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Helen Diller Family Compr Cancer Ctr
COREY LARGMAN, PHD

Professor in Residence, Medicine, Dermatology; and Director, Molecular Hematopoiesis Research, UCSF
Member, UCSF Biomedical Sciences Graduate Program (BMS) and Herbert Boyer Program in Biological Sciences (PIBS)

CONTACT

largman@cgl.ucsf.edu
(415) 750-2254 (voice)
(415) 221-4262 (fax)

Box 0120, UCSF; San Francisco, CA 94143-0120

additional websites:

Largman Lab Website

EDUCATION

Reed College, Portland OR, BA, 1966, Chemistry
M.I.T., Cambridge, MA, PhD, 1970, Organic Chemistry
MRC Lab Molecular Biology, Cambridge, Eng., post-doc, 1970-71
Dept. Biochemistry, UC Berkeley, Berkeley, CA, post-doc, 1971-74, Protein Chemistry
Dept. Biochemistry. UCSF (Wm. Rutter's Lab, sabbatical, 1982-83, Molecular Biology

PROFESSIONAL EXPERIENCE

1974-1982

Assist. Director, Enzymology Research Laboratory, Martinez VA Medical Center

1989

Associate Chief of Staff for Research, Acting; Martinez VA Medical Center

1982-1992

Director Core Biochemistry Laboratory; VA Medical Center, Martinez, Calif.

1985-1991

VA Associate Career Scientist/GS14

1992-present

Career Scientist, Veterans Affairs Research Service, San Francisco VA Medical Center

1991-1998

Adjunct Professor, Dept. of Medicine and Dermatology, UCSF School of Medicine

1998-present

Research Scientist, NCIRE

1999-present

Professor in Residence, Medicine, UCSF

HONORS & AWARDS

1965

N.S.F. Undergraduate Trainee

1966

N.S.F. Graduate Trainee

1967-1970

N.I.H. Graduate Fellow

1970

NATO Postdoctoral Fellow

1971

American Cancer Society Postdoctoral Fellow

1972-1973

N.I.H. Postdoctoral Fellow

1985

VA Associate Career Scientist

1991

VA Career Scientist

2001-present

NIGMS Advisory Council

2002-present

VA Medical Research Advisory Council

1998-2003

Board of Directors, NCIRE

SELECTED PUBLICATIONS

Largman, C, Brodrick JW, Geokas MC, Sischo WM, & Johnson JH: Formation of a Stable Complex Between Human Proelastase 2 and ƒ¿1-protease Inhibitor. J. Biol. Chem. 254:8516-8523, 1979.

Largman, C, Brodrick, JW, Geokas, MC, and Johnson, JH: Demonstration of huma pancreatic anionic trypsinogen in normal serum by RIA. Biochim. Biophys. Acta 543: 450-454, 1979

Largman, C, Ray, SB, Brodrick, JW, and Geokas, MC: Clearance and Metabolism of Circulating Pancreatic Proelastase in the Rat. Am. J. Physiol. 239: G504-G510, 1980.

Glaser, C, Brodrick, J, Drechsel, D, Karick, L, Graceffo, M, & Largman, C: Fluorescence Polarization Studies on the Interaction of Active Site Modified Chymotrypsins with ƒ¿1protease Inhibitor. Biochemistry 21: 556-561, 1982.

Largman, C: Characterization of Rat Pancreatic Elastase. Biochemistry 22: 3763-3770, 1983

Craik, CS, Largman, C, Fletcher, T, Roczniak, S, Fletterick, R and Rutter, WJ: Redesigning Trypsin: Alteration of Substrate Specificity. Science 228: 291-297, 1985

Fletcher, TS, Alhadeff, M, Craik, CS, and Largman, C: Isolation and Characterization of a cDNA Encoding Rat Cationic Trypsinogen. Biochemistry 26: 3081-3086, 1987

Shen, WF, Fletcher, TS, and Largman, C: Primary Structure of Human Pancreatic Protease E Determined by Sequence Analysis of the Cloned mRNA. Biochemistry 26: 3447-3452, 1987

Craik, CS, Roczniak, S, Largman, C, and Rutter, WJ: The Catalytic Role of the Active Site Aspartic Acid in Serine Proteases. Science 237: 909-913, 1987

Shen, WF, Largman, C, Lowney, P, Corral, J, Detmer, K, Hauser, CA, Simonitch, TA, Hack, FM, and

Lawrence, HJ: Lineage-Restricted Expression of Homeobox-containing Genes in Human hematopoietic cell lines. Proc. Natl. Acad. Sci. USA 86: 8536-8540, 1989

Shen, WF, Detmer, K, Simonitch, T, Lawrence, HJ, & Largman, C: Alternative splicing of the Hox 2.2 homeobox gene in human hematopoietic cells & murine embryonic & adult tissues. Nuc. Acids Res. 19: 539-545, 1991

Shen, WF, Detmer, K, Mathews, CHE, Hack, FM, Morgan, DA, Largman, C, & Lawrence, HJ: Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines. EMBO J. 11: 983-989: 1992

Sauvageau, G, Landsorp, PM, Eaves, CE, Hogge, DE, Dragowska, WH, Reid, DS, Largman, C, Lawrence, HJ, and Humphries, KR: Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc. Natl. Acad. Sci. USA, 91: 12223-12227, 1994

Chang, CP, Shen, WF, Rozenfeld, S, Lawrence, HJ, Largman, C, & Cleary, ML. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of HOX proteins. Genes & Devel., 9:663-674, 1995

Sauvageau, G, Thorsteinsdottir, U, Eaves, CJ, Lawrence, HJ, Largman, C, Lansdorp, PM, and Humphries, RK: Expansion of hematopoietic stem cells as a result of HOXB4 overexpression in murine bone marrow cells. Genes & Devel. 9:1753-1765, 1995

Shen, WF, Chang, CP, Rozenfeld, S, Sauvageau, G, Humphries, RK, Lu, M, Lawrence, HJ, Cleary, M, & Largman, C: HOX Homeodomain proteins exhibit selective complex stabilities with Pbx and DNA. Nucl. Acids Res. 24, 898-906, 1996

Chang, CP, Brocchieri, L, Shen, WF, Largman, C, and Cleary, ML: Pbx modulation of Hox homeodomain N-terminal arm establishes a gradient of DNA-binding specficities across the Hox locus. Mol. Cell. Biol., 16: 1734-1745, 1996

Shen, WF, Chang, CP, Rozenfeld, S, Sauvageau, G, Humphries, RK, Lu, M, Lawrence, HJ, Cleary, M, & Largman, C: HOX Homeodomain proteins exhibit selective complex stabilities with Pbx and DNA. Nucl. Acids Research, 24: 898-906, 1996

Chang, CP, Brocchieri, L, Shen, WF, Largman, C, & Cleary, M: Pbx modulation of Hox homeodomain N-terminal arm establishes a gradient of DNA-binding specficities across the Hox locus. Mol. Cell. Biol., 16: 1734-1745, 1996

Thorsteinsdottir, U, Sauvageau, G, Hough, MR, Dragowska, V, Landsdorp, P, Lawrence, HJ, Largman, C, & Humphries, RK: Overexpression of HOXA10 in primary hematopoietic cells enhances proliferation & alters differentiation of primitive & more mature progenitors.Mol. Cell. Biol. 17, 495-505, 1997

Sauvageau, G, Thorsteinsdottir, U, Hough, MR, Hugo, P, Lawrence, HJ, Largman, C, and Humphries, RK: Defective development of ab T lymphocytes and progressive myeloproliferation in mice reconstituted with bone marrow cells overexpressing HOXB3. Immunity,6: 13-22, 1997

Shen, WF, Rozenfeld, S, Lawrence, HJ, Largman, C: The Abd-B-like Mammalian HOX protein family is subdivided by the ability to form DNA binding complexes with Pbx1a. J. Biol. Chem. 272: 8198-8906, 1997

Shen, WF, Montgomery, J, Rozenfeld, S, Lawrence, HJ, Buchberg, A, and Largman, C: AbdB-like Hox proteins stabilize DNA binding by the Meis homeodomain proteins. Mol. Cell. Biol., 17: 6448-6458, 1997

Shen, WF, Rozenfeld, S, Kwong, A, Kmves, L, Lawrence, HJ, and Largman, C: HOXA9 forms triple complexes with PBX2 & MEIS1 in myeloid cells. Mol. Cell. Biol: 19, 3051-3061, 1999

Kömüves, LG, Shen, WF, Kwong, A, Stelnicki, E, Rozenfeld, S, Oda, Y, Blink, AL, Krishnan, K, Lau, B, Mauro, T, and Largman, C: Changes in HOXB6 homeodomain protein structure and localization during human epidermal development and differentiation, Dev. Dyn., 218: 636-647, 2000

Shen, WF, Krishnan, K, Lawrence, HJ, and Largman, C: The HOX homeodomain proteins block CBP histone acetyltransferase activity. Mol. Cell. Biol. 21:7509-7522, 2002

Kömüves, LG, Michael, E, Arbeit, JM, Ma, XK, Kwong, A, Stelnickl, E, Rozenfeld, S, Morimune, M, Yu, QC, and Largman, C: HOXB4 homeodomain protein is a candidate for regulating keratinocyte proliferation in developing epidermis and skin disorders. Dev. Dyn. 224: 58-68, 2002

Kömüves, LG, Ma, XK, Stelnicki, E, Rozenfeld, S, Oda, Y, and Largman, C: HOXB13 homeodomain protein is cytoplasmic throughout fetal skin development. Dev. Dyn. 227: 192-202, 2003

Dorsam, TS, Ferrell, MC, Dorsam, PG, Vijapurkar, U, Khodabakhsh, D, Pau, B, Bernstein, H, Haqq, MC, Largman, C, and Lawrence, HJ: The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells. Blood 103:1676-1684, 2004

Vijapukar, U, Fischbach, N, Shen, WF, Brandts, C, Stokoe, D, Lawrence, HJ, and Largman, C: Protein Kinase C-mediated phosphorylation of the leukemia-associated HOXA9 protein impairs its DNA binding ability and induces myeloid differentiation, Mol. Cell. Biol. 24: 3827-37, 2004

Shen, WF, Chroback, D, Krishnan, K, Lawrence, HJ, & Largman, C: HOXB6 protein is bound to CBP and represses erythropoiesis in a DNA binding-dependent, PBX interaction-independent process J. Biol. Chem. 2004 in press

Fischbach, N, Rozenfeld, S, Shen, WF, Fong, S, Chrobak, D, Ginzinger, D, Kogan, SC, Radhakrishnan, A, Le Beau, MM, Largman, C, and Lawrence, HJ: HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo. Blood, 2004. in press

3/15/05

photo: Chris T. Anderson

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