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Faculty Detail    
Name CHRISTOPHER A KLUG
  
Campus Address SHEL 510 Zip 2182
Phone  (205) 934-1424
E-mail  chrisk@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Microbiology  Microbiology Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Hughes Med-Grad Fellowship Program 
Immunology 
Integrative Genetics Graduate Program 

Biographical Sketch 
Christopher A. Klug, Professor, Departments of Microbiology, Biochemistry, Genetics and Pathology. Received his B.S. degree in Biology from Wheaton College in 1987. He received his Ph.D. degree from the Department of Molecular Genetics and Cell Biology at the University of Chicago in 1993, where he worked on early lymphocyte development in the laboratory of Dr. Harinder Singh. His postdoctoral research was in the laboratory of Dr. Irving Weissman at Stanford University, where he studied hematopoietic stem cell biology as an Irvington Institute Fellow before coming to UAB as an Assistant Professor in 1997.



Research/Clinical Interest
Title
Hematopoietic stem cell biology, acute leukemia, and pancreatic cancer
Description
The major research focus of our laboratory is to understand the underlying mechanisms regulating hematopoietic stem cell (HSC) self-renewal and how normal HSC developmental programs are subverted in the context of acute myeloid leukemia (AML). We are also interested in understanding the underlying molecular events controlling cell fate decisions within the hematopoietic system, especially within the lymphoid lineages. Animal models of acute myeloid leukemia are generated by introducing fusion genes derived from commonly observed chromosomal translocations found in human AML into mouse stem cells using retroviral vectors. The genetically modified stem cells are then used to regenerate the blood system of another animal, where leukemia development can readily be followed. Two of the translocations that we have modeled in mice, the inv(16) and the AML1-ETO translocation, are the two most common cytogenetic abnormalities in AML, accounting for about 20% of all AML cases in man. The current dogma is that AML is a disease that is sustained by an abnormal HSC population that has acquired specific genetic mutations and epigenetic changes that promote leukemia development. Current efforts are underway to understand how these mutations/changes affect the stem cell population and contribute to the development of leukemia. Recently, our laboratory has also initiated studies modeling pancreatic cancer in mice. Pancreatic cancer is one of the most fatal human malignancies, with an overall 5-year survival rate of less than 4 percent. Our studies are focused on developing novel therapeutic agents to treat advanced cancer and to identify markers that would be useful in diagnosis of early-stage neoplasia using the animal models.

Selected Publications 
Publication PUBMEDID
Hahm, K., Cobb, B.S., McCarty, A.S., Brown, K.E., Klug, C.A., Lee, R., Akashi, K., Weissman, I.L., Fisher, A.G., and Smale, S.T. (1998) Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes and Development 12, 782-796.  9512513 
Klug, C.A., Morrison, S.J., Masek, M., Hahm, K., Smale S.T., and Weissman, I.L. (1998) Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc. Natl. Acad. Sci. USA 95, 657-662.  9435248 
Klug, C.A., Gerety, S.J., Shah, P., Chen, Y., Rice, N.R., Rosenberg, N., and Singh, H. (1994) The v-abl tyrosine kinase negatively regulates NF-?B/rel factors and blocks kappa gene transcription in pre-B lymphocytes, Genes and Development 8, 678-687.  7926758 
Thal, M.A., Carvalho, T.L., He, T., Kim, H-G., Gao, H., Hagman, J., and Klug, C.A. (2009) Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage. Proc. Natl. Acad. Sci. USA 106:552-557.  19122139 
Ko, R. M., Kim, H-G., Wolff, L., and Klug, C. A. (2008) Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia. Leuk. Res. 32:1101-1111.  18037485 
Kim, H-G., Kojima, K, Swindle, C. S., Cotta, C. V., Huo, Y., Reddy, V., and Klug, C. A. (2008) FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia. Blood 111:1567-1574.  17967943 
Kojima, K., Vickers, S. M., Adsay, N. V., Jhala, N. C., Kim, H-G., Schoeb, T. R., Grizzle, W. E., and Klug, C. A. (2007) Inactivation of Smad4 accelerates KrasG12D-mediated pancreatic neoplasia. Cancer Res. 67:8121-8130.  17804724 
Zhang, Z., Swindle, C. S., Bates, J. T., Ko, R., Cotta, C. V., and Klug, C.A. (2007) Expression of a non-DNA-binding isoform of Helios induces T cell lymphoma in mice. Blood 109:2190-2197.  17110463 
Wang, N., Kim, H-G., Cotta, C. V., Wan, M., Tang, Y., Klug, C.A., and Cao, X. (2006) TGF?/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability. EMBO J. 25:1469-1480.  16525506 
Moreno-Miralles, I., Pan, L., Keates-Baleeiro, J., Durst-Goodwin, K., Yang, C., Kim, H.G., Thompson, M.A., Klug, C.A., Cleveland, J.L., Hiebert, S.W. (2005) The INV(16) cooperates with ARF haploinsuffiency to induce acute myeloid leukemia. J. Biol. Chem. 280:40097-40103.  16199529 
Kim, H-G., de Guzman, C. G., Swindle, C. S., Cotta, C. V., Gartland, G., Scott, E. W., and Klug, C.A. (2004) The ETS-family transcription factor, PU.1, is necessary for the maintenance of fetal liver hematopoietic stem cells. Blood 104:3894-3900.  15328162 
Witt, C. M., Hurez, V., Swindle, C. S., Hamada, Y., and Klug, C.A. (2003) Activated Notch2 potentiates CD8 lineage maturation and promotes the selective development of B1 B cells. Mol. Cell. Biol. 23:8637-8650.  14612407 
Swindle, C. S., Kim, H. G., and Klug, C.A. (2004) CpG mutations in the U3 and R regions of the MSCV LTR repress silencing in embryonic stem cells. J. Biol. Chem. 279:34-41.  14559924 
Purohit, S. J., Stephan, R. P., Kim, H. G., Herrin, B. R., Gartland, L., and Klug, C.A. (2003) Determination of lymphoid cell fate is dependent on the expression status of the IL-7 receptor. EMBO J. 22:5511-5521.  14532123 
Zheng, Z., Cotta, C.V., Stephan, R.P., de Guzman, C.G., and Klug, C.A. (2003) Enforced expression of EBF in hematopoietic stem cells restricts lymphopoiesis to the B cell lineage. EMBO J. 22:4759-4769.  12970188 
Witt, C. M., Won, W-J., Hurez, V., and Klug, C.A. (2003) Notch2 haplo-insufficiency results in diminished B1 B cells and a severe reduction in marginal zone B cells. J. Immunol. 171:2783-2788.  12960298 
Cotta, C.V., Zhang, Z., and Klug, C.A. (2003) Pax5 determines B versus T cell fate and does not block early myeloid-lineage development. Blood. In press.  12560221 
de Guzman, C.G., Warren, A.J., Zhang, J., Gartland, L., Erickson, P., Drabkin, H., Hiebert, S.W., and Klug, C.A. (2002) Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol. Cell. Biol. 22, 5506-5517.  12101243 
Park, I-K., He, Y., Lin, F., Laerum O., Bumgarner, R., Klug, C.A., Cheshier, S., Li, K., Doyle, M.J., Kuhr, C., Sun, Y., Schummer, M., Goldsmith, A., Clarke, M.F., Weissman, I.L., Hood, L., and Li, L. (2002) Differential Gene Expression Profiling of Adult Murine Hematopoietic Stem Cells. Blood 99, 488-498.  11781229 
Ernst, P., Hahm, K., Cobb, B.S., Brown, K.E., Trinh, L.A., McCarty, A.S., Merkenschlager, M., Klug, C.A., Fisher, A.G., and Smale, S.T. (1999) Mechanisms of transcriptional regulation in lymphocyte progenitors: insight from an analysis of the terminal transferase promoter. Cold Spring Harb. Symp. Quant. Biol. 64: 87-97  11232341 
Park, I-K, Klug, C.A., Weissman, I.L., Li, L., Hood, L., Nanamori, M., Neubig, R.R., and Clarke, M.F. (2001) Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. J. Biol. Chem. 276, 915-923.  11042171 
Klug, C.A., Cheshier, S., and Weissman, I.L. (2000) Inactivation of a GFP retrovirus occurs at multiple levels in long-term repopulating stem cells and their differentiated progeny. Blood 96, 894-901.  10910902 
de Guzman, C.G., Johnson, A., and Klug, C.A. (2002) The ETO domain is necessary for the developmental abnormalities associated with AML1-ETO expression in the hematopoietic stem cell compartment in vivo. Blood Cells, Mol. Dis. In press.