed, R., R. S. Simon, M. Matloubian, S. R. Kolhekar, P. J. Southern, and D. M. Friedman. 1988. Genetic analysis of in vivo selected viral variants causing chronic infection: importance of mutation in the L RNA segment of lymphocytic choriomeningitis virus. J. Virol. 62:3301-3308.
Matloubian, M., T. Somasundaram, S. R. Kolhekar, R. Selvakumar, and R. Ahmed. 1990. Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice. J. Exp. Med. 172:1043-1048.
Ahmed, R., C. S. Hahn, T. Somasundaram, L. Villarete, M. Matloubian, and J. H. Strauss. 1991. Molecular basis of organ-specific selection of viral variants during chronic infection. J. Virol. 65:4242-4247.
Matloubian, M., S. R. Kolhekar, T. Somasundaram, and R. Ahmed. 1993. Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus. J. Virol. 67:7340-7349.
Matloubian, M., R. J. Concepcion, and R. Ahmed. 1994. CD4+ T cells are required to sustain CD8+ cytotoxic T cell responses during chronic viral infection. J. Virol. 68:8056-8063.
Walsh, C. M., M. Matloubian, C. C. Liu, R. Ueda, C. G. Kurahara, J. L. Christensen, M. T. F. Huang, J. Ding-E Young, R. Ahmed, and W. R. Clark. 1994. Immune function in mice lacking the perforin gene. Proc. Natl. Acad. Sci. USA, 91:10854-10858.
Slifka, M. K., M. Matloubian, and R. Ahmed. 1995. Bone marrow is a major site of long-term antibody production after acute viral infection. J. Virol. 69:1895-1902.
Shen, H., M. K. Slifka, M. Matloubian, E. R. Jensen, R. Ahmed, and J. F. Miller. 1995. Recombinant Listeria monocytogenes as a live vaccine vehicle for the induction of protective anti-viral cell mediated immunity. Proc. Natl. Acad. Sci. USA, 92:3987-3991.
Clark, W. R., C. Walsh, A. Glass, M. Matloubian, and R. Ahmed. 1995. Cell-mediated cytotoxicity in perforin-less mice. Intl. Rev. Immun. 13:1-14.
Clark, W. R., C. M. Walsh, A. Glass, F. Hayashi, M. Matloubian, and R. Ahmed. 1995. Molecular pathways of CTL-mediated cytotoxicity. Immunol. Rev. 146:33-44.
Slifka, M. K., H. Shen, M. Matloubian, E. R. Jensen, J. F. Miller, and R. Ahmed. 1996. Antiviral cytotoxic T-cell memory by vaccination with recombinant L. monocytogenes. J. Virol. 70:2902-2910.
Van der Most, R. G., A. Sette, C. Oseroff, J. Alexander, K. Murali-Krishna, L. L. Lau, S. Southwood, J. Sidne, R. W. Chesnut, M. Matloubian, and R. Ahmed. 1996. Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection. J. Immunol. 157:5543-5554.
Matloubian, M., M. Suresh,. M. Galvan, A. Glass, K Chow, J. K. Whitmire, C. M. Walsh, W. R. Clark, and R. Ahmed. A role for perforin in down regulating T cell responses during chronic viral infection. 1999 J. Virol. 73:2527-2536. 14. Matloubian, M., A. David, S. Engel, J. E. Ryan, and J. G. Cyster. A transmembrane CXC chemokine is ligand for HIV-coreceptor Bonzo. 2000 Nature Immunology 1:298-304.
Thomas Chen 9/84 to 6/88 Princeton University B.A. 9/88 to 6/94 Stanford University Ph.D. 9/88 to 6/96 Stanford University M.D.
Stock, A., Mottonen, J., Chen, T., and Stock, J. (1987) Identification of a possible nucleotide binding site in CheW, a protein required for sensory transduction in bacterial chemotaxis. J. Biol. Chem. 262: 535-537.
Stock, A., Chen, T., Welsh, D., and Stock, J. (1988) CheA protein, a central regulator of bacterial chemotaxis, belongs to a family of proteins that control gene expression in response to changing environmental conditions. Proc. Natl. Acad. Sci. USA 85: 1403-1407.
Zelenetz, A. Z., Chen, T. T., Levy, R. (1991) Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell. J. Exp. Med. 173: 197-207.
Zelenetz, A. D., Campbell, M. J., Bahler, D. W., Takahashi, S., Oren, R., Esserman, L., Umetsu, D. T., Kwak, L. W., Maloney, D. G., Brown, S, Chen, T. T., Andria, M. L., Levy, S., Miller, R. A., and Levy, R. (1991) Follicular lymphoma: a model of lymphoid tumor progression in man. Annals of Oncology 2(Suppl 2): 115-22.
Bahler, D. W., Zelenetz, A. D., Chen, T. T., and Levy, R. (1992) Antigen selection in human lymphomagenesis. Cancer Res.(Suppl) 52: 5547s-5551s.
Zelenetz, A. D., Chen, T. T., and Levy, R. (1992) Clonal expansion in follicular lymphoma occurs subsequent to antigenic selection. J. Exp. Med. 176: 1137-1148.
Chen, T. T., Tao, M.-H., and Levy, R. (1994) Idiotype-cytokine fusion proteins as cancer vaccines: Relative efficacy of ILÐ2, ILÐ4, and granulocyteÐmacrophage colonyÐstimulating factor. J. Immunol. 153(10): 4775-4787.
Chen, T. T. and Levy, R. (1995) Induction of autoantibody responses to GMÐCSF by hyperimmunization with an IdÐGMÐCSF fusion protein. J. Immunol. 154(7): 3105-3117.
Syrengelas, A. D., Chen, T. T., Levy, R. (1996) DNA immunization induces protective immunity against B-cell lymphoma. Nature Medicine 2(9):1038-1041.
Chen, T. T., Schapiro, J. M. and Loutit, J. (1996) Prosthetic valve endocarditis due to Legionella pneumophila. J Cardiovasc Surg 37: 631-633.
