Biomedical Research Education & Training
Faculty Member

Weaver, Alissa M., M.D., Ph.D.
Associate Professor of Cancer Biology
Associate Professor of Pathology, Microbiology and Immunology

Lab Url: http://people.vanderbilt.edu/~alissa.weaver/

Phone Number: 615-936-3529

Email Address: alissa.weaver@vanderbilt.edu

Weaver, Alissa's picture
Academic history
B.S., Stanford University, Stanford, CA
B.A. , Stanford University, Stanford, CA
Ph.D. , University of Virginia, Charlottesville, VA
M.D., University of Virginia, Charlottesville, VA

Office Address   Mailing Address

748 PRB

771 PRB 23rd Ave S @ Pierce 37232


Research Keywords
actin, cortactin, WASp family, cell motility, cancer, invasion, metastasis, migration, src kinases, Arp2/3 complex, breast cancer, chemotaxis, live cell imaging, fluorescence imaging, cytoskeleton, genetic manipulation, microscopy,Biochemistry,Kinase,Malignancy,Membrane,Molecular medicine,Signal transduction,Tyrosine phosphorylation

Research Specialty
Dynamic actin assembly for cell motility and cancer metastasis.

Research Description
Cell motility is important for a number of physiologic and pathologic processes, including wound healing, immune system function, axon guidance, and cancer cell metastasis. In order for a cell to move, it must rapidly rearrange its actin cytoskeleton to produce the required cell shape changes and to generate force. Among the various forms of actin structures in cells, the most dynamic (assembled and disassembled in a matter of seconds) are the branched actin filament networks nucleated by the Arp2/3 protein complex. Arp2/3 complex is essential for plasma membrane protrusion at the leading edge of migrating cells and is also important in such processes as endocytosis, cell-cell junction formation, and the formation of subcellular structures used for cancer cell invasion (invadopodia).
Activation of Arp2/3 complex in cells occurs in response to a variety of signals, including from growth factors, src family kinases, and rho GTPases. Cellular activators include members of the Wiskott-Aldrich Syndrome family of proteins (WASps) and cortactin, a src kinase substrate that is overexpressed in a number of epithelial cancers. A major goal of the laboratory is to understand how Arp2/3-activators and associated signaling molecules contribute to cell motility and cancer invasion. We use a variety of techniques including siRNA, live-cell imaging, and biochemistry. Specific projects include: 1) cortactin and WASp family function in lamellipodial protrusion and cell motility; 2) actin assembly in membrane trafficking and autocrine secretion; 3) role of cortactin in head and neck squamous carcinoma progression; 4) molecular regulation of invadopodia; 5) determining critical parameters for invasion of breast cancer cells in three dimensions; and 6) interdisciplinary projects focused on mathematical modeling of cancer invasion.



Figure 1: Breast cancer cell stained with rhodamine-phalloidin to reveal filamentous actin (left panel) at sites of invasion into fluorescent basement membrane (middle panel: FITC-fibronectin). Right panel: merge of images.
. . . . . . . . . .

Publications
Branch, KM, Hoshino, D, and Weaver, AM. Adhesion rings surround invadopodia and promote maturation. Biology Open, 1, 711-722, 2012

Hoshino, D, Jourquin, J, Emmons, SW, Miller, T, Goldgof, M, Costello, K, Tyson, DR, Brown, B, Lu, Y, Prasad, NK, Zhang, B, Mills, GB, Yarbrough, WG, Quaranta, V, Seiki, M, and AM Weaver. Network analysis of the focal adhesion to invadopodia transition identifies a PI3K-PKCa invasive signaling axis. Science Signaling(11 September 2012), ra66, 2012

Hoshino, D, Koshikawa, N, Suzuki, T, Quaranta, V, Weaver, AM, Seiki, M, and K Ichikawa. Establishment and validation of computational model for MT1-MMP dependent ECM degradation and intervention strategies.. PLoS Computational Biology, 8(4), e1002479, 2012

Kirkbride, KC, Hong, NH, French, CL, Clark, ES, Jerome, WG, Weaver, AM. Regulation of late endosomal/lysosomal maturation and trafficking by cortactin affects Golgi morphology. Cytoskeleton (Hoboken), 69(9), 625-43, 2012

Kirkbride, KC, Sung, BH, Sinha, S, Weaver, AM. Cortactin: a multifunctional regulator of cellular invasiveness. Cell Adh Migr, 5(2), 187-98, 2011 PMCID:3084985

Parekh, A, Ruppender, NS, Branch, KM, Sewell-Loftin, MK, Lin, J, Boyer, PD, Candiello, JE, Merryman, WD, Guelcher, SA, Weaver, AM. Sensing and modulation of invadopodia across a wide range of rigidities. Biophys J, 100(3), 573-82, 2011 PMCID:3030182

Sung, B.H. and A.M. Weaver. Cortactin regulation of lysosomal secretion drives fibronectin deposition and cell motility. Bioarchitecture, 1, 257-260, 2011

Sung, BH, Zhu, X, Kaverina, I, Weaver, AM. Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion. Curr Biol, 21(17), 1460-9, 2011 PMCID:3175319

Liu, S, Yamashita, H, Weidow, B, Weaver, AM, Quaranta, V. Laminin-332-beta1 integrin interactions negatively regulate invadopodia. J Cell Physiol, 223(1), 134-42, 2010 PMCID:2835765

Potdar, AA, Jeon, J, Weaver, AM, Quaranta, V, Cummings, PT. Human mammary epithelial cells exhibit a bimodal correlated random walk pattern. PLoS One, 5(3), e9636, 2010 PMCID:2835765

Clark, ES, Brown, B, Whigham, AS, Kochaishvili, A, Yarbrough, WG, Weaver, AM. Aggressiveness of HNSCC tumors depends on expression levels of cortactin, a gene in the 11q13 amplicon. Oncogene, 28(3), 431-44, 2009 PMCID:2709457

Parekh, A, Weaver, AM. Regulation of cancer invasiveness by the physical extracellular matrix environment. Cell Adh Migr, 3(3), 288-92, 2009 PMCID:2835765

Potdar, AA, Lu, J, Jeon, J, Weaver, AM, Cummings, PT. Bimodal analysis of mammary epithelial cell migration in two dimensions. Ann Biomed Eng, 37(1), 230-45, 2009

Weaver, AM. Regulation of cancer invasion by reactive oxygen species and Tks family scaffold proteins. Sci Signal, 2(88), pe56, 2009 PMCID:2835765

Alexander, NR, Branch, KM, Parekh, A, Clark, ES, Iwueke, IC, Guelcher, SA, Weaver, AM. Extracellular matrix rigidity promotes invadopodia activity. Curr Biol, 18(17), 1295-9, 2008 PMCID:2555969

Clark, ES, Weaver, AM. A new role for cortactin in invadopodia: Regulation of protease secretion. Eur J Cell Biol, 2008 PMCID:2566933

Jeon, J, Alexander, NR, Weaver, AM, Cummings, PT. Protrusion of a Virtual Model Lamellipodium by Actin Polymerization: A Coarse-grained Langevin Dynamics Model. J Stat Phys, 133(1), 79-100, 2008 PMCID:2846375

Weaver, AM. Cortactin in tumor invasiveness. Cancer Lett, 265(2), 157-66, 2008 PMCID:2460566

Weaver, AM. Invadopodia. Curr Biol, 18(9), R362-4, 2008

Wegner, AM, Nebhan, CA, Hu, L, Majumdar, D, Meier, KM, Weaver, AM, Webb, DJ. N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses. J Biol Chem, 283(23), 15912-20, 2008 PMCID:2414292

Clark, ES, Whigham, AS, Yarbrough, WG, Weaver, AM. Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res, 67(9), 4227-35, 2007

Anderson, AR, Weaver, AM, Cummings, PT, Quaranta, V. Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment. Cell, 127(5), 905-15, 2006

Weaver, AM. Invadopodia: specialized cell structures for cancer invasion. Clin Exp Metastasis, 23(2), 97-105, 2006

Bryce, NS, Clark, ES, Leysath, JL, Currie, JD, Webb, DJ, Weaver, AM. Cortactin promotes cell motility by enhancing lamellipodial persistence. Curr Biol, 15(14), 1276-85, 2005

Quaranta, V, Weaver, AM, Cummings, PT, Anderson, AR. Mathematical modeling of cancer: the future of prognosis and treatment. Clin Chim Acta, 357(2), 173-9, 2005

Weaver, AM. Cytoskeletal interactions with the outside world. Dev Cell, 9(1), 35-8, 2005

Br?!bek, J, Constancio, SS, Shin, NY, Pozzi, A, Weaver, AM, Hanks, SK. CAS promotes invasiveness of Src-transformed cells. Oncogene, 23(44), 7406-15, 2004

Kinley, AW, Weed, SA, Weaver, AM, Karginov, AV, Bissonette, E, Cooper, JA, Parsons, JT. Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion. Curr Biol, 13(5), 384-93, 2003

Weaver, AM, Young, ME, Lee, WL, Cooper, JA. Integration of signals to the Arp2/3 complex. Curr Opin Cell Biol, 15(1), 23-30, 2003

Weaver, AM, Heuser, JE, Karginov, AV, Lee, WL, Parsons, JT, Cooper, JA. Interaction of cortactin and N-WASp with Arp2/3 complex. Curr Biol, 12(15), 1270-8, 2002

Cooper, JA, Wear, MA, Weaver, AM. Arp2/3 complex: advances on the inner workings of a molecular machine. Cell, 107(6), 703-5, 2001

Weaver, AM, Karginov, AV, Kinley, AW, Weed, SA, Li, Y, Parsons, JT, Cooper, JA. Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr Biol, 11(5), 370-4, 2001

Weed, SA, Karginov, AV, Schafer, DA, Weaver, AM, Kinley, AW, Cooper, JA, Parsons, JT. Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex. J Cell Biol, 151(1), 29-40, 2000 PMCID:2189811

Hussaini, IM, Brown, MD, Weaver, AM, Carpenter, J, Karns, LR, Vandenberg, SR, Gonias, SL. Stable antisense RNA expression neutralizes the activity of low-density lipoprotein receptor-related protein and promotes urokinase accumulation in the medium of an astrocytic tumor cell line. Antisense Nucleic Acid Drug Dev, 9(2), 183-90, 1999

Harthun, NL, Weaver, AM, Brinckerhoff, LH, Deacon, DH, Gonias, SL, Slingluff, CL. Activated alpha 2-macroglobulin reverses the immunosuppressive activity in human breast cancer cell-conditioned medium by selectively neutralizing transforming growth factor-beta in the presence of interleukin-2. J Immunother, 21(2), 85-94, 1998

Harthun, N.L., Weaver, A.M., Deacon, D.H., Gonias, S.L., and C.L. Slingluff. Production of soluble immunosuppressive factors by human breast cancer and the neutralization of these factors by activated a2-macroglobulin. Surgical Forum, 47, 485-487, 1997

Weaver, AM, Hussaini, IM, Mazar, A, Henkin, J, Gonias, SL. Embryonic fibroblasts that are genetically deficient in low density lipoprotein receptor-related protein demonstrate increased activity of the urokinase receptor system and accelerated migration on vitronectin. J Biol Chem, 272(22), 14372-9, 1997

Weaver, AM, Lysiak, JJ, Gonias, SL. LDL receptor family-dependent and -independent pathways for the internalization and digestion of lipoprotein lipase-associated beta-VLDL by rat vascular smooth muscle cells. J Lipid Res, 38(9), 1841-50, 1997

Weaver, AM, McCabe, M, Kim, I, Allietta, MM, Gonias, SL. Epidermal growth factor and platelet-derived growth factor-BB induce a stable increase in the activity of low density lipoprotein receptor-related protein in vascular smooth muscle cells by altering receptor distribution and recycling. J Biol Chem, 271(40), 24894-900, 1996

Webb, DJ, Weaver, AM, Atkins-Brady, TL, Gonias, SL. Proteinases are isoform-specific regulators of the binding of transforming growth factor beta to alpha 2-macroglobulin. Biochem J, 320 ( Pt 2), 551-5, 1996 PMCID:1217964

Weaver, AM, Owens, GK, Gonias, SL. Native and activated forms of alpha 2-macroglobulin increase expression of platelet-derived growth factor alpha-receptor in vascular smooth muscle cells. Evidence for autocrine transforming growth factor-beta activity. J Biol Chem, 270(51), 30741-8, 1995

Webb, DJ, Hussaini, IM, Weaver, AM, Atkins, TL, Chu, CT, Pizzo, SV, Owens, GK, Gonias, SL. Activated alpha 2-macroglobulin promotes mitogenesis in rat vascular smooth muscle cells by a mechanism that is independent of growth-factor-carrier activity. Eur J Biochem, 234(3), 714-22, 1995

McCoy, JJ, Weaver, AM, Petri, WA. Use of monoclonal anti-light subunit antibodies to study the structure and function of the Entamoeba histolytica Gal/GalNAc adherence lectin. Glycoconj J, 11(5), 432-6, 1994

Earnhardt, RC, Kindler, DD, Weaver, AM, Cornett, G, Elahi, D, Veldhuis, JD, Hanks, JB. Hyperinsulinemia after pancreatic transplantation. Prediction by a novel computer model and in vivo verification. Ann Surg, 218(4), 428-41; discussion 441-3, 1993 PMCID:1242995


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
09/23/2012