KEITH MOSTOV

RECENT PROFESSIONAL SCHOOL TEACHINGTeaching Hours

COURSE LECTURE LAB CONFERENCE EXAM YEARS

Med. School Curriculum 2 40 6 04

Med. School Curriculum 42 6 01, 02, 03

IDS 100 2 48 4 25 97, 98, 00,

Biochemistry 110 2 1 97, 98

Biochemistry 112 2 1 97, 98

PH292 (UCB) 2 01

RECENT GRADUATE SCHOOL TEACHINGTeaching hours

GRADUATE

COURSES

LECTURE CONFERENCE EXAM YEARS

BMS 260 8 6 01, 02, 03, 04

Cell Biology 245 10 2 97, 98, 05

Cell Biology 245 2 6 02, 04

Cell Biology 245 15 6 99, 00, 03,

Oral Biology 225 2 97, 98, 99, 00, 01, 02

Gene Therapy 170.23 2 00

Teaching Award NominationNominated for “An Outstanding Lecture Award” by first-year medical students for IDS 100, 1999.

Post-doctoral Fellows1. Neil Simister, 1985-89 Supported by EMBO and Cancer Research Institute.

Currently Associate Professor, Brandeis University.2. Phil Breitfeld, 1986-89 Supported by NIH Physician-Scientist Award.

Currently Professor and Chief of Pediatric Hematology/Oncology, University of Indiana Medical Center.

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3. James Casanova, 1988-91 Supported by ACS and Cystic Fibrosis Foundation.Currently Professor, University of Virginia Health Sciences Center.

4. Gerard Apodaca, 1989-95 Supported by Cancer Research Institute and American Heart Association.Currently Professor, University of Pittsburgh.

5. Curtis Okamoto, 1990-94 Supported by Damon Runyon-Walter Winchell. Currently Professor, University of Southern California.

6. Benjamin Aroeti, 1990-94 Supported by Human Frontiers of Science Program Organization and American Heart Association. Currently Professor, and Chairman, Program of Cell and Developmental Biology Hebrew University, Jerusalem.

7. Morgane Bomsel, 1990-92 Supported by CNRS.Currently at Institut Cochin, Paris.

8. Wenxia Song, 1992-94 Supported by American Heart Association.Currently Assistant Professor, Dept. of Immunology and Microbiology, University of Maryland, College Park, MD.

9. Steven Chapin, 1992-2000 Supported by ACS. Currently Senior Research Scientist, Arizeke Pharmaceuticals.

10. Yoram Altschuler, 1993-2000 Supported by Cancer Research Institute.Assistant Professor, Hadassah Medical School, Jerusalem (9/00)

11. Karen Singer, 1994-97 Supported by Cystic Fibrosis Foundation.Currently Senior Scientist, Metabolex, Inc. Hayward, CA.

12. Janice Richman-Eisenstat, 1994-98Supported by Parker B. Francis Foundation.Currently Assistant Professor, Dept. of Medicine (Pulmonary), University of Mannitoba, Winnipeg, Mannitoba, Canada

13. Thomas Weimbs, 1994-99 Supported by Alexander von Humbolt Foundation.Currently Assistant Professor, Cleveland Clinic

14. Seng-Hui Low, 1994-99 Supported by Irvington Institute.Currently Assistant Professor, Cleveland Clinic

15. Frederic Luton, 1994-99 Supported by CNRS. Currently Assistant Professor, INSERM, Valbonne, France

16. Daniel Balkovetz, 1995-96 Supported by NIH. Currently Assistant Professor, University of Alabama at Birmingham.

17. Marcel Verges, 1995-2004 Supported by Spanish Government. Currently Asst Prof, Univ. Valencia, Spain

18. Joshua Lipschutz, 1997-2001 Currently Assistant Professor, University of Pennsylvania. Supported by NIH K08.

19 Steen Hansen, 1997-2000 Supported by Weimann Foundation. Currently Assistant Professor, Boston Biomedical Research Institute.

20. Barbara Kazmierczak, 1997-2001 Supported by Howard Hughes Physician-Scientist (joint with Joanne Engel). Currently Assistant Professor, Yale University.

21. Mirjam Zegers, 1998- Supported by American Cancer Society. Currently Assistant Prof., Univ. Chicago

22. Martin ter Beest, 1998- Supported by Cystic Fibrosis Foundation. Currently Assistant Prof., Univ. Chicago.

23. Sven van IJzendoorn, 1999-2001 Supported by HFSPO. Currently Assoc. Prof., Univ. Groningen, 24. Wei Yu, 2000- Supported by American Heart Association Fellowship25. Anirban Datta, 2001- Supported by Susan G. Komen Breast Cancer Foundation26. Tao Su, 2001- Supported by NIH

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27. Arlinet Kierbel-2001- Supported by NIH (Joint with Joanne Engel)28. Lucy O’Brien 2001-05 Currently scientist, UC Berkeley29. Paul Brakeman 2002-05 Currently Asst Prof, UCSF Dept Pediatriatrics30. Fernando Martin 2003- Supported by HFSPO.31. Kathleen Liu 2003-05 Currently Instructor, UCSF Division of Nephrology32. Minji Kim 2003- Supported by California Tobacco-Related Disease Fellowship33. Toshiyuki Yamaji 2003-06 Currently Asst Prof., RIKEN, Japan 34. Max Levin 2003-05 Currently Assistant Professor, University of Goteborg, Sweden35. Naoki Tanimizu 2004 Supported by Japanese Government 36. Leonid Katz 2004-06 Currently Principal Scientist, Merck.37. Dennis Eastburn 2005 Supported by Ruth Kirschstein NRSA (NIH F32).38. David Bryant, 2006 Supported by Australian Government39. Catherine Jacobson, 2006 Supported by NIH Training Grant40. Annette Shewan, 2006 Supported by C.J. Martin Fellowship (Australia)

Visiting Professors1. Jeanine Wiener-Kronish, 1991-92 Vice-chair, Dept of Anesthesia, UCSF2. Carlos Enrich, 1993-94 Professor, University of Barcelona, Spain.3. Suzanne Fleiszig, 1994-96 Professor, UC Berkeley4. Ama Gassama, 2002-2006 Senior Researcher, INSERM, Toulouse, France5. Pascale Leroy, 2003- Senior Researcher, CNRS, Marseille, France

Graduate StudentsFull-time students1. Michael Cardone, Department of Anatomy, 1989-95. Currently Postdoctoral Fellow, MIT.2. James Arden, Department of Pharmaceutical Chemistry, 1989-90. Currently Associate Professor,

Cornell University Medical College.3. Anne Pollack, Department of Anatomy, 1991-96. Currently Postdoctoral Fellow, University of Arizona,

Tucson.4. Lucy O’Brien, Biomedical Sciences Program, 1995-2001, Currently Postdoctoral Fellow, UCSF

Laboratory rotations1. Anne de Bruyn Kops, Whitehead Institute, 1985-1986.2. Michael Cardone, Department of Anatomy, Spring 19893. Anne Pollack, Department of Anatomy, Winter 19914. Iris Roth, Biomedical Sciences Program, Summer 19925. Lucy O’Brien, Biomedical Sciences Program, Spring 19946. Michael Penn, MSTP, Autumn 19947. Lani Keller, PIBS Tetrad, Winter 20048. Clara Dey, PIBS Tetrad, Spring 20049. Isla Cheung, PIBS Tetrad, Spring 200510. Teddy Lam, PSPG, Summer 2005

Visiting Graduate Students1. Nina Do, UC Berkeley, 1995-962. Cindy Jun, UC Berkeley, 1995-963. Leo Mok, UC Berkeley, 1995-964. Sven van IJzendoorn, University of Groningen, Netherlands, 1996-97

Visiting Undergraduate Students

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1. Leonard Katz, UC Santa Cruz, 1994-952. Elena Kleiman, UC Berkeley, 1995-963. Ellen Katz, UC Berkeley, 1999-

Student Qualifying CommitteesAngela Porter, Department of AnatomyDarren Wong, Department of Pharmaceutical ChemistryJames Arden, Department of Pharmaceutical ChemistryIris Roth, Biomedical Sciences ProgramChris van Ooij, Biomedical Sciences ProgramJennifer Zamanian, PIBS TetradJessica Blumstein, PIBS TetradDianne Wakeham, Department of Pharmaceutical ChemistryDavid Sanchez, BMSMarla Abodeely, BMSRobert Gage, PSPGKelly DuBois, BMSBen Laufer, PSPGJeremy Wilbur, PIBS BiophysicsClara Dey, PIBS TetradLani Keller, PIBS TetradIsla Cheung, PIBS Tetrad

Student Thesis CommitteesThesis Committee, Eric Grote, PIBS TetradThesis Committee, Vivian Wong, Department of PhysiologyThesis Committee, James Arden, Department of Pharmaceutical ChemistryThesis Examiner, Seng-Hui Low, National University of SingaporeThesis Committee, Chris van Ooij, Biomedical Sciences ProgramThesis Examiner, Sven van IJzendorn, Univeristy of GroningenThesis Committee, Shoumita Dasgupta, PIBS TetradThesis Committee, Jessica Blumstein, PIBS TetradThesis Examiner, Tao Su, University of SidneyThesis Committee, Marla Abodeely, Biomedical Sciences ProgramThesis Committee, Chantilly Munson, PIBS TetradThesis Committee, Isla Cheung, PIBS TetradThesis Examiner, Purnima Bhat, University of Melbourne

Mentoring and other Educational ActivitiesGave workshop at Meharry Medical College on “How to Write and Publish Scientific Papers”, 1988Judge, British Society for Cell Biology Student Poster Competition, 1993Mentor, K21 Scientist Development Award, Mark von Zastrow, Assistant Professor, Department of

Psychiatry, UCSF, 1994Organized High School Program, American Society for Cell Biology, San Francisco, CA, 1994Judge, Vienna Institute of Molecular Pathology, Spring Meeting Student Poster Competition, 1998Scientific Advisory Board, NIH Research Center for Minority Institutions, Universidad Central del Caribe,

Puerto Rico, 2001-presentAmerican Society for Cell Biology, Women in Cell Biology Career Lunch, Table Leader, 2001, 03, 05Ernest E. Just Symposium, Medical University of South Carolina, 2006

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DEPARTMENTAL, UNIVERSITY, AND PROFESSIONAL SERVICE

Member, Department of Biochemistry and Biophysics (joint appointment)Member, Cell Biology Program, Program in Biological SciencesMember, Biomedical Sciences ProgramMember, Liver CenterMember, Cardiovascular Research InstituteMember, UCSF Comprehensive Cancer CenterMember, Program in Pharmaceutical Sciences and PharmacogeneticsMember, Program in Host-Pathogen Interactions

University Committee Service

1989-1990Seminar Committee, Department of Anatomy (organized 20 very well attended seminars.)Ad hoc committees for faculty appointments.MSO Search Committee, Department of Anatomy

1990-1991Committee on Minicourses, Department of BiochemistryCommittee on MD with Thesis, School of MedicineCo-organizer, Membrane Traffic Journal ClubAd hoc committees for faculty appointmentsFaculty Search Committee, Proctor Foundation

1991-1992Seminar Committee, Cardiovascular Research InstituteCommittee on MD with Thesis, School of MedicineLibrary Committee, Academic SenateOrganizer, Biweekly Membrane Traffic MeetingCo-organizer, Membrane Traffic Journal ClubGlass Facility Committee, Department of AnatomyGraduate Admissions Committee, PIBSSeminar Committee, Seminars in BiologyFaculty Search, Department of AnatomySearch Committee, University Library, Director of Information Resources and Services

1992-1993Executive Committee, Biomedical Services Graduate ProgramCurriculum Committee, Biomedical Services Graduate ProgramAd hoc Committee for Faculty AppointmentsSeminar Committee, Seminars in BiologyCommittee on MD with Thesis, School of MedicineGlassware Facility Committee, Department of AnatomyCo-organizer, Membrane Traffic Journal ClubLibrary Committee, Academic SenateCommittee on Mini-courses, Department of BiochemistryGraduate Admissions Committee, PIBSCommittee on UCSF Fellows Program

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1993-1994Executive Committee, Biomedical Sciences Graduate ProgramCurriculum Committee, Biomedical Sciences Graduate ProgramCommittee on MD with Thesis, School of MedicineCo-organizer, Membrane Traffic Journal ClubSeminar Committee, Seminars in BiologyGlassware Facility Committee, Department of AnatomyLibrary Committee, Academic SenateAppointments and Promotions Committee, CVRIGraduate Admissions Committee, PIBSAd hoc Committee for Faculty AppointmentsCurriculum Development and Program Enrichment Committee, Graduate Program in Oral BiologyCommittee on UCSF Fellows Program

1994-1995Curriculum Committee, Biomedical Sciences Graduate ProgramCo-organizer, Membrane Traffic Journal ClubSeminar Committee, Seminars in BiologyGraduate Admissions Committee, PIBSAd Hoc Committee for Faculty Appointments and PromotionsCommittee on UCSF Fellows ProgramAdvisory Committee, Graduate Program in Oral Biology

1995-1996Research Evaluation and Allocation CommitteeCurriculum Committee, Biomedical Sciences Graduate ProgramCo-organizer, Membrane Traffic Journal ClubGraduate Admissions Committee, PIBSAd Hoc Committee for Faculty PromotionsAdvisory Committee, Graduate Program in Oral Biology

1996-1997Research Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubGraduate Admissions Committee, PIBSChairman, Selection Committee for Culpeper Foundation Medical ScholarChairman, Department of Anatomy DNA Sequencer CommitteeCommittee for the Review of Appointments and Advancements to the Academic Administrator/Academic

Coordinator Series

1997-1998Vice-chairman, Department of AnatomyExecutive Committee, Department of AnatomyResearch Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubGraduate Admissions Committee, PIBSChairman, Selection Committee for Culpeper Foundation Medical ScholarChairman, Department of Anatomy DNA Sequencer CommitteeCommittee for the Review of Appointments and Advancements to the Academic Administrator/Academic

Coordinator Series

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1998-1999Vice-chairman, Department of AnatomyExecutive Committee, Department of AnatomyResearch Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubGraduate Admissions Committee, PIBSChairman, Selection Committee for Culpeper Foundation Medical ScholarChairman, Department of Anatomy DNA Sequencer CommitteeCommittee for the Review of Appointments and Advancements to the Academic Administrator/Academic

Coordinator SeriesMolecular Medicine Training Program Selection Committee

1999-2000 (On sabbatical autumn, 1999)Co-Chair, PIBS Journal ClubResearch Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubAdmissions interviewer, PIBS, BMS, MSTPAd hoc Committees for Faculty PromotionsCurriculum Development Committee, BMSSelection Committee, Phi Beta Kappa Graduate Scholarship

2000-2001Joint Information Technology Governance CommitteeResearch Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubAdmissions interviewer, PIBS, BMS, MSTPAd hoc Committees for Faculty PromotionsBMS Cell Biology Course committeeCo-Director, Sandler Family Facility for Live Cell Confocal Microscopy

2001-2002Executive Committee, Liver CenterJoint Information Technology Governance CommitteeResearch Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubAdmissions interviewer, PIBS, BMS, MSTPAd hoc Committees for Faculty PromotionsBMS Cell Biology Course committeeCo-Director, Sandler Family Facility for Live Cell Confocal amd MultiphotonMicroscopyPostdoctoral Training Grant Selection committee, Department of Biochemistry and BiophysicsUCSF Selection Committee, Culpeper Scholar in Medical SciencesUCSF Selection Committee, Searle Scholar

2002-2003Executive Committee, Liver CenterJoint Information Technology Governance CommitteeResearch Evaluation and Allocation CommitteeCo-organizer, Membrane Traffic Journal ClubAdmissions interviewer, PIBS, BMS, MSTPAd hoc Committees for Faculty PromotionsBMS Cell Biology Course committeeCo-Director, Sandler Family Facility for Live Cell Confocal amd MultiphotonMicroscopy, ParnassusDirector, Sandler Family Facility for Live Cell Confocal and Multiphoton Microscopy, Mission BayPostdoctoral Training Grant Selection committee, Department of Biochemistry and BiophysicsUCSF Selection Committee, Culpeper Scholar in Medical SciencesSearch Committee, Chief Division of Nephrology

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2003-2004Executive Committee, Liver CenterJoint Information Technology Governance CommitteeFaculty Search Committee, BMS/PIBS OphthalmologyFaculty Search Committee, BMS/PIBS NephrologyResearch Evaluation and Allocation CommitteeAdmissions interviewer, PIBS, BMS, MSTP, Molecular MedicineAd hoc Committees for Faculty PromotionsBMS Cell Biology Course committeeDirector, Sandler Family Facility for Live Cell Confocal and Multiphoton Microscopy, Mission BayPostdoctoral Training Grant Selection committee, Department of Biochemistry and BiophysicsUCSF Selection Committee, Searle Scholar

Meetings Organized and ChairedWorkshop on Immunoglobulin Transport, FASEB, Saxtons River, VT, 1988Session on Transcytosis at FASEB meeting on Fc Receptors, Copper Mountain, CO, 1990Bay Area Membrane Molecular Biology Meeting, 1991Session on Targeting in Epithelial Cells at UCLA Keystone Meeting on Cell Polarity, Tamarron, CO, 1993Co-Chair, Mini-symposium on Cell Polarity, ASCB Meeting, San Francisco, CA 1994Chair, Keystone Meeting on Cell Polarity, Lake Tahoe, CA 1996Co-Chair, Mini-symposium on Cell Polarity, ASCB Meeting, San Francisco, CA 1998Co-Chair, Mini-symposium on Cell Polarity, ASCB Meeting, Washington, DC 2001Co-chair, Special interest subgroup on small GTPases, ASCB Meeting, San Francisco, CA 2002Co-Organizer, EMBO Meeting on Epithelial Polarity in Development and Disease, Carry Le Rouet, France,

2004Keystone Symposia, Cell Biology Advisory Council, 2004-

Advisory Committees at Other UniversitiesMembrane Traffic Center, Johns Hopkins UniversityRenal Division, Epithelial Cell Biology Center, University of PittsburghPolycystic Kidney Disease Center, Mt. Sinai School of Medicine, New York.

Society ServiceAmerican Society for Cell Biology, Local Arrangements Committee, 1994. Organized High School

Teachers and Students ProgramAmerican Society for Cell Biology, Congressional Liaison Committee, 1999-American Society for Cell Biology, Pre-doctoral Travel Award Committee, 1998American Society for Cell Biology, Women in Cell Biology Career Lunch, Table Leader, 2001-Society for Mucosal Immunology, Publication Committee. 1999-presentAmerican Cancer Society, Council for Extramural Grants, 2004-. Keystone Symposia, Cell Biology Advisory Council, 2004-American Society for Cell Biology, National Award Selection Committee

International ServiceWorld Health Organization—International Union of Immunoglogical Societies,

Nomenclature Committee, Subcommittee on Fc Receptor Nomenclature, 1992-presentU.S. Civilian Research Development Foundation for the Independent States of the Former Soviet Union,

2001-presentAdvisor to U.S. Defense Threat Reduction Agency Consultant to International Science and Technology Center, St Petersburg, Russia.

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Scientific Advisory Board, NIH Research Center for Minority Institutions, Cell and Molecular Biology Center, Universidad Central del Caribe, Puerto Rico, 2001-present

Scientific Advisor, Cancer Stem Cell Research Center, Torino, Italy, 2005-.

Editorial BoardsMolecular Biology of the Cell, Editorial Board1997-2001, Associate Editor 2002-In 2003 I made decisions on 66 manuscripts for Molecular Biology of the Cell.

International Review of Cytology, 1987-PresentGuest Editor, Seminars in Cell Biology, 1991Traffic, 1999-PresentBioMed Central Cell Biology, 2000-presentGuest Editor, METHODS, 2003

Reviewer ActivitiesIn 2003 I reviewed 75 manuscripts for Science, Cell, Molecular Cell, Developmental Cell, Neuron, Immunity, Nature, Nature Cell Biology, Nature Biotechnology, Nature Reviews Molecular Cell Biology, EMBO Journal, Journal of Cell Biology, Molecular Biology of the Cell, PNAS, Journal of Biological Chemistry, Traffic, Journal of Cell Science, Journal of Clinical Investigation, Journal of Immunology, and other journals.

As Associate Editor of Molecular Biology of the Cell, I handle approximately 6-8 manuscripts per month.

I am an ad hoc reviewer of an average of two grants per month, primarily for NSF, and also for the VA, and agencies in England, Switzerland, Ireland, Italy, Israel, HFSP, and Wellcome Trust.

Member, American Cancer Society, Council on Extramural Grants, 2004-. This Council oversees the entire extramural research budget of the ACS and makes policy recommendations for the extramural program. NIH, CMBK Study Section, 2004-NCI, External oversight of intramural program, 2004.Regular Member: Cell Biology Study Section (Cellular Organization Panel), NSF, 1995-2002Member: Special Study Sections, National Cancer Institute, 1992, 1993Member: Special Study Sections, NIAID, 1996, 1997, 2000 American Cancer Society, Cell Biology Study Section, Ad Hoc, 1994National Institute of Allergy and Infectious Diseases, Special Emphasis Panel, 1996, 2000National Institute of Diabetes and Digestive and Kidney Disease, Special Emphasis Panel, 2000, 2003Ad hoc Member, Telethon Career Project, Italian Telethon, 1999.National Institute of Child Health and Human Development, External oversight of intramural program, 2002;

Professional SocietiesAmerican Society for Cell BiologyAmerican Association for Advancement of ScienceSociety for Mucosal Immunology (Member since inception)American Society for Microbiology

Other Community ServiceParents Committee, Room Parent, Jewish Community Center, Rosenberg Preschool, 1995-98

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Golden Gate Heights Neighborhood Association, Neighborhood Emergency Response Team, 1996-presentNational Yiddish Book Center, member, 1988-presentBeyt Tikkun (synagogue), member, 1996-98Congregation Beth Sholom, member 1998-1999Congregation Bnai Emmunah, member 2000-presentSan Francisco Youth Synchronized Skating Team, fundraising, 1999-2000

Patents (all assigned to UC Regents)

U.S. Patent 6855810, issued February 15, 2005, “Ligands directed to the non-secretory component, non-stalk region of the pIgR and methods of use thereof

US Patent 6,808,709, issued October 26, 2004, “Immunoglobulins containing protection proteins and their use.”

US Patent 6,340,743, issued January 22, 2002, “Antibodies to pIgR Stalk”

US Patent 8,856,383, issued March, 2000, “Cellular Internalization of pIgR Stalk and Associated Ligands”

US Patent 6,046,037, issued April 4, 2000, “Method for producing immunoglobulins containing protection proteins in plants and their use.”

US Patent 6,303,341, issued October 16, 2001, “Method for producing immunoglobulins containing protection proteins in plants and their use.”

U.S. Patent Application 09/292,274, "Protein Transport Assays"

U.S. Patent Application 60/192,198, “Anti-pIgR antibodies with improved transcytosis.”

EXTRAMURAL RESEARCH SUPPORT

Past

NIH New Investigator Award R23 AI 21752Transepithelial transport of immunoglobulins(At Whitehead Institute)10/1/84—6/30/87$105,000 Total Direct Costs

Hood FoundationTransport of immunoglobulins across intestinal cells(At Whitehead Institute)1/1/88—12/31/87$35,000 Total Direct Costs

Searle Scholar AwardPolarized traffic in epithelial cells7/1/89—6/30/92

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$162,000 Total Direct Costs

Cancer Research Institute Investigator AwardMembrane protein sorting7/1/90—6/30/94$200,000 Total Direct Costs

Charles E. Culpeper Foundation Scholar in Medical ScienceProtein sorting in polarized cells7/1/92—6/30/95$300,000 Total Direct Costs

Edward Mallinckrodt Foundation Medical ScholarEpithelial Membrane Traffic10/1/92—9/30/95$175,000 Total Direct Costs

NIH Gene Therapy Center, Pilot ProjectApical Uptake of DNA7/l/93-6/30/95$100,000 Total Direct Costs

American Heart Association Established Investigator7/1/93-6/30/98$255,000 Total Direct Costs

American Cancer SocietyRegulation of transcytosisIM-789777/1/95—6/30/98$321,000 Total Direct Costs

NIH R01 AI39161A novel method for intestinal absorption of antibodies9/1/95-8/31/00$513,003 Total Direct Costs

NIH R21DK55722A novel method for mucosal gene delivery 4/1/99-3/31/01$200,000 Total Direct Costs

NIH R44AI41895 (SBIR Phase 2) (P.I. Kerry Petersen at LI-COR Corp.)Detecting biomolecules with near-infrared fluorescence10/1/99-9/30/01$291,000 Total Direct Costs

DOD/US Army Breast CancerMembrane traffic alterations in epithelial cancer9/30/97-10/29/00

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$201,534 Total Direct Costs

Current (All Mostov P.I.)

NIH R01 AI25144Transport of immunoglobulins across epithelial cells(Grant originated at Whitehead Institute and moved to UCSF)7/1/87—6/30/92$771, 938 Total Direct Costs

Competitive Renewal Funded8/1/92-7/31/97$930,575 Total Direct Costs

Competitive Renewal Funded8/1/97-7/31/02$1,083,640 Total Direct Costs

Competitive Renewal Funded (MERIT Award, 10 years)8/1/02-7/31/12$2,500,000 Total Direct Costs

NIH RO1 DK067153-01Control of orientation of epithelial polarity4/1/04-3/31/09$1,250,000 Total Direct Costs

NIH R01 HL55980Host cell determinants in Pseudomonas pneumonia12/1/95—11/30/98$439,644 Total Direct Costs

Competitive Renewal Funded4/1/99-3/31/04$1,170,244 Total Direct Costs

NIH R01 AI36953Regulation of transcytosis of immunoglobulins10/1/95-9/30/00$761,651 Total Direct Costs

Competitive Renewal Funded10/1/00/-8/31/05$750,000 Total Direct Cost

NIH RO1DK58061Novel method for mucosal transport of protein drugs

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6/1/01-5/31/06$630,000 Total Direct Cost

NIH P01 AI053194I am PI on this Program Project Grant, as well as leader of Project 1 and Director of Cores A and C.

Project 1Molecular control of epithelial wound healing09/30/02-03/31/07$708,223 Total Direct Cost

Core AAdministrative Core09/30/02-03/31/07$211,759 Total Direct Cost

Core CMulitiphoton and confocal live cell imaging09/30/02-03/31/07$284,509 Total Direct Cost

NIH S10 RR0179734/1/03-3/31/04Multiphoton Microscope Facility for UCSF Mission Bay$496,002 Total Direct Costs.

INVITED TALKS AT MEETINGS

7/81 Gordon Conference: Red Blood Cells

5/82 New York Academy of Science, Mucosal Immunology Meeting

7/82 Gordon Conference: Lysosomes

9/84 World Congress on Cell Biology, Tokyo, Symposium: Membrane Traffic

9/84 Satellite Meeting on Membrane Recycling, Kyoto, Japan

11/84 Cold Spring Harbor, Banbury Meeting on Membrane Traffic

5/85 French Society for Immunology, Annual Meeting, Keynote Speaker

9/85 European Molecular Biology Laboratory, Membrane Traffic Course

11/85 ASCB Annual Meeting, Mini-symposium on Cell Polarity

7/86 Gordon Conference: Lysosomes

8/86 FASEB Summer Conference: Receptors

12/86 ASCB: Mini-symposium: Cell Polarity

1/87 Salk Institute Symposium

3/87 Recombinant DNA Congress, San Francisco

4/87 FASEB: Mini-symposium on Epithelial Polarity

6/87 FASEB Summer Meeting: Fc Receptors

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7/87 Gordon Conference: Membrane Molecular Biology

7/87 Gordon Conference: Membrane Transport

9/87 International Germinal Center Congress, Oslo, Norway

10/87 EMBO Meeting on Cell Polarity, Bandol, France

11/87 Upjohn Meeting on Advanced Drug Delivery

5/88 FASEB: Mini-symposium on Epithelial Polarity

7/88 Gordon Conference: Lysosomes

8/88 FASEB Summer Conference: Receptors

9/88 Joint ASCB/EMBO Meeting on Intracellular Traffic, Pitlochry, Scotland

10/88 UCSF Laurel Heights Biotechnology Conference

1/89 ASCB Mini-symposium: Endocytosis

5/89 American Gastroenterological Association Meeting

7/89 Gordon Conference: Membrane Molecular Biology

7/89 Gordon Conference: Membrane Transport

6/90 Gordon Conference: Lysosomes

6/90 FASEB Summer Conference: Fc Receptors

7/90 International Congress on Mucosal Immunology, Tokyo, Plenary Lecture

8/90 World Congress on Gastroenterology, Satellite Meeting on Mucosal Immunology, Sydney

12/90 ASCB Mini Symposium: Cell Polarity

2/91 Gordon Conference: Angiotensin

6/91 IRBM Symposium on Gene Expression During Liver Differentiation and Disease, Sorrento, Italy

6/91 International Falk Symposium on Hepatic Endocytosis, Hamburg, Germany (Keynote Speaker)

8/91 FASEB Summer Conference: Gastrointestinal Tract

6/92 Gordon Conference: Lysosomes

7/92 International Congress on Cell Biology, Madrid, Symposium: Endocytosis

2/93 Keystone Symposium on Epithelial and Neuronal Polarity

2/93 Keystone Symposium on Genetic and In Vitro Analysis of Cell Compartmentalization.

2/93 Keystone Symposium on Emerging Principles for Vaccine Development: Antigen Processing and Presentation

3/93 Gordon Conference: Molecular Pharmacology

3/93 Society for Inherited Metabolic Disorders Annual Meeting, Asilomar

4/93 British Society for Cell Biology, Norwich, England

7/93 FASEB Summer conference: Protein Kinases

11/93 American Gastroenterological Association Winter Conference: Gastrointestinal Transport

7/94 Gordon Conference: Lysosomes

12/94 ASCB Mini-symposium: Cell Polarity

6/95 Cold Spring Harbor Symposium

7/95 FASEB Meeting: Gastrointestinal Tract

8/95 Danish Cancer Society, Copenhagen

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11/95 American Society for Nephrology, San Diego

2/96 Keystone Symposium: Cell Polarity

7/96 FEBS Meeting, Barcelona, Spain

8/96 Society for Industrial Microbiology, Raleigh-Durham, North Carolina

9/97 European Science Foundation, Endocytosis Meeting, Barcelona, Spain

4/98 R.R. Bensley Award Lecture, FASEB Meeting, San Francisco

5/98 Institute of Molecular Pathology Cancer Symposium, Vienna, Austria

10/98 American Society of Nephrology, Philadelphia

12/98 American Society of Cell Biology, Minisymposium on Cell Polarity, San Francisco (session co-chair)

3/99 Rockefeller University/Cornell Medical College MD/PhD Program Anniversary Symposium

8/00 BioCity Symposium, University of Turku, Finland

3/01 ASCB Keith Porter Symposium, Airlie, Virginia

5/01 Symposium in honor of Gunter Blobel, 65th Birthday, Max Planck Institute, Dresden, Germany

5/01 Rockefeller University Centennial Symposium, New York City

7/01 Keystone Symposium on Drug Delivery, Breckenridge, Colorado

7/01 British Society for Pharmacology, Dublin, Ireland

8/01 International Workshop on Developmental Nephrology, Victoria, British Columbia

9/01 INSERM Laudat Conference on Epithelial Polarity, Aix-les-Bains, France

9/01 Jacques Monod/EMBO Conference on Microfilament Function, Giese, France

11/01 ColdSpring Harbor/Banbury Conference on Tubulogenesis, Huntington, NY

12/01 American Society of Cell Biology, Minisymposium on Cell Polarity, Washington, DC (session co-chair)

6/02 Institute of Biopreparations, Conference on Cytokines, Inflammation and Immunity, St. Petersburg, Russia.

9/02 International Society for Differentiation, Lyon, France

12/02 American Society of Cell Biology, Session on monomeric GTPases. San Francisco.

5/03 American Society for Microbiology, Session on Epithelia-Pathogen Interactions, Washington, DC.

5/03 Digestive Diseases Week, Orlando, FL

6/03 Gordon Conference on Small GTPases, Ventura, CA.

7/03 FASEB Meeting on GI System, Tucson, AZ

9/03 European Science Foundation, Endocytosis Meeting, Naples, Italy

11/03 American Society for Nephrology, San Diego, CA

11/03 Bay Area Membrane Traffic Meeting.

1/04 Keystone Symposium on Rab GTPases, Breckenridge, CO

1/04 Timberline Meeting on Cell Polarity, Mt. Hood, Oregon

3/04 EMBO Meeting on Epithelial Polarity in Development and Disease, Carry Le Rouet, France, 2004

4/04 FASEB Symposium on Epithelial Polarity, Washington, D.C.

9/04 Welcome Meeting on Cell Organization, Singapore

3/05 Keystone Meeting on Cell Polarity, Coeur d'Alene, Idaho

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4/05 FASEB Symposium on Cell Polarity, San Diego, CA

5/05 EMBO/IRCC Meeting on Invasive Growth, Torino, Italy

6/06 Japanese Society of Developmental Biology Symposium, Sendai, Japan

8/05 FASEB Meeting on Polycystic Kidney Disease, Keynote Speaker, Saxtons River, VT

9/05 American Liver Foundation Symposium, Boston, MA

10/05 Cooperative Biological Research Review, St. Petersburg, Russia

12/05 Society for Basic Urologic Research/Eur. Soc. for Urological Research, Miami, FL

2/06 Developmental Vascular Biology Workshop, Pacific Grove, CA

2/06 Ernest Just Symposium, Medical University of South Carolina, Charleston, SC

5/06 Max-Delbrueck Center Meeting on Epithelial Organization and Organ Development, Berlin, Germany

6/06 Lunenfeld Institute Symposium on Cell Polarity, Toronto, Canada

6/06 Novartis Foundation Symposium on Vascular Development, London, UK.

6/06 Royal Society of Medicine/Physiological Society meeting on Angiogenesis, London, UK.

12/06 ASCB Meeting on Lipid Signaling, San Diego, CA

12/06 ASCB Meeting on Epithelial Systems Biology, San Diego, CA

4/07 Experimental Biology, Plenary Session. Washington, D.C.

INVITED RESEARCH SEMINARS

10/80 European Molecular Biology Laboratory

10/80 University of Milan, Italy, Institute of Pharmacology

10/80 University of Lausanne, Switzerland, Department of Biochemistry

10/80 University of Naples, Italy, Department of Biochemistry

11/81 Rockefeller University, Laboratory of Cell Physiology

4/82 New York University, Department of Pathology

2/83 New York Blood Center

10/83 Yale University, Department of Cell Biology

10/83 NIH, Laboratory of Pathology

2/84 MIT, Department of Biology

2/84 SUNY Downstate Medical Center, Department of Pathology

10/84 Harvard University, Department of Cell and Developmental Biology

12/84 Harvard University, Department of Biochemistry and Molecular Biology

12/84 Tufts University, Department of Cell Biology

5/85 Pasteur Institute, Paris, Department of Molecular Biology

8/85 Collaborative Research Co., Lexington, MA

9/85 University of Lausanne, Switzerland, Department of Biochemistry

10/85 Harvard University, Department of Cellular Biology and Anatomy

10/85 Yale University, Department of Cell Biology

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12/85 McGill University, Department of Molecular Biology

5/86 Cornell University, Department of Cell Biology and Anatomy

5/86 Biogen, Cambridge, MA

5/86 New York University, Department of Cell Biology

9/86 Harvard Medical School, Joslin Diabetes Center

11/86 Massachusetts General Hospital, Laboratory of Gastroenterology

11/86 SUNY Downstate Medical Center, Department of Cell Biology

12/86 NIH Laboratory of Cell Biology

1/87 Columbia University, Department of Physiology

2/87 Princeton University, Department of Molecular Biology

3/87 Stanford University, Department of Biochemistry

3/87 Genentech

3/87 UCSF, Department of Biochemistry and Biophysics

4/87 Brandeis, Department of Biology

5/87 Rockefeller University

7/87 University of Pennsylvania, Department of Pathology

7/87 Cambridge Neuroscience Research Company

9/87 Norwegian Cancer Research Institute

9/87 University of Bergen, Norway, Department of Immunology

10/87 Weslyan University, Department of Molecular Biology

2/88 Dartmouth Medical College, Department of Biochemistry

5/88 Alkermees Research Co.

10/88 University of Massachusetts, Amherst, Department of Biochemistry

10/88 Yale Medical School, Section on Immunology

10/88 Mehary Medical College, Department of Biochemistry

10/88 University of Illinois Medical College, Chicago, Department of Immunology

10/88 Fox Chase Cancer Center

9/89 Stanford University, Immunology Program

9/89 Athena Neurosciences Co.

10/89 UCSF, Department of Anatomy

10/89 UCSF, CVRI

11/89 UCSF, Department of Microbiology and Immunology

2/90 Cornell Medical College, Department of Cell Biology

2/90 Annual NOVO Lecture, Danish Biological Society

2/90 European Molecular Biology Laboratory, Heidelberg

2/90 Academy of Sciences, Department of Molecular Biology, East Berlin

7/90 Kyushu University, Fukuota, Japan, Department of Molecular Biology

8/90 University of Melbourne, Australia, Department of Pathology

8/90 Heart Research Institute, Sydney

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11/90 Stanford University, Department of Pharmacology

2/91 Lawrence Berkeley Laboratory

2/91 University of California, Berkeley, Department of Molecular and Cell Biology

3/91 University of Colorado, Department of Cellular and Structural Biology

6/91 Princeton University, Department of Molecular Biology

6/91 University of Basel, Biocenter

6/91 Cornell University Medical College, Department of Cell Biology

6/91 Albert Einstein College of Medicine, Department of Anatomy and Structural Biology

8/91 Whitehead Institute

1/92 Stanford University, Department of Microbiology and Immunology

3/92 Vanderbilt University, Department of Pharmacology

4/92 Monsanto Corporation

4/92 Washington University, St. Louis, Program in Immunology

7/92 Tel Aviv University, Department of Biochemistry

7/92 Hebrew University, Lautenberg Center for Immunology

7/92 Weizmann Institute, Department of Chemical Immunology

4/93 Memorial Sloan Kettering Cancer Research Institute, Laboratory of Cellular Biophysics

4/93 Guys and St. Thomas’ Medical School, London, Department of Immunology

10/93 University of Kentucky, Department of Microbiology and Immunology

1/94 UCSF, Cardiovascular Research Institute

2/94 Vollum Institute, Oregon Health Sciences University

3/94 University of Utah, Department of Pathology

4/94 University of Arizona, Department of Cell Biology and Anatomy

7/94 Mount Desert Island, Biological Laboratory, Bar Harbor, Maine

8/94 Alza Corporation, Palo Alto, California

1/95 University of Alabama, Birmingham, Department of Physiology

5/95 Mayo Medical Center, Rochester, MN, Department of Biochemistry

9/95 University of Wisconsin, Madison, WI, Department of Biochemistry

1/96 Chiron Corp., Emeryville, California

8/96 LI-COR Corp., Lincoln, Nebraska

9/96 Case-Western Reserve University, Cleveland, Ohio

1/97 Inhale Therapeutic Systems, Palo Alto, CA

3/97 Stanford University, Department of Biochemistry, Palo Alto, CA

4/97 University of Chicago, Department of Physiological and Pharmacological Sciences, Chicago, IL

5/97 Cornell University Medical College, Department of Biochemistry, New York, NY

8/97 LI-COR Corp., Lincoln, Nebraska

10/97 Immunex Corp., Seattle, WA

5/98 Cornell Univeristy, Department of Physiology, NY.

9/98 UCSF, Department of Pediatrics

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10/98 Washington University, St. Louis, Keynote Speaker, Mallinckrodt Symposium

1/99 California Institute of Technology, Pasadena, CA, Department of Biology.

3/99 Cornell University, Department of Cell Biology

5/99 New York University School of Medicine, Department of Cell Biology

8/99 UCSF, Division of Nephrology

9/99 Indiana University School of Medicine, Division of Nephrology

11/99 Yale University School of Medicine, Department of Cell Biology

12/99 University of Alabama at Birmingham, Department of Cell Biology

4/00 Columbia University College of Physicians and Surgeons, Department of Physiology

4/00 Mt. Sinai School of Medicine, Department of Biochemistry

7/00 University of North Carolina, Chapel Hill, Department of Pharmacology

8/00 Baylor University, Houston, TX, Department of Biochemistry

9/00 NIH, National Institute of Child Health and Human Development

10/00 St. Jude Children’s Research Hospital, Memphis, TN

11/00 Albert Einstein Medical College, New York, NY, Department of Molecular Pharmacology

1/01 University of Southern California, Department of Pharmaceutical Sciences

1/01 Princeton University, Princeton NJ, Department of Molecular Biology

2/01 School of Medicine, University of Southern California

9/01 Institut Curie, Paris, France

2/02 Emory University, Atlanta, GA, Department of Pathology

3/02 Vanderbilt University, Nashville, TN, Department of Microbiology

4/02 University of Pittsburgh, Pennsylvania, Department of Cell Biology

5/02 Northwestern University, Evanston IL. Department of Molecular Biology

10/02 Protein Design Labs, Freemont, CA.

1/03 Scripps Research Insitute, La Jolla, CA, Department of Cell Biology

3/03 Harvard Medical School, Boston MA, Digestive Diseases Center.

4/03 University of California, San Francisco, CA, Liver Center

4/03 Universidad Central del Caribe, Puerto Rico, Center for Neurobiology

4/03 Cornell University, Department of Cell Biology, New York

4/03 Rutgers University, Department of Molecular Biology, New Jersey

4/04 UCSF, Division of Nephrology

10/04 University of Illinois, Department of Pharmacology, Chicago, Illinois

2/05 Oregon Health and Science University, Department of Developmental and Cell Biology, Portland, OR

3/05 University of Pennsylvania, Department of Biology, Philadelphia, Pennsylvania

5/06 EMBL, Heidelberg, Germany

5/06 University of Iowa, Department of Anatomy and Cell Biology, Iowa City, Iowa

6/06 San Raffaele Scientific Institute, Milan, Italy

6/06 Ludwig Institute, London, UK

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02/07 Memorial Sloan Ketterin Cancer Center, NY, NY

04/07 Fox Chase Cancer Center, Distinguished Lecturer, Philadelphia, PA

04/07 Max Planck Institute for Cell Biology and Genetics, Dresden, Germany

05/07 University of Illinois at Chicago, Department of Biological Sciences, Chicago, IL

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RESEARCH PROGRAM: Epithelial polarity and morphogenesis

The most fundamental type of organization of cells in metazoa is that of epithelia. Epithelial cells form sheets of cells that line surfaces and internal cavities. The simplest metazoa, such as hydra, consist largely of two concentric cylinders of epithelial cell sheets. Most internal organs in higher animals, such as the respiratory, digestive, genito-urinary and vascular systems are lined by a single layer of epithelial cells. We are studying both the structure of individual epithelial cells and how they are organized into multicellular tissues and organs. We are focused on three basic questions:

1. How is the polarization of epithelial cells determined? Epithelial cells are highly polarized, with an apical surface facing the lumen of the cavity and a basolateral surface facing other cells and extracellular matrix. Epithelial cells have a conserved set of protein complexes, such as the Par3/Par6 complex, which are needed to become polarized. Upstream of these complexes, we have discovered a new pathway that determines the orientation of polarization, that is which way the cell points. Alterations in this pathway can cause cells to reverse polarity, so that the apical surface now points away from the central lumen. We have found that this pathway starts with assembly of the laminin-rich extracellular matrix around the cells, followed by integrin signaling at the basolateral surface. The signal for orientation of polarity must then move across the cells; this may be mediated by transcellular movement of the small GTPase, Cdc42. Finally, Cdc42 apparently promotes the organization of the Par3/Par6 and other complexes at the apical surface of the cell.

2. Once the initial orientation of polarity is determined, how does the cell execute this program to become fully polarized? The apical and basolateral surfaces of the cell have completely different protein and lipid compositions, and so the cell has mechanisms to specifically sort these components to one surface or the other. The lipid phosphatidyl inositol 3,4,5-P3 (PIP3) is a crucial determinant of this process. Normally PIP3 is found only at the basolateral surface. Ectopic localization of PIP3 to the apical surface can transform this apical surface into basolateral surface, by causing the relocalization of normally basolateral proteins to the apical surface, as well as removal of apical proteins from this transformed surface. Proteins and lipids are transported to the apical or basolateral surfaces by vesicular carriers. The fusion of these carriers with the surface involves syntaxin proteins, which are found on the target membrane. We have found that syntaxin 4 is exclusively basolateral, while syntaxin 3 is exclusively apical. Ectopic localization of syntaxin 3 to the basolateral surface causes misdelivery of apical proteins to the basolateral surface. This data indicate that PIP3 and syntaxins specify where vesicles are delivered to in the cell.

3. The basic building block of most epithelial organs are tubes, lined by epithelial cells. How do epithelial cells organize themselves into tubes? We have found that when epithelia cells remodel to form tubes, they start by partially dedifferentiating, losing their epithelial polarity and taking on many of the properties of migrating fibroblasts. The cells then migrate to positions where they will form the new tube. The cells then re-differentiate, reacquiring epithelial polarity and creating new lumens between the cells. Tubulogenesis can thus be conceptualized as occurring in two stages, dedifferentiation and re-differentiation.

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Selected publications.

van IJzendoorn, S.C.D., Tuvim, M.J., Weimbs, T., Dickey, B.F., and Mostov, K.E. Direct interaction between Rab3b and the polymeric immunoglobulin receptor controls ligand-stimulated transcytosis in epithelial cells. Develop. Cell, 2:219-228, 2002

I conceived, directed and interpreted this work. Van IJzendoorn was a post-doc in my lab who performed all the experiments. The middle authors contributed reagents.

O’Brien, L.E., Zegers, M.M.P., and Mostov, K.E. Opinion: Building epithelial architecture: insights from three-dimensional culture models. Nat. Rev. Mol. Cell Biol. 3:531-537, 2002

This Opinion piece proposed several novel concepts and has been highly influential in the field. For instance, new computer modeling studies have been done based on ideas proposed in this paper. I conceived of the ideas. Much of the writing was done by O’Brien in close collaboration with me. Zegers did the drawings.

Yu, W., O’Brien, L.E., Wang, F., Bourne, H., Mostov, K.E., and Zegers, M.M.P. Hepatocyte growth factor switches orientation of polarity and mode of movement during morphogenesis of multicellular epithelial structures. Mol. Biol. Cell, 14:748-763, 2003.

I conceived, directed and interpreted this work. Yu and Zegers were post-docs in my lab who did the work. The other authors provided reagents.

O'Brien, L.E., Tang., K., Kats E.S., Schutz-Geschwender, A., Lipschutz, J.A., Mostov, K.E., ERK and MMPs Sequentially regulate distinct stages of epithelial tubule development. Developmental Cell. In press. 2004.

I conceived, directed and interpreted this work. O’Brien was a student and then post-doc in my lab who did the work, assisted by Tang (a technician) and Katz (a summer student). Schutz-Geschwender and Lipschutz contributed to methodological development.

Vergés,  M., Luton, F., Gruber, C., Tiemann, F., Reinders, L., Huang, L., Burlingame, A., Haft, C.,  Mostov. K.E. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor.  Nat. Cell Biol. In press. August 2004.

I conceived, directed and interpreted this work. Vergés was a post-doc in my lab who did the work, with help from Luton, another post-doc in my lab and Gruber, a technician in my lab. Tiemann was a collaborator at a company who supplied reagents. Reinders and Huang were technicians in Burlingame’s lab who provided mass spectroscopy analysis. Haft was a collaborator at NIH who supplied reagents.

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