.

Department of Pathology, Microbiology, and Immunology

 

 

   Alissa M. Weaver, M.D., Ph.D.

 

 

Associate Professor

Dept of Cancer Biology

Dept of Pathology, Microbiology and Immunology

 

 

  Contact Information

 

 

Office Location:

748 PRB
   
Phone: 615-936-3529
 
Lab Url: http://people.vanderbilt.edu/~alissa.weaver/

 

  Campus Mail address: 

  Cancer Biology

  771 PRB (6840)


  US Mailing address:
  Cancer Biology
  Vanderbilt University School of Medicine
  771 PRB
  Nashville, TN 37232-6840
 

 

 

 

Education

 

 

M.D., University of Virginia, Charlottesville, VA
Ph.D. , University of Virginia, Charlottesville, VA
B.S., Stanford University, Stanford, CA
B.A. , Stanford University, Stanford, CA

 

 

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

 

 

Research Description

 

 

Cancer metastasis--the spread of cancer cells to distant organs--is what kills the majority of cancer patients. In order for cells to metastasize, they must acquire an invasive and motile phenotype, degrading and moving through tissue barriers. In addition, they must be able to survive and grow at distant sites in the body. The Weaver laboratory studies all aspects of this process. We are particularly focused on how secretion of small extracellular vesicles called exosomes from cells promotes aggressive, invasive behavior and facilitates tumor growth and metastasis. Specific projects include: 1) Induction of invasive protrusion formation and exosome secretion by deregulated signaling; 2) The role of exosome secretion in tumor progression; and 3) Trafficking of RNAs in cancer exosomes.




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.
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Publications

 

 

Bryce, NS, Reynolds, AB, Koleske, AJ, Weaver, AM. WAVE2 regulates epithelial morphology and cadherin isoform switching through regulation of Twist and Abl. PLoS One, 8(5), e64533, 2013

Hoshino, D, Branch, KM, Weaver, AM. Signaling inputs to invadopodia and podosomes. J Cell Sci, 126(Pt 14), 2979-89, 2013

Weaver, AM, Page, JM, Guelcher, SA, Parekh, A. Synthetic and tissue-derived models for studying rigidity effects on invadopodia activity. Methods Mol Biol, 1046, 171-89, 2013

Benesh, EC, Miller, PM, Pfaltzgraff, ER, Grega-Larson, NE, Hager, HA, Sung, BH, Qu, X, Baldwin, HS, Weaver, AM, Bader, DM. Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition. Mol Biol Cell, 24(22), 3496-510, 2013

Hoshino, D, Kirkbride, KC, Costello, K, Clark, ES, Sinha, S, Grega-Larson, N, Tyska, MJ, Weaver, AM. Exosome secretion is enhanced by invadopodia and drives invasive behavior. Cell Rep, 5(5), 1159-68, 2013

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

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

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

Branch, KM, Hoshino, D, Weaver, AM. Adhesion rings surround invadopodia and promote maturation. Biol Open, 1(8), 711-22, 2012

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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, 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

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

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

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, 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

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