Grunwald, Gerald B.
Gerald B. Grunwald, PhD
Jefferson Alumni Hall
Philadelphia, PA 19107
(215) 503-6690 fax
PhD, University of Wisconsin-Madison, Zoology (Developmental Biology) - 1981
MS, University of Wisconsin-Madison, Zoology (Developmental Biology) - 1978
BA (cum laude), Cornell University, Biological Sciences - 1976
Professor & Associate Dean
Research and Clinical Interests
Developmental biology and neuroscience; eye development and disease, analysis of the role of cadherin cell adhesion molecules in normal and abnormal embryonic development and in proliferative diseases of the nervous mechanisms of cadherin expression and function.
The research interests of our laboratory center on studies of the developmental biology and pathogenesis of the eye, especially of the neural retina, the retinal pigment epithelium, and the lens. We focus on analysis of cadherin cell adhesion molecule structure and function during these processes using cell biological, immunological, biochemical and molecular genetic approaches. Cadherins are cell surface integral membrane glycoproteins of approximately 130 kDa molecular weight that mediate calcium-dependent intercellular adhesion in a homophilic fashion. Cadherins are associated with the cytoskeleton via proteins called catenins. The cadherins are structurally conserved molecules that have been identified in all invertebrate and vertebrate metazoan species including humans. A hallmark of the cadherins is their participation in the formation of tight adhesions among epithelial and neural cells. Another hallmark of cadherins is their complex and dynamic pattern of expression during embryonic development, where it has been found that differential cadherin expression often correlates with the segregations and rearrangements of cell populations during embryonic development. Cadherin cell adhesion molecules are also expressed in mature tissues where they contribute to the maintenance of tissue stability, and their misexpression has been implicated in the pathogenesis of cancer and other proliferative disorders.
A major focus of our laboratory's current research has been directed at elucidating the genetic and epigenetic mechanisms that regulate the complex patterns of cadherin expression during development, and the specific functional role of cadherins during ocular development. We have identified multiple mechanisms that regulate cadherin expression and function during embryonic development. These include regulation of the level of mRNA expression, post-translational processing including protein kinase-mediated phosphorylation, rapid turnover at the cell surface mediated by an endogenous cell surface metalloprotease, and modulation of expression by growth factors. We have shown that N-cadherin is the target of protein tyrosine kinase-mediated post-translational modifications that affect its phosphorylation, stability and turnover in developing nervous tissues. We are working towards the identification and characterization of the cell surface metalloprotease that cleaves N-cadherin. We have identified cytokines such as EGF that coordinately regulate expression of distinct cadherin subtypes, and are exploring the signaling pathways and genetic mechanisms that control this expression. The possible role of altered cadherin expression and function in retinal pigment epithelial cells in proliferative vitreoretinopathy, and of neural retinal cells in retinoblastoma, is also being explored. We have determined that cadherin deficiency contributes to altered adhesive behavior among retinoblastoma cells, and that restoration of cadherin expression reverses this behavior. The long-term goal of our studies is to contribute to the structural and functional analysis of this fascinating family of molecules, and to clarify their role in both normal ocular development and in the onset and progression of proliferative diseases of the eye.
FUNDED GRANT SUPPORT AWARDS (TOTAL DIRECT COSTS LISTED)
As principal investigator
1981-1984: NIH NRSA Award F32HL06426, "Immunochemical analysis of synaptic molecules," $42,156.
1986-1989: NIH, National Eye Institute, RO1EY06658, "The role of cell adhesion in retinal pattern formation," $190,035.
1986-1989: March of Dimes, 5-569, "The role of cell adhesion in embryonic compartmentation," $76,000.
1987: NSF, DCB-8705524, "Sixth Annual Mid-Atlantic Regional Developmental Biology Meeting," $2,000.
1988: NSF, DCB-8806368, "Seventh Annual Mid-Atlantic Regional Developmental Biology Meeting," $2,000.
1988: NIH, BRSG Small Instrumentation Grant, "Ultracentrifuge," $30,650.
1991-1994: NIH, NEI R01EY06658, "The role of cell adhesion in retinal pattern formation," $261,070.
1990-1991: Institutional Research Grant (Thomas Jefferson University), "The Role of Cell Adhesion in Retinal Pattern Formation," $8,200.
1991-1995: NSF, BNS-9021703, "Post-translational Regulation of N-cadherin During Neural Development," $111,179.
1994-1997: NIH, NEI R01EY06658, "The role of cell adhesion in retinal pattern formation," $376,008.
1995-1999: NIH, NEI RO1EY10965, Cadherin function in lens development, $339,516.
1997-2001: NIH, NEI RO1EY06658, Cell adhesion in retinal development and pathology, $612,036.
2001-2007: NIH, NEI RO1EY06658, Cell adhesion in retinal development and pathology, $800,000.
2003-2008: NIH, NIEHS T32ES07282. Cellular and molecular determinants of birth defects, $825,591.
2006-2008: Institutional Pilot Research Grant, Thomas Jefferson University and Wills Eye Hospital, Analysis of intrinsic and extrinsic modulators of retinal pigment epithelial cell phenotype, $15,000.
As co-principal investigator
1989-1992: NIH, NINCDS, N522093 "Afferent organization in neurologically mutant mice," $308,512.
1992-1995: NIH, NINDS, NS22093, "Afferent organization in neurologically mutant mice," $256,642.
1987-1990: NIH, NEI, F32EY06067, "Study of a cell adhesion molecule in retina development," $63,996, for Laura Lagunowich.
1993: NSF and American Society for Cell Biology, Cell Biology Teacher Research Fellowship, $6,350, for Donna Peterson.
1993-1996: NIH, NEI, F32EY06470, "Characterization of the retinal N-cadherin protease", $81,200, for Celeste Ferreira.
1994: NSF and American Society for Cell Biology, Cell Biology Teacher Research Fellowship, $6,350, for Donna Peterson.
1997-2000: NIH, NEI, F32EY06787, Cadherin expression and function in lens development, $104,600, for Lilley Leong.
1999-2002: NIH, NIEHS, F32ES05893, Cadherins as molecular targets of environmental pollutants, $106,788, for Markus Dey.
PROFESSIONAL SOCIETY MEMBERSHIPS, INCLUDING OFFICES HELD
Society for Developmental Biology
Representative to FASEB Summer Conferences Advisory Committee (2004-present)
Society for Cell Biology
Society for Neuroscience
Secretary-Treasurer, Potomac Chapter (1983-1985)
Councilor, Philadelphia Chapter (1986-1987)
Vice president, Philadelphia Chapter (1987-1988)
President, Philadelphia Chapter (1988-1989, 1990-1991)
American Association for the Advancement of Science
Association for Research in Vision and Ophthalmology
New York Academy of Sciences
Service on Jefferson Medical College Administrative Committees and Related Activities
1987-1993, 1994-2001: Member, Committee on Research.
1987-1992: Member, Dean's Overage Research Program Subcommittee of Committee on Research.
1988: Student Advocate, Jefferson Medical College Judicial Board.
1991-1995: Member, Judicial Board.
1991-1993: Member, Deans'' Advisory Committee of the Professorial Faculty.
1992: Vice-chairman, Basic Science Departments Review Committee, Liaison Committee on Medical Education Self-Study.
1992-1993: Chairman, Pilot Studies Subcommittee of the Committee on Research,.
1993: Invited speaker, Jefferson Medical College Parent's Day.
1993: Discussion leader, Jefferson Medical College Faculty Retreat.
1994: Invited speaker, Jefferson Medical College Parent's Day.
1995-2001: Chairman, Committee on Research.
1995: Invited speaker, Jefferson Medical College Parents Day.
1996: Invited speaker, Jefferson Medical College Parents Day.
1995-1996: Chairman, Ad Hoc Scientific Misconduct Inquiry Committee.
1997: Invited speaker, Jefferson Medical College Parents Day.
1996-1997: Chairman, Ad Hoc Scientific Misconduct Inquiry Committee.
1998: USMLE Step 1 Board Reviewer.
1998-2003: Member, Committee on Faculty Affairs.
1998: Invited speaker, Jefferson Medical College Parents Day.
1998-present: Jefferson Medical College Representative to American Association of Medical Colleges Group on Graduate Research, Education and Training.
1999-2000: Chairman, Committee on Graduate Education in the Basic Sciences, Liaison Committee on Medical Education Institutional Self-Study.
1999-2000: Chairman, Ad Hoc Scientific Misconduct Inquiry Committee.
1999-present: Member, MD/PhD Program Steering Committee.
2000: Member, Ad hoc Research Strategic Planning Committee.
2000: Member, Ad hoc Computational Biology and Bioinformatics Committee.
2001-2003: Member, Ad hoc Committee on Postdoctoral Fellow Policy.
2002: Member, Gratz Prize Selection Committee.
2002: Chair, Ad Hoc Sabbatical Leave Committee
2002-2004: Member, Committee on Committees.
2005: Chair, Ad Hoc Gene Transfer Committee
2006: Gratz Prize Selection Committee
2006-present: Member, LCME Institutional Setting Committee
2006-present: Member, Jefferson Medical College First Year Steering Committee
Service on University Administrative Committees and Related Activities
1989-1995: Preceptor, Philadelphia High School/Thomas Jefferson University Program.
1990-present; Member, Institutional Biosafety Committee.
1992-2002: Chairman, Recombinant DNA Subcommittee of the Institutional Biosafety Committee.
1993: Participant, site visit for Middle States Accreditation Evaluation.
1993: Delegate, Cultural Diversity Workshop.
1994-1995: Marshall, University Opening Exercises.
1995-present: Marshall, University Commencement.
1995-1999: Member, Faculty Club Board.
1996-1997: Vice president, Faculty Club Board of Directors.
1997-1999: President, Faculty Club Board of Directors.
1997-2002: Member, Selection Committee, the Lennox K. Black International Prize for Excellence in Medicine.
2000-2001: Member, TJU Web Committee.
2001-present: Member, Jefferson Information Technology Advisory Committee.
2001-2003: Member, Academic Services Committee
2001-2004: Co-coordinator, Steering Committee, Middle States Commission on Higher Education Self-Study.
2001: Member, Ad Hoc University Commons Capitol Expenditure Committee
2002: Member, Ad Hoc 9/11 Remembrance Committee
2002-present: Chairman, TJU Institutional Biosafety Committee
2002-present: Chairman, TJU Conflict of Interest Committee
2002-present: Member, Campus Life and Safety Committee
2003-present: Member, Jeff-IT Advisory Committee
2003-present: Member, Jeff-IT Academic Services Committee
2003-present: Member, Jeff-IT Research Services Committee
2003-present: Member, TJU Student Life and Safety Committee
2004-present: Member, TJU Housing Advisory Group
2004: Member, Search Committee for Director, Central Animal Facility
2004: Member, Executive Search Committee, University Counsel
2004-present: President, Jefferson Faculty Club Board of Directors
2005: Co-chair, University Strategic Planning Committee on Graduate and Postgraduate Education.
2005: Member, Basic and Clinical Neuroscience Research Strategic Planning Committee
2005-present: Member, Advisory Committee on Postdoctoral Affairs
2006-present: Member, Criminal Background Check Committee
2006-present: Member, Banner Consolidation and Reimplementation Steering Committee
2006-present: Member, TJU Research Compliance Committee
INSTITUTIONAL EDUCATIONAL AND RESEARCH ADMINISTRATION APPOINTMENTS
Service on Jefferson Medical College Departmental Committees
1986-1987: Member, Anatomy Faculty Search Committee.
1987-1988: Member, Anatomy Faculty Search Committee
1986-1988: Chairman, Faculty Search Committee, jointly between Anatomy and Ophthalmology,.
1987-1994: Member, Anatomy Chairman's Advisory Committee.
1987-1991: Chairman, Anatomy Seminar Committee.
1987-1994: Chief, Division of Neuroscience, Dept. of Anatomy.
1990-1994: Chairman, Anatomy and Developmental Biology Graduate Program Committee.
1991: Chairman, Anatomy Faculty Search Committee.
1992: Chairman, Anatomy Faculty Search Committee.
1999-2003: Member, Pathology, Anatomy and Cell Biology Appointments and Promotions Committee.
2003-present: Member, Pathology, Anatomy and Cell Biology Research Committee
2003-present: Member, Pathology, Anatomy and Cell Biology Education Committee
2003-present: Member, Pathology, Anatomy and Cell Biology Appointments and Promotions Committee
2005-2007: Member, Faculty Search Committee
Service on Jefferson College of Graduate Studies Administrative Committees and Related Activities
1986-1988: Member, Seminar Committee, Jefferson Neuroscience Program.
1987-1994: Chairman, Faculty Membership Committee, Developmental Biology Program.
1987-1995: Member, Steering Committee, Gibbon Scholar MD/PhD Program.
1987-1988: Coordinator, Gibbon Scholar MD/PhD Laboratory Rotations.
1987-present: Admissions interviewer, MD/PhD program.
1989-1990, 1992-present: Member, CGS Graduate Council.
1989-1990: Member, Ad Hoc Committee on Faculty Appointments, Graduate Council.
1989-1995 Chairman, MD/Ph.D. Program Curriculum Committee.
1990-1994, 2001-2002: Member, CGS Graduate Council Travel Fellowship Committee.
1991: Speaker, CGS Alumni Association Postdoctoral Career Conference.
1993-1995: Chairman, CGS Graduate Council Curriculum Committee.
1993: Participant, Site Visit for Middle States Accreditation Evaluation.
1994-2005: Director, Developmental Biology and Teratology Graduate Program.
1995-1996: Secretary, CGS Graduate Council.
1996-1997: Chairman, CGS Graduate Council Faculty Appointments Committee.
1996-1998, 1999-2002: Member, CGS Graduate Council Faculty Appointments Committee.
1996-1998: Faculty advisor, Thomas Jefferson University Graduate Student Association.
1998-present: Director, MS Program in Cell and Developmental Biology.
1999-2001: Member, CGS Graduate Council Committee on Student Affairs.
1998-1999, 2000-2001, 2003-present: Member, CGS Graduate Council Committee on Curriculum.
2005-present: Chairman, Neuroscience Ph.D. Program Student Affairs Committee
TEACHING EXPERIENCE: LECTURES, LABORATORY INSTRUCTION, AND COURSE ADMINISTRATION
Medical College Courses
Lectures and laboratory instruction
1986-present: ID105, Microscopic Anatomy, lecturer and laboratory instructor.
1986-present: ID150, The Systems: Neuroscience, lecturer, laboratory instructor, and small group instructor.
1986-1988: Sophomore Seminar in Neuroscience, lecturer.
1992-present: ANAT403, Advanced Basic Science Neuroanatomy, instructor.
1994-2002: Biochemistry, lecturer or small group instructor.
1994-1996: Medical Scholars Program, problem-based learning small group facilitator.
2006-present: ANAT105, Human Form and Development, lecturer.
Graduate Medical Education
2006-present: Neurology and Neurosurgery Residents Review, lecturer.
2004-present: Grant Writing Workshop, facilitator.
1987-1988: Course director, Sophomore Seminar in Neuroscience.
1988-present: Course director, Neuroanatomy component of ID150, The Systems: Neuroscience.
1992-present: Course director, Anatomy 403: Advanced Basic Science, Neuroscience.
1994-1996: Member, Problem-Based Learning Course Committee.
1998-present: Assistant Course Director, ID150: The Systems: Neuroscience.
2006-present: Course Director, ID105: The Systems: Microscopic Anatomy.
College of Health Professions Courses
1987: Neuroanatomy, lecturer.
College of Graduate Studies Courses
1987-present: CB615, Embryology, lecturer.
1987-present: CB625, Mechanisms of Development, lecturer.
1992-present: NS700, Introduction to Neuroscience, lecturer.
1994-2003: PA510, Cell Biology, lecturer.
1998: DB705, Developmental Neurobiology, instructor.
1998-2000: GC615, Grants Management, lecturer.
1998-present: PR530, Laboratory Biosafety, lecturer.
1998-present: CB635, Mechanisms of Teratogenesis, lecturer.
2004-present: GC550, Foundations of Biomedical Sciences, lecturer.
2005-present: CB560, Principles of Cell Biology, lecturer.
2005-present: NS715, Cellular and Molecular Neuroscience, lecturer.
1986, 1987, 1995, 1998-2004: Course coordinator for DB616, Current Topics in Developmental Biology.
1988, 1994-2002: Course coordinator for DB625, Mechanisms of Development.
1992-present: Course coordinator for NS700, Introduction to Neuroscience.
1998: Course coordinator for DB705, Developmental Neurobiology.
1998-2000: Course coordinator for GC615, Grants Management.
1999-2002: Course coordinator for PR530, Laboratory Biosafety.
2002-present: Course coordinator for CB615, Embryology.
2005-present: Course coordinator for CB560, Principles of Cell Biology
Awards & Honors
1972-1976: Cornell University Arts and Sciences Dean's Scholarship.
1972-1976: New York State Regents Scholarship.
1973, 1974: Dean's List, College of Arts and Sciences, Cornell University.
1976: B.A. cum laude, Cornell University.
1976-1981: N.I.H.Predoctoral Traineeship in Developmental Biology.
1981-1984: N.I.H. National Research Service Award.
1982: Elected to Sigma Xi.
1984-1985: N.I.H. Senior Staff Fellowship.
1986-1988: Basil O'Connor Scholar Research Award, March of Dimes Birth Defects Foundation.
1992: The Jefferson Medical College Black and Blue Charity Ball Award, presented by the students of Jefferson Medical College.
1992: The Christian R. and Mary F. Lindback Foundation Award for Distinguished Teaching, Jefferson Medical College.
1996: Burroughs Wellcome Visiting Professorship in the Basic Medical Sciences, Burroughs Wellcome Fund and Federation of American Societies for Experimental Biology.
1996: Wellcome Lecturer, Marshall University School of Medicine, Huntington, WV.
1997: Opening Symposium Lecture, Association for Research in Vision and Ophthalmology, Ft. Lauderdale, FL.
1994-1999: Member and Chairman (1998-1999), Visual Sciences C Study Section, Center for Scientific Review, National Institutes of Health, Bethesda, MD.
1998: Loris and David Rich Lecturer in Visual Science, University of Alabama at Birmingham.
2002: Honorary Life Member, Jefferson College of Graduate Studies Alumni Association.
2003: Vice-chair, Gordon Conference on Cell Contact and Adhesion.
2005: Chair, Gordon Conference on Cell Contact and Adhesion.
2007: Dean's Citation for Significant Contributions to the Advancement of Education at Jefferson Medical College, Jefferson University.
2007: Faculty Award for Neuroscience Education (Inaugural Awardee), Ph.D. Program in Neuroscience, Jefferson University.
2007: Distinguished Mentor Award (Inaugural Awardee), Jefferson Postdoctoral Association and Office of Postdoctoral Affairs, Jefferson University.
2008: Teacher of the Year, Freshman Year Class of 2011, Jefferson Medical College, Jefferson University.
Most Recent Peer-Reviewed Publications
- A century of cell adhesion: From the blastomere to the clinic part 1: Conceptual and experimental foundations and the pre-molecular era
- Microphthalmia-associated transcription factor (MITF) promotes differentiation of human retinal pigment epithelium (RPE) by regulating microRNAs-204/211 expression
- Modulation of MCT3 expression during wound healing of the retinal pigment epithelium
- Metals and Cell Adhesion
- Transcriptional regulatory network analysis during epithelial-mesenchymal transformation of retinal pigment epithelium
- Cadherins and NCAM as potential targets in metal toxicity
- N-cadherin function is required for differentiation-dependent cytoskeletal reorganization in lens cells in vitro
- Differential expression of N- and B-cadherin during lens development
- Chapter 3 Cadherin Cell adhesion molecules in development and disease
- Difkereyiiai. spatio temporal expression paturns of v and b-cadherins correlate with specific morphogenetic events during lens development
- In vivo analysis ok in-c adhlr1n cell adhesion molecule function in ocular development using transgenic mice expressing tissue-specific dominant-negative mutations
- Evidence that tyrosine phosphorylation regulates N-cadherin turnover during retinal development
- Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos
- Discovery and Analysis of the Classical Cadherins
- Cadherin cell adhesion molecules in retinal development and pathology
- Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo
- Ca2+ influx and neurite growth in response to purified N-cadherin and laminin
- Structure/function analysis of the integrin β1 subunit by epitope mapping
- Analysis of protein variations in adult and postnatal day 11 staggerer and lurcher mutant mice
- The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules