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Scientist Profile

Ira Mellman

Vice President: Research Oncology
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"At Genentech, I found that you can do your science at the highest possible level, engage the most profound problems you can imagine, have access to a research environment and infrastructure unimaginable at an academic institution, and also have the opportunity - and the challenge - to make a difference."
 

I came to Genentech in the Spring of 2007 after more than 20 years as a faculty member at the Yale University School of Medicine, where I was chair of my department, a member of the Ludwig Institute for Cancer Research, and scientific director of the Yale Cancer Center.

I ran a large and successful laboratory, I was surrounded by valued friends and colleagues, and I worked at one of the world's great universities. I had the perfect job, but I came to Genentech anyway. Why? Because at Genentech, I found that you can do your science at the highest possible level, engage the most profound problems you can imagine, have access to a research environment and infrastructure unimaginable at an academic institution, and also have the opportunity - and the challenge - to make a difference.

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My Focus

I am a cell biologist, a scientific 'generalist' who is interested in understanding the cellular mechanisms responsible for complex phenomena. I began my career unraveling the pathways and functional significance of endocytosis, and over the years, applied the insights achieved to elucidate two key problems: the generation and maintenance of cell polarity and the cell biological basis of the immune response.

Although these two problems may appear disparate, they are united by a reliance on a common set of fundamental mechanisms grounded in molecular cell biology.

Our work on the immune response has concentrated on dendritic cells, a recently described cell type that is responsible for initiating all antigen-specific immune responses. A complex family of cells of as yet uncertain provenance, we have found that dendritic cells are uniquely proficient at stimulating T-cell responses because they exhibit an incredible array of specializations that optimize and regulate the endocytic and secretory pathways for antigen endocytosis, the generation of antigenic peptides bound to molecules of the major histocompatability complex (MHC), and the functional interaction with cognate T and B lymphocytes.

In the area of cell polarity, our group has been responsible for elucidating how protein-encoded signals control the distribution of membrane proteins to the appropriate domain of polarized cells such as epithelial cells and neurons. In anticipation of our move to Genentech, the group has now begun to focus more on a more systems-oriented aspect polarity: how membrane traffic and signal transduction are responsible for cellular and tissue morphogenesis, and how these processes break down in cancer.

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Publications & Recognition
  • Spatial control of EGF receptor activation by reversible dimerization on living cells
  • Nature 2010 Mar 7
  • Chung I, Akita R, Vandlen R, Toomre D, Schlessinger J, Mellman I
  • View Abstract on PubMed
  • Mature dendritic cells use endocytic receptors to capture and present antigens
  • Proc Natl Acad Sci USA 2010 Mar 2; 107(9): 4287-92
  • Platt CD, Ma JK, Chalouni C, Ebersold M, Bou-Reslan H, Carano RA, Mellman I, Delamarre L
  • View Abstract on PubMed
  • Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells
  • J Exp Med 2009 Feb 16; 206(2): 399-410
  • Goldszmid RS, Coppens I, Lev A, Caspar P, Mellman I, Sher A
  • View Abstract on PubMed
 
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  • The Rockefeller University
  • Postdoctoral Fellow
  • 1978-1980
  • Yale University School of Medicine, Genetics
  • Ph.D.
  • 1974-1978
  • Oberlin College and Conservatory of Music, Biology
  • B.A.
  • 1969-1973
Publications & Recognition
  • Spatial control of EGF receptor activation by reversible dimerization on living cells
  • Nature 2010 Mar 7
  • Chung I, Akita R, Vandlen R, Toomre D, Schlessinger J, Mellman I
  • View Abstract on PubMed
  • Mature dendritic cells use endocytic receptors to capture and present antigens
  • Proc Natl Acad Sci USA 2010 Mar 2; 107(9): 4287-92
  • Platt CD, Ma JK, Chalouni C, Ebersold M, Bou-Reslan H, Carano RA, Mellman I, Delamarre L
  • View Abstract on PubMed
  • Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells
  • J Exp Med 2009 Feb 16; 206(2): 399-410
  • Goldszmid RS, Coppens I, Lev A, Caspar P, Mellman I, Sher A
  • View Abstract on PubMed
  • Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis
  • J Cell Biol 2009 Jan 26; 184(2): 281-96
  • Mao YS, Yamaga M, Zhu X, Wei Y, Sun HQ, Wang J, Yun M, Wang Y, Di Paolo G, Bennett M, Mellman I, Abrams CS, De Camilli P, Lu CY, Yin HL
  • View Abstract on PubMed
  • Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I
  • Nat Immunol 2008 May; 9(5): 551-7
  • Di Pucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, Montes M, Xue Y, Mellman I, Banchereau J, Connolly JE
  • View Abstract on PubMed
  • Maturation modulates caspase-1-independent responses of dendritic cells to Anthrax lethal toxin
  • Cell Microbiol 2008 May; 10(5): 1190-207
  • Reig N, Jiang A, Couture R, Sutterwala FS, Oqura Y, Flavell RA, Mellman I, Van der Goot FG
  • View Abstract on PubMed
  • Spinophilin participates in information transfer at immunological synapses
  • J Cell Biol 2008 Apr 21; 181(2): 203-11
  • Bloom O, Unternaehrer JJ, Jiang A, Shin JS, Delamarre L, Allen P, Mellman I
  • View Abstract on PubMed
  • Par3 functions in the biogenesis of the primary cilium in polarized epithelial cells
  • J Cell Biol 2007 Dec 17; 179(6): 1133-40
  • Sfakianos J, Togawa A, Maday S, Hull M, Pypaert M, Cantley L, Toomre D, Mellman I
  • View Abstract on PubMed
  • Disruption of E-cadherin-medicated adhesion induces a functionally distinct pathway of dendritic cell maturation
  • Immunity 2007 Oct; 27(4): 610-24
  • Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, Jiang S, Whitney JA, Connolly J, Banchereau J, Mellman I
  • View Abstract on PubMed
  • Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
  • Nature 2007 Oct 4; 449(7162): 564-9
  • Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Wang YH, Su B, Nestle FO, Zal T, Mellman I, Schroder JM, Liu YJ, Gilliet M
  • View Abstract on PubMed
  • Private lives: reflections and challenges in understanding the cell biology of the immune system
  • Science 2007 Aug 3; 317(5838): 625-7
  • Mellman I
  • View Abstract on PubMed
  • Rab10 is involved in basolateral transport in polarized Madin-Darby canine kidney cells
  • Traffic 2007 Jan; 8(1): 47-60
  • Schuck S, Gerl MJ, Ang A, Manninen A, Keller P, Mellman I, Simons K
  • View Abstract on PubMed
  • The tetraspanin CD9 mediates lateral association of MHC class II molecules on the dendritic cell surface
  • Proc Natl Acad Sci U S A 2007 Jan 2; 104(1): 234-9
  • Unternaehrer JJ, Chow A, Pypaert M, Inaba K, Mellman I
  • View Abstract on PubMed
  • Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination
  • Nature 2006 Nov 2; 444(7115): 115-8
  • Shin JS, Ebersold M, Pypaert M, Delamarre L, Hartley A, Mellman I
  • View Abstract on PubMed
  • Endosomes come of age
  • In: Dikic I, editor. Endosomes. Georgetown: Landes Bioscience; 2006
  • Mellman I
  • Quantitative and dynamic assessment of the contribution of the ER to phagosome formation
  • Cell 2005 Oct 7; 123(1): 157-70
  • Touret N, Paroutis P, Terebiznik M, Harrison RE, Trombetta S, Pypaert M, Chow A, Jiang A, Shaw J, Yip C, Moore HP, van der Wel N, Houben D, Peters PJ, de Chastellier C, Mellman I, Grinstein S
  • View Abstract on PubMed
  • Trombetta ES.Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis
  • J Exp Med 2006 Sep 4; 203(9): 2049-55
  • Delamarre L, Couture R, Mellman I
  • View Abstract on PubMed
  • Vectorial insertion of apical and basolateral membrane proteins in polarized epithelial cells revealed by quantitative 3D live cell imaging
  • J Cell Biol 2006 Mar 27; 172(7): 1035-44
  • Hua W, Sheff D, Toomre D, Mellman I
  • View Abstract on PubMed
  • Cell biology of antigen processing in vitro and in vivo
  • Annu Rev Immunol 2005; 23: 975-1028
  • Trombetta ES, Mellman I
  • View Abstract on PubMed
  • Transcytosis of NgCAM in epithelial cells reflects differential signal recognition on the endocytic and secretory pathways
  • J Cell Biol 2005 Aug 15; 170(4): 595-605
  • Anderson E, Maday S, Sfakianos J, Hull M, Winckler B, Sheff D, Folsch H, Mellman I
  • View Abstract on PubMed
  • Trombetta ES. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate
  • Science 2005 Mar 11; 307(5715): 1630-4
  • Delamarre L, Pack M, Chang H, Mellman I
  • View Abstract on PubMed
  • Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells
  • J Cell Biol 2004 Nov 8; 167(3): 531-43
  • Ang AL, Taguchi T, Francis S, Folsch H, Murrells LJ, Pypaert M, Warren G, Mellman I
  • View Abstract on PubMed
  • Immunotherapy: bewitched, bothered, and bewildered no more
  • Science 2004 Jul 9; 305(5681): 197-200
  • Steinman RM, Mellman I
  • View Abstract on PubMed
  • The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains
  • J Cell Biol 2003 Oct 27; 163(2): 351-62
  • Folsch H, Pypaert M, Maday S, Pelletier L, Mellman I
  • View Abstract on PubMed
  • Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation
  • J Exp Med 2003 Jul 7; 198(1): 111-22
  • Delamarre L, Holcombe H, Mellman I
  • View Abstract on PubMed
  • Activation of lysosomal function during dendritic cell maturation
  • Science 2003 Feb 28; 299(5611): 1400-3
  • Trombetta ES, Ebersold M, Garrett W, Pypaert M, Mellman I
  • View Abstract on PubMed
  • A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor
  • Cell 2001 Jun 1; 105(5): 575-85
  • Koivisto UM, Hubbard AL, Mellman I
  • View Abstract on PubMed
  • Distribution and function of AP-1 clathrin adaptor complexes in polarized epithelial cells
  • J Cell Biol 2001 Feb 5; 152(3): 595-606
  • Folsch H, Pypaert M, Schu P, Mellman I
  • View Abstract on PubMed
  • Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane
  • Nature 2002 Aug 29; 418(6901): 988-94
  • Chow A, Toomre D, Garrett W, Mellman I
  • View Abstract on PubMed
  • Dendritic cells: specialized and regulated antigen processing machines
  • Cell 2001 Aug 10; 106(3): 255-8
  • Mellman I, Steinman RM
  • View Abstract on PubMed
  • Developmental control of endocytosis in dendritic cells by Cdc42
  • Cell 2000 Aug 4; 102(3): 325-34
  • Garrett WS, Chen LM, Kroschewski R, Ebersold M, Turley S, Trombetta S, Galán JE, Mellman I
  • View Abstract on PubMed
  • Transport of peptide-MHC class II complexes in developing dendritic cells
  • Science 2000 Apr 21; 288(5465): 522-7
  • Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaehrer J, Steinman RM, Mellman I
  • View Abstract on PubMed
  • The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli
  • J Exp Med 2000 Mar 20; 191(6): 927-36
  • Inaba K, Turley S, Iyoda T, Yamaide F, Shimoyama S, Reis e Sousa C, Germain RN, Mellman I, Steinman RM
  • View Abstract on PubMed
  • The road taken: past and future foundations of membrane traffic
  • Cell 2000 Jan 7; 100(1): 99-112
  • Mellman I, Warren G
  • View Abstract on PubMed
  • A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells
  • Cell 1999 Oct 15; 99(2): 189-98
  • Folsch H, Ohno H, Bonifacino JS, Mellman I
  • View Abstract on PubMed
  • Cdc42 controls secretory and endocytic transport to the basolateral plasma membrane of MDCK cells
  • Nat Cell Biol 1999 May; 1(1): 8-13
  • Kroschewski R, Hall A, Mellman I
  • View Abstract on PubMed
  • The receptor recycling pathway contains two distinct populations of early endosomes with different sorting functions
  • J Cell Biol 1999 Apr 5; 145(1): 123-39
  • Sheff DR, Daro EA, Hull M, Mellman I
  • View Abstract on PubMed
  • A diffusion barrier maintains distribution of membrane proteins in polarized neurons
  • Nature 1999 Feb 25; 397(6721): 698-701
  • Winckler B, Forscher P, Mellman I
  • View Abstract on PubMed
  • Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells
  • J Exp Med 1998 Dec 7; 188(11): 2163-73
  • Inaba K, Turley S, Yamaide F, Iyoda T, Mahnke K, Inaba M, Pack M, Subklewe M, Sauter B, Sheff D, Albert M, Bhardwaj N, Mellman I, Steinman RM
  • View Abstract on PubMed
  • Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells
  • Cell 1998 Jun 26; 93(7): 1135-45
  • Pierre P, Mellman I
  • View Abstract on PubMed
  • Inhibition of endosome function in CHO cells bearing a temperature-sensitive defect in the coatomer (COPI) component epsilon-COP
  • J Cell Biol 1997 Dec 29; 139(7): 1747-59
  • Daro E, Sheff D, Gomez M, Kreis T, Mellman I
  • View Abstract on PubMed
  • Developmental regulation of MHC class II transport in mouse dendritic cells
  • Nature 1997 Aug 21; 388(6644): 787-92
  • Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman RM, Mellman I
  • View Abstract on PubMed
  • Ii chain controls the transport of major histocompatibility complex class II molecules to and from lysosomes
  • J Cell Biol 1997 Apr 7; 137(1): 51-65
  • Brachet V, Raposo G, Amigorena S, Mellman I
  • View Abstract on PubMed
  • Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes
  • Nature 1994 May 12; 369(6476): 113-20
  • Amigorena S, Drake JR, Webster P, Mellman I
  • View Abstract on PubMed
  • Common signals control low density lipoprotein receptor sorting in endosomes and the Golgi complex of MDCK cells
  • Cell 1993 Sep 24; 74(6): 1053-64
  • Matter K, Whitney JA, Yamamoto EM, Mellman I
  • View Abstract on PubMed
  • Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants
  • Cell 1992 Nov 27; 71(5): 741-53
  • Matter K, Hunziker W, Mellman I
  • View Abstract on PubMed
  • The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway
  • Cell 1992 Sep 4; 70(5): 729-40
  • van der Sluijs P, Hull M, Webster P, Male P, Goud B, Mellman I
  • View Abstract on PubMed
  • Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes
  • Science 1992 Jun 26; 256(5065): 1808-12
  • Amigorena S, Bonnerot C, Drake JR, Choquet D, Hunziker W, Guillet JG, Webster P, Sautes C, Mellman I, Fridman WH
  • View Abstract on PubMed
  • Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant
  • Cell 1991 Sep 6; 66(5): 907-20
  • Hunziker W, Harter C, Matter K, Mellman I
  • View Abstract on PubMed
  • Toxoplasma gondii: fusion competence of parasitophorous vacuoles in Fc receptor-transfected fibroblasts
  • Science 1990 Aug 10; 249(4969): 641-6
  • Joiner KA, Fuhrman SA, Miettinen HM, Kasper LH, Mellman I
  • View Abstract on PubMed
  • Fc receptor isoforms exhibit distinct abilities for coated pit localization as a result of cytoplasmic domain heterogeneity
  • Cell 1989 Jul 28; 58(2): 317-27
  • Miettinen HM, Rose JK, Mellman I
  • View Abstract on PubMed
  • Two distinct subpopulations of endosomes involved in membrane recycling and transport to lysosomes
  • Cell 1988 Jan 15; 52(1): 73-83
  • Schmid SL, Fuchs R, Male P, Mellman I
  • View Abstract on PubMed
  • Endosomes
  • Trends in Biochem Sci 1983 78: 245-250
  • Helenius A, I. Mellman, D. Wall D, Hubbard A
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Awards & Honors
  • National Academy of Sciences, Member - 2011
  • Elected Foreign Member, European Molecular Biology Organization (EMBO)--2005
  • Keynote Lecture, Center for Immunology at Marseille-Luminy--2005
  • Elected Foreign Member, European Molecular Biology Organization (EMBO)--2005
  • Elected Member, American Academy of Arts & Sciences--2003
  • President's Lecturer, Memorial Sloan-Kettering Cancer Center (twice)
  • Yale Science and Engineering Society Medal--1985
  • Johnson-Sokatch Lecture, University of Oklahoma; Storer Lecture, University of California Davis
  • Chancellor's Lecture, University of California Riverside
  • Dean's Lecturer, University of Virginia Medical School
  • Phillip Levine Lecture, The Rockefeller University--2003
  • Cornell-LICR Partnership Cancer Biology Lecture
  • Sterling Professorship, Yale University School of Medicine
  • ISI Highly Cited Author
  • Alex B. Novikoff Lecture, Lysosomes Gordon Research Conference
  • 3M Distinguished Lecturer, University of Western Ontario
  • American Cyanamid Lecturer, Princeton University--2000
  • Kroc Lecture, Harvard Medical School--1999
  • E.P. Abraham Lecture, Oxford University--1999
  • Naidorf Award, Columbia University
  • Student Research Day Lecturer, University of Connecticut; University of Cincinnati
  • Mt. Sinai School of Medicine Dean's Lecture
  • Director's Institute Lecturer, NIH
  • President's Research Development Award, Leukemia Society of America--1983
  • Swebilius Award--1981
  • Junior Faculty Research Award, American Cancer Society--1981
  • Fellow of the Leukemia Society of America--1978
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Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.