Kathrin H. Kirsch

KirschAssociate Professor

Boston University School of Medicine
Silvio Conte Building, Office: K123C, Lab: K112
72 E. Concord Street
Boston, MA 02118

Phone: 617-638-4376
Lab Phone:


Dipl-Biol, Humboldt University, Berlin, Germany
PhD, Ludwig Maximilians University, Munich, Germany
Post-doctoral Training: The Rockefeller University, New York, NY

BU Profile


Ana de la Cueva
Postdoctoral associate

Research Interests

My laboratory is working on delineating molecular mechanisms that are important for tumor initiation and progression, with a specific focus on the expanding family of cytoplasmic adapter proteins.  We are investigating the participation of p130Cas family proteins in growth regulation in cancers of the mammary gland. We have developed a transgenic animal model expressing a dominant-interfering p130Cas to investigate the role(s) of this molecule in normal mammary development and in breast cancer in vivo induced by aberrant expression of ErbB and Src family tyrosine kinases.  Recently we have identified another adapter that associates with the SH3 domain of p130Cas, named CD2AP/CMS. We have found that CD2AP associates with the ubiquitin ligase c-Cbl in response to growth factors stimulation, and with F-actin.  Moreover, we showed that CD2AP forms heterotypic complexes with its family member CIN85, and that both molecules bundle F-actin in vitro. Our current work with CD2AP is focused on its roles in growth factor signaling, cell adhesion and migration, and in growth factor-mediated remodeling of the actin cytoskeleton. In a collaborative effort with Dr. Sonenshein and Dr. Trackman, we are working on elucidating the mechanism of action of lysyl oxidase (LOX) on inhibition of Ras-mediated transformation. We have demonstrated that the propeptide region of LOX attenuates Ras- and Her-2/neu-dependent breast cancers in vitro and in xenograft models. Studies are in the progress to elucidate the mechanism of this inhibition.  We are also investigating the activation of cancer associated fibroblasts (CAF) and their role in breast cancer progression. Long-term goals are to determine the potential for use the propeptide or derivatives in treatment of patients with Her-2/neu or Ras-mediated breast disease.

Research Themes

Cell Biology

Representative Publications

Pubmed Search

  • Kumbrink J, de la Cueva A, Soni S, Sailer N, Kirsch KH. A truncated phosphorylated p130Cas substrate domain is sufficient to drive breast cancer growth and metastasis formation in vivo. Tumour Biol. 2016 Feb 11. PubMed
  • Rouka E, Simister PC, Janning M, Kumbrink J, Konstantinou T, Muniz JR, Joshi D, O”Reilly N, Volkmer R, Ritter B, Knapp S, von Delft F, Kirsch KH, Feller SM. Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3). J Biol Chem. 2015 Oct 16; 290(42):25275-92. PubMed
  • Kumbrink J, Soni S, Laumbacher B, Loesch B, Kirsch KH. Identification of Novel Crk-associated Substrate (p130Cas) Variants with Functionally Distinct Focal Adhesion Kinase Binding Activities. J Biol Chem. 2015 May 8; 290(19):12247-55. PubMed
  • Chen CH, Ho YC, Ho HH, Chang IC, Kirsch KH, Chuang YJ, Layne MD, Yet SF. Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration. Cardiovasc Res. 2013 Dec 1; 100(3):461-71. PubMed
  • Sato S, Zhao Y, Imai M, Simister PC, Feller SM, Trackman PC, Kirsch KH, Sonenshein GE. Inhibition of CIN85-mediated invasion by a novel SH3 domain binding motif in the lysyl oxidase propeptide. PLoS One. 2013; 8(10):e77288. PubMed
  • p130Cas acts as survival factor during PMA-induced apoptosis in HL-60 promyelocytic leukemia cells. Kumbrink J, Kirsch KH. Int J Biochem Cell Biol. 2013 Mar;45(3):531-5.
  • Insulin Inhibits Lipolysis in Adipocytes via the Evolutionarily Conserved mTORC1-Egr1-ATGL-Mediated Pathway.Chakrabarti P, Kim JY, Singh M, Shin YK, Kim J, Kumbrink J, Wu Y, Lee MJ, Kirsch KH, Fried SK, Kandror KV. Mol Cell Biol. 2013 Sep;33(18):3659-66.
  • Expression of a phosphorylated substrate domain of p130Cas promotes PyMT-induced c-Src-dependent murine breast cancer progression. Zhao Y, Kumbrink J, Lin BT, Bouton AH, Yang S, Toselli PA, Kirsch KH. Carcinogenesis. 2013 Aug 16. [Epub ahead of print]
  • Blimp1 activation by AP-1 in human lung cancer cells promotes a migratory phenotype and is inhibited by the lysyl oxidase propeptide. Yu Z, Sato S, Trackman PC, Kirsch KH, Sonenshein GE. PLoS One. 2012;7(3):e33287. Epub 2012 Mar 15.
  • Kumbrink, J and Kirsch K.H.  Regulation of p130Cas/BCAR1 expression in tamoxifen sensitive and tamoxifen resistant breast cancer cells by EGR1 and NAB2.  (2012) Neoplasia: 1-13.
  • Kumbrink, J and Kirsch K.H. Targeting Cas family proteins as novel treatment for breast cancer, Breast Cancer – Current and Alternative Therapeutic Modalities. Esra Gunduz and Mehmet Gunduz (Ed.), InTech. (2011) ISBN: 978-953-307-776-5, 37-62.Targeting Cas Family Proteins as a Novel Treatment for Breast Cancer
  • Sánchez-Morgan, N., Kirsch K.H.,Trackman, P.C. and Sonenshein, G.E. The Lysyl Oxidase Propeptide Interacts with the Receptor Protein Type Phosphatase-Kappa and Inhibits b-Catenin Transcriptional Activity in Lung Cancer Cells. Mol Cell Biol. (2011) 31:3286-3297
  • Sato S., Trackman, P.C., Mäki, J., Myllyharju, J., Kirsch, K.H., and Sonenshein, G.E. The Ras Signaling Inhibitor LOX-PP Interacts with Hsp70 and c-Raf to Reduce Erk Activation and Transformed Phenotype of Breast Cancer Cells. Mol Cell Biol. (2011) 31:2683-2695.
  • Min C., Zhao Y., Romagnoli M., Trackman P.C., Sonenshein G.E., and Kirsch K.H. Lysyl Oxidase Propeptide Sensitizes Pancreatic and Breast Cancer Cells to Doxorubicin-Induced Apoptosis. J Cell Biochem. (2010) 111:1160-1168.
  • Palamakumbura A.H., S.R. Vora, M.A. Nugent, K.H. Kirsch G.E. Sonenshein and P.C. Trackman. Lysyl Oxidase Pro-peptide Inhibits Prostate Cancer Cell Growth by Mechanisms that Include FGF-2 Cell Binding and Signaling. Oncogene. (2009) Jul 13. [Epub ahead of print]. PMID: 19597471
  • Min C., Z. Yu, K.H. Kirsch, Y. Zhao, S.R. Vora, P.C. Trackman, D.B. Spicer, L. Rosenberg, J.R. Palmer and G.E. Sonenshein. A loss of function polymorphism in the propeptide domain of the LOX gene and breast cancer. Cancer Res. (2009) 69:6685-6693. PMID: 19654310
  • Soni, S., B.-T. Lin, A. August, R.I. Nicholson, K.H. Kirsch*. Expression of a phosphorylated p130Cas substrate domain attenuates the phosphatidylinositol 3-kinase/Akt survival pathway in tamoxifen resistant breast cancer cells. J. Cell. Biochem. (2009) 107:364-375. PMID: 19330798
  • Zhao, Y., C. Min, S. Vora, P.C. Trackman, G.E. Sonenshein, K.H. Kirsch*. The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of FAK and p130Cas in breast cancer cells. J. Biol. Chem (2009) 284: 1385-1393.  PMID: 19029090
  • Min C, K.H. Kirsch, Y. Zhao, S. Jeay, A.H. Palamakumbura, P.C. Trackman, G.E. Sonenshein. The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/neu-driven breast cancer. Cancer Res. (2007) 67:1105-12.
  • Gaidos G, S. Soni, D.J. Oswald, P.A. Toselli, and K.H. Kirsch. Structure and function analysis of the CMS/CIN85 protein family identifies actin-bundling properties and heterotypic-complex formation. J Cell Sci. (2007) 120:2366-77.
  • Wang X., K. Belguise, N. Kersual, K.H. Kirsch, N.D. Mineva, F. Galtier, D. Chalbos, and G.E. Sonenshein. Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2. Nat Cell Biol. (2007) 9:470-478
  • Kirsch K.H., M. Kensinger, H. Hanafusa, and A. August. A p130Cas tyrosine phosphorylated substrate domain decoy disrupts v-Crk signaling. (2002) BMC Cell Biol. 3:18
  • Kirsch, K.H., M.-M. Georgescu, T. Shishido, W. Y. Langdon, R. Birge and H. Hanafusa. The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl though a tyrosine phosphorylation-regulated Src homology 3 domain interaction. J. Biol. Chem. (2001) 276:4957-4963.
  • Kirsch, K.H., M.-M. Georgescu, S. Ishimaru, and H. Hanafusa. CMS: An adapter molecule involved in cytoskeletal rearrangements. Proc. Natl. Acad. Sci. USA (1999) 96:6211-6216.
  • Kirsch, K.H., M.-M. Georgescu, and H. Hanafusa. Direct binding of p130Cas to guanine nucleotide exchange factor C3G. J. Biol. Chem. (1998) 273:25673-25679.