Department of Reproductive Medicine

David Schlaepfer

Business Address:
UCSD Moores Cancer Center
Department of Reproductive Medicine
3855 Health Science Dr., Rm. 2332
La Jolla, CA 92093-0803
Telephone:
(858) 822-3444
E-mail: dschlaepfer@ucsd.edu


Professional Positions

2007- Professor, Department of Reproductive Medicine

UCSD Moores Cancer Center, La Jolla, CA

2006-2007 Tenured Associate Professor, Department of Immunology

The Scripps Research Institute, La Jolla, CA.

2001-2006 Associate Professor, Department of Immunology

The Scripps Research Institute, La Jolla, CA.

1996-2001 Assistant Professor, The Scripps Research Institute, La Jolla, CA.

1993-1996 Postdoctoral Research Associate, Molecular Biology and Virology Lab,

The Salk Institute for Biological Studies, La Jolla, CA.

Laboratory of Dr. Tony Hunter

1985-1987 Research Assistant, University of California Irvine.

Education

Ph.D. Biological Sciences, 1987-1992

Department of Biological Chemistry, University of California, Irvine, CA

Dissertation: Characterization of Annexin Calcium Binding Proteins.

Laboratory of Dr. Harry Haigler

B.A. Biology (cum laude), June, l985

Princeton University, Princeton, NJ

Thesis: Olfactory Inputs Modify Feeding Behavior in Limax maximus.

Honors

2005 Established Investigator Award, American Heart Association

1995 Santa Cruz Biotechnology Investigator Award

1994 American Cancer Society Postdoctoral Fellowship

1992 NIH NRSA Postdoctoral Fellowship

1987 University of California Regents' Fellowship

1985 Award of Excellence in Undergraduate Research, Princeton University

Professional Activities

2008 Study Section Member, NIH, Tumor Cell Biology (ad hoc)

2007 Co-chairperson, AACR Mini-symposia, Non-Receptor Mediated Signaling

2007 Grant Reviewer, Cancer Research, UK Group

2006 Grant Reviewer, Cancer Research, UK Group

2006 Study Section Member, US Army Medical Research Breast Cancer Program

2006 Grant Reviewer, US-Israel Binational Science Foundation

2005 Grant Reviewer, Dutch Cancer Society

2005 Study Section Member, NIH, Cell Structure and Function (ad hoc)

2004 Study Section Member, NIH, Cancer Molecular Pathology (ad hoc)

2004 Study Section Member, NIH, Pathobiochemistry (ad hoc)

2004 Grant Reviewer, Association for International Cancer Research

2004 Grant Reviewer, Alberta Foundation for Medical Research

2003 Study Section Member, NIH, CDF-4 (ad hoc)

2002-03 Grant Reviewer, National Science Foundation

2002-05 Study Section Member, AHA Western States Consortium 5A

2001 Study Section Member American Cancer Society, Cancer Biology

Society Membership

American Society for Cell Biology

American Association for Cancer Research

American Heart Association Scientific Council Member

Invited Seminars (since 1999)

5/1999 Department of Stomatology, University of California San Francisco

8/1999 Salk-EMBL Meeting, Oncogenes and Growth Control

3/2000 Keystone Symposia, Regulation of Signaling Pathways by Integrins

6/2000 The 16th Annual Meeting on Oncogenes, La Jolla, CA.

8/2000 Tyrosine Phosphorylation and Cell Signaling, La Jolla, CA

12/2000 Mini-Symposia Co-Chair, American Society for Cell Biology National Meeting

2/2001 Gordon Research Conference on Fibronectin and Integrins, Ventura, CA

3/2001 Harvard Medical School, Cancer Biology Program, Boston, MA

5/2001 UCSF Comprehensive Cancer Center, San Francisco, CA

5/2001 Scripps, Vascular Biology Seminar Series

7/2001 Gordon Res. Conference, Mol. Basis of Cell Proliferation, Colby Sawyer College, NH

8/2002 Tyrosine Phosphorylation and Cell Signaling, Session Chair, La Jolla, CA

8/2002 RIKEN Institute, Tokyo, Japan

8/2002 Novartis, Japan

7/2003 University of Wuerzburg, Germany

7/2003 Beatson International Conference on Cell Signaling, Glasgow, Scotland

7/2003 AACR National Meeting, Cell Motility and Invasion Symposia, Washington, DC

7/2003 The Burnham Institute, La Jolla, CA

11/2003 Columbia University School of Medicine, NY

09/2004 Cornell University School of Medicine, NY

10/2005 University of California San Diego, Department of Pathology

10/2005 Plexxikon Inc., Berkeley, CA

11/2005 La Jolla Mesa 1st Annual Cell Signaling Symposia

11/2005 University of Pennsylvania, Department of Pharmacology

11/2006 Loyola University, Department of Microbiology and Immunology, Chicago, IL.

1/2007 Poniard Pharmaceuticals, South San Francisco, CA.

1/2007 Pfizer Lecture at the Institut de recherches cliniques de Montréal, Canada.

8/2007 FASEB Summer Research Conference, Tucson, AZ.

Journal Responsibilities

Ad hoc Reviewer (average 15-20 papers/year)

Cancer Cell, Developmental Cell, Nature Cell Biology, Circulation Research, Blood, PNAS, EMBO Journal, Molecular and Cellular Biology, Journal of Cell Biology, Cancer Research, Journal of Cell Science, Oncogene, Experimental Cell Research, Molecular Biology of the Cell

University Activities

2001 Graduate Cell Biology Course, Lectures on Integrins and Cell Signaling

2003-2005 Graduate Advisor, Daniel A. Hanson

2005-2006 Member, Immunology Faculty Awards Committee

2006-2007 Graduate Advisory Committee Member, James Lim (Ph.D. candidate)

2006 Co-organizer, 2nd Annual La Jolla Mesa Cell Signaling Symposia

2007- Graduate Advisory Committee Member, Miller Huang (Ph.D. candidate)

2007-2008 Reproductive Medicine Faculty Search Committee Member

2008 UCSD Faculty Senate Representative, Reproductive Medicine

2008 Co-organizer, Tumor microenvironment journal club, Moores Cancer Center

Past Trainees

David J. Sieg, Ph.D. (1997-2000)

Current Position: Invitrogen, Carlsbad, CA.

Christof R. Hauck, Ph.D. (1998-2001)

Current Position: Professor, University of Konstanz, Germany

Candice K. Klingbeil, Ph.D. (1998 to 2000)

Daniel A. Hanson, BS (2003 to 2005), graduated with Masters degree.

Joie Bernard-Trifilo, Ph.D. (2004-2006)

Current Position: Technical Consultant, Millipore-Chemicon Inc., Temecula, CA

Shawn Hou, Ph.D. (2004-2006)

Current Position: Scientific Writer, Abraxis Bioscience Inc., Los Angeles, CA

Satyajit K. Mitra, Ph.D. (2002-2006)

Current Position: Scientist, OncoMed Pharmaceuticals, Mountain View, CA.

Yangmi Lim, Ph.D. (2005-2006)

Current Position: Scientist, Mogam Research Institute, Korea.

Rafaela Canete-Soler, Ph.D. (2006-2007)

Current Position: Adjunct Assistant Professor, University of Pennsylvania, PA

Honggang Yu, M.D., (2006-2007)

Current Position: Division Chief, Gastrology, Renmin Hospital of Wuhan University.

Student Interns

Shannon Reider (UCSD: 1999-2001)

Datsun Hsia (UCSD: 2002-2004)

Aileen Chi (UCSD: 2003-2004)

Trang Tran Vo (UCSD: 2004-2005)

Current Trainees

Ssang-Taek Lim, Ph.D. from University of Alabama Birmingham. November 2003 to present.

Lihua Wu, M.D., Ph.D., from UC San Diego. May 2006 to present.

Alok Tomar, Ph.D., from the University of Tennessee. October 2006 to present.

Ju-Ock Nam, Ph.D., from Kyungpook University School of Medicine, Korea. January 2008.

D. Schlaepfer as Mentor on Postdoctoral Fellowships Awarded

David Sieg, Ph.D., American Cancer Society (1998-2000)

Christof Hauck, Ph.D., Deutsche Forschungsgemeinschaft (1998-2000)

Satyajit Mitra, Ph.D., California Tobacco-Related Disease Research Program (2003-2005).

Yang Mi Lim, PhD., Korean Research Foundation (2005-2006).

Ssang-Taek Lim, Ph.D., American Heart Association (2007-2009).

Research Publications (in chronological order)

  1. Sheets, E.E., Giugni, T.D., Coates, G.G., Schlaepfer, D.D., and Haigler, H.T. (1987). Epidermal growth factor-dependent phosphorylation of a 35-kilodalton protein in placental membranes. Biochemistry 26: 1164-1172.

  2. Haigler, H.T., Schlaepfer, D.D., and Burgess, W.H. (1987). Characterization of Lipocortin I and an unrelated 35-kDa Protein as epidermal growth factor receptor/kinase substrates and phospholipase A2 inhibitors. J. Biol. Chem. 262: 6921-6930.

  3. Schlaepfer, D.D. and Haigler, H.T. (1987). Characterization of calcium-dependent phospholipid binding and phosphorylation of lipocortin I. J. Biol. Chem. 262: 6931-6937.

  4. Schlaepfer, D.D., Mehlman, T., Burgess, W.H., and Haigler, H.T. (1987). Structural and functional characterization of Endonexin II, a calcium and phospholipid-binding Protein. Proc. Natl. Acad. Sci. USA 84: 6078-6082.

  5. Kaplan, R., Jaye, M., Burgess, W.H., Schlaepfer, D.D., and Haigler, H.T. (1988). Cloning and expression of a cDNA for human Endonexin II, a calcium and phospholipid binding protein. J. Biol. Chem. 26: 8037-8043.

  6. Schlaepfer, D.D., and Haigler, H.T. (1988). In vitro protein kinase C phosphorylation sites of placental Lipocortin I. Biochemistry 27: 4253-4258.

  7. Schlaepfer, D.D., and Haigler, H.T. (1990). Expression of Annexins as a function of cellular growth state. J. Cell Biol. 111: 229-238.

  8. Schlaepfer, D.D., Jones, J., and Haigler, H.T. (1992). Inhibition of protein kinase C by Annexin V. Biochemistry 31: 1886-1891.

  9. Schlaepfer, D.D., Fisher, D.A., Brandt, M.E., Bode, H.R., Jones, J., and Haigler, H.T. (1992). Identification of a novel Annexin in Hydra vulgaris: Characterization, cDNA cloning, and protein kinase C phosphorylation of Annexin XII. J. Biol. Chem. 267: 9529-9539.

  10. Schlaepfer, D.D., Bode, H.R., and Haigler, H.T. (1992). Distinct cellular expression pattern of Annexins in Hydra vulgaris. J. Cell Biol. 118: 911-928.

  11. Schlaepfer, D.D., Hanks, S.K., Hunter, T., and van der Geer, P. (1994). Integrin-mediated signal transduction linked to Ras Pathway by Grb2 Binding to Focal adhesion kinase. Nature 372: 786-791.

  12. Leucke, H. Chang, B.T., Mailliard, W.S., Schlaepfer, D.D., and Haigler, H.T. (1995). Crystal structure of the Annexin XII hexamer and implications for bilayer insertion. Nature 378: 512-515.

  13. Mailliard, W., Haigler, H.T., and Schlaepfer, D.D. (1996). Calcium dependent binding of S-100C to the amino-terminal domain of Annexin I. J. Biol. Chem. 271: 736-741.

  14. Schlaepfer, D.D. and Hunter, T. (1996). Evidence for in Vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase (FAK) by Src-family protein-tyrosine kinases. Mol. Cell. Biol. 16: 5623-5633.

  15. Schlaepfer, D.D., Broome, M.A., and Hunter, T. (1997). Fibronectin-stimulated signaling from a FAK and c-Src complex; Involvement of the Grb2, p130Cas, and Nck adaptor proteins. Mol. Cell. Biol. 17: 1702-1713.

  16. Schlaepfer, D.D. and Hunter, T. (1997). FAK overexpression enhances Ras-dependent integrin signaling to ERK2/Mitogen-activated Protein Kinase through interactions with and activation of c Src. J. Biol. Chem. 272: 13189-13195.

  17. Li, S., Kim, M., Hu Y.L., Jalali, S., Schlaepfer, D.D., Hunter, T., Chien, S., and Shyy, J.Y.J., (1997). Fluid shear stress activation of FAK: Linking integrins to mitogen-activated protein kinases. J. Biol. Chem. 272: 30455-30462.

  18. Schlaepfer, D.D., Jones, K.C., and Hunter, T. (1998). Multiple Grb2-mediated integrin-stimulated signaling pathways to ERK2/mitogen-activated protein kinase: Summation of both c Src and FAK-initiated tyrosine phosphorylation events. Mol. Cell. Biol. 18: 2571-2585.

  19. Sieg, D.J., Ilic, D., Jones, K.C., Damsky, C.H., Hunter, T, and Schlaepfer, D.D. (1998). Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to promote FAK-/- cell migration. EMBO J. 17: 5933-5947.

  20. Ilic, D., Almeida, E.A., Schlaepfer, D.D., Dazin, P., Aizawa, S., and Damsky, C.H. (1998). Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis. J. Cell Biol. 143: 547-560.

  21. Sieg, D.J., Hauck, C.R., and Schlaepfer, D.D. (1999). Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J. Cell Sci. 112: 2677-2691.

  22. Almeida, E.A., Ilic, D., Han, Q., Hauck, C.R., Jin, F., Kawakatsu, H., Schlaepfer, D.D., and Damsky, C.H. (2000). Matrix survival signaling: from fibronectin via focal adhesion kinase to c Jun NH2-terminal kinase. J. Cell Biol. 149: 741-754.

  23. Li, E., Stupack, D.G., Brown, S. L., Klemke, R., Schlaepfer, D.D., and Nemerow, G.R. (2000). Association of p130Cas with phosphatylinositol 3-kinase mediates adenovirus cell entry. J. Biol. Chem. 275: 14729-14735.

  24. Sieg, D.J., Hauck, C.R., Ilic, D., Klingbeil, C.K., Schaefer, E.. Damsky, C.H., and Schlaepfer, D.D. (2000). FAK integrates growth factor and integrin signals to promote cell migration. Nature Cell Biol. 2: 249-256.

  25. Ren X.D., Kiosses, W.B., Sieg, D.J., Otey, C., Schlaepfer, D.D., and Schwartz, M.A. (2000). Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J. Cell Sci. 113: 3673-3678.

  26. Lebrun, P., Baron, V., Hauck, C.R., Schlaepfer, D.D., and Van Obberghen, E. (2000). Cell adhesion and focal adhesion kinase regulate insulin receptor substrate-1 expression. J. Biol. Chem. 275: 38371-38377.

  27. Hauck, C.R., Hsia, D.A, and Schlaepfer, D.D. (2000). Focal adhesion kinase facilitates platelet-derived growth factor-BB-stimulated ERK2 activation required for chemotaxis migration of vascular smooth muscle cells. J. Biol. Chem. 275: 41092-41099.

  28. Reddy, M.A., Wass, C.A., Kim, K.S., Schlaepfer, D.D., and Prasadarao, N.V. (2000). Involvement of focal adhesion kinase in Escherichia coli invasion of human brain microvascular endothelial cells. Infect. Immun. 68: 6423-6430.

  29. Klingbeil, C.K., Hauck, C.R., Hsia, D.A., Jones, K.C., Reider, S.R., and Schlaepfer, D.D. (2001). Targeting Pyk2 to b1-Integrin-containing focal contacts rescues fibronectin-stimulated signaling and haptotactic motility defects of focal adhesion kinase-null cells. J. Cell Biol. 152: 97-110.

  30. Hauck, C.R., Hunter, T., and Schlaepfer, D.D. (2001). The v-Src SH3 Domain facilitates a cell adhesion-independent association with focal adhesion kinase. J. Biol. Chem. 276: 17653-17662.

  31. Hauck, C.R., Sieg, D.J., Hsia, D.A., Loftus, J.C., Gaarde, W.A., Monia, B.P., and Schlaepfer, D.D. (2001). Inhibition of FAK expression or activity disrupts EGF-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res. 61: 7079-7090.

  32. Izaguirre, G., Aguirre, L., Hu, Y.P., Lee, H.Y., Schlaepfer, D.D., Aneskievich, B.J., and Haimovich, B. (2001). The cytoskeletal/non-muscle isoform of a-actinin is phosphorylated on its actin binding domain by the focal adhesion kinase. J. Biol. Chem. 276: 28676-28685.

  33. Han, J., Liu, S., Rose, D.M., Schlaepfer, D.D., and Ginsberg, M.H. (2001). Phosphorylation of integrin a4 cytoplasmic domain regulates paxillin binding. J. Biol. Chem. 276: 40903-40909.

  34. Eliceiri, B.P., Puente, X.S., Hood, J.D., Stupack, D.G., Huang, X.Z., Schlaepfer, D.D., Sheppard, D., and Cheresh, D.A. (2002). Src-mediated coupling of focal adhesion kinase to integrin avb5 in vascular endothelial growth factor signaling. J. Cell Biol. 157: 149-159.

  35. Hauck, C.R., Hsia, D.A., Ilic, D., and Schlaepfer, D.D. (2002). v-Src SH3-enhanced interaction with focal adhesion kinase at b1 integrin-containing invadopodia promotes cell invasion. J. Biol. Chem. 277: 12487-12490. (Accelerated Publication).

  36. Hauck, C.R., Hsia, D.A., Puente, X.S., Cheresh, D.A., and Schlaepfer, D.D. (2002). FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. EMBO J. 21: 6289-6302.

  37. Hsia, D.A., Mitra, S.K., Hauck, C.R., Streblow, D.N., Nelson, J.A., Ilic, D., Haung, S., Li, E., Nemerow, G.R., Leng, J., Spencer, K.S.R., Cheresh, D.A., and Schlaepfer, D. D. (2003). Differential regulation of cell motility and invasion by FAK. J. Cell Biol. 160: 753-767.

  38. Zhai, J., Lin, H., Nie, H., Wu, J., Cañete-Soler, R., Schlaepfer, W.W., and Schlaepfer, D.D. (2003) Direct interaction of focal adhesion kinase with p190RhoGEF. J. Biol. Chem. 278: 24865-24873.

  39. Rose, D.M., Liu, S., Woodside, D.G., Han, J., Schlaepfer, D.D., and Ginsberg, M.H. (2003). Paxillin binding to the a4 integrin subunit stimulates LFA-1 (Integrin aLb2)-dependent T cell migration by augmenting the activation of Pyk2/FAK tyrosine kinases. J. Immunol. 170: 5912-5918.

  40. Streblow, D.N., Vomaske, J., Smith, P., Melnychuk, R., Hall, L., Pancheva, D., Smit, M., Casarosa, P. Schlaepfer, D.D., and Nelson, J.A. (2003). Human cytomegalovirus chemokine receptor US28 induced SMC migration is mediated by focal adhesion kinase and Src. J. Biol. Chem. 278: 50456-50465.

  41. Ilic, D., Kovacic, B., Johkura, K., Schlaepfer, D.D., Tomacevic, N., Han, Q., Kim, J.B., Howerton, K., Baumbusch, C., Ogiwara, N., Streblow, D., Nelson J., Dazin, P., Shino, Y., Sasaki, K., and Damsky, C.H. (2004). FAK promotes fibronectin matrix organization and fibrillar adhesions. J. Cell Sci. 117: 177-187.

  42. Palazzo, A.F., Eng, C.H.L, Schlaepfer, D.D., Marcantonio, E.E., and Gundersen, G.G. (2004). Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science 303: 836-839.

  43. Meyer, A., Gastwirt, R. F., Schlaepfer, D.D., and Donoghue, D.J. (2004). The cytoplasmic tyrosine kinase Pyk2 as a novel effector of fibroblast growth factor receptor 3 activation. J. Biol. Chem. 279: 28450- 28457.

  44. Urbinati, C., Bugatti, A., Giacca, M., Schlaepfer D., Presta, M., and Rusnati, M. (2005). avb3 integrin engagement by free or substrate-immubilized HIV-1 Tat: signal transduction and biological consequences in endothelial cells. J. Cell Sci. 118: 3949-3958.

  45. Hsia, D.A., Lim, S.T., Bernard-Trifilo, J.A., Mitra, S.K., Tanaka, S., den Hertog, J., Streblow, D.N., Ilic, D., Ginsberg, M.H., and Schlaepfer, D.D. (2005). Integrin a4b1 promotes FAK-independent cell motility via a4 cytoplasmic domain-specific activation of Src. Mol. Cell. Biol. 25: 9700-9712.

  46. Benlimame, N., He, Q., Xiao, D., Xu, Y.J., Loignon, M., Schlaepfer, D.D., and Alaoui-Jamali, M.A. (2005). FAK signaling is critical for ErbB-2/ErbB-3 receptor cooperation for oncogenic transformation and invasion. J. Cell Biol. 171: 505-516.

  47. Hu, B., Jarzynka, M.J., Guo, P., Imanishi, Y., Schlaepfer, D.D., and Cheng, S.Y. (2006). Angiopoietin-2 induces glioma cell invasion by stimulating MMP-2 expression through the avb1-integrin and FAK signaling pathway. Cancer Res. 66: 775-783.

  48. Mitra, S.K., Lim. S.T., Chi, A., and Schlaepfer, D.D. (2006). Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model. Oncogene 25: 4429-4440.

  49. Mitra, S.K., Mikolon, D., Molina, J., Hsia, D.A., Hanson, D. A., Chi, A., Lim. S.T., Bernard-Trifilo, J.T., Ilic, D., Stupack, D.G., Cheresh, D.A., and Schlaepfer, D.D. (2006). Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene 25: 5969-5984.

  50. Ilic, D, Mao-Qiang, M., Crumrine, D., Dolganov, G., Larocque, N., Xu, P., Demerjian, M., Brown, B.E, Lim, S.T, Ossovskaya, V., Schlaepfer, D.D., Fisher, S.J., Feingold, K.R., Elias, P.M., Mauro, T.M. (2007). FAK controls pH-Dependent epidermal barrier homeostasis by regulating actin-directed NHE1 plasma membrane localization. Am. J. Physiol. 170:2055-67.

  51. Schlaepfer, D.D., Hou. S., Lim, S.T., Tomar, A., Yu, H., Lim, Y., Hanson, D.A., Uryu, S.A., Molina, J., and S.K. Mitra (2007). Tumor necrosis factor-a stimulates FAK activity required for mitogen-activated kinase-dependent interleukin 6 expression. J. Biol. Chem. 282: 17450-17459.

  52. Wu, L., Bernard-Trifilo, J.A., Lim, Y., Lim, S.T., Mitra, S.K., Uryu, S., Chen, M., Pallen, C.J., Cheung, N.K.V, Mikolon, D., Mielgo, A., Stupack, D.G., and Schlaepfer, D.D. (2007). Distinct FAK-Src activation events promote a5b1- and a4b1-stimulated neuroblastoma cell motility. Oncogene, in press.

  53. Lim, S.-T., Chen, X.L., Hanson, D.A., Lim, Y., Vo, T.T., Howerton, K., Dazin, P. Fisher, S.J., *Schlaepfer, D.D., and Ilic, D. (2007). Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Molecular Cell, in press. *Corresponding author

  54. Lim, Y., Lim, S.-T., Tomar, A., Gardel, M., Bernard-Trifilo, J.A., Chen, X.L., Uryu, S., Canete-Soler, R., Zhai, J., Lin, H., Schlaepfer, W.W., Nalbant, P., Bokoch, G.M., Ilic, D., Waterman-Storer, C., and Schlaepfer, D.D. (2008). Pyk2 and FAK connections to p190RhoGEF regulate RhoA activity, focal adhesion formation, and cell motility. J. Cell Biol., in press.

  55. Weis, S.M., Lim, S.-T., Lutu-Fuga, K.M., Barnes, L.A., Chen, X.L., Göthert, J.R., Shen, T.-L., Guan, J.-L., Schlaepfer, D.D., and Cheresh, D.A. (2008). Compensatory role for Pyk2 during angiogenesis in adult mice lacking endothelial cell FAK. (submitted).

Invited Reviews

  1. Haigler, H.T., Fitch, J.M., Jones, J.M., and Schlaepfer, D.D. (1989). Two Lipocortin-like proteins, Endonexin II and Anchorin CII, may be alternate splices of the same gene. TIBS 14: 48-50.

  2. Haigler, H.T. and Schlaepfer, D.D. (1990). Expression of Lipocortin 1 and Endonexin II as a function of cellular growth state. Prog. Clin. Biol. Res. 349: 91-98.

  3. Schlaepfer, D.D. and Hunter, T. (1996). Signal transduction from the Extracellular matrix: Role of focal adhesion protein-tyrosine kinase FAK. Cell Struct. Function 21: 445-450.

  4. Schlaepfer, D.D. and Hunter, T. (1998). Integrin signalling and tyrosine phosphorylation: just the FAKs? TICB: 8: 151-157.

  5. Schlaepfer, D.D., Hauck, C.R., and Sieg, D.J. (1999). Signaling from focal adhesion kinase. Progr. Biophys. Mol. Biol. 71 (3-4), 435-478.

  6. Hauck, C.R., Hsia, D.A., and Schlaepfer D.D. (2002). The focal adhesion kinase - a regulator of cell migration and invasion. IUBMB Life 53: 1-5.

  7. Hauck, C.R., Klingbeil, C.K., and Schlaepfer, D.D. (2000). FAK functions as a receptor-proximal signaling component required for cell migration. Immunol. Res. 2.5-3: 293-303.

  8. Schlaepfer, D.D. and Mitra, S.K. (2004). Multiple connections link FAK to cell motility and invasion. Curr. Opin. Genet. Dev. 14: 92-101.

  9. Schlaepfer, D.D., Mitra, S.K., and Ilic, D. (2004). Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochem. Biophys. Acta. 1692: 77-102.

  10. Mitra, S.K., Hanson, D.H., and Schlaepfer, D.D. (2005). Focal adhesion kinase: In command and control of cell motility. Nature Rev. Mol. Cell. Biol. 6: 56-68.

  11. Mitra, S.K., and Schlaepfer, D.D. (2006). Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr. Opin. Cell. Biol. 18: 516-523.

Book Chapter & Methods Papers

  1. Pollard, H.B., Burns, A. Lee, Rojas, E., Schlaepfer, D.D., Haigler, H.T., and Broklehurst, K. (1989). Purification and biochemical assay of Synexin, and of the homologous calcium-dependent membrane-binding proteins, Endonexin II and Lipocortin 1. Meth. Cell Biol. 31: 207-227.

  2. Haigler, H.T. and Schlaepfer, D.D. (1992). Annexin I phosphorylation and secretion. In "The Annexins" pgs. 11-22 (ed., Stephen Moss) Portland Press, London.

  3. Bernard-Trifilo, J.A., Lim, S.T., Hou, S., Ilic, D., and Schlaepfer, D.D. (2006). Analyzing FAK and Pyk2 in early integrin signaling events. Current Protocols in Cell Biology. Chap 14.7.1-14.7.35, John Wiley and Sons, Inc.

Research Support

ONGOING

NIH (National Cancer Institute)

2RO1 CA75240-08 (PI: Schlaepfer) 07-01-97 to 03-31-09

Title: Tyrosine phosphorylation in integrin signaling

The objective of this grant is to analyze the signal transduction events generated by transmembrane integrin binding to extracellular matrix proteins. Emphasis is placed on the positive and negative regulation of Pyk2 tyrosine kinase activity by integrin alpha subunit-initiated signals.

NIH (National Cancer Institute)

RO1 CA102310-04 (PI: Schlaepfer) 07-01-03 to 04-30-09

Title: Role of focal adhesion kinase in tumorigenesis

FAK is over-expressed and highly tyrosine phosphorylated as a function of tumor progression. We will test the overall hypothesis that elevated FAK expression and activity provides a selective advantage promoting solid tumor growth through the enhancement of anchorage-independent cell survival, through the regulation of metalloproteinase expression, and through the release of angiogenic factors in vivo.

American Heart Association

0540115N (PI: Schlaepfer) 01-01-05 to 12-31-09

Established Investigator Award

Title: Deciphering the role of FAK activity in cell motility and survival

By using reconstitution approach with catalytically-defective mutants of FAK with FAK-null embryonic stem cells and shRNA-expressing human endothelial cells, we will test the hypothesis that FAK activity is required for endothelial cell blood vessel formation but not necessarily for cell survival signaling.

Poniard Pharmaceuticals

UCSD CCTSD01 (PI: Schlaepfer) 08-15-07 to 08-14-09

Title: Testing FAK Inhibitors as Anti-tumor Agents

Small molecule inhibitors to FAK (FAK-I) developed by Poniard Pharmaceuticals will be evaluated as to: 1) whether they function in tumor cells to inhibit FAK tyrosine phosphorylation and whether there is a dose-response relationship to these changes; 2) whether tumor cell FAK inhibition is associated with changes in cell motility, invasion or matrix degradation, cell proliferation, or anchorage-independent cell survival; and 3) to determine whether FAK-I reduce tumor growth in mouse xenograft models.

PENDING RENEWALS

NIH (National Cancer Institute)

2R01 CA87038-07 (PI: Schlaepfer) 07-01-08 to 6-30-13

Title: Mechanisms of FAK in cell motility

Regulated cell migration is important in development and wound healing whereas uncontrolled motility can lead to immune diseases and tumor spread. Our goal is to understand the molecular mechanisms of FAK action in promoting both focal adhesion (FA) formation and turnover during cell migration. These studies using cell biological and mouse genetic analyses will fill key gaps in our understanding of the basic signaling events regulating cell movement and underlying processes such as tumor invasion.

NEW GRANT APPLICATIONS

NIH (National Cancer Institute)

RO1 HL093156 (PI: Schlaepfer) 07-01-08 to 6-30-13

Title: FAK signals controlling endothelial cell survival and motility

FAK inactivates p53 in a kinase-independent manner through N-terminal FAK FERM domain-mediated nuclear translocation and enhancement of Mdm2-dependent p53 ubiquitination. As we find that FAK localizes to both integrin-associated signaling sites and to the nucleus of ECs, we will test the hypothesis that FAK controls EC survival and motility-morphogenesis through differential kinase-independent (FERM-nuclear) and kinase-dependent (FAK-integrin) mechanisms, respectively. These studies will provide important insights for designing therapeutic agents of cardiovascular diseases.

COMPLETED RESEARCH GRANTS

NIH (National Cancer Institute)

R01 CA87038-06 (PI: Schlaepfer) 07-01-02 to 06-30-07

Title: Role of FAK in promoting cell motility

The goal of this project is to elucidate the specific FAK N- and C-terminal domain-mediated interactions that mediate either FAK N-terminal domain binding to the epidermal growth factor (EGF) receptor or FAK C-terminal domain association with fibronectin-activated b1-integrin containing complexes, respectively. The importance of these molecular connections for normal directed cell motility will be tested.

Poniard Pharmaceuticals

SFP 1656

Title: Small molecule inhibitors to focal adhesion kinase (FAK)

(PI: Laing, co-PI, Schlaepfer) 12-01-06 to 6-30-07

The overall goal of this proposal create and make available novel FAK-related reagents, cell lines, and expertise to perform small molecule screens for inhibitors to FAK. Lead compounds to be developed by Chris Liang's medicinal chemistry group at Scripps Florida.

NIH (Equipment Grant)

S10 R021014 (PI: Gascoigne, Schlaepfer co: PI) 04-01-06

Title: Leica two-photon microscope for in vivo imaging

This instrument will allow the user group to radically improve their ability to perform experiments on understanding the mechanisms of cell motility in development and disease.

Novartis

SFP-1457 (PI: Schlaepfer) 10/1/02-09/30/05

Title: Role of FAK catalytic activity in tumorigenesis

The objective of this project is to determine how FAK operates as a signaling scaffold and to develop model cell systems for the evaluation of pharmacological inhibitors in proof of principle studies.

American Cancer Society

RPG-98-109 (PI: Schlaepfer) 01/01/1998-12/31/2000

Title: Src interactions and signaling events promoting cell transformation

The goal of this proposal was to identify the molecular mechanisms promoting the formation of a stable complex between activated Src and FAK and to determine the role of FAK in promoting Src-initiated downstream signaling events.

American Heart Association 07/01/1998-06/30/2001

Grant-in-Aid (PI: Schlaepfer)

Title: Role adaptor proteins in vascular smooth muscle cell motility

This project was focused on understanding the role of Grb2 and Nck adaptor proteins in connecting platelet-derived growth factor receptor to the control of cell motility.

Faculty