Kathrin H. Kirsch, PhD

Associate Professor, Biochemistry

Kathrin Kirsch
(617) 638-4376
72 E. Concord St Silvio Conte (K)

Biography

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.

Other Positions

  • Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences

Education

  • Ludwig-Maximilians-Universität München, PhD

Publications

  • Published on 4/25/2017

    Sánchez-Morgan N, Kirsch KH, Trackman PC, Sonenshein GE. UXT Is a LOX-PP Interacting Protein That Modulates Estrogen Receptor Alpha Activity in Breast Cancer Cells. J Cell Biochem. 2017 Aug; 118(8):2347-2356. PMID: 28106301.

    Read at: PubMed
  • Published on 2/11/2016

    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 Aug; 37(8):10665-73. PMID: 26867768.

    Read at: PubMed
  • Published on 8/20/2015

    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. PMID: 26296892.

    Read at: PubMed
  • Published on 3/24/2015

    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. PMID: 25805500.

    Read at: PubMed
  • Published on 10/22/2013

    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. PMID: 24167568.

    Read at: PubMed
  • Published on 8/23/2013

    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. PMID: 23975851.

    Read at: PubMed
  • Published on 7/15/2013

    Chakrabarti P, Kim JY, Singh M, Shin YK, Kim J, Kumbrink J, Wu Y, Lee MJ, Kirsch KH, Fried SK, Kandror KV. Insulin inhibits lipolysis in adipocytes via the evolutionarily conserved mTORC1-Egr1-ATGL-mediated pathway. Mol Cell Biol. 2013 Sep; 33(18):3659-66. PMID: 23858058.

    Read at: PubMed
  • Published on 7/3/2013

    Zhao Y, Kumbrink J, Lin BT, Bouton AH, Yang S, Toselli PA, Kirsch KH. Expression of a phosphorylated substrate domain of p130Cas promotes PyMT-induced c-Src-dependent murine breast cancer progression. Carcinogenesis. 2013 Dec; 34(12):2880-90. PMID: 23825155.

    Read at: PubMed
  • Published on 12/31/2012

    Kumbrink J, Kirsch KH. p130Cas acts as survival factor during PMA-induced apoptosis in HL-60 promyelocytic leukemia cells. Int J Biochem Cell Biol. 2013 Mar; 45(3):531-5. PMID: 23287717.

    Read at: PubMed
  • Published on 3/15/2012

    Yu Z, Sato S, Trackman PC, Kirsch KH, Sonenshein GE. Blimp1 activation by AP-1 in human lung cancer cells promotes a migratory phenotype and is inhibited by the lysyl oxidase propeptide. PLoS One. 2012; 7(3):e33287. PMID: 22438909.

    Read at: PubMed

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